bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-reported patient safety competence among Canadian medical students and postgraduate trainees: a cross-sectional survey
Authors: Doyle Patricia , VanDenKerkhof Elizabeth G , Edge Dana S , Ginsburg Liane , Goldstein David H 
Published: January 2015

BackgroundQuality and patient safety (PS) are critical components of medical education. This study reports on the self-reported PS competence of medical students and postgraduate trainees.MethodsThe Health Professional Education in Patient Safety Survey was administered to medical students and postgraduate trainees in January 2012. PS dimension scores were compared across learning settings (classroom and clinical) and year in programme.ResultsSixty-three percent (255/406) of medical students and 32% (141/436) of postgraduate trainees responded. In general, both groups were most confident in their learning of clinical safety skills (eg, hand hygiene) and least confident in learning about sociocultural aspects of safety (eg, understanding human factors). Medical students’ confidence in most aspects of safety improved with years of training. For some of the more intangible dimensions (teamwork and culture), medical students in their final year had lower scores than students in earlier years. Thirty-eight percent of medical students felt they could approach someone engaging in unsafe practice, and the majority of medical students (85%) and postgraduate trainees (78%) agreed it was difficult to question authority.ConclusionsOur results suggest the need to improve the overall content, structure and integration of PS concepts in both classroom and clinical learning environments. Decreased confidence in sociocultural aspects of PS among medical students in the final year of training may indicate that culture in clinical settings negatively affects students’ perceived PS competence. Alternatively, as medical students spend more time in the clinical setting, they may develop a clearer sense of what they do not know.
Arterial lactate levels in an emergency department are associated with mortality: a prospective observational cohort study
Authors: Datta Deepankar , Walker Craig , Gray Alasdair James , Graham Catriona 
Published: January 2015

ObjectivesLactate measurements are routinely carried out in emergency departments and are associated with increased mortality in septic patients. However, no definitive research has been carried out into whether lactate measurements can be used as a prognostic marker in a clinically unwell population in the emergency department.MethodsWe carried out a prospective observational cohort study in consecutive patients whose arterial lactate concentration was measured in the emergency department of a tertiary referral hospital assessing 110 000 patients per year between 11th May and 11th August 2011. The main outcome measure was 30-day mortality.ResultsThere were 120 deaths (16.1%) at 30 days postattendance in our cohort of 747 patients. Multivariate logistic regression revealed lower lactate levels were associated with 30-day survival: ORs for 30-day death compared with lactate ≥4 were 0.125 (95% CI 0.068 to 0.229) for lactate <2 and 0.273 (95% CI 0.140 to 0.533) for lactate 2–<4. Kaplan–Meier analysis showed a survival difference when dividing lactate concentrations into strata (p<0.0001). This survival difference was maintained when septic diagnoses were taken into account.ConclusionsA single arterial lactate measurement on presentation to the emergency department predicts 30-day mortality independent of other measures of illness severity.
Tumor-Derived Osteopontin Reprograms Normal Mammary Fibroblasts to Promote Inflammation and Tumor Growth in Breast Cancer
Authors: Sharon Yoray , Raz Yael , Cohen Noam , Ben-Shmuel Amir , Schwartz Hila , Geiger Tamar , Erez Neta 
Published: January 2015

Abstract
Breast tumors are characterized by an extensive desmoplastic stroma, abundantly populated by fibroblasts. Cancer-associated fibroblasts (CAF) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. CAF also orchestrate tumor-promoting inflammation in multiple tumor types, including breast cancer. However, the mechanisms through which normal tissue fibroblasts are reprogrammed to tumor-promoting CAFs are mainly obscure. Here, we show that mammary fibroblasts can be educated by breast cancer cells to become activated to a proinflammatory state that supports malignant progression. Proteomic analysis of breast cancer cell–secreted factors identified the secreted proinflammatory mediator osteopontin, which has been implicated in inflammation, tumor progression, and metastasis. Osteopontin was highly secreted by mouse and human breast cancer cells, and tumor cell–secreted osteopontin activated a CAF phenotypes in normal mammary fibroblasts in vitro and in vivo. Osteopontin was sufficient to induce fibroblast reprogramming and neutralizing antibodies against osteopontin-blocked fibroblast activation induced by tumor cells. The ability of secreted osteopontin to activate mammary fibroblasts relied upon its known receptors CD44 and αVβ3 integrin. Strikingly, osteopontin silencing in tumor cells in vivo attenuated stromal activation and inhibited tumor growth. Our findings establish a critical functional role for paracrine signaling by tumor-derived osteopontin in reprograming normal fibroblasts into tumor-promoting CAFs. Cancer Res; 75(6); 963–73. ©2015 AACR.
TLR2 Limits Development of Hepatocellular Carcinoma by Reducing IL18-Mediated Immunosuppression
Authors: Li Shinan , Sun Rui , Chen Yongyan , Wei Haiming , Tian Zhigang 
Published: January 2015

