bluuebunny/crossref_metadata_2025_split huggingface dataset:
Graduate Education for the Future: New Models and Methods for the Clinical and Translational Workforce
Authors: Begg Melissa D. , Bennett L. Michelle , Cicutto Lisa , Gadlin Howard , Moss Marc , Tentler John , Schoenbaum Ellie 
Published: December 2015

AbstractThis paper is the third in a five‐part series on the clinical and translational science educational pipeline, and it focuses on strategies for enhancing graduate research education to improve skills for interdisciplinary team science. Although some of the most cutting edge science takes place at the borders between disciplines, it is widely perceived that advancements in clinical and translational science are hindered by the “siloed” efforts of researchers who are comfortable working in their separate domains, and reluctant to stray from their own discipline when conducting research. Without appropriate preparation for career success as members and leaders of interdisciplinary teams, talented scientists may choose to remain siloed or to leave careers in clinical and translational science all together, weakening the pipeline and depleting the future biomedical research workforce. To address this threat, it is critical to begin at what is perhaps the most formative moment for academics: graduate training. This paper focuses on designs for graduate education, and contrasts the methods and outcomes from traditional educational approaches with those skills perceived as essential for the workforce of the future, including the capacity for research collaboration that crosses disciplinary boundaries.
On the role of sinigrin (mustard oil) in a tritrophic context: plant–aphid–aphidophagous hoverfly
Authors: AMIRI‐JAMI ALIREZA , SADEGHI‐NAMAGHI HUSSEIN , GILBERT FRANCIS , MORAVVEJ GHOLAMHOSSEIN , ASOODEH AHMAD 
Published: December 2015

1. Plant secondary metabolites can govern prey–predator interactions by altering the diet breadth of predators and sometimes provide an ecological refuge to prey. Brassicaceae plants and their specialist pests can be used as a model system for understanding the role of chemically mediated effects restricting the diet breadth of natural enemies, and consequently the occurrence of enemy‐free space for the specialist pest.2. The objective of the present study was to test the performance of the generalist predatorEpisyrphus balteatusDe Geer(Diptera:Syrphidae) fed on the specialist herbivoreBrevicoryne brassicaeL.(Homoptera:Aphididae), reared on two different brassica species: black mustard (Brassica nigra), a wild species with high levels of sinigrin; and canola (Brassica napus), a cultivated species without sinigrin.3. The preference and performance of the predator and the performance of the prey were measured. Sinigrin was quantified by high‐performance liquid chromatography in both leaf samples and aphids reared on the two host plants.4. The cabbage aphid performed better on canola than on black mustard. The performance of the predator on this aphid when reared on canola was clearly better than when reared on black mustard. Females had a higher overall preference for cabbage aphids reared on canola than on black mustard.5. The ability of aphids reared on plants with high glucosinolate content to reduce the performance of their generalist predators indicates that the presence ofB.nigramay provide enemy‐free space for the cabbage aphid from its predator, a concept that has useful application in the context of biological control for agricultural systems.
Bendamustine and rituximab in combination with lenalidomide in patients with chronic lymphocytic leukemia
Authors: Maurer Christian , Pflug Natali , Bahlo Jasmin , Kluth Sandra , Rhein Christina , Cramer Paula , Gross‐Ophoff Carolin , Langerbeins Petra , Fink Anna‐Maria , Eichhorst Barbara , Kreuzer Karl‐Anton , Fischer Norbert , Tausch Eugen , Stilgenbauer Stephan , Böttcher Sebastian , Döhner Hartmut , Kneba Michael , Dreyling Martin , Binder Mascha , Hallek Michael , Wendtner Clemens‐Martin , Bergmann Manuela , Fischer Kirsten ,   the German CLL Study Group
Published: December 2015

