bluuebunny/crossref_metadata_2025 huggingface dataset:
CD38 Inhibits Prostate Cancer Metabolism and Proliferation by Reducing Cellular NAD+ Pools
Authors: Chmielewski Jeffrey P. , Bowlby Sarah C. , Wheeler Frances B. , Shi Lihong , Sui Guangchao , Davis Amanda L. , Howard Timothy D. , D'Agostino Ralph B. , Miller Lance D. , Sirintrapun S. Joseph , Cramer Scott D. , Kridel Steven J.
Published: August 2018

Tumor cells require increased rates of cell metabolism to generate the macromolecules necessary to sustain proliferation. They rely heavily on NAD+ as a cofactor for multiple metabolic enzymes in anabolic and catabolic reactions. NAD+ also serves as a substrate for PARPs, sirtuins, and cyclic ADP-ribose synthases. Dysregulation of the cyclic ADP-ribose synthase CD38, the main NAD'ase in cells, is reported in multiple cancer types. This study demonstrates a novel connection between CD38, modulation of NAD+, and tumor cell metabolism in prostate cancer. CD38 expression inversely correlates with prostate cancer progression. Expressing CD38 in prostate cancer cells lowered intracellular NAD+, resulting in cell-cycle arrest and expression of p21Cip1 (CDKNA1). In parallel, CD38 diminishes glycolytic and mitochondrial metabolism, activates AMP-activated protein kinase (AMPK), and inhibits fatty acid and lipid synthesis. Pharmacologic inhibition of nicotinamide phosphoribosyltransferase (NAMPT) mimicked the metabolic consequences of CD38 expression, demonstrating similarity between CD38 expression and NAMPT inhibition. Modulation of NAD+ by CD38 also induces significant differential expression of the transcriptome, producing a gene expression signature indicative of a nonproliferative phenotype. Altogether, in the context of prostate cancer, the data establish a novel role for the CD38–NAD+ axis in the regulation of cell metabolism and development.

Implications: This research establishes a mechanistic connection between CD38 and metabolic control. It also provides the foundation for the translation of agents that modulate NAD+ levels in cancer cells as therapeutics. Mol Cancer Res; 16(11); 1687–700. ©2018 AACR.
Knockdown of Long Non-Coding RNA GAS5 Increases miR-23a by Targeting ATG3 Involved in Autophagy and Cell Viability
Authors: Li Lexing , Huang Chunxiao , He Yulong , Sang Zhan , Liu Guoquan , Dai Hanchuan
Published: August 2018

Background/Aims: Autophagy is a process of evolutionarily conservative degradation, which could maintain cellular homeostasis and cope with various types of stress. LncRNAs are considered as competing endogenous RNAs (ceRNAs) contributing to autophagy. GAS5 has been suggested as a new potential factor to mediate autophagy pathway and the underlying mechanism remains to be further confirmed. This study was taken to identify the effect of GAS5/miR-23a/ATG3 axis on autophagy and cell viability. Methods: The western blotting assay was used to detecte the protein levels of LC3, mTOR, Beclin-1, ATG3, ATG5-ATG12 complex and p62. The mRNA level of Pre-miR-23a, Pri-miR-23a, miR-23a, GAS5, LC3, mTOR and ATG3 were quantified by real-time RT-PCR. Dual-luciferase reporter assays were performed to confirm the direct binding of miR-23a and ATG3 or GAS5. Cell viability was evaluated by CCK-8 and flow cytometry. Results: We showed that miR-23a could directly suppress ATG3 expression in 293T cells, which suggested that ATG3 was identified as a target of miR-23a. MiR-23a mimics could restrain LC3 II, Beclin1 levles and ATG5-ATG12 complex formation. Meanwhile, miR-23a also increased the expression of mTOR and p62. Notably, there was a putative miR-23a-binding site in GAS5. MiR-23a overexpression might suppress the GAS5 expression, but the repressive effect was abolished by mutation of binding sites. Importantly, overexpression of GAS5 could inhibit the mature miR-23a and has no effect on miR-23a precursors. Knockdown of GAS5 suppressed the expression of LC3 II, ATG3 and ATG5-ATG12 complex formation, whereas p62 and mTOR levels were promoted. The further results showed that miR-23a overexpression and GAS5 inhibition both significantly suppressed cell viability and promoted the apoptosis rate following LPS stimulation, and knockdown of miR-23a exhibited the opposite effects. Conclusions: Our study revealed that down-regulation GAS5 attenuated cell viability and inhibited autophagy through ATG3-dependent autophagy by regulating miR-23a expression. The results suggested that GAS5/miR-23a/ATG3 axis might be a novel regulatory network contributing to a better understanding of regulation on autophagy program and cell viability.
MicroRNA-224 Promotes Pancreatic Cancer Cell Proliferation and Migration by Targeting the TXNIP-Mediated HIF1α Pathway
Authors: Zhu Guanghui , Zhou Lianming , Liu Haijun , Shan Yuanzhou , Zhang Xueli
Published: August 2018

