bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Human Factors/Ergonomics in the Science of Security
Authors: Proctor Robert W. , Chen Jing 
Published: May 2015

Objective: The overarching goal is to convey the concept of science of security and the contributions that a scientifically based, human factors approach can make to this interdisciplinary field. Background: Rather than a piecemeal approach to solving cybersecurity problems as they arise, the U.S. government is mounting a systematic effort to develop an approach grounded in science. Because humans play a central role in security measures, research on security-related decisions and actions grounded in principles of human information-processing and decision-making is crucial to this interdisciplinary effort. Method: We describe the science of security and the role that human factors can play in it, and use two examples of research in cybersecurity—detection of phishing attacks and selection of mobile applications—to illustrate the contribution of a scientific, human factors approach. Results: In these research areas, we show that systematic information-processing analyses of the decisions that users make and the actions they take provide a basis for integrating the human component of security science. Conclusion: Human factors specialists should utilize their foundation in the science of applied information processing and decision making to contribute to the science of cybersecurity.
A longitudinal fMRI investigation in acute post-traumatic stress disorder (PTSD)
Authors: Ke Jun , Zhang Li , Qi Rongfeng , Li Weihui , Hou Cailan , Zhong Yuan , He Zhong , Li Lingjiang , Lu Guangming 
Published: May 2015

Background Neuroimaging studies have implicated limbic, paralimbic, and prefrontal cortex in the pathophysiology of chronic post-traumatic stress disorder (PTSD). However, little is known about the neural substrates of acute PTSD and how they change with symptom improvement. Purpose To examine the neural circuitry underlying acute PTSD and brain function changes during clinical recovery from this disorder. Material and Methods Nineteen acute PTSD patients and nine non-PTSD subjects who all experienced a devastating mining accident underwent clinical assessment as well as functional magnetic resonance imaging (fMRI) scanning while viewing trauma-related and neutral pictures. Two years after the accident, a subgroup of 17 patients completed a second clinical evaluation, of which 13 were given an identical follow-up scan. Results Acute PTSD patients demonstrated greater activation in the vermis and right posterior cingulate, and greater deactivation in the bilateral medial prefrontal cortex and inferior parietal lobules than controls in the traumatic versus neutral condition. At follow-up, PTSD patients showed symptom reduction and decreased activation in the right middle frontal gyrus, bilateral posterior cingulate/precuneus, and cerebellum. Correlation results confirmed these findings and indicated that brain activation in the posterior cingulate/precuneus and vermis was predictive of PTSD symptom improvement. Conclusion The findings support the involvement of the medial prefrontal cortex, inferior parietal lobule, posterior cingulate, and vermis in the pathogenesis of acute PTSD. Brain activation in the vermis and posterior cingulate/precuneus appears to be a biological marker of recovery potential from PTSD. Furthermore, decreased activation of the middle frontal gyrus, posterior cingulate/precuneus, and cerebellum may reflect symptom improvement.
Impact of exercise on diurnal and nocturnal markers of glycaemic variability and oxidative stress in obese individuals with type 2 diabetes or impaired glucose tolerance
Authors: Farabi Sarah S , Carley David W , Smith Donald , Quinn Lauretta 
Published: May 2015

Objective: We measured the effects of a single bout of exercise on diurnal and nocturnal oxidative stress and glycaemic variability in obese subjects with type 2 diabetes mellitus or impaired glucose tolerance versus obese healthy controls. Methods: Subjects (in random order) performed either a single 30-min bout of moderate-intensity exercise or remained sedentary for 30 min at two separate visits. To quantify glycaemic variability, standard deviation of glucose (measured by continuous glucose monitoring system) and continuous overlapping net glycaemic action of 1-h intervals (CONGA-1) were calculated for three 12-h intervals during each visit. Oxidative stress was measured by 15-isoprostane F2t levels in urine collections for matching 12-h intervals. Results: Exercise reduced daytime glycaemic variability (ΔCONGA-1 = −12.62 ± 5.31 mg/dL, p = 0.04) and urinary isoprostanes (ΔCONGA-1 = −0.26 ± 0.12 ng/mg, p = 0.04) in the type 2 diabetes mellitus/impaired glucose tolerance group. Daytime exercise-induced change in urinary 15-isoprostane F2t was significantly correlated with both daytime standard deviation ( r = 0.68, p = 0.03) and with subsequent overnight standard deviation ( r = 0.73, p = 0.027) in the type 2 diabetes mellitus/impaired glucose tolerance group. Conclusion: Exercise significantly impacts the relationship between diurnal oxidative stress and nocturnal glycaemic variability in individuals with type 2 diabetes mellitus/impaired glucose tolerance.
Suicide in National Collegiate Athletic Association (NCAA) Athletes
Authors: Rao Ashwin L. , Asif Irfan M. , Drezner Jonathan A. , Toresdahl Brett G. , Harmon Kimberly G. 
Published: May 2015

