bluuebunny/crossref_metadata_2025 huggingface dataset:
A stochastic model for error correction of kinetochore-microtubule attachments and its coupling to the spindle assembly checkpoint
Authors: Banerjee Anand , Adames Neil , Peccoud Jean , Tyson John J.
Published: February 2019

To divide replicated chromosomes equally between daughter cells kinetochores must attach to microtubules emanating from opposite poles of the mitotic spindle. Two mechanisms, namely, error correction and ‘spindle assembly checkpoint’ work together to facilitate this process. The error correction mechanism recognizes and detaches erroneous kinetochore-microtubule attachments, and the spindle assembly checkpoint delays the onset of anaphase until all the kinetochores are properly attached. Kinases and phosphatases at the kinetochore play a key role in proper functioning of these two mechanisms. Here we present a stochastic model to study how the opposing activities of kinases and phosphatases at the kinetochore affect error correction of kinetochore-microtubule attachments and checkpoint signaling in budding yeast, Saccharomyces cerevisiae. We show that error correction and biorientation of chromosomes occurs efficiently when the ratio between kinase activity of Ipl1 and the activity of an opposing phosphatase is a constant (balance point), and derive an approximate analytical formula that defines the balance point. Analysis of the coupling of the spindle assembly checkpoint signal to error correction shows that its strength remains high when the Ipl1 activity is equal to (or larger than) the value specified by the balance point, and the activity of another kinase, Mps1, is much larger (approximately 30 times larger) than its opposing phosphatase (PP1). We also find that the geometrical orientation of sister chromatids does not significantly improve the probability of their reaching biorientation, which depends entirely on Ipl1-dependent microtubule detachment.

Author summary

The kinetochore, the master regulator of chromosome segregation, integrates signals from different chromosome attachment states to generate an appropriate response, like the destabilization of erroneous kinetochore-microtubule attachments, stabilization of correct attachments, maintenance of the spindle assembly checkpoint signal until all kinetochores are properly attached, and finally silencing of checkpoint when biorientation is achieved. At a molecular level the job is carried out by kinases and phosphatases. The complexity of the interactions between these kinases and phosphatases makes intuitive analysis of the control network impossible, and a systems-level model is needed to put experimental information together and to generate testable hypotheses. Here we present such a model for the process of error correction and its coupling to the spindle assembly checkpoint in budding yeast. Using the model, we characterize the balance between kinase and phosphatase activities required for removing erroneous attachments and then establishing correct stable attachments between kinetochore and microtubule. We also analyze how the balance affects the strength of the spindle assembly checkpoint signal.
Information and genetic counselling for psychiatric risks in children with rare disorders
Authors: Cuthbert Andrew , Challenger Aimee , Hall Jeremy , den Bree Marianne BM van
Published: February 2019

Background:

The diagnosis of developmental disorders is being transformed by advances in whole genome technologies. However, continuing uncertainties about the individual risks and potential severity of psychiatric impacts attributed to causal genomic variants limits the availability of comprehensive family-oriented information. In addition, there is insufficient evidence about how the parents of children with developmental disorders comprehend the facts and implications of their diagnosis through genetic counselling, nor how they gather developmental and mental health information to guide their understanding.

Methods:

Parents of children (aged 0–17 years) referred to paediatric genetics services completed an anonymous online 46-item survey about: (i) the experience of attending services to receive their child’s genetic diagnosis, and (ii) the availability, quality and helpfulness of information about psychiatric and neurodevelopmental conditions associated with genomic disorders.

Findings:

Two-hundred and eighty-six families (199 UK and 87 USA) completed the survey. One-in-three UK and one-in-five US respondents were dissatisfied with how their child’s genetic diagnosis was communicated. Satisfaction was predicted by face-to-face communication (odds ratio 2·91 [95% CI 1·43–5·94]; p=0·003); results being presented by genetics specialists (2·97 [1·41–6·26]; p=0·004); receiving clear explanations (5·14 [2·58– 10·26]; p<0·001); receiving support (2·99 [1·21–7·36], p=0·017); and male gender of the tested child (2·56 [1·28–5·14]; p=0·008). Compared to health-related information on developmental delay or intellectual disability, parents were more likely to obtain information about psychiatric manifestations from non-professional lay sources than from clinical specialists (p<0·001). This was particularly evident for families in the UK compared to the USA (p<0·001). Parents considered information from rare disorder support groups to be more helpful than from genetics specialists (odds ratio 11·0 [95% CI 5·08–86·75]; p<0·001), or paediatricians (11·0 [1·42–85·20]; p=0·006), or internet sites (15·5 [3·71–64·77]; p<0·001), which in turn proved more helpful than information provided by geneticists (2·5 [1·44–4·31]; p=0·001).

Interpretation:

Psychiatric comorbidity is a common feature of rare genomic disorders, but the paucity of suitable information available from clinical specialists suggests families are not optimally informed about these challenges. Wider implementation of genomic testing in general medicine should include adequate training in genetic counselling to ensure best practice in communicating and explaining complex test results supported by comprehensive, family-oriented information.