AbstractPurposeA phase I/II trial to assess safety and efficacy of the combination bendamustine, rituximab, and lenalidomide (BRL) in patients with chronic lymphocytic leukemia (CLL).Patients and MethodsSeventeen relapsed or refractory (R/R) and five previously untreated (FL) CLL patients were enrolled in the trial. In the R/R cohort, four different dose levels of lenalidomide (maximum 15 mg/d) were used. In the FL cohort, lenalidomide was dose escalated from 5 mg/d to 15 mg/d. Bendamustine was used at doses of 50 or 90 mg/m2 for R/R or FL treatment, respectively. 375 mg/m2 Rituximab were used for the first and 500 mg/m2 for subsequent treatment courses. Treatment consisted of up to six courses of 28 d.ResultsThe maximal tolerable dose of lenalidomide was 5 mg/d. The response rate was 47.1% in R/R and 60% in FL patients. Median progression‐free survival was 8.0 months. Median overall survival was 22.9 and 12.3 months, respectively, in R/R and FL patients. Grade 3/4 hematological toxicity was observed in 71.4%, and severe infections in 47.6% of patients. Due to high toxicity and low response rate of BRL, the trial was closed prematurely.ConclusionBRL was associated with a high toxicity rate, a high number of treatment interruptions, and a low remission rate. Therefore, BRL cannot be considered an appropriate treatment option for patients with CLL.
Utilizing an integrated infrastructure for outcomes research: a systematic review
Authors: Dixon Brian E. , Whipple Elizabeth C. , Lajiness John M. , Murray Michael D. 
Published: December 2015

AbstractObjectiveTo explore the ability of an integrated health information infrastructure to support outcomes research.MethodsA systematic review of articles published from 1983 to 2012 by Regenstrief Institute investigators using data from an integrated electronic health record infrastructure involving multiple provider organisations was performed. Articles were independently assessed and classified by study design, disease and other metadata including bibliometrics.ResultsA total of 190 articles were identified. Diseases included cognitive, (16) cardiovascular, (16) infectious, (15) chronic illness (14) and cancer (12). Publications grew steadily (26 in the first decade vs. 100 in the last) as did the number of investigators (from 15 in 1983 to 62 in 2012). The proportion of articles involving non‐Regenstrief authors also expanded from 54% in the first decade to 72% in the last decade. During this period, the infrastructure grew from a single health system into a health information exchange network covering more than 6 million patients. Analysis of journal and article metrics reveals high impact for clinical trials and comparative effectiveness research studies that utilised data available in the integrated infrastructure.DiscussionIntegrated information infrastructures support growth in high quality observational studies and diverse collaboration consistent with the goals for the learning health system. More recent publications demonstrate growing external collaborations facilitated by greater access to the infrastructure and improved opportunities to study broader disease and health outcomes.ConclusionsIntegrated information infrastructures can stimulate learning from electronic data captured during routine clinical care but require time and collaboration to reach full potential.
Special AT‐rich sequence‐binding protein 2 (SATB2) expression is sensitive but may not be specific for osteosarcoma as compared with other high‐grade primary bone sarcomas
Authors: Davis Jessica L , Horvai Andrew E 
Published: December 2015

AimsThe diagnosis of osteosarcoma, although important for eligibility in clinical trials and proper therapy, may be challenging when no bone or osteoid matrix is identified on biopsy. Therefore, other adjunct tests have been sought to help confirm the diagnosis. Special AT‐rich sequence‐binding protein 2 (SATB2) has been shown as a reliable marker of osteoblastic differentiation. The aim of this study was to examine SATB2 expression in osteosarcomas and other primary bone sarcomas, in order to evaluate its diagnostic utility in discriminating osteogenic from non‐osteogenic sarcomas.Methods and resultsForty‐eight pretreated osteosarcoma biopsies, including 26 whole‐section cases and 22 tumours on tissue microarrays, and 36 non‐osteogenic bone sarcomas were evaluated. Forty‐five of 48 (94%) osteosarcomas showed nuclear immunoreactivity for SATB2 (all whole‐slide sections showed expression). Positive SATB2 expression was observed in 11 of 22 (50%) undifferentiated pleomorphic sarcomas (UPSs), and in five of 11 (45%) fibrosarcomas; expression was absent in two pleomorphic rhabdomyosarcomas and in the one leiomyosarcoma. The sensitivity of SATB2 for osteosarcoma was 94%, and the specificity was 55%. Stronger‐intensity staining was observed in osteosarcoma (P < 0.0001).ConclusionsSATB2 is a sensitive marker for osteosarcoma; however, it is not specific, with expression being observed in other high‐grade primary bone sarcomas. Intriguingly, the lack of specificity may suggest that the undifferentiated sarcomas (UPSs and fibrosarcomas) with SATB2 expression actually represent osteosarcomas that produce too little matrix to be detected with routine sampling or consist of osteoblast precursors that do not synthesize matrix.
Evaluation of the anti‐wrinkle effect of an ascorbic acid‐loaded dissolving microneedle patch via a double‐blind, placebo‐controlled clinical study
Authors: Lee C. , Yang H. , Kim S. , Kim M. , Kang H. , Kim N. , An S. , Koh J. , Jung H. 
Published: December 2015

