bluuebunny/crossref_metadata_2025_split huggingface dataset:
Political events and mood among young physicians: a prospective cohort study
Authors: Frank Elena , Nallamothu Brahmajee K , Zhao Zhuo , Sen Srijan 
Published: December 2019

AbstractObjectiveTo study the effects of recent political events on mood among young physicians.DesignProspective cohort study.SettingUnited States medical centres.Participants2345 medical interns provided longitudinal mood data as part of the Intern Health Study between 2016 and 2018.Main outcome measuresMean mood score during the week following influential political and non-political events as compared with mean mood during the preceding four week control period.ResultsWe identified nine political events and eight non-political events for analysis. With the start of internship duties in July, the mean decline in mood for interns was −0.30 (95% confidence interval −0.33 to −0.27, t=−17.45, P<0.001). The decline in mood was of similar magnitude following the 2016 presidential election (mean mood change −0.32, 95% confidence interval −0.45 to −0.19, t=−4.73, P<0.001) and subsequent inauguration (mean mood change −0.25, 95% confidence interval −0.37 to −0.12, t=−3.93, P<0.001). Further, compared with men, women reported greater mood declines after both the 2016 election (mean gender difference 0.31, 95% confidence interval 0.05 to 0.58, t=2.33, P=0.02) and the inauguration (mean gender difference 0.25, 95% confidence interval 0.01 to 0.49, t=2.05, P=0.04). Overall, there were statistically significant changes in mood following 66.7% (6/9) of political events assessed. In contrast, none of the non-political events included in the analysis were statistically significantly associated with a change in mood.ConclusionsMacro level factors such as politics may be correlated with the mood of young doctors. This finding signals the need for further evaluation of the consequences of increasing entanglement between politics and medicine moving forward for young physicians and their patients.
Exposure to tobacco marketing in bars predicts subsequent use of multiple tobacco products among non-tobacco-using college students
Authors: Herrera Ana Laura , Pasch Keryn E , Marti C Nathan , Loukas Alexandra , Perry Cheryl 
Published: December 2019

BackgroundDue to other marketing restrictions, one venue where tobacco companies concentrate their marketing efforts to reach young adults is bars/nightclubs.ObjectiveThis study examined the relationship between exposure to tobacco marketing in bars/nightclubs and number of alternative tobacco/nicotine products used 6 months later among college students.MethodsParticipants were 1,406 students aged 18–29 years old who reported going to bars or nightclubs at least rarely (M age=21.95; 67% female; 46% non-Hispanic white). Students completed an online survey in fall 2014/spring 2015 (wave 1) and again 6 months later (wave 2). Multilevel Poisson regression models were used to assess the relationship between exposure to three types of marketing at bars/nightclubs at wave 1 (tobacco/nicotine product advertisements; free samples; industry representatives) and number of tobacco products used (range=0–5) at wave 2, controlling for school type (2 year vs 4 year), age, sex, race/ethnicity and frequency of bar visits. An interaction between the number of wave 1 products and each marketing variable was tested.ResultsGreater exposure to free samples and tobacco industry representatives at bars/nightclubs predicted a greater number of products used 6 months later, but only among wave 1 non-tobacco users and not among tobacco users. Exposure to advertisements at bars/nightclubs did not predict the number of products used 6 months later.ConclusionTobacco companies claim that marketing is targeted to those who already use the product, not to non-users. However, the current study indicates tobacco marketing in bars and nightclubs may encourage use among non-users and has no influence on current users.
Perceptual Expectations Modulate Low-Frequency Activity: A Statistical Learning Magnetoencephalography Study
Authors: Zhou Ying Joey , Pérez-Bellido Alexis , Haegens Saskia , de Lange Floris P. 
Published: December 2019

Abstract
Perceptual expectations can change how a visual stimulus is perceived. Recent studies have shown mixed results in terms of whether expectations modulate sensory representations. Here, we used a statistical learning paradigm to study the temporal characteristics of perceptual expectations. We presented participants with pairs of object images organized in a predictive manner and then recorded their brain activity with magnetoencephalography while they viewed expected and unexpected image pairs on the subsequent day. We observed stronger alpha-band (7–14 Hz) activity in response to unexpected compared with expected object images. Specifically, the alpha-band modulation occurred as early as the onset of the stimuli and was most pronounced in left occipito-temporal cortex. Given that the differential response to expected versus unexpected stimuli occurred in sensory regions early in time, our results suggest that expectations modulate perceptual decision-making by changing the sensory response elicited by the stimuli.
4. The Giant Sword and the Cross
Authors: Pettit Edward 
Published: December 2019

