bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic implications of melanoma heterogeneity
Authors: Hachey Stephanie J. , Boiko Alexander D. 
Published: April 2016

AbstractOver the last decade, the treatment of metastatic melanoma has been revolutionized by the translation of molecular insights into therapeutic benefit for patients. These include advances in immunotherapeutic and small‐molecule approaches aimed at destroying cells with immunogenic antigens or gene mutations. Despite these advances, the limited durability of clinical response and eventual disease progression underscores a need for better understanding of mechanisms underlying tumor development. Current targeted therapies are developed partly based on the rationale that tumors are primarily clonal with respect to mutant oncogene or cell surface antigen target. However, with the advancement of cell isolation and transplantation approaches coupled with deep sequencing and mutation detection techniques, it has become increasingly clear that tumors are polyclonal. As a result, sensitive malignant cells are eradicated by treatment while the remaining tumor cell populations are conferred varying degrees of resistance and survival advantages by harbouring or acquiring certain epigenetic and genetic abnormalities. Tumor heterogeneity thus represents a major obstacle to the successful application of current therapies. Gaining insights into the cellular and molecular aspects of tumor diversity will not only facilitate the development and selection of therapeutic targets but also promote the evolution of precision medicine. In this viewpoint, we will discuss the implications of tumor heterogeneity for the treatment of metastatic melanoma and propose approaches to accelerate the translation of scientific discovery into improved clinical outcomes.
Opioids and skin homeostasis, regeneration and ageing – What's the evidence?
Authors: Bigliardi Paul L. , Dancik Yuri , Neumann Christine , Bigliardi‐Qi Mei 
Published: April 2016

AbstractWhat has the opioid receptor system, known for beneficial as well as disastrous effects in the central nervous system, to do with skin? The question is appropriate considering the fact that the nervous system and the skin both derive from the ectoderm. As part of the skin neuroendocrine system, the opioid receptor system exemplifies the closeness between the nervous system and the skin. Overexpression of the δ‐opioid receptor in keratinocytes yields dysregulation of involucrin, loricrin, and filaggrin, proteins essential to the integrity of the skin barrier. The μ‐opioid receptor ligand β‐endorphin, produced in the pituitary gland and a variety of skin cells, promotes wound healing via regulation of cytokeratin 16 and TGF‐β type II receptor expression in keratinocytes. These and other published results discussed in this viewpoint are evidence for the fundamental role of the skin opioid receptor system in skin homeostasis, regeneration and ageing. While considerable progress in understanding the opioid receptors’ function on the cellular level has been made, there is a need to link these results to physiological observations for the development of local skin therapies.
EMMPRIN/CD147 is an independent prognostic biomarker in cutaneous melanoma
Authors: Caudron Anne , Battistella Maxime , Feugeas Jean‐Paul , Pages Cécile , Basset‐Seguin Nicole , Mazouz Dorval Sarra , Funck Brentano Elisa , Sadoux Aurélie , Podgorniak Marie‐Pierre , Menashi Suzanne , Janin Anne , Lebbé Céleste , Mourah Samia 
Published: April 2016

AbstractCD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in‐transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P < 0.05 for both) in primary melanoma patients. CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P < 10−8). Multivariate analysis retained CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P < 0.05 for both). CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker.
Non‐invasive objective devices for monitoring the inflammatory, proliferative and remodelling phases of cutaneous wound healing and skin scarring
Authors: Ud‐Din Sara , Bayat Ardeshir 
Published: April 2016