Background/Aims: MicroRNAs (miRNAs) have been shown to participate in the development of pancreatic ductal adenocarcinoma (PDAC) by modulating multiple cellular processes. Increased miR-224 expression enhances proliferation and metastasis in human cancers. This study aimed to investigate the role of miR-224 and its underlying mechanism of action in PDAC. Methods: BrdU, MTT, and cell migration assays were performed to determine cell proliferation, viability, and migration, respectively. The binding sites of miR-224 were identified using a luciferase reporter system, whereas protein expression of target genes was determined by immunoblotting and immunofluorescence analyses. A BALB/c nude mouse xenograft model was used to evaluate the role of miR-224 in vivo. Results: We demonstrated that miR-224 expression was enhanced in PDAC cells and tissues, and was related to migration and proliferation. Noticeably, miR-224 overexpression promoted the proliferation, migration, and metastasis of Panc1 cells, while miR-224 inhibition had the reverse effect on PDAC cells. Moreover, we found that thioredoxin-interacting protein (TXNIP) is a target of miR-224. The results also indicated that miR-224 inversely regulated TXNIP by binding directly to its 3′-untranslated region, which resulted in the activation of hypoxia-inducible factor 1α (HIF1α). Further, either TXNIP re-expression or HIF1α depletion abolished the effects of miR-224 on the proliferation and migration of PDAC cells in vitro and in vivo. Regarding the relationship of TXNIP and HIF1α, we found that TXNIP mediated the nuclear export of HIF1α and its degradation by forming a complex with HIF1α. Conclusion: The miR-224-TXNIP-HIF1α axis may be useful in developing novel therapies for PDAC.
The RNA-Binding Protein PCBP1 Functions as a Tumor Suppressor in Prostate Cancer by Inhibiting Mitogen Activated Protein Kinase 1
Authors: Zhang Yingying , Meng Lin , Xiao Lin , Liu Ruiwang , Li Zhonghai , Wang Ying-lei
Published: August 2018

Background/Aims: Poly r(C) binding protein (PCBP) 1 or heterogeneous ribonucleoprotein (hnRNP) E1 is a RNA binding protein functional in multiple biological processes. In prostate cancer (PCa), PCBP1 loss was shown to be involved with increased stemness in PCacells; however, the underlying mechanism remains unclear. Method: The role of PCBP1 in prostate tumor formationwas determined by xenograft assays. Immunoprecipitationand mass spectrometry were performed to find the pathways altered after PCBP1 knockdown. Cell proliferation, migration, invasion, and soft agar colony formationassays and xenograft assays were used to determine the role of target protein pathogenesis regulation and formation of PCa. QRT-PCR was performedto quantify relative mRNA expression. Results: The expression of mitogen activated protein kinase 1 (MAPK1) or extracellular signal regulated kinase 2 (ERK2) was increased following PCBP1 loss. Attenuation of MAPK1 inhibited in vitro and in vivo tumorigenicity and metastasis in PCa cell line, PC3. Overexpression of MAPK1 in the PC3 cells increased the tumorigenicity and metastasis. Analysis of PCBP1 and MAPK1 mRNA levels in 25 PCa patients compared to tumor-adjacent normal tissue confirmed an inverse correlation between PCBP1 and MAPK1 expression. Conclusions: PCBP1 can act as a suppressor of tumor in prostate epithelial cells by inhibiting MAPK1 expression.
miRNA-125b Regulates Osteogenic Differentiation of Periodontal Ligament Cells Through NKIRAS2/NF-κB Pathway
Authors: Xue Nan , Qi Lin , Zhang Guorong , Zhang Yang
Published: August 2018

Background/Aims: Osteogenesis of periodontal ligament cells (PDLCS) is essential for alveolar bone repair. Varieties of factors have been found involved in the regulation of PDLCs osteoblast differentiation. Aim of this study was to identify microRNA as a regulator of the os-teogenic differentiation of PDLCs. Methods: The CD markers were analyzed by flow cytometry analysis. Osteoblast differentiation of PDLCs was induced by treatment with dexamethasone, β-glycerol phosphate and α-ascorbic acid. The expression of osteoblastic phenotype was evaluated after the induction by simultaneous monitoring of alkaline phosphatase activity, the expression of genes involved in osteoblastic differentiation by RT-qPCR and Western Blot, and mineralization at the same time. MicroRNA and NKIRAS2 expression was determined by RT-qPCR. Luciferase reporter assays were performed to test whether miR-125b is capable of interacting with the 3’UTR sequence of NKIRAS2. The possible signaling pathway was determined by Western Blot. Results: In this study, we found that the expression of miR-125b was down regulated during the process of ostoblast differentiation of PDLCs. When the expression of miR-125b was up regulated, the osteogenic differentiation of PDLCs was inhibited. During this process, the over-expressed miR-125b led to the activation of NF-κB. NF-κB inhibitor interacting RAS-like 2 (NKIRAS2) is one of target gene of miR-125b, and it is a regulator of NF-κB signaling that plays various roles in osteoblastic differentiation. We demonstrate thatmiR-125b is involved in osteogenic differentiation of PDLCs. Conclusion: Our data support the hypothesis that that miR-125b attenuates PDLCs osteoblastic differentiation by targeting NKIRAS2 and enhancing NF-κB signaling.
Structural changes in bird communities before and after coppice management practices: a comparison using a diversity/dominance approach
Authors: Battisti Corrado , Marini Francesca
Published: August 2018