AbstractObjectiveAlthough an ascorbic acid‐loaded dissolving microneedle patch has been developed to improve anti‐wrinkle effects, an efficacy evaluation with a control group has not yet been performed. In this study, the anti‐wrinkle effect of an ascorbic acid‐loaded dissolving microneedle patch was evaluated in a double‐blind clinical study with a control group. In addition, a cumulative skin irritation and sensitization potential of the ascorbic acid‐loaded dissolving microneedle patch was performed.MethodsTwenty‐three subjects were selected for anti‐wrinkle effect evaluation in a double‐blind clinical study. Subjects were divided into two groups. Group I subjects applied an ascorbic acid‐loaded dissolving microneedle patch on a crow's feet area on the left side of the face and a control sample on a crow's feet area on the right side of the face every 4 days. Group II subjects placed the same patches on opposite sides of the face. Global Photodamage Score and skin replica analysis were conducted by visual inspection and skin visiometer, respectively. A skin irritation and sensitization assessment was performed on 51 subjects using the modified Shelanski & Shelanski procedure. Cumulative skin irritation potential and skin sensitization of the ascorbic acid‐loaded dissolving microneedle patch and control sample were evaluated.ResultsSkin treated with the ascorbic acid‐loaded dissolving microneedle patch showed a statistically significant improvement in both the Global Photodamage Score and visiometer R values (P < 0.05) compared with the control sample. The R2 value (maximum roughness), in particular, showed a highly significant improvement (P < 0.01). The skin irritation and sensitization assessment demonstrated that the ascorbic acid‐loaded dissolving microneedle patch did not induce any cumulative skin irritation potential or skin sensitization.ConclusionsAn ascorbic acid‐loaded dissolving microneedle patch produced a significant anti‐wrinkle effect without skin irritation and sensitization problems. This cosmetic dissolving microneedle patch can be used efficiently in the anti‐wrinkle cosmetic field with patient convenience.
In vitro assessment of a collagen/alginate composite scaffold for regenerative endodontics
Authors: Devillard R. , Rémy M. , Kalisky J. , Bourget J.‐M. , Kérourédan O. , Siadous R. , Bareille R. , Amédée‐Vilamitjana J. , Chassande O. , Fricain J.‐C. 
Published: December 2015

AbstractAimTo develop a biological scaffold that could be moulded to reproduce the geometry of a gutta‐percha point with precision and allow the differentiation of mesenchymal stem cells into osteoblasts to be used as a regenerative endodontic material.MethodologyA collagen/alginate composite scaffold was cast into a sodium alginate mould to produce a gutta‐percha point‐like cone. Prior to gelation, the cone was seeded with human stem cells from the apical papilla (SCAPs) to evaluate cell/scaffold interactions. The reconstructed tissue was characterized after 8 days in culture. Elastic modulus, tissue compaction and cell differentiation were assessed. Student t‐tests and the Mann–Whitney U test were performed.ResultsThe fabrication method developed enabled the shape of a gutta‐percha point to be mimicked with great accuracy and reproducibility (P = 0.31). Stem cells seeded into this composite scaffold were able to spread, survive and proliferate (P < 0.001). Moreover, they were able to differentiate into osteoblasts and produce calcified osseous extracellular matrix (P < 0.001). The construct showed no significant contraction after 8 days, preserving its shape and tip diameter (P = 0.58).ConclusionsThe composite scaffold could present substantial benefits compared to synthetic materials. It could provide a favourable healing environment in the root canal conducive for regenerative endodontics and is therefore appropriate to be evaluated in vivo in further studies.
Behaviour of human dental pulp cells cultured in a collagen hydrogel scaffold cross‐linked with cinnamaldehyde
Authors: Kwon Y. S. , Lee S. H. , Hwang Y. C. , Rosa V. , Lee K. W. , Min K. S. 
Published: December 2015