Funding:

The Waterloo Foundation: Changing Minds Programme (506296); The Medical Research Council (MRC) Research Grant: Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (MR/N022572/1).
ATAT1-enriched vesicles promote microtubule acetylation via axonal transport
Authors: Even Aviel , Morelli Giovanni , Scaramuzzino Chiara , Gladwyn-Ng Ivan , Le Bail Romain , Shilian Michal , Freeman Stephen , Magiera Maria M , AS Jijumon , Malgrange Brigitte , Brone Bert , Dietrich Paula , Dragatsis Ioannis , Janke Carsten , Saudou Frederic , Weil Miguel , Nguyen Laurent
Published: February 2019

Microtubules are polymerized dimers of α- and β-tubulin that underlie a broad range of cellular activities. Acetylation of α-tubulin by the acetyl-transferase ATAT1 modulates microtubule dynamics and functions in neurons. However, it remains unclear how and why this enzyme acetylates microtubules over long distances in axons. Here, we show that loss of ATAT1 impairs axonal transport in neurons and cell free motility assays confirm a requirement of tubulin acetylation for proper bidirectional vesicular transport. Moreover, we demonstrate that the main cellular pool of ATAT1 is transported at the cytosolic side of neuronal vesicles that are moving along axons. Altogether, our data suggest that axonal transport of ATAT1-enriched vesicles is the predominant driver of α-tubulin acetylation in axons.
Integrative Functional Network Interactions Underlie the Association between Physical Activity and Cognition in Neurodegenerative Diseases
Authors: Shih Chia-Hao , Sklerov Miriam , Browner Nina , Dayan Eran
Published: February 2019

Physical activity (PA) has preventive and possibly restorative effects in aging-related cognitive decline, which relate to intrinsic functional interactions (functional connectivity, FC) in large-scale brain networks. Preventive and ameliorative effects of PA on cognitive decline have also been documented in neurodegenerative diseases, such as Parkinson's disease (PD). However, the neural substrates that mediate the association between PA and cognitive performance under such neurological conditions remain unknown. Here we set out to examine if the association between PA and cognitive performance in PD is mediated by FC in large-scale sensorimotor and association brain networks. Data from 51 PD patients were analyzed. Connectome-level analysis based on a whole-brain parcellation showed that self-reported levels of PA were associated with increased FC between, but not within the default mode (DMN) and salience networks (SAL) (p < .05, false discovery rate corrected). Additionally, multiple parallel mediation analysis further demonstrated that FC between left lateral parietal nodes in the DMN and rostral prefrontal nodes in the SAL mediated the association between PA and executive function performance. These findings are in line with previous studies linking FC in large-scale association networks with the effects of PA on cognition in healthy aging. Our results extend these previous results by demonstrating that the association between PA and cognitive performance in neurodegenerative diseases such as PD is mediated by integrative functional interactions in large-scale association networks.
An RNA-binding protein secreted byListeria monocytogenesactivates RIG-I signaling
Authors: Pagliuso Alessandro , Tham To Nam , Allemand Eric , Robertin Stevens , Dupuy Bruno , Bertrand Quentin , Bécavin Christophe , Koutero Mikael , Najburg Valérie , Nahori Marie-Anne , Stavru Fabrizia , Dessen Andréa , Muchard Christian , Lebreton Alice , Komarova Anastassia V. , Cossart Pascale
Published: February 2019

Recent studies have reported on the presence of bacterial RNA within or outside extracellular membrane vesicles, possibly as ribonucleoprotein complexes. Proteins that bind and stabilize bacterial RNAs in the extracellular environment have not been reported. Here, we show that the bacterial pathogenListeria monocytogenessecretes a small RNA binding protein that we named Zea. We show that Zea binds and stabilizes a subset ofL. monocytogenesRNAs causing their accumulation in the extracellular medium. Furthermore, Zea binds RIG-I, the vertebrate non-self-RNA innate immunity sensor and potentiates RIG-I-signaling leading to interferon β production. By performingin vivoinfection, we finally show that Zea modulatesL. monocytogenesvirulence. Together, this study reveals that bacterial extracellular RNAs and RNA binding proteins can affect the host-pathogen crosstalk.
Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis
Authors: Campsie Paul , Childs Peter G. , Robertson Shaun N. , Cameron Kenny , Hough James , Salmerón-Sánchez Manuel , Tsimbouri Monica P. , Vichare Parag , Dalby Matthew J. , Reid Stuart
Published: February 2019

In regenerative medicine, techniques which control stem cell lineage commitment are a rapidly expanding field of interest. Recently, nanoscale mechanical stimulation of mesenchymal stem cells (MSCs) has been shown to activate mechanotransduction pathways stimulating osteogenesis in 2D and 3D culture. This has the potential to revolutionise bone graft procedures by creating cellular graft material from autologous or allogeneic sources of MSCs without using chemical induction. With the increased interest in mechanical stimulation of cells and huge potential for clinical use, it is apparent that researchers and clinicians require a scalable bioreactor system that provides consistently reproducible results with a simple turnkey approach. A novel bioreactor system is presented that consists of: a bioreactor vibration plate, calibrated and optimised for nanometre vibrations at 1 kHz, a power supply unit, which supplies a 1 kHz sine wave signal necessary to generate approximately 30 nm of vibration amplitude, and custom 6-well cultureware with toroidal shaped magnets incorporated in the base of each well for conformal attachment to the bioreactor’s magnetic vibration plate. The cultureware and vibration plate were designed using finite element analysis to determine the modal and harmonic responses, and validated by interferometric measurement. This helps ensure that the vibration plate and cultureware, and thus collagen and MSCs, all move as a rigid body, avoiding large deformations close to the resonant frequency of the vibration plate and vibration damping beyond the resonance. Assessment of osteogenic protein expression was performed to confirm differentiation of MSCs after initial biological experiments with the system, as well as atomic force microscopy of the 3D gel constructs during vibrational stimulation to verify that strain hardening of the gel did not occur. This shows that cell differentiation was the result of the nanovibrational stimulation provided by the bioreactor alone, and that other cell differentiating factors, such as stiffening of the collagen gel, did not contribute.
The LISA beamline at ESRF
Authors: d'Acapito Francesco , Lepore Giovanni Orazio , Puri Alessandro , Laloni Alessio , La Manna Fabrizio , Dettona Eric , De Luisa Aleksander , Martin Andrea
Published: February 2019

