bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postoperative hyperalgesia does not predict persistent post‐sternotomy pain; observational study based on clinical examination
Authors: Setälä P. , Kalliomäki M.‐L. , Järvelä K. , Huhtala H. , Sisto T. , Puolakka P. 
Published: December 2015

BackgroundPersistent post‐sternotomy pain is a common problem, but the risk of developing it varies among patients. We sought to find out whether the risk of persistent post‐sternotomy pain could be predicted by measuring the area of acute sensory dysfunction around the sternotomy wound. The secondary aim was to determine risk factors for persistent post‐sternotomy pain.Patients and methodsHundred patients who were scheduled to undergo elective coronary artery bypass surgery were recruited to the study. Patients were excluded if they had undergone previous cardiac surgery or if they lacked co‐operation. Preoperative pain scores were determined and the patients filled in questionnaires about depression, anxiety, and pain. The area of sensory dysfunction around the sternotomy wound was assessed by pin prick on postoperative day 4. The presence of persistent post‐sternotomy pain was determined at a follow‐up evaluation at 4–6 months after surgery.ResultsThe sizes of the area of hyperalgesia or overall sensory dysfunction were not associated with persistent post‐sternotomy pain. Independent risk factors for persistent post‐sternotomy pain were found to be smoking and high pain score on postoperative day 1. The prevalence of persistent post‐sternotomy pain in our study population was 38% analyzed by only the questionnaire and 15% according to the clinical examination.ConclusionMeasuring the area of hyperalgesia in the acute phase does not give any additional information on the risk of developing a persistent post‐sternotomy pain. We do thus not recommend measuring the area in this particular group of patients. Evaluation of pain by only a questionnaire risks to overestimate the presence of persistent post‐sternotomy pain as compared to clinical examination.
Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria
Authors: Xiong Zheng‐Mei , Choi Ji Young , Wang Kun , Zhang Haoyue , Tariq Zeshan , Wu Di , Ko Eunae , LaDana Christina , Sesaki Hiromi , Cao Kan 
Published: December 2015

SummaryHutchinson–Gilford progeria syndrome (HGPS), a fatal premature aging disease, is caused by a single‐nucleotide mutation in the LMNA gene. Previous reports have focused on nuclear phenotypes in HGPS cells, yet the potential contribution of the mitochondria, a key player in normal aging, remains unclear. Using high‐resolution microscopy analysis, we demonstrated a significantly increased fraction of swollen and fragmented mitochondria and a marked reduction in mitochondrial mobility in HGPS fibroblast cells. Notably, the expression of PGC‐1α, a central regulator of mitochondrial biogenesis, was inhibited by progerin. To rescue mitochondrial defects, we treated HGPS cells with a mitochondrial‐targeting antioxidant methylene blue (MB). Our analysis indicated that MB treatment not only alleviated the mitochondrial defects but also rescued the hallmark nuclear abnormalities in HGPS cells. Additional analysis suggested that MB treatment released progerin from the nuclear membrane, rescued perinuclear heterochromatin loss and corrected misregulated gene expression in HGPS cells. Together, these results demonstrate a role of mitochondrial dysfunction in developing the premature aging phenotypes in HGPS cells and suggest MB as a promising therapeutic approach for HGPS.
Population pharmacokinetic analysis of sifalimumab from a clinical phase IIb trial in systemic lupus erythematosus patients
Authors: Zheng Bo , Yu Xiang‐Qing , Greth Warren , Robbie Gabriel J. 
Published: December 2015

AimsSifalimumab, a human immunoglobulin (Ig) G1 monoclonal antibody against INF‐alpha, is being studied as a treatment for systemic lupus erythematosus (SLE). This analysis characterized population pharmacokinetics (PK) of sifalimumab following repeat fixed dose and evaluated the utility of fixed dosing vs. body weight normalized dosing in SLE patients.MethodsPK data were collected in a phase IIb study where 298 patients received multiple intravenous doses (200–1200 mg) of sifalimumab every 4 weeks for 52 weeks. A population pharmacokinetic model was developed using 3961 quantifiable serum concentrations and the impact of patient demographics, clinical indices and biomarkers on pharmacokinetic parameters was evaluated. The appropriateness of the final model was evaluated using visual predictive check and bootstrap.ResultsA two compartment model with first order elimination adequately described sifalimumab serum PK. The estimated typical clearance (CL) and central volume of distribution (V1) were 184 ml day–1 and 2.82 l with 24% and 16% between‐subject variability (BSV), respectively. Body weight, dose, 21 INF gene signature baseline and concomitant steroid use were identified as statistically significant covariates for CL and V1 and accounted for <10% of PK variability in the final model. Typical values and BSV of PK parameters from the current analysis with fixed dosing were similar to previous population PK results with body weight normalized dosing.ConclusionsThe transition from body weight normalized dosing to fixed dosing did not impact sifalimumab PK. These findings support the use of fixed dosing for sifalimumab in future clinical studies evaluating it as a potential treatment for SLE.
Effects of the scaffold proteins liprin‐α1, β1 and β2 on invasion by breast cancer cells
Authors: Chiaretti Sara , Astro Veronica , Chiricozzi Elena , de Curtis Ivan 
Published: December 2015