We report data on the effects of coppice management on breeding birds in paired oak woods of central Italy using a Before-After-Control-Impact sampling design, hypothesizing that this practice strongly affect abundance, richness and diversity at community level. Using point count method, we obtained first evidence of a coppice management effect acting as a stressor on the breeding bird assemblage structure. We observed a significant decrease in averaged species richness and abundance in coppiced areas before and after the coppicing practices, differently from the control area. Analogously, regression lines derived by species frequencies in diversity/dominance diagrams showed a different trends when comparing the coppiced areas before and after the cutting, indicating a stress in the latter. This pattern is supported by the H’ diversity and evenness values that changed abruptly between years only in the coppiced area. These changes can be related to the significant reduction in tree plant density before and after cutting, especially for those with a diameter between 7.5 and 23 cm.
Intraseasonal Effects of El Niño–Southern Oscillation on North Atlantic Climate
Authors: Ayarzagüena Blanca , Ineson Sarah , Dunstone Nick J. , Baldwin Mark P. , Scaife Adam A.
Published: August 2018

It is well established that El Niño–Southern Oscillation (ENSO) impacts the North Atlantic–European (NAE) climate, with the strongest influence in winter. In late winter, the ENSO signal travels via both tropospheric and stratospheric pathways to the NAE sector and often projects onto the North Atlantic Oscillation. However, this signal does not strengthen gradually during winter, and some studies have suggested that the ENSO signal is different between early and late winter and that the teleconnections involved in the early winter subperiod are not well understood. In this study, we investigate the ENSO teleconnection to NAE in early winter (November–December) and characterize the possible mechanisms involved in that teleconnection. To do so, observations, reanalysis data and the output of different types of model simulations have been used. We show that the intraseasonal winter shift of the NAE response to ENSO is detected for both El Niño and La Niña and is significant in both observations and initialized predictions, but it is not reproduced by free-running Coupled Model Intercomparison Project phase 5 (CMIP5) models. The teleconnection is established through the troposphere in early winter and is related to ENSO effects over the Gulf of Mexico and Caribbean Sea that appear in rainfall and reach the NAE region. CMIP5 model biases in equatorial Pacific ENSO sea surface temperature patterns and strength appear to explain the lack of signal in the Gulf of Mexico and Caribbean Sea and, hence, their inability to reproduce the intraseasonal shift of the ENSO signal over Europe.
Who listens to the top? Integration of the largest corporations across sectoral networks
Authors: Larsen Anton Grau , Ellersgaard Christoph Houman
Published: August 2018

Corporations use ties to other powerful organisations to influence the rules that structure their markets and the society in which they operate. The corporate interlocks created by board directors show how some corporations are more successful than others in integrating not only in the corporate world but also in other sectors. Neil Fligstein suggested that the best-organised and dominating corporations, or the incumbents, are the most successful in stabilising their markets. To explore the relationship between corporate networks and integration in other sectors in the setting of a small, open, but highly regulated economy, we analysed the intersection between the interlocking directorates among the top 1037 corporations in Denmark and seven other sectoral networks. We used a database containing 5079 affiliations and 56,536 positions, and show that the incumbents were better integrated across all sectors. The strong correlation between sectoral integration and turnover was deconstructed and an independent effect of prominence, or symbolic capital, was found. This suggests that when creating affiliations within and outside the corporate world it is not only the economic size that matters, but also the prestige of the firm.
Treating Co-Occurring Disorders in Jails: Outcome Findings From a Second Chance Act Offender Reentry Program
Authors: Miller J. Mitchell , Miller Holly Ventura , Barnes J. C.
Published: August 2018

Widespread implementation of offender reentry programming has increased justice program evaluations but few have featured research designs sufficiently rigorous to optimally inform policy. Program evaluations typically neglect program fidelity concerns to focus on outcome analysis that seldom feature optimal spuriousness reduction. The current study, the second component of a mixed-method design evidencing fidelity, presents the methods and outcome findings for the Delaware County Transition (DCT) Program, an Ohio jail-based crimesolutions.gov endorsed treatment intervention for dually diagnosed offenders. Review of the reentry and dual-diagnosis literature provides a background for description of the DCT program and methods employed to observe programming effects. Findings indicated DCT participation was associated with overall recidivism reductions and time to recidivism and orient discussion around related rehabilitative modalities.
‘Who said We are Politically Inactive?’: A Reappraisal of the Youth and Political Party Activism in Ghana 2004–2012 (A Case of the Kumasi Metropolis)
Authors: Owusu Nsiah Isaac
Published: August 2018

There is a prevailing opinion that, in almost every election, young people are the least likely to vote and these participation rates are continuously declining; youth membership of political parties is dropping (partisanship), they are less politically knowledgeable, do not participate in social or political activities, have low levels of political interest, and other factors. This research, conducted in the Kumasi Metropolis, shows that the youth are associated with political parties and thus provide a strong indication that the youth in Ghana are very active in politics and thus their engagement comes with factors that serve as a driving force.
Influence of structural parameters at microscale on the fiber reinforcement
Authors: Li Chen , Cantarel Arthur , Gong Xiaojing
Published: August 2018