This contribution provides a description of LISA, the new Italian Collaborating Research Group beamline operative at the European Synchrotron Radiation Facility. A presentation of the instruments available and optical devices is given as well as the main X-ray parameters (flux, energy resolution, focal spot dimensions, etc.) and comparison with theoretical calculations. The beamline has been open to users since April 2018 and will be ready at the opening of the Extremely Brilliant Source in late-2020.
Numerical investigation of nonlinear vibration analysis for triple-walled carbon nanotubes conveying viscous fluid
Authors: Mohamadi Bijan , Eftekhari S. Ali , Toghraie Davood
Published: February 2019

Purpose

The purpose of this paper is to investigate nonlinear vibrations of triple-walled carbon nanotubes buried within Pasternak foundation carrying viscous fluids.

Design/methodology/approach

Considering the geometry of nanotubes, the governing equations were initially derived using Timoshenko and modified couple stress theories and by taking into account Von-Karman expressions. Then, by determining boundary conditions, type of fluid motion, Knudsen number and, ultimately, fluid viscosity, the principal equation was solved using differential quadrature method, and linear and nonlinear nanotube frequencies were calculated.

Findings

The results indicated that natural frequency is decreased as the fluid velocity and aspect ratio increase. Moreover, as the aspect ratio is increased, the results converge for simple and fixed support boundary conditions, and the ratio of nonlinear to linear frequencies approaches. Natural frequency of vibrations and critical velocity increase as Pasternak coefficient and characteristic length increase. As indicated by the results, by assuming a non-uniform velocity for the fluid and a slip boundary condition at Kn = 0.05, reductions of 10.714 and 28.714% were observed in the critical velocity, respectively. Moreover, the ratio of nonlinear to linear base frequencies decreases as the Winkler and Pasternak coefficients, maximum deflection of the first wall and characteristic length are increased in couple stress theory.

Originality/value

This paper is a numerical investigation of nonlinear vibration analysis for triple-walled carbon nanotubes conveying viscous fluid.
An empirical study of the relationship between accounting conservatism and executive compensation-performance sensitivity
Authors: Zhang Xi , Gao Simon , Zeng Yi
Published: February 2019

Purpose

The purpose of this paper is to study the relationship between accounting conservatism and executive compensation-performance sensitivity with a view to identify the influence of accounting conservatism on the efficiency of executive compensation contracts.

Design/methodology/approach

This study uses multiple regression models based on the approach of Iyengar and Zampelli (2010), Clarkson et al. (2011) and Huang and Kisgen (2013) with the data from all of China’s listed non-financial firms over the period of 10 years to test the relationship between accounting conservatism and the sensitivity of executive compensation-performance.

Findings

This study finds a positive association between executive compensation and accounting-based measure of performance. More importantly, it reveals that conservatism has a positive relation with the executive compensation-performance sensitivity after controlling for a number of firm-specific factors and control variables. This study shows that the sensitivity of executive compensation to firm performance is higher for firms with higher accounting conservatism.

Originality/value

This is one of the few studies to examine the relationship between accounting conservatism and executive compensation-performance sensitivity. It provides supportive evidence to the argument that accounting conservatism, being an efficient governance mechanism, can help mitigate information risk and moral risk for agency problems.
Perceived uncertainty and use of environmental information in decision making
Authors: Abu-Rahma Ali , Jaleel Bushra
Published: February 2019

Purpose

This paper aims to investigate the nature and prevalence of environmental scanning as practiced by organizations in the United Arab Emirates (UAE) and explore the impact of perceived uncertainty on the way various information sources are used in managerial decision-making. Specifically, by targeting firms in the region, the paper examines whether the degree and frequency of scanning activities influence the relationship between perceived uncertainty and the use of environmental information in making strategic decisions.

Design/methodology/approach

The study uses a cross-sectional research design, with self-administered questionnaires as the main mode of data collection, and uses quantitative data analysis tools to answer the research questions.

Findings

The study finds that perceived environmental uncertainty significantly influences scanning efforts in an organization, which in turn influence the use of environmental information in decision-making. Additionally, findings suggest that while perceived source quality significantly influences frequency of scanning, the influence of perceived source accessibility on scanning is statistically insignificant.

Research limitations/implications

The results of this study have several implications for academics in the field of strategic management and industry professionals involved in long range planning. Results indicate that scanning activities should be more extensive and frequent when perceived uncertainty is high and indicates the potential value of timely market research to assess demand, gather consumer feedback and respond to changing needs of the customers.