Background: The National Collegiate Athletic Association (NCAA) has recently highlighted mental health concerns in student athletes, though the incidence of suicide among NCAA athletes is unclear. The purpose of this study was to determine the rate of suicide among NCAA athletes. Hypothesis: The incidence of suicide in NCAA athletes differs by sex, race, sport, and division. Study Design: Retrospective cohort study. Level of Evidence: Level 3. Methods: NCAA Memorial Resolutions list and published NCAA demographic data were used to identify student-athlete deaths and total participant seasons from 2003-2004 through 2011-2012. Deaths were analyzed by age, sex, race, division, and sport. Results: Over the 9-year study period, 35 cases of suicide were identified from a review of 477 student-athlete deaths during 3,773,309 individual participant seasons. The overall suicide rate was 0.93/100,000 per year. Suicide represented 7.3% (35/477) of all-cause mortality among NCAA student athletes. The annual incidence of suicide in male athletes was 1.35/100,000 and in female athletes was 0.37/100,000 (relative risk [RR], 3.7; P < 0.01). The incidence in African American athletes was 1.22/100,000 and in white athletes was 0.87/100,000 (RR, 1.4; P = 0.45). The highest rate of suicide occurred in men’s football (2.25/100,000), and football athletes had a relative risk of 2.2 ( P = 0.03) of committing suicide compared with other male, nonfootball athletes. Conclusion: The suicide rate in NCAA athletes appears to be lower than that of the general and collegiate population of similar age. NCAA male athletes have a significantly higher rate of suicide compared with female athletes, and football athletes appear to be at greatest risk. Clinical Relevance: Suicide represents a preventable cause of death, and development of effective prevention programs is recommended.
Inherited genetic variation in childhood acute lymphoblastic leukemia
Authors: Moriyama Takaya , Relling Mary V. , Yang Jun J. 
Published: May 2015

Abstract
Although somatically acquired genomic alterations have long been recognized as the hallmarks of acute lymphoblastic leukemia (ALL), the last decade has shown that inherited genetic variations (germline) are important determinants of interpatient variability in ALL susceptibility, drug response, and toxicities of ALL therapy. In particular, unbiased genome-wide association studies have identified germline variants strongly associated with the predisposition to ALL in children, providing novel insight into the mechanisms of leukemogenesis and evidence for complex interactions between inherited and acquired genetic variations in ALL. Similar genome-wide approaches have also discovered novel germline genetic risk factors that independently influence ALL prognosis and those that strongly modify host susceptibility to adverse effects of antileukemic agents (eg, vincristine, asparaginase, glucocorticoids). There are examples of germline genomic associations that warrant routine clinical use in the treatment of childhood ALL (eg, TPMT and mercaptopurine dosing), but most have not reached this level of actionability. Future studies are needed to integrate both somatic and germline variants to predict risk of relapse and host toxicities, with the eventual goal of implementing genetics-driven precision-medicine approaches in ALL treatment.
Redefining ALL classification: toward detecting high-risk ALL and implementing precision medicine
Authors: Hunger Stephen P. , Mullighan Charles G. 
Published: May 2015