In Chapter 4 the author continues to investigate the symbolism of the giant sword, consulting a variety of extant Anglo-Saxon and Scandinavian swords. Pettit suggests that the sword, both before its melting but especially after melting down to its golden hilt, could also link to the other principal symbol of Easter, the Cross of Christ. Pettit also considers the relevance of certain aspects of Beowulf’s fight with the dragon, such as Beowulf’s companion Wiglaf and the battle-standard that he claims from the dragon’s hoard.
5. Whose Sword Is It, Anyway?
Authors: Pettit Edward 
Published: December 2019

Chapter 5 concerns the ownership of the giant sword. Pettit argues that the giant sword could have been the possession of a ‘righteous solar deity’ before Grendel stole it. If so the monser was likely motivated by a desire not only for self-protection but also for sunlight. Pettit likens this to the theft of the lightning-hammer of Þórr, the Norse thunder-god, before highlighting the recurrent theme of thievery in Beowulf. Pettit then concludes with comments on the basis for detecting Germanic myth in the poem, considering the likelihood that it was written in a pre-Viking conquest England.
15. The Sun in the Pike
Authors: Pettit Edward 
Published: December 2019

Chapter 15 examines the Beowulf-poet’s description of Grendel’s mother as a ‘sword-greedy she-wolf’ of the sea. Pettit proposes that this characterization may identify her, if only fleetingly, as a wolfish fish, perhaps specifically a pike, with an appetite for swords of heavenly light. This idea finds parallel more or less closely in Finnish accounts of a pike’s swallowing of a spark of heavenly fire or of golden eggs from which the sun was formed; in Old Norse accounts of pike that swallowed, or trembled on, swords analogous to Beowulf’s giant sword; in a sun-devouring (and possibly solar-staff-swallowing) wolf-serpent on the Gosforth Cross; in ancient dragons such as the Babylonian Tiamat and Indian Vŗtra; and in the Christian identification of Hell as the mouth of a monstrous sea-creature.
Patient and Provider Perspectives Regarding Enrollment in Head and Neck Cancer Research
Authors: Shuman Andrew G. , Gornick Michele C. , Brummel Collin , Kent Madison , Spector‐Bagdady Kayte , Biddle Elliot , Bradford Carol R. , Brenner J. Chad 
Published: December 2019

ObjectiveThe advent of precision oncology complicates how clinicians and participants understand how clinical care and research interface. Here we examine how key stakeholders perceive the utility of, and evaluate the decision to participate in, genomic sequencing head and neck cancer research. The goal of this study was to highlight unique considerations for our community as this type of research proliferates across the country.Study DesignProspective multimethod qualitative and quantitative embedded ethics protocol.SettingSingle‐institution National Cancer Institute–designated academic cancer center.Subjects and MethodsMultimethod study using paired surveys and semistructured interviews among patients and providers involved in a prospective precision head and neck oncology sequencing protocol (116 survey patient‐participants, response rate 82%) with 18 interviewees.ResultsParticipants were generally enthusiastic about enrollment in research, both to help future patients and as a way of giving back to the community. They described reliance on information from and trust in their cancer doctor regarding the decision to participate in research, but paradoxically there was discordance in how doctors and patients reported their respective influence in the decision‐making process. Clinicians also stressed the importance in separating clinical and research‐informed consent processes, although patients did not describe this tension.ConclusionAs we enter an era of increasing personalized medicine and targeted therapies, the relationship between clinicians, scientists, and patients plays a larger role in how we individualize and contextualize cancer research. Our data are another step toward the ultimate goal of respecting and protecting patients as participants in head and neck translational oncology.
Predicting the artificial immunity induced by RUTI® vaccine against tuberculosis using universal immune system simulator (UISS)
Authors: Pennisi Marzio , Russo Giulia , Sgroi Giuseppe , Bonaccorso Angela , Parasiliti Palumbo Giuseppe Alessandro , Fichera Epifanio , Mitra Dipendra Kumar , Walker Kenneth B. , Cardona Pere-Joan , Amat Merce , Viceconti Marco , Pappalardo Francesco 
Published: December 2019