Originality/value

The study addresses an identified gap in the literature and adds to the existing body of work by exploring organizational practices in a unique cultural context and assessing a conceptual model that links perceived uncertainty and environmental scanning to strategic management practices.
Damage assessment of reinforced concrete flat slabs through modal tests using impact excitation
Authors: Ferreira Gabriel S. , Guedes Tulio O. , Melo Lucas F. , Gonçalves Márcio S. , Pimentel Roberto
Published: February 2019

Purpose

In reinforced concrete (RC) structures, an evidence of damage is the presence of cracking. In order to evaluate the effect of damage on cracking pattern and natural frequency in RC slabs, two of such structures with different dimensions and reinforcement ratios were tested, in which cracks were induced through application of static load, followed by modal tests using impact excitation. The paper aims to discuss this issue.

Design/methodology/approach

The gradient of the fundamental natural frequency along the decay, the crack opening rate and also a global damage index based on changes of the fundamental natural frequency were evaluated.

Findings

The behaviour of the aforementioned gradient was distinct for both slabs, increasing monotonically with the cracking level for the slab with lowest reinforcement ratio, and increasing until 33 per cent of the collapse load and then decreasing afterwards for the slab with the highest ratio. Changes of the gradient were consistent with changes of the crack opening rate. Both results of gradient changes and cracking pattern brought evidence that the balance between open (old) and breathing (new) cracks differed between the slabs, and may be responsible for such differences.

Originality/value

Damage assessment in RC structures using vibration tests is mostly concentrated on beams. In this work, an advance is made by investigating slabs. The lack of a unique pattern of changes of the gradient implies that its absolute value is not generally suitable for the association with the damage level. However, the impact tests can be effectively used to detect early damage on slabs using this proposed parameter.
Assessing the impact of Minnesota's return to community initiative for newly admitted nursing home residents
Authors: Hass Zachary , Woodhouse Mark , Grabowski David C. , Arling Greg
Published: February 2019

Objective

To evaluate Minnesota's Return to Community Initiative's (RTCI) impact on community discharges from nursing homes.

Data Sources

Secondary data were from the Minimum Data Set and RTCI staff (April 2014 – December 2016). The sample consisted of 18 444 non‐Medicaid nursing home admissions in Minnesota remaining for at least 45 days, with high predicted probability of community discharge.

Study Design

The RTCI facilitates community discharge for non‐Medicaid nursing home residents by assisting with discharge planning, transitioning to the community, and postdischarge follow‐up. A key evaluation question is how many of those transitions were directly attributable to the program. Return to Community Initiative was implemented statewide without a control group. Program impact was measured using regression discontinuity, a quasi‐experimental design approach that leverages the programs targeting model.

Principal Findings

Return to Community Initiative increased community discharge rates by an estimated 11 percent (P < 0.05) for the targeted population. The program effect was robust to time and increased with level of facility participation in RTCI.

Conclusions

The RTCI had a modest yet significant impact on the community discharge rates for its targeted population. Findings have been applied in strengthening the RTCI's targeting approach and transitioning process.
Changes in Bread Quality, Antioxidant Activity, and Phenolic Acid Composition of Wheats During Early‐Stage Germination
Authors: Tian Wenfei , Ehmke Laura , Miller Rebecca , Li Yonghui
Published: February 2019

This study reported changes in baking properties, total phenolic content (TPC), antioxidant activity, and phenolic acid composition of three hard red winter wheat varieties during the early stage of seed germination. The wheats were sprouted at 30 °C and 95% relative humidity to achieve different germination levels based on falling number ranges (550 s for control flour; 350 s [low], 250 s [medium], and 120 s [high] for sprouted flours, respectively). Average germination times were 7, 8, and 10 hr for the low, medium, and high germinated samples, respectively. Most baking properties of sprouted whole flour were comparable to the control flour. However, TPC, flavonoid content, phenolic acids, and antioxidant activity of sprouted flour were lower than the control flour. To our knowledge, this is the first study that reported both baking properties and antioxidant potential of sprouted whole wheat flour from early‐stage germination. The study deepens the understanding of seed germination and the potential use of sprouted flour in baking industry.

Practical Application

This study evaluates the baking quality and nutraceutical value of sprouted whole wheat flour, which are key factors determining the application of sprouted flour in the baking industry. The results will contribute to the production of quality bakery products with enhanced nutraceutical benefits.
Bourbon and Rye Whiskeys Are Legally Distinct but Are Not Discriminated by Sensory Descriptive Analysis
Authors: Lahne Jacob , Abdi Hervé , Collins Thomas , Heymann Hildegarde
Published: February 2019

We present a Descriptive Analysis (DA) of a large representative sample (24 whiskeys) of two legally distinct types of American whiskeys: bourbon and rye whiskey (respectively distilled from a fermented “mashbill” of at least 51% corn or rye). We wanted to determine whether a trained panel could find sensory differences between these two products. We used standard DA: 11 judges were trained for 10 hours to develop a lexicon of 24 flavor, taste, and mouthfeel descriptors for the 24 whiskey samples (15 bourbons and 9 ryes). Then, subjects rated each whiskey sample on each attribute, using unstructured line scales, in standard good sensory‐evaluation conditions, and in triplicate. Results were analyzed using MANOVA, Barycentric Discriminant Analysis, and Hierarchical Cluster Analysis. Overall, while 10 descriptors significantly differentiated the whiskeys, no attribute or combination of attributes was predicted by mashbill: The judges did not find differences in sensory character between bourbon and rye whiskeys as categories. However, significant differences could be attributed to the producer of the whiskey and to age at bottling. These results are important because American whiskey has recently become staggeringly popular, and because there is a consistent belief that bourbon and rye whiskeys—as categories—have distinct sensory characteristics.