Background InformationThe expression of the scaffold protein liprin‐α1 is upregulated in human breast cancer. This protein is part of a molecular network that is important for tumour cell invasion in vitro. Liprin‐α1 promotes invasion by supporting the protrusive activity at the leading edge of the migrating tumour cell and the degradation of the extracellular matrix by invadopodia. In this study, we have addressed the role of liprin‐α1 in the invasive process in vivo and of liprin‐proteins in tumor cell motility.ResultsThe human tumour cell line MDA‐MB‐231 expresses liprin‐α1 and is able to promote the formation of metastasis in mice. Liprin‐α proteins may hetero‐oligomerize with the members of the subfamily of the liprin‐β adaptor proteins. Analysis of the role of liprin‐β1 and liprin‐β2 has shown that while liprin‐β1 contributes positively to tumour cell motility in vitro; liprin‐β2 has a negative effect on both cell motility and invasion. Interestingly, we also observed differential effects on the ability of tumour cells to degrade the extracellular matrix, which is required for efficient invasion by tumour cells. In addition, analysis of the formation of lung metastases in vivo revealed that while the overexpression of liprin‐α1 in MDA‐MB‐231 cells did not evidently affect the metastatic process, silencing of the endogenous protein strongly impaired the formation of metastases by two independent invasion assays, without inhibiting the growth of primary tumours.ConclusionsOur data support an important role of distinct liprin family members in the regulation of tumour cell invasion, highlighting pro‐invasive and anti‐invasive effects by liprin‐α1 and liprin‐β2, respectively.SignificanceOur results indicate the importance of liprins in breast cancer cell invasion, and are expected to lead to future investigations on the mechanisms underlying the effects of distinct liprin proteins in different processes linked to tumor cell migration and invasion.
Structure and scale of the mechanics of mammalian dental enamel viewed from an evolutionary perspective
Authors: Lucas Peter W. , Philip Swapna M. , Al‐Qeoud Dareen , Al‐Draihim Nuha , Saji Sreeja , van Casteren Adam 
Published: December 2015

SUMMARYMammalian enamel, the contact dental tissue, is something of an enigma. It is almost entirely made of hydroxyapatite, yet exhibits very different mechanical behavior to a homogeneous block of the same mineral. Recent approaches suggest that its hierarchical composite form, similar to other biological hard tissues, leads to a mechanical performance that depends very much on the scale of measurement. The stiffness of the material is predicted to be highest at the nanoscale, being sacrificed to produce a high toughness at the largest scale, that is, at the level of the tooth crown itself. Yet because virtually all this research has been conducted only on human (or sometimes “bovine”) enamel, there has been little regard for structural variation of the tissue considered as evolutionary adaptation to diet. What is mammalian enamel optimized for? We suggest that there are competing selective pressures. We suggest that the structural characteristics that optimize enamel to resist large‐scale fractures, such as crown failures, are very different to those that resist wear (small‐scale fracture). While enamel is always designed for damage tolerance, this may be suboptimal in the enamel of some species, including modern humans (which have been the target of most investigations), in order to counteract wear. The experimental part of this study introduces novel techniques that help to assess resistance at the nanoscale.
Biomarkers of alopecia areata disease activity and response to corticosteroid treatment
Authors: Fuentes‐Duculan Judilyn , Gulati Nicholas , Bonifacio Kathleen M. , Kunjravia Norma , Zheng Xiuzhong , Suárez‐Fariñas Mayte , Shemer Avner , Guttman‐Yassky Emma , Krueger James G. 
Published: December 2015