AbstractAimTo investigate the effects of the cross‐linking agent cinnamaldehyde (CA) on differentiation of human dental pulp cells (hDPCs) cultured in a collagen hydrogel, which may be useful as a scaffold for regenerative endodontic therapy.MethodologyThe odontogenic potential of hDPCs exposed to CA was examined using alkaline phosphatase (ALP) activity, Alizarin red S staining and real‐time polymerase chain reaction for odontogenic gene expression. The morphological features of hDPCs cultured in CA‐treated collagen were evaluated by scanning electron microscopy. Determination of cell numbers for evaluating proliferation was assessed by optical and fluorescence microscopy. To assess the mechanical properties of collagen treated with CA, setting time, compressive strength and surface roughness were measured. Statistical analysis was performed using Student's t‐test compared with control (P = 0.05).ResultsCA per se did not increase ALP activity, calcium nodule formation and expression of odontogenic‐related markers (P > 0.05). On the contrary, the proliferation and odontogenic differentiation of hDPCs cultured in a collagen scaffold was promoted in the presence of CA (P < 0.05). The setting time was significantly shortened, and the compressive strength and surface roughness were increased by treatment with CA (P < 0.05).ConclusionsCross‐linking of collagen scaffolds by CA had beneficial effects with respect to attachment, proliferation and differentiation of hDPCs. Consequently, the application of cross‐linking agents such as CA may represent a new strategy for dentine–pulp complex regeneration.
Securitization of migration and the far right: the case of Greek security professionals
Authors: Lazaridis Gabriella , Skleparis Dimitris 
Published: December 2015

AbstractSince the events of 9/11, security concerns have gained unprecedented dominance on western governments' national and international political agendas; Greece has been no exception. The success or failure of a far right party, like Golden Dawn, depends on the effectiveness of the government to regulate immigration and to develop policies aimed at combating the racism which pervades the political culture of society at this particular juncture, when the country is experiencing severe crisis. The aim is to provide an account of the rationale of the securitization of migration from the perspective of Greek security professionals. We argue that the extreme securitizing perceptions of security professionals have been exploited and assisted by far‐right extremist groups, which instilled racial violence, hate speech/crime into society, resulting in patterned, unreflective, and routinized security practices and discourses which are more in line with the beliefs and values advocated by the extreme right.
Changes in blood monocyte Toll‐like receptor and serum surfactant protein A reveal a pathophysiological mechanism for community‐acquired pneumonia in patients with type 2 diabetes
Authors: Que Y. , Shen X. 
Published: December 2015

BackgroundThe lung is one of the target organs of microangiopathy in diabetes mellitus (DM); patients with type 2 diabetes mellitus (T2DM) are vulnerable to pneumonia, and a variety of pathophysiological mechanisms has been described.AimThis study aimed to determine the pathophysiological mechanism of community‐acquired pneumonia (CAP) in T2DM patients.MethodsA total of 90 individuals was included in this study comprised of three groups (n = 30): healthy control, T2DM and T2DM+ CAP groups. Toll‐like receptor (TLR)2 and 4 protein and messenger RNA expression in peripheral blood monocytes(PBMC) was assessed by western blot and reverse transcription–polymerase chain reaction, respectively, and surfactant protein A (SP‐A) levels were examined in serum samples by enzyme‐linked immunosorbent assay.ResultsIn T2DM and T2DM+CAP groups, levels of both TLR2/4 protein and mRNA in PBMC were decreased compared with controls (P <0.05), with lower levels observed in the T2DM+CAP group in comparison with T2DM patients (P <0.05). The serum SP‐A levels in T2DM+CAP individuals were significantly higher than the values obtained for T2DM patients (P <0.05). It also showed apparent increases when compared with that in controls although no statistical significance was detected.ConclusionIn T2DM patients with pneumonia, TLR2/4 levels in PBMC and serum SP‐A were altered, maybe playing an important role in the susceptibility to pneumonia in T2DM patients.
Electromagnetic Contact‐Force Sensing Electrophysiological Catheters: How Accurate Is the Technology?
Authors: BOURIER FELIX , HESSLING GABRIELE , AMMAR‐BUSCH SONIA , KOTTMAIER MARC , BUIATTI ALESSANDRA , GREBMER CHRISTIAN , TELISHEVSKA MARTA , SEMMLER VERENA , LENNERZ CARSTEN , SCHNEIDER CHRISTINE , KOLB CHRISTOF , DEISENHOFER ISABEL , REENTS TILKO 
Published: December 2015