Abstract
Acute lymphoblastic leukemia (ALL) is the commonest childhood tumor and remains a leading cause of cancer death in the young. In the last decade, microarray and sequencing analysis of large ALL cohorts has revolutionized our understanding of the genetic basis of this disease. These studies have identified new ALL subtypes, each characterized by constellations of structural and sequence alterations that perturb key cellular pathways, including lymphoid development, cell-cycle regulation, and tumor suppression; cytokine receptor, kinase, and Ras signaling; and chromatin modifications. Several of these pathways, particularly kinase-activating lesions and epigenetic alterations, are logical targets for new precision medicine therapies. Genomic profiling has also identified important interactions between inherited genetic variants that influence the risk of leukemia development and the somatic genetic alterations that are required to establish the leukemic clone. Moreover, sequential sequencing studies at diagnosis, remission, and relapse have provided important insights into the relationship among genetic variants, clonal heterogeneity, and the risk of relapse. Ongoing studies are extending our understanding of coding and noncoding genetic alterations in B-progenitor and T-lineage ALL and using these insights to inform the development of faithful experimental models to test the efficacy of new treatment approaches.
Interleukin-15 is required for immunosurveillance and immunoprevention of HER2/neu-driven mammary carcinogenesis
Authors: Croci Stefania , Nanni Patrizia , Palladini Arianna , Nicoletti Giordano , Grosso Valentina , Benegiamo Giorgia , Landuzzi Lorena , Lamolinara Alessia , Ianzano Marianna L. , Ranieri Dario , Dall’Ora Massimiliano , Iezzi Manuela , De Giovanni Carla , Lollini Pier-Luigi 
Published: May 2015

Abstract
Introduction
We previously demonstrated that HER2/neu-driven mammary carcinogenesis can be prevented by an interleukin-12 (IL-12)-adjuvanted allogeneic HER2/neu-expressing cell vaccine. Since IL-12 can induce the release of interleukin-15 (IL-15), in the present study we investigated the role played by IL-15 in HER2/neu driven mammary carcinogenesis and in its immunoprevention.

Methods
HER2/neu transgenic mice with homozygous knockout of IL-15 (here referred to as IL15KO/NeuT mice) were compared to IL-15 wild-type HER2/neu transgenic mice (NeuT) regarding mammary carcinogenesis, profile of peripheral blood lymphocytes and splenocytes and humoral and cellular responses induced by the vaccine.

Results
IL15KO/NeuT mice showed a significantly earlier mammary cancer onset than NeuT mice, with median latency times of 16 and 20 weeks respectively, suggesting a role for IL-15 in cancer immunosurveillance. Natural killer (NK) and CD8+ lymphocytes were significantly lower in IL15KO/NeuT mice compared to mice with wild-type IL-15. The IL-12-adjuvanted allogeneic HER2/neu-expressing cell vaccine was still able to delay mammary cancer onset but efficacy in IL-15-lacking mice vanished earlier: all vaccinated IL15KO/NeuT mice developed tumors within 80 weeks of age (median latency of 53 weeks), whereas more than 70 % of vaccinated NeuT mice remained tumor-free up to 80 weeks of age. Vaccinated IL15KO/NeuT mice showed less necrotic tumors with fewer CD3+ lymphocyes and lacked perforin-positive infiltrating cells compared to NeuT mice. Concerning the anti-vaccine antibody response, antibody titer was unaffected by the lack of IL-15, but less antibodies of IgM and IgG1 isotypes were found in IL15KO/NeuT mice. A lower induction by vaccine of systemic interferon-gamma (IFN-γ) and interleukin-5 (IL-5) was also observed in IL15KO/NeuT mice when compared to NeuT mice. Finally, we found a lower level of CD8+ memory cells in the peripheral blood of vaccinated IL15KO/NeuT mice compared to NeuT mice.

Conclusions
We demonstrated that IL-15 has a role in mammary cancer immunosurveillance and that IL-15-regulated NK and CD8+ memory cells play a role in long-lasting immunoprevention, further supporting the potential use of IL-15 as adjuvant in immunological strategies against tumors.
The preclinical pharmacology of the high affinity anti-IL-6R Nanobody® ALX-0061 supports its clinical development in rheumatoid arthritis
Authors: Van Roy Maarten , Ververken Cedric , Beirnaert Els , Hoefman Sven , Kolkman Joost , Vierboom Michel , Breedveld Elia , ‘t Hart Bert , Poelmans Sofie , Bontinck Lieselot , Hemeryck Alex , Jacobs Sandy , Baumeister Judith , Ulrichts Hans 
Published: May 2015

Abstract
Introduction
The pleiotropic cytokine interleukin-6 (IL-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (RA). ALX-0061 is a bispecific Nanobody® with a high affinity and potency for IL-6 receptor (IL-6R), combined with an extended half-life by targeting human serum albumin. We describe here the relevant aspects of its in vitro and in vivo pharmacology.