Abstract
Immune mechanisms underlying hepatocellular carcinoma (HCC) are not well understood. Here, we show that the Toll-like receptor TLR2 inhibits production of the proinflammatory cytokine IL18 and protects mice from DEN-induced liver carcinogenesis. On this protocol, Tlr2−/− mice exhibited more aggressive HCC development associated with impaired CD8+ T-cell function. Furthermore, Ly6ChighIL18Rα+ myeloid-derived suppressor cells (MDSC) were increased in number in the livers of Tlr2−/− mice before tumor onset. MDSC in this setting exhibited higher iNOS levels that could inhibit IFNγ production and CD8+ T-cell proliferation in vitro. Notably, Tlr2−/− hepatocytes produced more mature IL18 after DEN treatment that was sufficient to drive MDSC accumulation there. IL18 adminstration was sufficient to induce accumulation of MDSC, whereas hepatocyte-specific silencing of IL18 in Tlr2−/− mice decreased the proportion of MDSC, increased the proportion of functional CD8+ T cells, and alleviated HCC progression. IL18 production was mediated by caspase-8 insofar as the decrease in its silencing was sufficient to attenuate levels of mature IL18 in Tlr2−/− mice. Furthermore, the TLR2 agonist Pam3CSK4 inhibited both caspase-8 and IL18 expression, decreasing MDSC, increasing CD8+ T-cell function, and promoting HCC regression. Overall, our findings show how TLR2 deficiency accelerates IL18-mediated immunosuppression during liver carcinogenesis, providing new insights into immune control that may assist the design of effective immunotherapies to treat HCC. Cancer Res; 75(6); 986–95. ©2015 AACR.
Rhythmic Gamma Stimulation Affects Bistable Perception
Authors: Cabral-Calderin Yuranny , Schmidt-Samoa Carsten , Wilke Melanie 
Published: January 2015

Abstract
When our brain is confronted with ambiguous visual stimuli, perception spontaneously alternates between different possible interpretations although the physical stimulus remains the same. Both alpha (8–12 Hz) and gamma (&gt;30 Hz) oscillations have been reported to correlate with such spontaneous perceptual reversals. However, whether these oscillations play a causal role in triggering perceptual switches remains unknown. To address this question, we applied transcranial alternating current stimulation (tACS) over the posterior cortex of healthy human participants to boost alpha and gamma oscillations. At the same time, participants were reporting their percepts of an ambiguous structure-from-motion stimulus. We found that tACS in the gamma band (60 Hz) increased the number of spontaneous perceptual reversals, whereas no significant effect was found for tACS in alpha (10 Hz) and higher gamma (80 Hz) frequencies. Our results suggest a mechanistic role of gamma but not alpha oscillations in the resolution of perceptual ambiguity.
Oscillator-Interference Models of Path Integration Do Not Require Theta Oscillations
Authors: Orchard Jeff 
Published: January 2015

Navigation and path integration in rodents seems to involve place cells, grid cells, and theta oscillations (4–12 Hz) in the local field potential. Two main theories have been proposed to explain the neurological underpinnings of how these phenomena relate to navigation and to each other. Attractor network (AN) models revolve around the idea that local excitation and long-range inhibition connectivity can spontaneously generate grid-cell-like activity patterns. Oscillator interference (OI) models propose that spatial patterns of activity are caused by the interference patterns between neural oscillators. In rats, these oscillators have a frequency close to the theta frequency. Recent studies have shown that bats do not exhibit a theta cycle when they crawl, and yet they still have grid cells. This has been interpreted as a criticism of OI models. However, OI models do not require theta oscillations. We explain why the absence of theta oscillations does not contradict OI models and discuss how the two families of models might be distinguished experimentally.
Communicating future overheating risks to building design practitioners: Using the Low Carbon Futures tool
Authors: Gul Mehreen Saleem , Jenkins DP , Patidar S , Menzies GF , Banfill PFG , Gibson GJ 
Published: January 2015

The Low Carbon Futures tool provides a probabilistic assessment of future overheating risks and cooling demands for domestic and nondomestic buildings in the UK. The approach adopted for the development of the Low Carbon Futures tool includes academic rigour within the development of the calculation engine, and also practitioner feedback throughout the process. This paper discusses the journey of the tool from modelling and simulation to the practitioner engagement, which took place by means of a questionnaire, focus groups and interviews with building design professionals aimed at understanding how the issue of overheating in buildings is being addressed. Throughout these events, the synergies between designing for low-carbon targets and designing for a future climate were explored. A final dissemination event was held to identify output styles that could be generated by the Low Carbon Futures tool that would be more practical and useful for specific client types. The workshop discussions serve to shape the outputs from the tool, and the feedback gathered will be used to inform a number of output styles, based on client type. Practical application: This paper outlines the development of the Low Carbon Futures tool for analysing overheating risks in buildings and discusses the practitioner feedback obtained from industry professionals on the use and applicability of the tool, in a final event hosted by the Low Carbon Futures research team in London. This event confirmed that practitioners need to be comfortable with the layout and format of the output in order to communicate its meaning and possible implications to a range of clients. A balanced output is required, which conveys some of the complexity of the underlying analysis, but which is easily understood and conveyed to a potentially lay audience.
A Survey on Characteristics of Japanese Academic Job Market and Evaluation
Authors: Domon Koji , Kitamura Yoshihiro 
Published: January 2015