In this paper, a random configuration model for fiber arrangement is proposed and implemented in a computer code. This development enables the investigation of the effect of the random arrangements of the fibers inside the tow on the permeability and the flow properties. Four parameters are considered including three microstructural parameters: side length of the domain L, variation of radii Δ r, minimum interfiber distance δmin, and one macro parameter: porosity ɛ. Finite element method is performed for the transverse flow of porous media with random arrangements of fibers. Morris method for global sensitivity analysis is used to study the influence of four parameters. The results have shown that the porosity ɛ has the most obvious influence on the fiber reinforcement permeability.
An assessment of thermosetting infiltrate in powder-based composites made by additive manufacturing
Authors: Lizardo Breno Ferreira , Vieira Luciano Machado Gomes , Carlos Campos Rubio Juan , Panzera Tulio Hallak , Davim João Paulo
Published: August 2018

Rapid prototyping for material deposition or additive manufacturing has been widely used for short time production of parts with complex geometry in small series. The three-dimensional printing process needs post-processing to improve the strength, stiffness and/or surface finish of the parts. Printed parts in pristine condition are generally very brittle with a porous structure, so infiltrates have been introduced to improve their mechanical and physical characteristics. This work investigates the effect of two infiltrates, epoxy polymer and cyanoacrylate, under a vacuum pressure system on the mechanical properties of powder-based composites made by three-dimensional printing. Samples printed under pristine and infiltrated conditions were tested under tensile, flexural, compressive and impact loadings. The infiltrated samples achieved superior mechanical properties, especially when the epoxy polymer was applied via a vacuum system. The microstructural analysis showed that the infiltrates were not able to penetrate the entire sample, revealing a porous structure in the centre, mainly when the cyanoacrylate was used. The epoxy polymer infiltrate was able to substantially increase the mechanical performance of three-dimensional samples, being a promising material when higher structural requirements are required.
Effects of Starch on Oral Health: Systematic Review to Inform WHO Guideline
Authors: Halvorsrud K. , Lewney J. , Craig D. , Moynihan P.J.
Published: August 2018

A systematic review was conducted to update evidence on the effect of total dietary starch and of replacing rapidly digestible starches (RDSs) with slowly digestible starches (SDSs) on oral health outcomes to inform updating of World Health Organization guidance on carbohydrate intake. Data sources included MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, LILACS, and Wanfang. Eligible studies were comparative and reported any intervention with a different starch content of diets or foods and data on oral health outcomes relating to dental caries, periodontal disease, or oral cancer. Studies that reported total dietary starch intake or change in starch intake were included or where comparisons or exposure included diets and foods that compared RDSs and/or SDSs. The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) statement, and evidence was assessed with the GRADE Working Group guidelines. From 6,080 papers identified, 33 (28 studies) were included in the RDS versus SDS comparison: 15 (14 studies) assessed the relationship between SDS and/or RDS and dental caries; 16 (12 studies) considered oral cancer; and 2 studied periodontal disease. For total starch, 23 papers (22 studies) were included: 22 assessed the effects on dental caries, and 1 considered oral cancer. GRADE assessment indicated low-quality evidence, suggesting no association between total starch intake and caries risk but that RDS intake may significantly increase caries risk. Very low-quality evidence suggested no association between total starch and oral cancer risk, and low-quality evidence suggested that SDS decreases oral cancer risk. Data on RDS and oral cancer risk were inconclusive. Very low-quality data relating to periodontitis suggested a protective effect of whole grain starches (SDS). The best available evidence suggests that only RDS adversely affects oral health.
Modelling Everyday Understandings of Mortality: A Qualitative Enquiry
Authors: McEwan Oona , McDermott Mark R. , Hefferon Kate
Published: August 2018

With few exceptions, much of the literature on mortality awareness (MA; the realization of one’s own and other’s mortality), though based on quantitative research, is focused on its negative effects and processes associated with fearing its occurrence. However, recent studies have demonstrated that MA is multifaceted and can be associated with positive processes and outcomes. Here, everyday understandings of MA were investigated using grounded theory. Ten participants engaged in one-off semistructured interviews about their everyday experiences of MA. Grounded theory analysis revealed four main themes: (a) Moments of MA, (b) Functionality of MA, (c) Coping strategies for MA, and (d) Inability to cope with MA. Each of these themes is composed of two to five subthemes. The results supported the notion that MA is experienced in a multidimensional manner, which appears to align with elements of the Multidimensional Mortality Awareness Measure and Model. Furthermore, positive and/or negative outcomes appeared to depend on the function attributed to MA by the individual. Therefore, the ability to attribute such function to MA appears to be important in our understanding of this key existential issue.
How Reconceptualization of the Self Is Negotiated in Psychotherapy: An Exploratory Study of the Therapeutic Collaboration
Authors: Ribeiro Eugénia , Gonçalves Miguel M. , Santos Beatriz
Published: August 2018