Methods
ALX-0061 is composed of an affinity-matured IL-6R-targeting domain fused to an albumin-binding domain representing a minimized two-domain structure. A panel of different in vitro assays was used to characterize the biological activities of ALX-0061. The pharmacological properties of ALX-0061 were examined in cynomolgus monkeys, using plasma levels of total soluble (s)IL-6R as pharmacodynamic marker. Therapeutic effect was evaluated in a human IL-6-induced acute phase response model in the same species, and in a collagen-induced arthritis (CIA) model in rhesus monkeys, using tocilizumab as positive control.

Results
ALX-0061 was designed to confer the desired pharmacological properties. A 200-fold increase of target affinity was obtained through affinity maturation of the parental domain. The high affinity for sIL-6R (0.19 pM) translated to a concentration-dependent and complete neutralization of sIL-6R in vitro. In cynomolgus monkeys, ALX-0061 showed a dose-dependent and complete inhibition of hIL-6-induced inflammatory parameters, including plasma levels of C-reactive protein (CRP), fibrinogen and platelets. An apparent plasma half-life of 6.6 days was observed after a single intravenous administration of 10 mg/kg ALX-0061 in cynomolgus monkeys, similar to the estimated expected half-life of serum albumin. ALX-0061 and tocilizumab demonstrated a marked decrease in serum CRP levels in a non-human primate CIA model. Clinical effect was confirmed in animals with active drug exposure throughout the study duration.

Conclusions
ALX-0061 represents a minimized bispecific biotherapeutic of 26 kDa, nearly six times smaller than monoclonal antibodies. High in vitro affinity and potency was demonstrated. Albumin binding as a half-life extension technology resulted in describable and expected pharmacokinetics. Strong IL-6R engagement was shown to translate to in vivo effect in non-human primates, demonstrated via biomarker deregulation as well as clinical effect. Presented results on preclinical pharmacological properties of ALX-0061 are supportive of clinical development in RA.
Mesenchymal stromal cell therapy attenuated lung and kidney injury but not brain damage in experimental cerebral malaria
Authors: Souza Mariana C , Silva Johnatas D , Pádua Tatiana A , Torres Natália D , Antunes Mariana A , Xisto Debora G , Abreu Thiago P , Capelozzi Vera L , Morales Marcelo M , Sá Pinheiro Ana A. , Caruso-Neves Celso , Henriques Maria G , Rocco Patricia RM 
Published: May 2015

Abstract
Introduction
Malaria is the most relevant parasitic disease worldwide, and still accounts for 1 million deaths each year. Since current antimalarial drugs are unable to prevent death in severe cases, new therapeutic strategies have been developed. Mesenchymal stromal cells (MSC) confer host resistance against malaria; however, thus far, no study has evaluated the therapeutic effects of MSC therapy on brain and distal organ damage in experimental cerebral malaria.

Methods
Forty C57BL/6 mice were injected intraperitoneally with 5 × 106Plasmodium berghei-infected erythrocytes or saline. After 24 h, mice received saline or bone marrow (BM)-derived MSC (1x105) intravenously and were housed individually in metabolic cages. After 4 days, lung and kidney morphofunction; cerebrum, spleen, and liver histology; and markers associated with inflammation, fibrogenesis, and epithelial and endothelial cell damage in lung tissue were analyzed.

Results
In P. berghei-infected mice, BM-MSCs: 1) reduced parasitemia and mortality; 2) increased phagocytic neutrophil content in brain, even though BM-MSCs did not affect the inflammatory process; 3) decreased malaria pigment detection in spleen, liver, and kidney; 4) reduced hepatocyte derangement, with an increased number of Kupffer cells; 5) decreased kidney damage, without effecting significant changes in serum creatinine levels or urinary flow; and 6) reduced neutrophil infiltration, interstitial edema, number of myofibroblasts within interstitial tissue, and collagen deposition in lungs, resulting in decreased lung static elastance. These morphological and functional changes were not associated with changes in levels of tumor necrosis factor-α, keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8), or interferon-γ, which remained increased and similar to those of P. berghei animals treated with saline. BM-MSCs increased hepatocyte growth factor but decreased VEGF in the P. berghei group.