AbstractObjective evaluation of cutaneous wounds through the use of non‐invasive devices is important for diagnosis, monitoring treatment response and can lead to the development of improved theranostic strategies. The need for objective monitoring of wound healing and scar formation is evident as this enables accurate diagnosis, evaluation and prognosis for clinicians and allows for the standardisation and validation of methodology for researchers. Therefore, this review provides an overview of the current application of non‐invasive objective technologies for the assessment of wound healing through the different phases of repair. We propose that cutaneous healing parameters can be split into three core domains: anatomical, mechanical and physiological. These categories can be further subdivided with respect to specific phases of healing. There is no single instrument, which can measure all the parameters of healing simultaneously; thus, it is important to choose the correct device for the particular healing characteristics being monitored. However, multiprobe systems, which include a number of devices connected to one main unit, are useful as they enable multiple measurements of different parameters. Many of the devices have not been validated against histological examination. Additionally, some of the instruments have not been evaluated in all wound or scar types and may not be useful throughout all phases of cutaneous wound healing. In conclusion, non‐invasive objective devices are useful in the assessment of cutaneous wound healing, as these tools can link the treatment and diagnosis by evaluating response to treatment and thus could aid as a marker for healing and scar maturation.
Extracellular superoxide dismutase ameliorates house dust mite‐induced atopic dermatitis‐like skin inflammation and inhibits mast cell activation in mice
Authors: Lee Yun Sang , Choi Jung‐Hye , Lee Ji‐Hyun , Lee Han‐Woong , Lee Weontae , Kim Woo Taek , Kim Tae‐Yoon 
Published: April 2016

AbstractExtracellular superoxide dismutase (EC‐SOD) is an enzyme that catalyses the dismutation of superoxide anions. It has multiple functions, such as reactive oxygen species scavenging, anti‐angiogenic, anti‐inflammatory, antichemotatic and antitumor activities. Recently, we demonstrated that EC‐SOD inhibits ovalbumin‐induced allergic airway inflammation in mice. However, the anti‐allergic effect of EC‐SOD on skin tissue and the role of EC‐SOD in mast cells, which are important for allergic responses, have not been well studied. In this study, we investigated whether EC‐SOD can alleviate atopic dermatitis in mice and inhibit mast cell activation. Treatment with human recombinant EC‐SOD ameliorated house dust mite‐induced atopic dermatitis in mice. Furthermore, the levels of pro‐allergic cytokine gene expression and histamine release increased in EC‐SOD KO mast cells and decreased in EC‐SOD overexpressing mast cells, suggesting that EC‐SOD inhibits mast cell activation. Consistently, a passive cutaneous anaphylaxis experiment showed more blood leakage from EC‐SOD KO mouse ear skin, implying that the lack of EC‐SOD increases allergic responses. These results suggest that EC‐SOD inhibits mast cell activation and atopic dermatitis and that the loss of EC‐SOD causes more severe allergic responses, implying that EC‐SOD might be a good drug candidate for treatment of allergic disorders, such as atopic dermatitis.
Value Capture: A Valid Means of Funding PPPs?
Authors: Connolly Ciaran , Wall Anthony 
Published: April 2016

AbstractThis paper considers the use of value capture (VC) as a means of financing public‐private partnerships (PPPs) in the United Kingdom (UK). Although some VC techniques are used in the UK, they are employed more widely in the United States of America. After considering the traditional approach to financing UK PPPs, this paper describes the main VC finance instruments. The findings of a series of case studies are then presented and conclusions drawn. While VC financing may prove unpopular with those bearing the cost of infrastructure improvements, it is recommended that such instruments are considered by UK policy makers.
Numbers versus Narrative: An Examination of a Controversy
Authors: Dumay John , Rooney Jim 
Published: April 2016

AbstractCompeting actor interpretations of Intellectual Capital Statements (ICS) may explain diverse opinions on their effectiveness in practice. Adopting Callon's (1986) moments of translation, we find that actors in our case study adapt ICS numbers and narrative to create specific inscriptions, privileging one over the other to suit their interests. This allows IC controversy to survive rather than be resolved or the network to fail.
Budget Rules and Flexibility in the Public Sector: Towards a Taxonomy
Authors: Di Francesco Michael , Alford John 
Published: April 2016