This case study explores the collaboration that occurs between therapist and client when reconceptualization innovative moments emerge. Reconceptualization innovative moments are exceptions to the problematic self-narrative that brought the client to therapy and are associated with successful psychotherapy. Reconceptualization innovative moments have two main components: a contrast between a past problematic facet and a current, more adjusted one (e.g., before I did/thought/felt X . . . , now, I do/think/feel Y) and an attribution for what allowed this transformation to occur (e.g., this was possible because I realized Z). The collaboration between therapist and client was analyzed using the Therapeutic Collaboration Coding System, which conceptualizes the relationship as collaborative or as noncollaborative. The majority of interactions in this case were clearly collaborative, with the therapist and client working inside the therapeutic zone of proximal development, which is typical of successful psychotherapy cases. Reconceptualization innovative moments begin with collaborative exchanges in which the therapist supported the problem and the client elaborated on the change afterward. Implications of these findings for change in psychotherapy are discussed.
Diagnostic Nomenclatures in the Mental Health Professions as Public Policy
Authors: Zachar Peter
Published: August 2018

Commentary on Standards and Guidelines for the Development of Diagnostic Nomenclatures and Alternatives in Mental Health Research and Practice.
The Road to Cynicism: The Political Consequences of Online Satire Exposure in China
Authors: Shao Li , Liu Dongshu
Published: August 2018

This article examines two competing theories explaining the effects of political satire on citizens in an authoritarian context. The “activism” proposition argues that political satire works as a form of resistance to erode people’s support for the regime and encourages collective action. The “cynicism” proposition argues that while satire discourages regime support, it also discourages political participation. Our online survey experiment on young Chinese Internet users provides evidence supporting the cynicism proposition. Satire consumption reduces audiences’ political trust, deflates their political efficacy, and discourages them from participating in politics, as it reduces the perceived severity of political problems and implies that audience participation is useless. We conclude that the dissemination of political satire may stabilize the authoritarian regime temporarily but induces it to become erosive in the long run.
Built Capital as a Catalyst for Community-Based Tourism
Authors: Kline Carol , McGehee Nancy , Delconte John
Published: August 2018

This article focuses on the role of built capital as a catalyst for the development of other forms of capital in collective community-based tourism projects. As part of a regional initiative, modest built capital projects were implemented in six small towns in the Appalachian region of North Carolina. To discover how each community was affected, the impacts of these physical changes were documented, evaluated and categorized using Flora’s Community Capitals Framework. Over 100 interviews of stakeholders revealed how each project created new social and human capital, improving the community’s psyche, fostering confidence, camaraderie, gratification, and a sense of purpose both within and beyond the tourism-based focus. Additional capitals were cultivated, including spin-off projects, increased visitation by tourists, elected official support, and a more entrepreneurial community. Informants overwhelmingly reported that the physical changes acted as a symbol of the cohesiveness created from the community-centered and participatory approach.
Call Your Representatives: Connecting Classroom Learning to Real-world Policy Action
Authors: Ghoshal Raj
Published: August 2018

This article presents an in-class exercise that teaches students how to call elected officials about a course-related issue of their choice. The goals are to connect classroom learning with real-life action, to show that contacting elected officials need not be difficult or intimidating, and to help students develop a sense of efficacy that can contribute to ongoing engagement. I describe the exercise and present evidence that it led students to call their elected officials, most for the first time ever. I show that students find the exercise interesting and empowering and that it increases their civic comfort and self-reported likelihood of contacting a representative in the future.
EURAMED’s vision on medical radiation protection (research)
Authors: Hoeschen C.
Published: August 2018

While many areas of radiation protection have formed so-called ‘platforms’ in Europe which provide strategic research agendas for their areas of interest, this did not happen for a long while for medical exposure, which is the application of ionising radiation that causes the greatest man-made exposure, at least in first world countries. Finally, in 2015, a European medical radiation protection strategic research agenda was set up, and a corresponding platform was launched in 2016. This was named ‘EURAMED’ – the European Alliance for Medical Radiation Protection Research. In its strategic research agenda, EURAMED defined its vision for medical radiation protection and the corresponding research needed. Five major topics were identified, ranging from measurements of medical application-related parameters such as exposures and image quality and radiation biology aspects relevant for medical applications to individual optimisation strategies, to optimal use of techniques and harmonisation of practises, and finally to justification of the use of ionising radiation in medicine, all based on sufficient infrastructures for quality assurance. The ultimate goal is to reduce radiation exposure and risk individually for patients and staff by interdisciplinary research between clinicians, physicists, and engineers. Therefore, it is essential that the results are translated into clinical practice.
Effects of supervised exercise compared to non-supervised exercise early after total hip replacement on patient-reported function, pain, health-related quality of life and performance-based function – a systematic review and meta-analysis of randomized controlled trials
Authors: Hansen Sebrina , Aaboe Jens , Mechlenburg Inger , Overgaard Søren , Mikkelsen Lone Ramer
Published: August 2018

Background:

The rehabilitation after a total hip replacement varies in degree of supervision; however, it remains unknown whether supervised programmes are more effective than non-supervised.

Objective:

This study compared the effectiveness of supervised exercise compared to non-supervised home-based exercise after total hip replacement on patient-reported function, hip-pain, health-related quality of life and performance-based function.

Methods:

A systematic review and meta-analysis of randomized controlled trials investigating the effect of supervised exercise compared to non-supervised home-based exercise. An electronic search was performed in Medline, Embase and CINAHL on 14 March 2018. The methodological quality was assessed using the Cochrane Risk of Bias tool.