Practical Application

This research contradicts popular and expert beliefs about the distinction between the popular and important American rye and bourbon whiskeys. A comprehensive sensory DA study of 24 American whiskeys with different mashbills (9 ryes and 15 bourbons) shows that—while each whiskey is individually distinct on a number of sensory dimensions—sensory differences between rye and bourbon whiskeys as product categories cannot be predicted by mashbill. For producers, consumers, and researchers, this research points to the need for new theories on the origins of flavors in whiskey, as it is now clear that the grain content alone cannot predict sensory qualities.
Apoptosis in patients with primary antiphospholipid antibody syndrome
Authors: Tang Kuo‐Tung , Hsieh Tsu‐Yi , Chao Ya‐Hsuan , Li Ju‐Pi , Lan Joung‐Liang , Lin Chi‐Chien , Chen Der‐Yuan
Published: February 2019

Aim

Dysregulated apoptosis has been implicated in autoimmune diseases. In the present study, we investigated the apoptosis‐related cytokines and apoptosis in patients with primary antiphospholipid syndrome (pAPS).

Method

We prospectively recruited 12 pAPS patients, 17 antiphospholipid antibody (APA)‐positive systemic lupus erythematosus (SLE) patients without APS manifestations (APA+SLE), 13 SLE patients with secondary APS (APS+SLE) and 10 healthy controls (HCs). Plasma levels of soluble apoptosis‐inducing ligands and cytokines, and the expression levels of apoptosis‐inducing ligands in peripheral blood mononuclear cells, were determined. In addition, blood lymphocytes/monocytes apoptosis were determined in six pAPS patients and six HCs, using flow cytometric analysis of caspase 3, 8 and 9 activities.

Results

There was a trend toward higher plasma levels of soluble tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (sTRAIL), interleukin‐10 (IL‐10) and TNF‐α in pAPS patients when compared with HCs. We also observed higher plasma levels of IL‐10 and TNF α in APA+SLE and APS+SLE patients when compared with HCs. However, there was no significant difference in blood lymphocytes/monocytes apoptosis between pAPS patients and HCs.

Conclusion

There was a trend toward elevated plasma levels of sTRAIL, IL‐10 and TNF‐α, but no evidence for dysregulated apoptosis in pAPS patients.
Validation of algorithms to identify knee osteoarthritis patients in the claims database
Authors: Park Ha‐Rim , Im SeulGi , Kim Hyoungyoung , Jung Sun‐Young , Kim Dalho , Jang Eun Jin , Sung Yoon‐Kyoung , Cho Soo‐Kyung
Published: February 2019

Background

To identify knee osteoarthritis (OA) patients among OA patients in the claims database.

Methods

All patients with OA diagnostic codes for any sites (M15 to M19) in 2014 were recruited from a single academic referral hospital. After excluding patients who had inflammatory arthritis or were less than 50 years of age, we identified data for the overall OA population. Radiographic knee OA of Kellgren and Lawrence grades ≥2 is considered the gold standard for knee OA, and we evaluated the sensitivity, specificity, and positive predictive value (PPV) of three operational definitions using the diagnostic codes in the claims database. The operational definitions were: (1) gonarthrosis (M17); (2) any site of OA (M15 to M19) with knee X‐ray; and (3) (1) or (2).

Results

A total of 7959 OA patients were included in this study of whom 74.5% were women. The PPV of gonarthrosis (M17) was 0.67 (95% CI 0.65‐0.69), and sensitivity was 0.44 (95% CI 0.42‐0.46). The PPV and sensitivity of any OA site (M15 to M19) with knee X‐ray were 0.65 (95% CI 0.62‐0.67), and 0.37 (95% CI 0.35‐0.39), respectively. When knee OA was defined as satisfying either of the two above definitions, PPV was 0.63 (95% CI 0.62‐0.65) and sensitivity 0.55 (95% CI 0.53‐0.57).

Conclusions

Knee OA patients can be identified in a claims database using the algorithms of gonarthrosis (M17) or any site of OA (M15 to M19) with a performed knee X‐ray.
Serum miR‐214 as a novel biomarker for ankylosing spondylitis
Authors: Kook Hyun Yi , Jin So‐Hee , Park Pu‐Reum , Lee Seung‐Jin , Shin Hong‐Joon , Kim Tae‐Jong
Published: February 2019

Objective

Serum microRNA (miR) in ankylosing spondylitis (AS) patients has been rarely identified. The objective of this study was to find AS‐specific miR in sera of patients with AS.

Methods

Total RNAs were isolated from whole sera of patients with AS, patients with rheumatoid arthritis (RA), and healthy controls (HC) using miRNeasy Serum/Plasma Kit. The presence of miR was assayed using Agilent 2100 Bioanalyzer Small RNA assay. Each RNA sample was used for miR microarray. To verify microarray results, candidate circulating miRs were validated by quantitative polymerase chain reaction (qPCR) using samples from patients with AS (n = 65), patients with RA (n = 25), and HCs (n = 39). Cycle threshold values were converted to copy numbers by drawing a standard curve using a synthetic chemical standard. All clinical values were also evaluated at the time of miR isolation.