AbstractThe practices and norms of public budgeting have often been seen as a brake on the flexibility needed of government organisations. This remains true despite historically significant financial management reforms designed around budgetary devolution. Seeing flexibility as operating along two dimensions – devolution and discretion – this paper revisits the underlying features of traditional public budgeting to develop a taxonomy of six generic ‘budget rules’. By isolating key properties of budget control, the paper uses two of the more prominent rules – annuality and purpose – to illustrate how the rules interact to generate control capacity, as well as the scope for rule variability in promoting increased flexibility.
Delayed autumn phenology in the Northern Hemisphere is related to change in both climate and spring phenology
Authors: Liu Qiang , Fu Yongshuo H. , Zhu Zaichun , Liu Yongwen , Liu Zhuo , Huang Mengtian , Janssens Ivan A. , Piao Shilong 
Published: April 2016

AbstractThe timing of the end of the vegetation growing season (EOS) plays a key role in terrestrial ecosystem carbon and nutrient cycles. Autumn phenology is, however, still poorly understood, and previous studies generally focused on few species or were very limited in scale. In this study, we applied four methods to extract EOS dates from NDVI records between 1982 and 2011 for the Northern Hemisphere, and determined the temporal correlations between EOS and environmental factors (i.e., temperature, precipitation and insolation), as well as the correlation between spring and autumn phenology, using partial correlation analyses. Overall, we observed a trend toward later EOS in ~70% of the pixels in Northern Hemisphere, with a mean rate of 0.18 ± 0.38 days yr−1. Warming preseason temperature was positively associated with the rate of EOS in most of our study area, except for arid/semi‐arid regions, where the precipitation sum played a dominant positive role. Interestingly, increased preseason insolation sum might also lead to a later date of EOS. In addition to the climatic effects on EOS, we found an influence of spring vegetation green‐up dates on EOS, albeit biome dependent. Our study, therefore, suggests that both environmental factors and spring phenology should be included in the modeling of EOS to improve the predictions of autumn phenology as well as our understanding of the global carbon and nutrient balances.
Home hemodialysis in children
Authors: Hothi Daljit K , Stronach Lynsey , Sinnott Kate 
Published: April 2016

AbstractPediatric home hemodialysis is infrequently performed despite a growing need globally among patients with end‐stage renal disease who do not have immediate access to a kidney transplant. In this review, we expand the scope of the Implementing Hemodialysis in the Home website and associated supplement published previously in Hemodialysis International and offer information tailored to the pediatric population. We describe the experience and outcomes of centers managing pediatric patients, and offer recommendations and practical tools to assist clinicians in providing quotidian dialysis for children, including infrastructural and staffing needs, equipment and prescriptions, and patient selection and training.
A retrospective analysis of triptan and dhe use for basilar and hemiplegic migraine
Authors: Mathew Paul G. , Krel Regina , Buddhdev Bhuvin , Ansari Hossein , Joshi Shivang G. , Spinner Warren D. , Klein Brad C. 
Published: April 2016