Results:

Seven studies were included with a total of 389 participants. A small and non-significant difference in favour of the supervised groups was found in patient-reported function (standardized mean difference (SMD) −0.22 (95% confidence interval (CI) −0.46 to 0.02)), hip-related pain (SMD −0.03 (95% CI −0.27 to 0.21)), health-related quality of life (mean difference (MD) −3.08 (95% CI −6.29 to 0.14)) and performance-based function (SMD −0.26 (95% CI −0.68 to 0.17)) at end of treatment and in patient-reported function (MD −1.31 (95% CI −3.79 to 1.16)) at the 6- to 12-month follow-up.

Limitations:

The literature search was systematic, but limited to three databases. The overall quality of evidence was downgraded to moderate due to lack of blinding in included studies.

Conclusion:

Supervised exercise was not significantly effective compared to non-supervised home-based exercise on patient-reported function, pain, health-related quality of life and performance-based function after primary total hip replacement.

Others:

PROSPERO registration number: CRD42017055604.
Communicating end-of-life care goals and decision-making among a multidisciplinary geriatric inpatient rehabilitation team: A qualitative descriptive study
Authors: Bloomer Melissa J , Botti Mari , Runacres Fiona , Poon Peter , Barnfield Jakqui , Hutchinson Alison M
Published: August 2018

Background:

In geriatric inpatient rehabilitation settings, where the goal is to optimise function, providing end-of-life care can be challenging.

Aim:

The aim of this study is to explore how end-of-life care goals and decision-making are communicated in a geriatric inpatient rehabilitation setting.

Design:

The design is a qualitative descriptive design using semi-structured individual and group interviews.

Setting/participants:

This study was conducted in a 154-bed facility in metropolitan Melbourne, Australia, providing geriatric inpatient rehabilitation for older patients; medical, nursing and allied health clinicians, who had cared for an inpatient who died, were recruited.

Data collection:

Participants were interviewed using a conversational approach, guided by an ‘aide memoire’.

Results:

A total of 19 clinicians participated in this study, with 12 interviewed individually and the remaining 7 clinicians participating in group interviews. The typical patient was described as older, frail and with complex needs. Clinicians described the challenge of identifying patients who were deteriorating towards death, with some relying on others to inform them. How patient deterioration and decision-making was communicated among the team varied. Communication with the patient/family about dying was expected but did not always occur, nor was it always documented. Some clinicians relied on documentation, such as commencement of a dying care pathway to indicate when a patient was dying.

Conclusion:

Clinicians reported difficulties recognising patient deterioration towards death. Uncertainty and inconsistent communication among clinicians about patient deterioration negatively impacted team understanding, decision-making, and patient and family communication. Further education for all members of the multidisciplinary team focusing on how to recognise and communicate impending death will aid multidisciplinary teams to provide quality end-of-life care when required.
Sensory stimulation in acute stroke therapy
Authors: von Bornstädt Daniel , Gertz Karen , Lagumersindez Denis Nielsen , Seners Pierre , Baron Jean-Claude , Endres Matthias
Published: August 2018

The beneficial effects of cortical activation for functional recovery after ischemic stroke have been well described. However, little is known about the role of early sensory stimulation, i.e. stimulation during first 6 h after stroke onset even during acute treatment. In recent years, various preclinical studies reported significant effects of acute sensory stimulation that range from entire neuroprotection to increased infarct volumes by 30–50%. Systematic knowledge about the effect of acute sensory stimulation on stroke outcome is highly relevant as stroke patients are subject to uncontrolled sensory stimulation during transport, acute treatment, and critical care. This article discusses the current stage of knowledge about acute sensory stimulation and provides directions for future experimental and clinical trials.
Prediction of Real-World Drug Effectiveness Prelaunch: Case Study in Rheumatoid Arthritis
Authors: Didden Eva-Maria , Ruffieux Yann , Hummel Noemi , Efthimiou Orestis , Reichenbach Stephan , Gsteiger Sandro , Finckh Axel , Fletcher Christine , Salanti Georgia , Egger Matthias
Published: August 2018

Background. Decision makers often need to assess the real-world effectiveness of new drugs prelaunch, when phase II/III randomized controlled trials (RCTs) but no other data are available. Objective. To develop a method to predict drug effectiveness prelaunch and to apply it in a case study in rheumatoid arthritis (RA). Methods. The approach 1) identifies a market-approved treatment ( S) currently used in a target population similar to that of the new drug ( N); 2) quantifies the impact of treatment, prognostic factors, and effect modifiers on clinical outcome; 3) determines the characteristics of patients likely to receive N in routine care; and 4) predicts treatment outcome in simulated patients with these characteristics. Sources of evidence include expert opinion, RCTs, and observational studies. The framework relies on generalized linear models. Results. The case study assessed the effectiveness of tocilizumab (TCZ), a biologic disease-modifying antirheumatic drug (DMARD), combined with conventional DMARDs, compared to conventional DMARDs alone. Rituximab (RTX) combined with conventional DMARDs was identified as treatment S. Individual participant data from 2 RCTs and 2 national registries were analyzed. The model predicted the 6-month changes in the Disease Activity Score 28 (DAS28) accurately: the mean change was -2.101 (standard deviation [SD] = 1.494) in the simulated patients receiving TCZ and conventional DMARDs compared to -1.873 (SD = 1.220) in retrospectively assessed observational data. It was -0.792 (SD = 1.499) in registry patients treated with conventional DMARDs. Conclusion. The approach performed well in the RA case study, but further work is required to better define its strengths and limitations.
An Exploratory Application of Eye-Tracking Methods in a Discrete Choice Experiment
Authors: Vass Caroline , Rigby Dan , Tate Kelly , Stewart Andrew , Payne Katherine
Published: August 2018