Background: During the Meiji era, at the end of the 19th century, Japan introduced western systems into many fields, economically developing later than other industrially developed countries. Japan introduced a higher education system modeled on the German system, focusing not on education but on research. The historical background has shaped contemporary Japanese academia differently from that of the United States and the European Union. In addition, because of geographical and linguistic barriers in Asia, intercommunication with researchers in other developed countries has been much less than that between the United States and the European Union, leaving Japanese academia relatively isolated. Method: We survey the characteristics of the Japanese academic system in higher education, using the latest published data. Result: This article indicates a concentration of research at former imperial universities and a rigidity of movement among universities both internationally and domestically. Furthermore, small differences in salary levels have provided little incentive to perform research. However, while most universities in Japan have not introduced evaluation systems for promotion and salary that are heavily dependent on journal rankings, as in the European Union and United States, Japanese academic performance has not declined. Conclusion: This article suggests that in Japan, salary incentives, the impact factor, and so on have had little influence on academic performance. Even though cultural and historical differences between countries affect academic behaviors, we hope that this article might trigger consideration of other possible evaluation schemes for the future.
Serum sCD95L concentration in patients with spinal cord injury
Authors: Biglari Bahram , Büchler Axel , Swing Tyler , Child Christopher , Biehl Elisabeth , Reitzel Tim , Bruckner Tom , Ferbert Thomas , Korff Sebastian , Rief Harald , Gerner Hans-Jürgen , Moghaddam Arash 
Published: January 2015

Objective To determine serum concentrations of soluble CD95 ligand (sCD95L) in patients with traumatic spinal cord injury. Methods Patients with traumatic spinal cord injury were recruited. Blood was collected on admission to hospital and at 4 h, 9 h, 12 h, 24 h, 3 days, 7 days, and 2, 4, 8 and 12 weeks postadmission. Serum concentrations of sCD95L were determined via immunoassay. Result The study included 23 patients. Mean sCD95L concentrations were significantly lower at 4 h, 9 h, 12 h and 24 h than at admission, and were significantly higher at 8 and 12 weeks, compared with admission. Conclusion The serum sCD95L concentration fell significantly during the first 24 h after traumatic spinal cord injury. Concentrations then rose, becoming significantly higher than admission levels at 8 weeks. sCD95L may represent a possible therapeutic target for traumatic spinal cord injury.
Meningeal norepinephrine produces headache behaviors in rats via actions both on dural afferents and fibroblasts
Authors: Wei Xiaomei , Yan Jin , Tillu Dipti , Asiedu Marina , Weinstein Nicole , Melemedjian Ohannes , Price Theodore , Dussor Gregory 
Published: January 2015

Background Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine. Methods NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model. Results Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6). Conclusions These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine.
Information overload: The differences that age makes
Authors: Benselin Jennifer C , Ragsdell Gillian 
Published: January 2015

Information overload has long been studied as a phenomenon that causes problems at the personal, social and organisational level. This study investigates overload from a new angle, that of the influence of age on perceptions of information overload. A combination of questionnaires, interviews and diaries were used to gain insight into people’s perceptions towards information overload. It was found that people of all ages suffer from information overload but young people are primarily affected by information literacy levels while older people are affected by technology. There was evidence of a link between age and technology use. A link was also found between job role and information overload and the impact technology has had on the quantity of information available. This research will benefit anyone, either individually or within an organisation, looking for ways to combat information overload. It identifies the influence of age on various factors and recommends actions that may be taken to reduce information overload. In particular, recommendations were made for further training in technology and information literacy. The paper is based on an approach not seen before in the literature as it investigates the effects of age on information overload by seeking to understand how perceptions towards information overload may differ between different age groups. It is anticipated that this paper will trigger further studies that could focus on the effect of job role on information overload and the likelihood of information addiction becoming a future concern.
Haematological and biochemical reference intervals in adult Maine Coon cat blood donors
Authors: Spada Eva , Antognoni Maria Teresa , Proverbio Daniela , Ferro Elisabetta , Mangili Vittorio , Miglio Arianna 
Published: January 2015