AbstractAlopecia areata (AA) is a common inflammatory disease targeting the anagen‐stage hair follicle. Different cytokines have been implicated in the disease profile, but their pathogenic role is not yet fully determined. We studied biopsies of pretreatment lesional and non‐lesional (NL) scalp and post‐treatment (intra‐lesional steroid injection) lesional scalp of 6 patchy patients with AA using immunohistochemistry and gene expression analysis. Immunohistochemistry showed increases in CD3+, CD8+ T cells, CD11c+ dendritic cells and CD1a+ Langerhans cells within and around hair follicles of pretreatment lesional scalp, which decreased upon treatment. qRT‐PCR showed in pretreatment lesional scalp (compared to NL) significant increases (P < 0.05) in expression of inflammatory markers (IL‐2, IL‐2RA, JAK3, IL‐15), Th1 (CXCL10 and CXCL9), Th2 (IL‐13, CCL17 and CCL18), IL‐12/IL‐23p40 and IL‐32. Among these, we observed significant downregulation with treatment in IL‐12/IL‐23p40, CCL18 and IL‐32. We also observed significant downregulation of several hair keratins in lesional scalp, with significant upregulation of KRT35, KRT75 and KRT86 in post‐treatment lesional scalp. This study shows concurrent activation of Th1 and Th2 immune axes as well as IL‐23 and IL‐32 cytokine pathways in lesional AA scalp and defined a series of response biomarkers to corticosteroid injection. Clinical trials with selective antagonists coupled with cytokine‐pathway biomarkers will be necessary to further dissect pathogenic immunity.
A potential contribution of altered cathepsin L expression to the development of dermal fibrosis and vasculopathy in systemic sclerosis
Authors: Yamashita Takashi , Asano Yoshihide , Taniguchi Takashi , Nakamura Kouki , Saigusa Ryosuke , Takahashi Takehiro , Ichimura Yohei , Toyama Tetsuo , Yoshizaki Ayumi , Miyagaki Tomomitsu , Sugaya Makoto , Sato Shinichi 
Published: December 2015

AbstractCathepsin L (CTSL) is a lysosomal proteolytic enzyme involved in inflammation and vascular and extracellular matrix remodelling, which are the three cardinal pathological events associated with systemic sclerosis (SSc). To elucidate the potential role of CTSL in the development of SSc, we here investigated CTSL expression in the lesional skin of patients with SSc and SSc animal models and the clinical correlation of serum CTSL levels. CTSL expression was elevated in dermal small vessels of SSc patients compared with those of healthy controls. Consistently, CTSL mRNA levels were increased in SSc lesional skin samples, but not in cultivated SSc dermal fibroblasts, compared with corresponding control samples from healthy individuals. Serum CTSL levels were significantly higher in SSc patients than in healthy controls and inversely correlated with skin score. Furthermore, the elevation of serum CTSL levels was linked to SSc vasculopathy. Supporting these results, Ctsl mRNA levels were decreased in the skin of bleomycin‐treated mice, an SSc animal model recapitulating its fibrotic aspect, and CTSL expression was enhanced in dermal small vessels of endothelial cell‐specific Fli1 knockout mice, reminiscent of SSc vasculopathy. Importantly, gene silencing of FLI1 induced CTSL mRNA expression and Fli1 occupied the CTSL promoter in human dermal microvascular endothelial cells. Collectively, these results suggest that endothelial CTSL up‐regulation partially due to Fli1 deficiency may contribute to the development of vasculopathy, while the decrease in dermal CTSL expression is likely associated with dermal fibrosis in SSc.
The importance of leisure reading to health sciences students: results of a survey
Authors: Watson Erin M. 
Published: December 2015

AbstractObjectiveTo determine what value health sciences students place on leisure reading, whether they prefer to read online or in print, what the principal barriers are to their reading and whether they wish to have a leisure reading collection at their health sciences library.MethodsIn October 2010, a link to a survey was sent to all 1800 students in health sciences professional programmes at the author's institution.ResultsTwo hundred and thirteen students (11.8%) responded. Most felt that leisure reading had helped in their development as health professionals and increased their empathy. They listed many benefits of reading, such as improved understanding of minority groups, reduced stress, and improved thinking and communication skills. The majority preferred to read books and magazines in print, while the largest number preferred reading newspapers in print as well. Lack of time, fatigue and the expense of purchasing reading materials were the greatest barriers to reading. A majority of students were in favour of having a leisure reading collection set up at their library.ConclusionsLeisure reading was valued by the respondents, who felt it provided personal and professional benefits. However, many indicated that circumstances made it difficult to participate in leisure reading.
Pharmacotherapies for renal cell carcinoma in Japan
Authors: Yoshimura Kazuhiro , Uemura Hirotsugu 
Published: December 2015