BackgroundPatients with basilar migraine (BM) and hemiplegic migraine (HM) have been excluded from triptan and DHE clinical trials due to a potential risk of ischemic vascular events, and the FDA mandates that package labeling state that they are contraindicated in BM and HM. The objective of this study was to demonstrate that triptans and DHE can be used for the abortive treatment of BM and HM without significant adverse ischemic vascular events.MethodsA retrospective chart review of patients with BM features or HM who received acute abortive treatment with either triptans or DHE was conducted at 4 headache centers to assess the frequency of ischemic vascular events after administration. The diagnoses of BM or HM were made by headache specialists based on The International Classification of Headache Disorders, 2nd edition (ICHD‐II). Searchable terms included BM, vertigo, dysarthria, diplopia, hemiplegia/hemiparesis, facial droop, weakness, confusion, altered consciousness, confusion, ataxia, and aphasia, as well as all triptans or DHE.ResultsThe study included 67 patients with BM features and 13 patients with HM. Among those receiving triptans, 40 were in the BM group and 5 were in the HM group. Among those receiving DHE, 27 were included in the BM group and 8 were in the HM group. No side effects of stroke or myocardial infarction were reported. In the triptan group, 5 patients reported adverse effects that included GI upset, rash, neck dystonia, nightmares, and flushing. In the DHE group, 5 patients had adverse events that included chest tightness, dystonic reaction, transient asymptomatic anterior T wave inversion, and agitation.ConclusionIn this retrospective study, triptans and DHE were used with no reported, subsequent acute/subacute ischemic vascular events for the abortive treatment of migraines with basilar and hemiplegic‐type features. Although the small sample sizes generated theoretical statistical event rates of 4.5% for BM and 23% for HM, there has been no clear evidence that BM and HM carry an actual elevated risk for vascular events compared with migraine with aura.
A 21–35 kDa Mixed Protein Component from Helicobacter pylori Activates Mast Cells Effectively in Chronic Spontaneous Urticaria
Authors: Tan Ran‐Jing , Sun He‐Qiang , Zhang Wei , Yuan Han‐Mei , Li Bin , Yan Hong‐Tao , Lan Chun‐Hui , Yang Jun , Zhao Zhuo , Wu Jin‐Jin , Wu Chao 
Published: April 2016

AbstractBackgroundHelicobacter pylori (H. pylori) seem to involve in the etiology of chronic spontaneous urticaria (CSU). But studies of the pathogenic mechanism are very little.MethodsIn this study, we detected the serum‐specific anti‐H. pylori IgG and IgE antibodies in 211 CSU and 137 normal subjects by enzyme‐linked immunosorbent assay (ELISA), evaluated the direct activation effects of H. pylori preparations and its protein components on human LAD2 mast cell line in vitro, and analyzed the specific protein ingredients and functions of the most effective H. pylori mixed protein component using liquid chromatography–mass spectrometry and ELISA assay.ResultsIn CSU patients, the positive rate of anti‐H. pylori IgG positive rate was significantly higher than that in normal controls, and the anti‐H. pylori IgE levels had no statistical difference between H. pylori‐infected patients with and without CSU. Further studies suggested that H. pylori preparations can directly activate human LAD2 mast cell line in a dose‐dependent manner and its most powerful protein component was a mixture of 21–35 kDa proteins. Moreover, the 21–35 kDa mixed protein component mainly contained 23 kinds of proteins, which can stimulate the release of histamine, TNF‐a, IL‐3, IFN‐γ, and LTB4 by LAD2 cells in a dose‐dependent or time‐dependent manner.ConclusionsA 21–35 kDa mixed protein component should be regarded as the most promising pathogenic factor contributing to the CSU associated with H. pylori infection.
Information‐seeking behaviour and information needs of LGBTQ health professionals: a follow‐up study
Authors: Morris Martin , Roberto K.R. 
Published: April 2016

AbstractBackgroundExcept for one study in 2004, the literature has no data on the information‐seeking behaviour of lesbian, gay, bisexual, transgender and queer/questioning (LGBTQ) health professionals. After a decade of change for LGBTQ people, and the growth of electronic information sources and social networks, it is appropriate to revisit this subject.ObjectivesTo gain an updated understanding of the information‐seeking behaviour of LGBTQ health professionals and of how medical libraries can provide a culturally competent service to such users.MethodsA mixed‐methods approach was adopted combining a Web‐based questionnaire with email follow‐up discussions. One hundred and twenty‐three complete responses were received, mostly from the USA and Canada, between November 2012 and October 2013.ResultsLGBTQ health professionals remain more comfortable seeking LGBTQ health information from a medical librarian whom they know to be LGBTQ because they perceive LGBTQ librarians as more likely to have specialist knowledge, or through concern that non‐LGBTQ librarians may be more likely to react in a stigmatising or discriminatory way. The study also provides evidence suggesting that online chat has marginal appeal for respondents seeking LGBTQ health information, despite its anonymity. Medical libraries seeking to demonstrate their cultural competency should provide visible evidence of this, such as through the creation of dedicated resource lists, promotion of LGBTQ literature on the library's website, and display of other symbols or statements supporting diversity.ConclusionOpportunities exist for LGBTQ health professionals and medical librarians to work together to ensure that medical libraries are culturally competent and welcoming spaces for LGBTQ patrons, that library collections match their needs, and in the creation of guides to ensure maximum access to the results of LGBTQ health research. Medical libraries should also consider nominating and, if necessary, training a specialist in LGBTQ health information. Such measures are more likely to be successful than reliance on online chat, despite contrary suggestions in the literature.
Endodontic regeneration and tooth revitalization in immature infected sheep teeth
Authors: Altaii M. , Cathro P. , Broberg M. , Richards L. 
Published: April 2016