Results

A total of 887 miRs were screened for three groups. Lower expression of miR‐214 in AS than in HC and RA was observed after normalization of raw data. Finally, lower expression of serum miR‐214 was confirmed in AS after validation by qPCR. Correlation analysis showed that the level of miR‐214 of AS was significantly associated with Ankylosing Spondylitis Disease Activity Score—C‐reactive protein (r = 0.299, P = 0.02). However, other disease‐specific variables showed no statistical significance: gender (P = 0.286), peripheral arthritis (P = 0.634), enthesitis (P = 0.464), dacylitis (P = 0.750), psoriasis (P = 0.552), inflammatory bowel disease (P = 0.369), human leukocyte antigen‐B27 positivity (P = 0.473), use of non‐steroidal anti‐inflammatory drugs (P = 0.448), and use of tumor necrosis factor‐blocker in the last 3 months (P = 0.505).

Conclusion

miR‐214 may serve as a noninvasive biomarker for diagnosis of AS. In addition, expression level of miR‐214 was associated with disease activity.
HLA‐B27 prevalence in axial spondyloarthritis patients and in blood donors in a Lebanese population: Results from a nationwide study
Authors: Ziade Nelly , Abi Karam Ghada , Merheb Georges , Mallak Iyad , Irani Laure , Alam Elie , Messaykeh Jamil , Menassa Jeanine , Mroue’ Kamel , Uthman Imad , Masri Abdel Fattah , Ghorra Pierre , Witte Torsten , Baraliakos Xenofon
Published: February 2019

Aim

To calculate the prevalence of human leukocyte antigen (HLA)‐B27 in axial spondyloarthritis patients (axSpA) compared to blood donors (BD) in Lebanon, to identify the clinical and radiological findings associated with HLA‐B27 and to estimate the proportion of patients fulfilling the clinical arm of the Assessment of the Spondyloarthritis International Association (ASAS) criteria.

Method

Consecutive Lebanese adult axSpA patients fulfilling the ASAS classification criteria were included from 12 rheumatology clinics across Lebanon. BD served as controls. A binary logistic regression was used to study the association between HLA‐B27 and the disease features.

Results

A total of 247 individuals were included (141 axSpA patients and 106 BD). The prevalence of HLA‐B27 was 3.8% in BD and 41.1% in axSpA. Overall, 39.7% of the axSpA patients fulfilled the clinical arm of the ASAS classification criteria. Sensitivity of HLA‐B27 for axSpA was 41.1%, specificity was 96.2%, positive predictive value was 93.6%, and negative predictive value was 55.13%. Positive likelihood ratio (LR) was 10.9 and negative LR was 1.63. We found a positive association of HLA‐B27 with family history of SpA and psoriasis.

Conclusion

Our study confirmed a low prevalence of HLA‐B27 in axSpA patients and BD in this Lebanese population, However, we found a high specificity and positive LR, as well as the same number of axSpA patients fulfilling the clinical arm of the ASAS criteria as in European studies. HLA‐B27 is therefore valuable for identification of axSpA in Lebanese patients despite the overall low prevalence in this population. Our results may guide future evaluations the role of HLA‐B27 in planning local referral strategies.
Prognostic nutritional index is associated with disease severity and relapse in ANCA‐associated vasculitis
Authors: Ahn Sung Soo , Jung Seung Min , Song Jason Jungsik , Park Yong‐Beom , Lee Sang‐Won
Published: February 2019

Aim

The prognostic nutritional index (PNI), calculated by serum albumin and peripheral blood lymphocyte count, is considered to reflect immune‐related nutritional status. In this study, we first investigated the clinical significance of PNI in patients with antineutrophil cytoplasmic antibody‐associated vasculitis (AAV).

Method

Medical records of 160 patients classified as AAV from October 2000 to September 2017 were reviewed. We calculated the Birmingham vasculitis activity score (BVAS) and collected laboratory data including erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP) level, white blood cell, lymphocyte, and platelet counts, and serum albumin, aspartate aminotransferase, and alanine aminotransferase levels at diagnosis. PNI at diagnosis was calculated as (10 × serum albumin [g/dL] + 0.005 × lymphocyte count [/mm3]). Associations between laboratory variables, PNI, and BVAS were assessed by linear regression analyses, and Cox proportional hazard analysis was used to evaluate factors associated with disease relapse.

Results

The mean age was 55.2 years and 48 patients (30.0%) were male. In univariable linear regression analysis, BVAS was positively correlated with ESR and CRP and negatively with lymphocyte count, serum albumin, and PNI (r = −0.307). In multivariable linear regression analysis, among ESR, CRP, and PNI, PNI was associated with BVAS (β = −0.299). PNI also significantly correlated with the included laboratory data. In Cox proportional hazard analysis, myeloperoxidase—antineutrophil cytoplasmic antibody positivity (odds ratio [OR] 2.875, P = 0.003) and PNI ≤36.75 (OR 2.066, P = 0.042) revealed to be independent predictors of disease relapse during the follow‐up period.