AbstractThe standard treatment for advanced renal cell carcinoma has changed dramatically in the past decade, from cytokine therapy to targeted therapy. Since sorafenib was approved in April 2008, four tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors have become available in Japan. Most Japanese renal cell carcinoma patients are treated by urologists who are involved in not only kidney surgeries, but also targeted therapy using tyrosine kinase inhibitors, as well as mammalian target of rapamycin inhibitors. Optimal treatment methods are selected from theoretically‐based global recommendations, such as the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines; however, real‐world clinical practice might be different from that in non‐Asian countries. This might be because of different practical conditions; for example, different adverse events and efficacy profiles, different healthcare system, and so on. In the present review, we examine current pharmacotherapy for renal cell carcinoma from evidence‐based global data, and compare the reality of Japanese clinical practice to explore the importance of individualized patient therapy.
A HOLISTIC APPROACH TO THE PREDICTIVE POWER OF EXPECTED VOLATILITY
Authors: van der Holst Gherben , Zwinkels Remco C. J. 
Published: December 2015

AbstractThe existing literature is highly dispersed regarding the relation between volatility and expected returns. We combine several volatility measures and empirical methods to give a holistic overview of this fundamental relation in finance. Results indicate that total and idiosyncratic volatility levels and volatility changes have predictive power in the cross‐section of expected excess stock returns. Volatility levels are positively and volatility changes are negatively related to future stock returns. Exponentially weighted moving average (EWMA), generalized autoregressive conditional heteroskedasticity (GARCH), and threshold GARCH (TGARCH) volatility measures have the greatest predictive power. Controlling for the short‐term reversal effect and illiquidity does not help explain the predictive power of expected volatility.
IN SEARCH OF CASH‐FLOW PRICING
Authors: Fabozzi Frank J. , Chen K. C. , Ma K. C. , West Jessica 
Published: December 2015

AbstractThere are varying views on the relative importance of cash flow versus earnings in the pricing of stocks. In this article, we identify which financial metric—cash flow or earnings—is more often used by investors in equity valuation and then investigate why investors focus on one more than the other. Our prior is that the practice of deviating from cash‐flow pricing, if it exists, can be explained by either rational herding or information cascades. We find that although stock prices are, on average, affected by short‐term earnings, cash‐flow pricing is used primarily to price what we classify as “negative” stocks—stocks that are generally characterized as illiquid, mispriced, or having a shorter trading history, negative earnings, or negative market performance. We find evidence consistent with the rational argument of information cascades. For stocks under close public scrutiny, investors tend to follow the decisions of others and feel compelled to conform to the majority even though their private information suggests otherwise. In the end, the choice to value stocks with either earnings or cash flow is still a rational one.
ALK1 expression in oral lichen planus: a possible relation to microvessel density
Authors: Hazzaa Hala H. A. , El‐Wakeel Naglaa M. , Attia Enas A. S. , Abo Hager Eman A. 
Published: December 2015

ObjectiveTo assess the expression of activin receptor‐like kinase 1 (ALK1) and investigate its possible relationship with microvessel density (MVD) in different forms of oral lichen planus (OLP) compared to controls' biopsies.MethodsBiopsies from 20 reticular/papular OLP (R/PLP), 20 atrophic/erosive OLP (A/ELP) patients, and 20 healthy subjects were immunohistochemically analyzed and statistically compared and correlated for ALK1 expression and MVD as assessed by CD34 expression.ResultsAll OLP specimens revealed the presence of positive cytoplasmic CD34 immunostaining in endothelial cells, with statistically high significant MVD in each of R/PLP (Median; M = 4.40) and A/ELP (M = 7.69) compared to controls (M = 1.16) (P < 0.001). Statistically significant MVD was found in A/ELP compared to R/PLP (P < 0.001). All control specimens revealed negative ALK1 immunostaining of the few inflammatory cells found, while 85% of A/ELP cases and 70% of R/PLP cases showed positively immunostained sections for ALK‐1, with statistically significant higher ALK1 expression In A/ELP (M = 1.95) compared to R/PLP (M = 0.86) (P = 0.005). No significant correlation between CD34 and ALK1 was detected in R/PLP (r = 0.081), while a barely moderate positive correlation was found in A/ELP (r = 0.396).ConclusionsALK1 expression and MVD are increased in OLP, particularly in A/ELP type.
In Vitro and Dietary Effects of Chitin on Cellular and Humoral Immune Parameters of Catla, Catla catla (Hamilton)
Authors: Sangma Timothy , Kamilya Dibyendu 
Published: December 2015