Abstract
Background
Tuberculosis (TB) represents a worldwide cause of mortality (it infects one third of the world’s population) affecting mostly developing countries, including India, and recently also developed ones due to the increased mobility of the world population and the evolution of different new bacterial strains capable to provoke multi-drug resistance phenomena. Currently, antitubercular drugs are unable to eradicate subpopulations of Mycobacterium tuberculosis (MTB) bacilli and therapeutic vaccinations have been postulated to overcome some of the critical issues related to the increase of drug-resistant forms and the difficult clinical and public health management of tuberculosis patients. The Horizon 2020 EC funded project “In Silico Trial for Tuberculosis Vaccine Development” (STriTuVaD) to support the identification of new therapeutic interventions against tuberculosis through novel in silico modelling of human immune responses to disease and vaccines, thereby drastically reduce the cost of clinical trials in this critical sector of public healthcare.

Results
We present the application of the Universal Immune System Simulator (UISS) computational modeling infrastructure as a disease model for TB. The model is capable to simulate the main features and dynamics of the immune system activities i.e., the artificial immunity induced by RUTI® vaccine, a polyantigenic liposomal therapeutic vaccine made of fragments of Mycobacterium tuberculosis cells (FCMtb). Based on the available data coming from phase II Clinical Trial in subjects with latent tuberculosis infection treated with RUTI® and isoniazid, we generated simulation scenarios through validated data in order to tune UISS accordingly to STriTuVaD objectives. The first case simulates the establishment of MTB latent chronic infection with some typical granuloma formation; the second scenario deals with a reactivation phase during latent chronic infection; the third represents the latent chronic disease infection scenario during RUTI® vaccine administration.

Conclusions
The application of this computational modeling strategy helpfully contributes to simulate those mechanisms involved in the early stages and in the progression of tuberculosis infection and to predict how specific therapeutical strategies will act in this scenario. In view of these results, UISS owns the capacity to open the door for a prompt integration of in silico methods within the pipeline of clinical trials, supporting and guiding the testing of treatments in patients affected by tuberculosis.
A computational approach based on the colored Petri net formalism for studying multiple sclerosis
Authors: Pernice Simone , Pennisi Marzio , Romano Greta , Maglione Alessandro , Cutrupi Santina , Pappalardo Francesco , Balbo Gianfranco , Beccuti Marco , Cordero Francesca , Calogero Raffaele A. 
Published: December 2019

Abstract
Background
Multiple Sclerosis (MS) is an immune-mediated inflammatory disease of the Central Nervous System (CNS) which damages the myelin sheath enveloping nerve cells thus causing severe physical disability in patients. Relapsing Remitting Multiple Sclerosis (RRMS) is one of the most common form of MS in adults and is characterized by a series of neurologic symptoms, followed by periods of remission. Recently, many treatments were proposed and studied to contrast the RRMS progression. Among these drugs, daclizumab (commercial name Zinbryta), an antibody tailored against the Interleukin-2 receptor of T cells, exhibited promising results, but its efficacy was accompanied by an increased frequency of serious adverse events. Manifested side effects consisted of infections, encephalitis, and liver damages. Therefore daclizumab has been withdrawn from the market worldwide. Another interesting case of RRMS regards its progression in pregnant women where a smaller incidence of relapses until the delivery has been observed.

Results
In this paper we propose a new methodology for studying RRMS, which we implemented in GreatSPN, a state-of-the-art open-source suite for modelling and analyzing complex systems through the Petri Net (PN) formalism. This methodology exploits: (a) an extended Colored PN formalism to provide a compact graphical description of the system and to automatically derive a set of ODEs encoding the system dynamics and (b) the Latin Hypercube Sampling with PRCC index to calibrate ODE parameters for reproducing the real behaviours in healthy and MS subjects.To show the effectiveness of such methodology a model of RRMS has been constructed and studied. Two different scenarios of RRMS were thus considered. In the former scenario the effect of the daclizumab administration is investigated, while in the latter one RRMS was studied in pregnant women.