Background. Discrete choice experiments (DCEs) are increasingly used to elicit preferences for benefit-risk tradeoffs. The primary aim of this study was to explore how eye-tracking methods can be used to understand DCE respondents’ decision-making strategies. A secondary aim was to explore if the presentation and communication of risk affected respondents’ choices. Method. Two versions of a DCE were designed to understand the preferences of female members of the public for breast screening that varied in how risk attributes were presented. Risk was communicated as either 1) percentages or 2) icon arrays and percentages. Eye-tracking equipment recorded eye movements 1000 times a second. A debriefing survey collected sociodemographics and self-reported attribute nonattendance (ANA) data. A heteroskedastic conditional logit model analyzed DCE data. Eye-tracking data on pupil size, direction of motion, and total visual attention (dwell time) to predefined areas of interest were analyzed using ordinary least squares regressions. Results. Forty women completed the DCE with eye-tracking. There was no statistically significant difference in attention (fixations) to attributes between the risk communication formats. Respondents completing either version of the DCE with the alternatives presented in columns made more horizontal (left-right) saccades than vertical (up-down). Eye-tracking data confirmed self-reported ANA to the risk attributes with a 40% reduction in mean dwell time to the “probability of detecting a cancer” ( P = 0.001) and a 25% reduction to the “risk of unnecessary follow-up” ( P = 0.008). Conclusion. This study is one of the first to show how eye-tracking can be used to understand responses to a health care DCE and highlighted the potential impact of risk communication on respondents’ decision-making strategies. The results suggested self-reported ANA to cost attributes may not be reliable.
Automated Severity Classification of AIDS Hospitalizations
Authors: Stitt Frank W. , Lu Ying , Dickinson Gordon M. , Klimas Nancy G.
Published: August 2018

To validate an automated AIDS severity-of-illness prognostic algorithm, 2,113 discharge summaries of HIV-infected patients were merged with the Problem-Oriented Medical Synopsis (POMS) and an HIV risk registry. The combination of a medically derived classification and staging algorithm with multivariate statistical techniques was used for automated severity-of-illness disease staging and prognostic assignment. The model correctly predicted the outcomes of 82% of all cases (death, survivorship) at discharge, and 66% of deaths.
Toward Representations for Medical Concepts
Authors: Evans David A. , Rothwell David J. , Monarch Ira A. , Lefferts Robert G. , Cote Roger A.
Published: August 2018

The authors characterize the problems inherent to mapping across or combining terms from different vocabularies, focusing especially on MeSH and SNOMED. They also describe the exploration of the development of a frame-based representation of SNOMED.
Using the UMLS to Bring the Library to the Bedside
Authors: Cimino James J. , Sideli Robert V.
Published: August 2018

This paper presents an algorithm that can be used to convert ICD9 terms to related MeSH terms. Preliminary evaluation indicates that together, the algorithm and the UMLS provide a reasonable resource for facilitating such conversions.
Peripheral Factors Affecting the Evaluation of Artworks
Authors: Mastandrea Stefano , Crano William D.
Published: August 2018

The goal of the research was to determine whether artworks said to be created by famous artists were appreciated more than the same artworks attributed to nonfamous artists. Analysis indicated that the works attributed to famous artists were more appreciated than the identical works attributed to nonfamous artists: The works were liked more and judged more interesting and beautiful (all p values < .001). Participants ( N = 309), all art nonexperts, also were willing to pay more to see the works if described as created by famous artists ( p < .001); importantly, however, no differences were found in ratings of the works’ comprehensibility. This pattern of results suggests that judgmental variations were attributable to participants’ peripheral processing of factors not intrinsic to the work itself. Dual process models of attitudes, popular in social psychology, were invoked to provide a framework for understanding the findings.
Hierarchical Cluster Analysis of Cytokeratins and Stem Cell Expression Profiles of Canine Cutaneous Epithelial Tumors
Authors: Kok Mun Keong , Chambers James K. , Ong Siew Mei , Nakayama Hiroyuki , Uchida Kazuyuki
Published: August 2018