Conclusions
BM-MSC treatment increased survival and reduced parasitemia and malaria pigment accumulation in spleen, liver, kidney, and lung, but not in brain. The two main organs associated with worse prognosis in malaria, lung and kidney, sustained less histological damage after BM-MSC therapy, with a more pronounced improvement in lung function.
Osteopontin mediates survival, proliferation and migration of neural stem cells through the chemokine receptor CXCR4
Authors: Rabenstein Monika , Hucklenbroich Joerg , Willuweit Antje , Ladwig Anne , Fink Gereon Rudolf , Schroeter Michael , Langen Karl-Josef , Rueger Maria Adele 
Published: May 2015

Abstract
Introduction
Osteopontin (OPN) is a phosphoglycoprotein with important roles in tissue homeostasis, wound healing, immune regulation, and stress responses. It is expressed constitutively in the brain and upregulated during neuroinflammatory responses; for example, after focal cerebral ischemia. To date, its effects on neural stem cells (NSC) remain to be elucidated and are, accordingly, the subject of this study.

Method
Primary fetal rat NSC were cultured as homogenous monolayers and treated with different concentrations of OPN. Fundamental properties of NSC were assessed following OPN exposure, including proliferative activity, survival under oxidative stress, migration, and differentiation potential. To elucidate a putative action of OPN via the CXC chemokine receptor type 4 (CXCR4), the latter was blocked with AMD3100. To investigate effects of OPN on endogenous NSC in vivo, recombinant OPN was injected into the brain of healthy adult rats as well as rats subjected to focal cerebral ischemia. Effects of OPN on NSC proliferation and neurogenesis in the subventricular zone were studied immunohistochemically.

Results
OPN dose-dependently increased the number of NSC in vitro. As hypothesized, this effect was mediated through CXCR4. The increase in NSC number was due to both enhanced cell proliferation and increased survival, and was confirmed in vivo. Additionally, OPN dose-dependently stimulated the migration of NSC via CXCR4. Moreover, in the presence of OPN, differentiation of NSC led to a significant increase in neurogenesis both in vitro as well as in vivo after cerebral ischemia.

Conclusion
Data show positive effects of OPN on survival, proliferation, migration, and neuronal differentiation of NSC. At least in part these effects were mediated via CXCR4. Results suggest that OPN is a promising substance for the targeted activation of NSC in future experimental therapies for neurological disorders such as stroke.
Reciprocal associations between smoking cessation and depression in older smokers: Findings from the English Longitudinal Study of Ageing
Authors: Shahab Lion , Gilchrist Gail , Hagger-Johnson Gareth , Shankar Aparna , West Elizabeth , West Robert 
Published: May 2015

BackgroundDepression is a particular problem in older people and it is important to know how it affects and is affected by smoking cessation.AimsTo identify reciprocal, longitudinal relationships between smoking cessation and depression among older smokers.MethodAcross four waves, covering six years (2002–2008), changes in smoking status and depression, measured using the 8-item Centre for Epidemiologic Studies Depression Scale, were assessed among recent ex-smokers and smokers (n = 2375) in the English Longitudinal Study of Ageing.ResultsIn latent growth curve analysis, smoking at baseline predicted depression caseness longitudinally and vice versa. When both processes were modelled concurrently, depression predicted continued smoking longitudinally (B(β) = 0.21 (0.27); 95% CI = 0.08–0.35) but not the other way round. This was the case irrespective of mental health history and adjusting for a range of covariates.ConclusionsIn older smokers, depression appears to act as an important barrier to quitting, although quitting has no long-term impact on depression.
Staff Incentive Scheme for Tourism Services Providers As an Effective Tool to Increase Employees’ Loyalty
Authors: Лысенко  , Lysenko V. 
Published: May 2015

The article identi es the main trends in the development of the tourist services market in the Belgorod region, analyzed employees’ satisfaction with their work,
develops a set of measures to build an e ective loyalty system using the methods of sta motivation, identi es customer requirements for the quali cation of
employees of tourism services providers, analyzes the main methods of training workers of the tourism industry. In order to deepen the research the author
conducted an analysis of meansof labor stimulation among tourism services providersof Belgorod region and conducted a survey of employees of tourism
services providers of Belgorod region with the aim of assessing incentive systems in modern organizations, classi ed working environment parameters that
must be corrected to increase the loyalty of tourism services providers’ employees. The results of the conducted research suggest that training and sta
development is an integral part of the formation of the tourism providers’ sta loyalty program. The study resulted in a proposition of the system of annual
events aimed at obtaining additional skills of the employees of Belgorod travel agencies.