Conclusions
We propose a new computational methodology to study RRMS disease. Moreover, we show that model generated and calibrated according to this methodology is able to reproduce the expected behaviours.
Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model
Authors: Kjellin Jonas , Pränting Maria , Bach Frauke , Vaid Roshan , Edelbroek Bart , Li Zhiru , Hoeppner Marc P. , Grabherr Manfred , Isberg Ralph R. , Hagedorn Monica , Söderbom Fredrik 
Published: December 2019

Abstract
Background
During infection by intracellular pathogens, a highly complex interplay occurs between the infected cell trying to degrade the invader and the pathogen which actively manipulates the host cell to enable survival and proliferation. Many intracellular pathogens pose important threats to human health and major efforts have been undertaken to better understand the host-pathogen interactions that eventually determine the outcome of the infection. Over the last decades, the unicellular eukaryote Dictyostelium discoideum has become an established infection model, serving as a surrogate macrophage that can be infected with a wide range of intracellular pathogens. In this study, we use high-throughput RNA-sequencing to analyze the transcriptional response of D. discoideum when infected with Mycobacterium marinum and Legionella pneumophila. The results were compared to available data from human macrophages.

Results
The majority of the transcriptional regulation triggered by the two pathogens was found to be unique for each bacterial challenge. Hallmark transcriptional signatures were identified for each infection, e.g. induction of endosomal sorting complexes required for transport (ESCRT) and autophagy genes in response to M. marinum and inhibition of genes associated with the translation machinery and energy metabolism in response to L. pneumophila. However, a common response to the pathogenic bacteria was also identified, which was not induced by non-pathogenic food bacteria. Finally, comparison with available data sets of regulation in human monocyte derived macrophages shows that the elicited response in D. discoideum is in many aspects similar to what has been observed in human immune cells in response to Mycobacterium tuberculosis and L. pneumophila.

Conclusions
Our study presents high-throughput characterization of D. discoideum transcriptional response to intracellular pathogens using RNA-seq. We demonstrate that the transcriptional response is in essence distinct to each pathogen and that in many cases, the corresponding regulation is recapitulated in human macrophages after infection by mycobacteria and L. pneumophila. This indicates that host-pathogen interactions are evolutionary conserved, derived from the early interactions between free-living phagocytic cells and bacteria. Taken together, our results strengthen the use of D. discoideum as a general infection model.
Profile and outcome of patients with upper gastrointestinal bleeding presenting to urban emergency departments of tertiary hospitals in Tanzania
Authors: Rajan Shaffin S. , Sawe Hendry R. , Iyullu Asha J. , Kaale Dereck A. , Olambo Nancy A. , Mfinanga Juma A. , Weber Ellen J. 
Published: December 2019