The diagnosis of cutaneous epithelial tumors (CETs) in dogs is based on predominant histological differentiation patterns. However, the expression of a broad panel of antigens has not been comprehensively examined with immunohistochemistry. The present study aims to establish a comprehensive expression profile and identify useful diagnostic markers for each CET type. Cytokeratin (CK), stem cell, and other associated markers were immunohistochemically examined in 110 canine CETs. Among these, CK16 was useful for differentiating between basal and squamous cell carcinomas. Acantholytic squamous cell carcinomas were positive for CK8, CK18, and CK19, suggesting their close association with the apocrine duct. Unlike their benign counterparts, sebaceous carcinomas coexpressed CK5/6 and adipophilin. Smooth muscle actin (SMA) and p63 immunostaining were useful for accurately distinguishing between glandular and ductal differentiation in apocrine tumors. A case of apocrine carcinoma and malignant myoepithelioma was identified using anti-SMA antibodies. Stem cell expression profiles (CK8, CK15, CK19, and CD34) of hair follicle tumors were discrete and indicative of their anatomic origins. The effectiveness of immunohistochemistry for tumor diagnosis was further confirmed by hierarchical cluster analysis, through which selected markers were able to sort CETs into specific groups: CK5/6, CK8, CK14, CK16, CK18, CK19, p63, adipophilin, and SMA sorted tumors of epidermal, apocrine, or sebaceous origin; while CK8, CK14, CK15, CK16, CK19, CD34, and p63 sorted hair follicle tumors in agreement with their histological differentiation. In conclusion, the present study provides comprehensive immunohistochemical information, which could complement histomorphological features for the future classification of canine CETs.
Grayanotoxin I Intoxication in Pet Pigs
Authors: Pischon Hannah , Petrick Anne , Müller Matthias , Köster Nils , Pietsch Jörg , Mundhenk Lars
Published: August 2018

Contaminated honey is a common cause of grayanotoxin intoxication in humans. Intoxication of animals, especially cattle, is usually due to ingestion of plants of the Ericaceae family, such as Rhododendron. Here, we report the ingestion of Pieris japonica as the cause of grayanotoxin I intoxication in 2 miniature pigs that were kept as pets. The pigs showed sudden onset of pale oral mucosa, tachycardia, tachypnea, hypersalivation, tremor, and ataxia that progressed to lateral recumbency. The pathological examination of one pig revealed no specific indications for intoxication except for the finding of plant material of Pieris japonica in the intestine. Grayanotoxin I was identified in the ingested plant, gastric content, blood, liver, bile, kidney, urine, lung, and skeletal muscle via HPLC-MS/MS. Grayanotoxin I should be considered as a differential etiological diagnosis in pigs with unspecific signs and discovery of ingested plant material as the only indication in the pathologic examination.
Tropical Keratopathy (Florida Spots) in Cats
Authors: Bolfa Pompei , Kelly Susyn J. , Wells Hannah C. , Sizeland Katie H. , Scott Erin M. , Kirby Nigel , Mudie Stephen , Armien Anibal G. , Haverkamp Richard G. , Kelly Patrick J.
Published: August 2018

The authors used microscopy and synchrotron-based small-angle X-ray scattering analysis (SAXS) to describe lesions macroscopically typical of tropical keratopathy (“Florida spots”) from 6 cats on St Kitts. Microscopically, there were varying degrees of epithelial hyperplasia and thinning of the cornea (by 4% to 18%) due to loss of corneal stroma associated with dense accumulations of collagen in the superficial stroma. The collagen fibrils in lesions were wider and had more variable diameters (39.5 ± 5.0 nm, mean ± SD) than in normal corneas (25.9 ± 3.6 nm; P < .01). There were occasional vacuoles (<1 μm) in the corneal epithelial basement membrane but no evidence of inflammation, edema, stromal neovascularization, fibrosis, acid-fast organisms, or structures suggestive of a fungal organism. SAXS analysis showed collagen fibril diameters and variation in size were greater in stroma containing the lesions compared to normal corneas (48.8 ± 4.5 nm vs 35.5 ± 2.6; P < .05). The d-spacing of collagen in the stroma of lesions and normal corneas was the same, but the average orientation index of collagen in lesions was greater (0.428 ± 0.08 vs 0.285 ± 0.03; P < .05). A survey revealed Florida spots lesions were static over time and became less obvious in only 1 of 6 affected cats adopted on St Kitts and taken to areas in the US where lesions are not reported. An anterior stromal collagen disorder with various degrees of epithelial hyperplasia is the pathologic hallmark of lesions clinically identical to Florida spots in cats from St Kitts.
Place formation and axioms for reading the natural landscape
Authors: Phillips Jonathan D
Published: August 2018

Nine axioms for interpreting landscapes from a geoscience perspective are presented, and illustrated via a case study. The axioms are the self-evident portions of several key theoretical frameworks: multiple causality; the law–place–history triad; individualism; evolution space; selection principles; and place as historically contingent process. Reading of natural landscapes is approached from a perspective of place formation. Six of the axioms relate to processes or phenomena: (1) spatial structuring and differentiation processes occur due to fluxes of mass, energy, and information; (2) some structures and patterns associated with those fluxes are preferentially preserved and enhanced; (3) coalescence occurs as structuring and selection solidify portions of space into zones (places) that are internally defined or linked by mass or energy fluxes or other functional relationships, and/or characterized by distinctive internal similarity of traits; (4) landscapes have unique, individualistic aspects, but development is bounded by an evolution space defined by applicable laws and available energy, matter, and space resources; (5) mutual adjustments occur between process and form (pattern, structure), and among environmental archetypes, historical imprinting, and environmental transformations; and (6) place formation is canalized (constrained) between clock-resetting events. The other three axioms recognize that Earth surface systems are always changing or subject to change; that some place formation processes are reversible; and that all the relevant phenomena may manifest across a range of spatial and temporal scales. The axioms are applied to a study of soil landscape evolution in central Kentucky, USA.