Conclusions

Prognostic nutritional index at diagnosis might be useful for assessing disease severity and predicting the prognosis of AAV patients.
The lesser anteater (Tamandua tetradactyla) is not tetradactyla, but pentadactyla
Authors: Machado Cruvinel Ana Cecília , Camargos de Britto Rosa Matheus , Lopes Guimarães Bruna Lívia , Ferreira Amaral Silva Cecília , de Sampaio da Silva Paulo Henrique , de Lima Borges Leão Cesar , Peixoto Juliano V. , Chrysostomo de Resende Júnior João , Cunha Lacreta Junior Antonio Carlos , Passamani Marcelo , Rodrigues da Cunha Barreto‐Vianna André , de Lima Eduardo M. M. , Corrêa Guimarães Gregório
Published: February 2019

The name of the species tetradactyla means “four digits.” In the literature, the hand of the lesser anteater (Tamandua tetradactyla) is described as having four digits (I, II, III and IV) with the absence of a fifth digit. The purpose of this study was to carry out an update adequately proposing an anatomical description of the T. tetradactyla hand. The present findings were analysed on the validation of Morse’s law for this species. In total, seven male cadavers were radiographed and dissected. We observed that the hand of the T. tetradactyla was formed by a carpus containing four bones in the proximal row, which in the medium lateral direction was the radial, intermediate, ulnar and accessory bones of the carpus, and the distal row was formed by carpal bones I, II, III and IV. There were five metacarpal bones (I, II, III, IV and V). The presence of five digits was verified but not confirmed with the literature. Digit I had two phalanges, the proximal and distal; digits II, III and IV had three phalanges: proximal, middle and distal. Digit five had only one phalanx, the proximal, but it was not externally visible. According to the findings of this study, the presence of the fifth digit raises the question of whether the term tetradactyla is the most appropriate to describe this species. This rudimentary fifth digit and the presence of a functional first digit show that the Morse’s law does not applies for the T. tetradactyla species.
Androgen deprivation therapy in nonmetastatic prostate cancer patients: Indications, treatment effects, and new predictive biomarkers
Authors: Fang Dong , Zhou Liqun
Published: February 2019

Men with prostate cancer with positive margins, extraprostatic extension, positive lymph nodes, high prostate‐specific antigen, or high Gleason Score are at high risk of recurrence following primary therapy. Androgen deprivation therapy (ADT), which includes medical/surgical castration, antiandrogen therapy, and combined androgen blockade, can be combined with primary therapy to shrink the tumor, reduce margin positivity, and reduce the risk of recurrence. However, many problems still remain, such as optimizing the application of ADT in the treatment of prostate cancer, for example, ideal patient population and optimal timing and duration of therapy. To investigate these problems, we searched PubMed for relevant publications on clinical studies of deprivation therapy for nonmetastatic prostate cancer. In this review, we discuss our findings on the role of ADT in the treatment of castrate‐sensitive nonmetastatic prostate cancer and the adverse effects associated with ADT. We also examine the recent advances in new predictive biomarkers for ADT, many of which are currently in the exploratory phase. Overall, the addition of ADT to primary therapy improves outcomes for patients with intermediate‐ or high‐risk prostate cancer.
Swept‐source optical coherence tomography angiography reveals vascular changes in intermediate uveitis
Authors: Tian Meng , Tappeiner Christoph , Zinkernagel Martin S. , Wolf Sebastian , Munk Marion R.
Published: February 2019

Purpose

To evaluate retinal and choroidal vascular changes in patients with intermediate uveitis with/without concomitant retinal vasculitis using wide field swept‐source optical coherence tomography angiography (OCTA).

Methods

In this study consecutive patients with intermediate uveitis ± vasculitis and healthy age‐matched controls were evaluated using central 3 × 3 mm OCTA scans and montage scans. Differences among the groups as well as the association between central changes assessed by 3 × 3 scans and wide field OCTA were evaluated.

Results

93 eyes of 58 patients with intermediate uveitis and 33 healthy age‐matched controls were included. The presence of a cystoid macular oedema (CME) was associated with capillary non‐and reduced perfusion of the superficial capillary plexus (SCP) (p = 0.03 and 0.02, respectively), and deep capillary plexus (DCP) (p = 0.02 and p ≤ 0.0001, respectively) of the 3 × 3 mm scans. The raw length, circularity and size of foveal avascular area (FAZ) significantly differed among the three groups. (p = 0.01, p = 0.045 and p = 0.004, respectively). Multivariable regression analysis revealed that the presence of epiretinal membranes (ERM) and CME rather than the disease entity contributed to the changes of FAZ size (R2 = 0.15, p = 0.0003) The mean vessel density (VD) of the SCP significantly differed among the three groups (intermediate uveitis with concomitant vasculitis: 16.8 ± 3.8 mm−1 vs intermediate uveitis only: 15.6 ± 4.4 mm−1 versus control: 18 ± 3.5 mm−1, p = 0.046). Multivariable regression analysis showed that the presence of CME rather than the disease entity impacted vessel density of SCP (R2 = 0.1, p = 0.016). There was no association between peripheral non‐ or reduced perfusion of the wide field OCTA slabs of the SCP and DCP and the VD of the 3 × 3 slabs.