Objectives The objectives of this study were to derive Maine Coon haematological and biochemical reference intervals (RIs) from adult healthy blood donors, to validate (or reject) the use of published RIs for the general feline population in this breed, and to evaluate the effects of age, sex and weight on the haematological and biochemical results. Methods Haematological and biochemical data were retrieved retrospectively from a database of 81 healthy adult Maine Coon cat blood donors and were analysed to generate normal RIs. RIs were determined and compared with established non-breed-specific feline RIs according to the Clinical and Laboratory Standards Institute guidelines and the American Society of Veterinary Clinical Pathology guidelines using Reference Value-Advisor (version 2.1) software. Results The age of the cats ranged from 1–8 years (mean 4.4 years), 42 were female and 39 were male, and weights ranged from 4.9–8.5 kg (mean 6.7 kg). New Maine Coon RIs were proposed for red blood cell count, mean corpuscular volume, mean corpuscular haemoglobin concentration, reticulocyte count and percentage. Haematocrit was higher in male cats (mean HCT 42.9% vs 41% in females; P = 0.001) and in heavier cats ( P = 0.003; slope 1.0, regression equation HCT = 35.1 + 1.0 × weight). New biochemical RIs were proposed for urea, aspartate aminotransferase, γ-glutamyl transpeptidase (GGT), alkaline phosphatase, total protein and albumin in Maine Coons. Females had higher GGT (median GGT value in females 4.0 vs 3.0 in males; P = 0.011) and albumin values (mean albumin value 3.3 in females vs 3.1 in males; P = 0.013). Conclusions and relevance Currently published RIs for some haematological and biochemical parameters are not appropriate for use in adult Maine Coon cats. A breed-specific variation could be a plausible explanation for the new haematological and serum biochemical analytes proposed in this study. Breed-specific RIs for Maine Coon cats will help prevent misinterpretation of laboratory results in diagnosis and in the selection of ideal blood donors.
Clozapine prescribing in the UK: views and experience of consultant psychiatrists
Authors: Tungaraza Tongeji E. , Farooq Saeed 
Published: January 2015

Objectives: It has been repeatedly shown that clozapine is underutilized and there is delayed use of it in clinical practice. Method: An online survey was sent to 2771 consultant psychiatrists registered with the Royal College of Psychiatrists in the UK. A total of 243 responded to this survey. The survey elicited their views and experiences in using clozapine as well as to identify what may be the underlying causes for its underutilization. Results: Over 75% acknowledged that they had good training in using clozapine and about 56% had clozapine-dedicated service. However, 40.5% preferred to use several other antipsychotics prior to considering clozapine. A third felt it was not safe to start clozapine in the community and 42% had less than five patients on clozapine. Eleven possible reasons for clozapine underutilization were identified including concerns about side effects, patients not wanting to have blood tests and lack of experience or knowledge. Knowledge deficiency in certain aspects of clozapine use were identified, e.g. a third of respondents did not know that the risk of agranulocytosis changes with time, 42.7% did not think that clozapine can reduce substance use, while 20% were not aware of its benefit in reducing suicidal risk. Conclusions: Important areas of concern such as managing side effects and deficiency in evidence-based use of clozapine were identified. These can be targeted in training and professional development programme.
Molecular mechanism and clinical impact of APOBEC3B-catalyzed mutagenesis in breast cancer
Authors: Harris Reuben S 
Published: January 2015

AbstractCancer genomic DNA sequences enable identification of all mutations and suggest targets for precision medicine. The identities and patterns of the mutations themselves also provide critical information for deducing the originating DNA damaging agents, causal molecular mechanisms, and thus additional therapeutic targets. A classic example is ultraviolet light, which crosslinks adjacent pyrimidines and leads to C-to-T transitions. A new example is the DNA cytosine deaminase APOBEC3B, which was identified recently as a source of DNA damage and mutagenesis in breast, head/neck, cervix, bladder, lung, ovary, and to lesser extents additional cancer types. This enzyme is normally an effector protein in the innate immune response to virus infection but upregulation in these cancer types causes elevated levels of genomic C-to-U deamination events, which manifest as C-to-T transitions and C-to-G transversions within distinct DNA trinucleotide contexts (preferentially 5’-TCA and 5’-TCG). Genomic C-to-U deamination events within the same trinucleotide contexts also lead to cytosine mutation clusters (kataegis), and may precipitate visible chromosomal aberrations such as translocations. Clinical studies indicate that APOBEC3B upregulation correlates with poorer outcomes for estrogen receptor-positive breast cancer patients, including shorter durations of disease-free survival and overall survival after surgery. APOBEC3B may therefore have both diagnostic and prognostic potential. APOBEC3B may also be a candidate for therapeutic targeting because inhibition of this non-essential enzyme is predicted to decrease tumor mutation rates and diminish the likelihood of undesirable mutation-dependent outcomes such as recurrence, metastasis, and the development of therapy resistant tumors.