Accuracy of Contact‐Force SensingBackgroundContact‐force (CF) sensing catheters are increasingly used in clinical electrophysiological practice due to their efficacy and safety profile. As data about the accuracy of this technology are scarce, we sought to quantify accuracy based on in vitro experiments.Methods and ResultsA custom‐made force sensor was constructed that allowed exact force reference measurements registered via a flexible membrane. A Smarttouch Surround Flow (ST SF) ablation catheter (Biosense Webster, Diamond Bar, CA, USA) was brought in contact with the membrane of the force sensor in order to compare the ST SF force measurements to force sensor reference measurements. ST SF force sensing technology is based on deflection registration between the distal and proximal catheter tip. The experiment was repeated for n = 10 ST SF catheters, which showed no significant difference in accuracy levels. A series of measurements (n = 1200) was carried out for different angles of force acting to the catheter tip (0°/perpendicular contact, 30°, 60°, 90°/parallel contact). The mean absolute differences between reference and ST SF measurements were 1.7 ± 1.8 g (0°), 1.6 ± 1.2 g (30°), 1.4 ± 1.3 g (60°), and 6.6 ± 5.9 g (90°). Measurement accuracy was significantly higher in non‐parallel contact when compared with parallel contact (P < 0.01).ConclusionsCatheter force measurements using the ST SF catheters show a high level of accuracy regarding differences to reference measurements and reproducibility. The reduced accuracy in measurements of 90° acting forces (parallel contact) might be clinically important when creating, for example, linear lesions.
Tissue‐specific variation in nonsense mutant transcript level and drug‐induced read‐through efficiency in the Cln1R151X mouse model of INCL
Authors: Thada Vaughn , Miller Jake N. , Kovács Attila D. , Pearce David A. 
Published: December 2015

AbstractAbout 10% of inherited diseases are caused by nonsense mutations [Trends Mol Med 18 (2012) 688], and nonsense suppression drug therapy promoting translation through premature stop codons is an emerging therapeutic approach. Infantile neuronal ceroid lipofuscinosis (INCL), a childhood neurodegenerative disease, results from mutations in the CLN1 gene encoding the lysosomal enzyme, palmitoyl‐protein thioesterase 1 (PPT1) [Biochim Biophys Acta 1832 (2013) 1806, Hum Mutat (2012) 63, Biochim Biophys Acta 1832 (2013) 1881]. The nonsense mutation p.R151X is the most common disease‐causing CLN1 mutation Hum Mutat (2012) 63. In the novel Cln1R151X mouse model of INCL, we found large, tissue‐specific variations in Cln1R151X mRNA level and PPT1 residual enzyme activity. These tissue‐specific differences strongly influenced the read‐through efficiency of ataluren (PTC124), a well‐known nonsense suppression drug. A two‐day treatment with ataluren (10 mg/kg) increased PPT1 enzyme activity in the liver and muscle, but not in any other tissue examined. Our study identifies a new challenge/hurdle for read‐through drug therapy: variable efficiency of read‐through therapy in the different tissues/organs because of tissue‐specific variations in nonsense mutant transcript levels.
Efficacy of pyrethroid and neonicotinoid insecticides for Melanotus communis (Gyll.) (Coleoptera: Elateridae) control in Florida sugarcane (Saccharum spp.)
Authors: Larsen N. A. , Nuessly G. S. , Cherry R. H. 
Published: December 2015

AbstractWireworms are important pests in newly planted sugarcane fields in Florida. Current management involves an integrated programme of cultural and chemical controls. Current chemical controls used are the organophosphates phorate and ethoprop. As federal regulations tighten the uses of organophosphates, effective chemicals from alternative classes of chemistry need to be found. The organophosphates were the only insecticides that effectively protected the emerging shoots from damage in our study. Phorate consistently reduced the number of wireworms. While the pyrethroids and neonicotinoids were able to protect the seed piece and non‐sprouted buds, they did not consistently protect shoots and tillers. Neither pyrethroids nor neonicotinoids caused wireworm mortality in excess of that which occurred naturally.
A thicker chorion gives ova of Atlantic salmon (Salmo salar L.) the upper hand against Saprolegnia infections
Authors: Songe M M , Willems A , Sarowar M N , Rajan K , Evensen Ø , Drynan K , Skaar I , van West P 
Published: December 2015

AbstractSince the ban of malachite green in the fish farming industry, finding alternative ways of controlling Saprolegnia infections has become of utmost importance. Much effort has been made to elucidate the mechanisms by which Saprolegnia invades fish eggs. Little is known about the defence mechanisms of the hosts, making some eggs more prone to infection than others. One clue might lie in the composition of the eggs. As the immune system in the embryos is not developed yet, the difference in infection levels could be explained by factors influenced by the mother herself, by either transferring passive immunity, influencing the physical aspects of the eggs or both. One of the physical aspects that could be influenced by the female is the chorion, the extracellular coat surrounding the fish egg, which is in fact the first major barrier to be overcome by Saprolegnia spp. Our results suggest that a thicker chorion in eggs from Atlantic salmon gives a better protection against Saprolegnia spp. In addition to the identification of differences in sensitivity of eggs in a fish farm set‐up, we were able to confirm these results in a laboratory‐controlled challenge experiment.