Conclusion

Although patients with intermediate uveitis and vasculitis present with reduced central vessel density compared to healthy age‐matched controls, these changes are presumably contributed to the presence of CME.
Merging social equity and conservation goals in IPBES
Authors: Sarkki Simo , Acosta García Nicolás
Published: February 2019

Article impact statement: Social equity can be enhanced in IPBES work to promote its positive impacts on conservation and local people.
Investigating the management of alcohol‐related presentations in an Australian teaching hospital
Authors: Qian Siyu , Irani Mudar , Brighton Renee , Yeo Wilfred , Reid David , Sinclair Barbara , Bresnahan Susan , Lynch Peter , Feng Xiaoqi , Yu Ping
Published: February 2019

Introduction and Aims

Alcohol‐related morbidity is estimated to range from 10–38% of the presentations to hospital emergency departments. This study aims to investigate the actual management process for alcohol‐related presentations in a teaching hospital in Australia.

Design and Methods

Retrospective audit was conducted on the electronic medical records of 210 presentations with a primary or secondary diagnosis of ‘alcohol use disorder’ at discharge between November 2016 and February 2017. Six key management steps were investigated: identification of alcohol use disorder, documentation, thiamine, alcohol withdrawal assessment, benzodiazepine for alcohol withdrawal and referral to the drug and alcohol consultation liaison service.

Results

Of all the 210 presentations, 77.1% (162) were identified with alcohol use disorder in the initial assessments; 64.3% (135) were documented with alcohol use history, 49.5% (104) were prescribed with thiamine, 48.1% (101) were assessed with the alcohol withdrawal scale, 41% (86) were prescribed with benzodiazepine for alcohol withdrawal and only 38.6% (81) were referred to the drug and alcohol consultation liaison service. Only 8.6% (18) of the initial presentations were directly related to alcohol. These presentations had a higher completion rate in each of the six steps than those (91.4%, 192) not directly related to alcohol. Only 6.2% (13) were formally screened for alcohol use.

Discussion and Conclusions

The findings suggest a need to improve the alcohol management practice in the hospital. Routine use of an alcohol screening tool can enable early identification of the alcohol use disorder and to improve the management of this problem in the hospital.
The forgotten season: the impact of autumn phenology on a specialist insect herbivore community on oak
Authors: Ekholm Adam , Tack Ayco J.M. , Bolmgren Kjell , Roslin Tomas
Published: February 2019

1. Variation in spring phenology – like tree budburst – affects the structure of insect communities, but impacts of autumn phenology have been neglected. Many plant species have recently delayed their autumn phenology, and the timing of leaf senescence may be important for herbivorous insects.

2. This study explored how an insect herbivore community associated with Quercus robur is influenced by variation in autumn phenology. For this, schools were asked to record, across the range of oak in Sweden, the autumn phenology of oaks and to conduct a survey of the insect community.

3. To tease apart the relative impacts of climate from that of tree phenology, regional tree phenology was first modelled as a function of regional climate, and the tree‐specific deviation from this relationship was then used as the metric of relative tree‐specific phenology.

4. At the regional scale, a warmer climate postponed oak leaf senescence. This was also reflected in the insect herbivore community: six out of 15 taxa occurred at a higher incidence and five out of 18 taxa were more abundant, in locations with a warmer
climate. Similarly, taxonomic richness and herbivory were higher in warmer locations.

5. Trees with a relatively late autumn phenology had higher abundances of leaf miners (Phyllonorycter spp.). This caused lower community diversity and evenness on trees with later autumn phenology.

6. The findings of the present study illustrate that both regional climate‐driven patterns and local variation in oak autumn phenology contribute to shaping the insect herbivore community. Community patterns may thus shift with a changing climate.
Knowledge of antibiotics and antimicrobial resistance amongst final year dental students of Polish medical schools—A cross‐sectional study
Authors: Struzycka Izabela , Mazinska Beata , Bachanek Teresa , Boltacz‐Rzepkowska Elzbieta , Drozdzik Agnieszka , Kaczmarek Urszula , Kochanska Barbara , Mielczarek Agnieszka , Pytko‐Polonczyk Jolanta , Surdacka Anna , Tanasiewicz Marta , Waszkiel Danuta , Hryniewicz Waleria
Published: February 2019

Introduction

Antimicrobial resistance has been one of the biggest global concerns. Dentists constitute an important group of antibiotic prescribers, and it was shown that their therapeutic decisions are not always rational. In this paper, we present knowledge of antibiotics prescription rules and antimicrobial resistance amongst graduating dentistry students from all dentistry faculties of medical universities in Poland, who will soon join the group of antibiotics prescribers.

Materials and methods

A questionnaire consisting of 28 questions was developed. The survey was conducted in May‐June 2015.

Results

The study group comprised a total of 752 students. About 54% expressed the opinion that dentists overprescribe antibiotics. One‐tenth thought that they can be used for the treatment of flu (7%) and common cold (11%). Respondents pointed to amoxicillin (46%) and clindamycin (44%) as the first‐choice treatment of dentoalveolar abscess, if medically indicated. More than half of the students (58%) suggested using doxycycline and metronidazole in aggressive periodontitis in an individual allergic to penicillin. The vast majority of students (97%) indicated that penicillins and cephalosporins were suitable for treatment of dental infections in pregnant women.

The majority of participants (82%) said that rheumatic disease, chronic immunosuppression, chronic kidney failure and a history of infective endocarditis required a prophylactic administration of antibiotics before or during endodontic treatment.

Conclusions

The research showed variable levels of understanding of antibiotics use amongst dental students in medical universities in Poland. Our results emphasise the need to educate dental students further regarding antibiotics and risks related to antibiotic misuse, especially in dental practice.