AbstractAimTo examine the response of immature sheep teeth with infected root canal systems to a commonly used pulp regeneration/revitalization protocol.MethodologyImmature mandibular right first incisors in four sheep were mechanically exposed and the pulps infected. The mandibular left first incisors remained intact as controls. Five weeks later, the experimental root canals were chemo‐mechanically cleaned and dressed with a triple‐antibiotic paste for 4 weeks, before bleeding was induced inside the canal by mechanically irritating the periapical tissues. A collagen dressing was packed coronally onto the blood clot and the canal orifice sealed with mineral trioxide aggregate and glass ionomer cement. Six months later, the mandibles were collected and the teeth with associated periapical tissues were analysed radiographically, with CT scanning, and by histology. The changes in root length, dentine thickness in the apical third (mesially and distally), and apical diameter were analysed using Student's t‐test.ResultsRadiographs revealed significant increases in root length, root wall thickness and narrowing of the apical diameter of the canals after treatment (P < 0.05), with no significant differences in root diameters found between the experimental and the control teeth (P > 0.05) on both radiographic and CT results. Root maturation and thickening of the walls due to hard tissue deposition was confirmed by histology in all experimental teeth. Hard tissues in the apical portion of the root were more developed than in the coronal portion.ConclusionEndodontic regeneration and tooth revitalization procedures in immature infected sheep teeth showed positive outcomes with similar increases in root length and development to the control teeth.
Ocular findings in patients with alopecia areata
Authors: Esmer Oktay , Karadag Remzi , Cakici Ozgur , Bilgili Serap Gunes , Demircan Yuhanize Tas , Bayramlar Huseyin , Karadag Ayse S. 
Published: April 2016

AbstractObjectivesThis study investigated ocular findings in patients with alopecia.MethodsA total of 42 patients with alopecia (31 male, 11 female; 84 eyes) and 45 healthy individuals (28 male, 17 female; 90 eyes) were enrolled in the study. Of the patients with alopecia, 34 had alopecia areata, seven had alopecia universalis, and one had ophiasis alopecia. Seven patients had eyebrow involvement and seven had eyelash involvement. Autorefractometry, keratometry, visual acuity, central corneal thickness and intraocular pressure (IOP) measurements, bilateral anterior and posterior segment examinations, Schirmer's tests, and visual field examinations were performed in both groups.ResultsThe mean ± standard deviation age of the subjects was 25.21 ± 10.88 years in the alopecia group and 28.24 ± 9.31 years in the control group. Lens abnormalities were observed in 35 eyes in the alopecia group and in 11 eyes in the control group (P < 0.05). Posterior segment abnormalities were seen in 29 eyes in the alopecia group and four eyes in the control group (P < 0.05). There were no statistically significant differences in age, sex, visual acuity, refractive error, keratometric findings, IOP, central corneal thickness, perimetry, or Schirmer's test results between the alopecia and control groups (P > 0.05).ConclusionsPatients with alopecia may have more lenticular and retinal findings than normal individuals, but those findings do not interfere with visual acuity. Close surveillance for the early onset of cataract formation is important in patients with alopecia.