AbstractImmunostimulants increase the immunocompetency and disease resistance of fish by enhancing immune responses. This study determined the in vitro and dietary effects of chitin on immune responses of catla, Catla catla. Catla head‐kidney leukocytes were cultured in complete RPMI‐1640 medium containing 0.01, 0.1, and 1.0 mg/mL of chitin. Leucocyte viability and different cellular immune responses, namely, respiratory burst, nitric oxide production, and leucocyte peroxidase content were analyzed in vitro. In the dietary experiment, chitin‐supplemented diets (0.5, 1.0, and 2.0% of feed) were fed to catla for 2 wk, and respiratory burst, serum lysozyme, and total protein contents were measured after 1 and 2 wk of feeding. Leucocytes incubated in vitro with chitin for 72 h maintained their viability. Chitin significantly (P < 0.05) enhanced all the immune responses in vitro. The lowest dose showed the best response. Dietary chitin also significantly stimulated all the immune parameters in a dose‐dependent manner with the highest dose showing the maximum responses. All the responses were higher after 1 wk of feeding and declined thereafter. The results suggest that chitin stimulates catla cellular and humoral immune responses in vitro and in vivo.
Effects of Different Diets on the Growth, Survival, and Nutritional Composition of Juvenile Cuttlefish,Sepia pharaonis
Authors: Peng Rui‐Bing , Le Ke‐Xin , Jiang Xia‐Min , Wang Yuan , Han Qing‐Xi 
Published: December 2015

AbstractThe aim of this experiment was to determine the optimal initial food for hatchling cuttlefish and to investigate the influence of dietary composition on the growth, survival, and nutritional composition of cultured juvenile cuttlefish,Sepia pharaonis. Six experimental food groups were designated:Artemia nauplii,Calanus sinicus, frozenHyperacanthomysis brevirostris,Ampithoe valida,H. brevirostris, and subadultArtemia. The results showed that survival, growth body biochemical composition of juvenile cuttlefish were significantly affected by experimental diets (P < 0.05). The optimum initial food wasH. brevirostris, yielding a growth rate as high as 6.39%/d and survival rate reaching 81%. Growth rate was significantly positively correlated with dietary protein, Lys, Met, Phe, Iie, Leu, Trp, Arg, Gly, Eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), and 16:0 (P < 0.05). Survival was significantly positively correlated with dietary protein, Lys, Met, Phe, Val, Thr, Iie, Leu, Trp, Arg, Gly,EPA,DHA, and 16:0 (P < 0.05). The dietary protein, lipid, Met, Val, Thr, Leu, 18:0, andEPAwere prone to accumulation within the body of juvenile cuttlefish (P < 0.05). These results demonstrate that juvenile cuttlefish exhibited the best growth rates and survival when fed a diet that supplied high‐protein, low‐fat, and larger quantities of Lys, Met, Phe, Val, Thr, Iie, Leu, Trp, Arg, Gly,EPA,DHA, and 16:0.
Glacier recession and the changing rockfall hazard: Implications for glacier tourism
Authors: Purdie Heather , Gomez Christopher , Espiner Stephen 
Published: December 2015

AbstractRapid recession and thinning of mountain glaciers worldwide are resulting in changes to glacier surface morphology, which are exacerbated by increased rockfall and debris accumulation at lateral margins. Rockfall can be a hazard to people visiting and working on glaciers. Relationships between rockfall and the changing glacier surface were explored at Fox Glacier, where tourism is a key industry. Using a simple rockfall model, it was found that rocks could travel a further 50 m out onto the glacier in 2012 compared with 2008. An improved understanding of natural hazards is essential to the sustainability of the industry, given the importance of glacier‐related tourism in the local and regional economies.