AbstractBackgroundUpper gastrointestinal bleeding (UGIB) is a common emergency department (ED) presentation with high morbidity and mortality. There is a paucity of data on the profile and outcome of patients who present with UGIB to EDs, especially within limited resource settings where emergency medicine is a new specialty. We aim to describe the patient profile, clinical severity and outcomes of the patients who present with UGIB to the ED of tertiary referral hospitals in Tanzania.MethodsThis was a prospective cohort study of consecutive adult (≥18 years) patients presenting to the EDs of Muhimbili National Hospital (ED-MNH) and MUHAS Academic Medical Centre (ED-MAMC), in Tanzania with non-traumatic upper gastrointestinal bleeding (UGIB) from July 2018 to December 2018. Patient demographic data, clinical presentation, and ED and hospital management provided were recorded. We used the clinical Rockall score to assess disease severity. The primary outcome of 7- day mortality was summarized using descriptive statistics. Regression analysis was performed to identify predictors of mortality.ResultsDuring the study period, 123 patients presented to one of the two EDs with an UGIB. The median age was 42 years (Interquartile range (IQR) 32–64 years), and 87 (70.7%) were male. Hematemesis with melena was the most frequently encountered ED complaint 39 (31.7%). Within 7 days, 23 (18.7%) patients died and one-third 8 (34.8%) of these died within 24 h. There were no ED deaths. About 65.1% of the patients had severe anemia but only 60 (48.8%) received blood transfusion in the ED. Amongst those with history of (h/o) esophageal varices 7(41.2%) did not receive octreotide. Upper GI endoscopy, was performed on 46 (37.4%) patients, of whom only 8 (17.4%) received endoscopy within 24 h (early UGI endoscopy). All patients who received early UGI endoscopy had a low or moderate clinical Rockall score i.e. < 3 and 3–4. No patient with scores of > 4 received early UGI endoscopy. Age > 40 years was a significant independent predictor of mortality (OR = 7.00 (95% CI 1.7–29.2). Having a high clinical Rockall score of ≥ 4 was a significant independent predictor of mortality (OR = 6.4 (95% CI 1.8–22.8).ConclusionsIn this urban ED in Sub-Saharan Africa, UGIB carried a high mortality rate. Age > 40 years and clinical Rockall score ≥ 4 were independent predictors of higher mortality. Future studies should focus on evaluating how to improve access to UGI endoscopy so as to improve outcomes.
Biosafety and biosecurity requirements for Orientia spp. diagnosis and research: recommendations for risk-based biocontainment, work practices and the case for reclassification to risk group 2
Authors: Blacksell Stuart D. , Robinson Matthew T. , Newton Paul N. , Ruanchaimun Soiratchaneekorn , Salje Jeanne , Wangrangsimakul Tri , Wegner Matthew D. , Abdad Mohammad Yazid , Bennett Allan M. , Richards Allen L. , Stenos John , Day Nicholas P. J. 
Published: December 2019

AbstractScrub typhus is an important arthropod-borne disease causing significant acute febrile illness by infection with Orientia spp.Using a risk-based approach, this review examines current practice, the evidence base and regulatory requirements regarding matters of biosafety and biosecurity, and presents the case for reclassification from Risk Group 3 to Risk Group 2 along with recommendations for safe working practices of risk-based activities during the manipulation of Orientia spp. in the laboratory.We recommend to reclassify Orientia spp. to Risk Group 2 based on the classification for RG2 pathogens as being moderate individual risk, low community risk. We recommend that low risk activities, can be performed within a biological safety cabinet located in a Biosafety Level (BSL) 2 core laboratory using standard personal protective equipment. But when the risk assessment indicates, such as high concentration and volume, or aerosol generation, then a higher biocontainment level is warranted. For, the majority of animal activities involving Orientia spp., Animal BSL 2 (ABSL2) is recommended however where high risk activities are performed including necropsies, Animal BSL (ABSL3) is recommended.
Prognostic implications of forkhead box protein O1 (FOXO1) and paired box 3 (PAX3) in epithelial ovarian cancer
Authors: Han Gwan Hee , Chay Doo Byung , Nam Sanghee , Cho Hanbyoul , Chung Joon-Yong , Kim Jae-Hoon 
Published: December 2019

AbstractBackgroundTranscription factors forkhead box protein O1 (FOXO1) and paired box 3 (PAX3) have been reported to play important roles in various cancers. However, their role in epithelial ovarian cancer (EOC) has not been elucidated yet. Therefore, we evaluated the expression and clinical significance of FOXO1 and PAX3 in EOC.MethodsImmunohistochemical analyses of FOXO1 and PAX3 in 212 EOCs, 57 borderline ovarian tumors, 153 benign epithelial ovarian tumors, and 79 nonadjacent normal epithelial tissues were performed using tissue microarray. Various clinicopathological variables, including the survival of EOC patients, were compared. In addition, the effect of FOXO1 on cell growth was assessed in EOC cell lines.ResultsFOXO1 and PAX3 protein expression levels were significantly higher in EOC tissues than in nonadjacent normal epithelial tissues, benign tissues, and borderline tumors (allp < 0.001). In EOC tissues, FOXO1 expression was positively correlated with PAX3 expression (Spearman’s rho = 0.118,p = 0.149). Multivariate survival analysis revealed that high FOXO1 expression (hazard ratio = 2.77 [95% CI, 1.48–5.18],p = 0.001) could be an independent prognostic factor for overall survival. Most importantly, high expression of both FOXO1 and PAX3 showed a high hazard ratio (4.60 [95% CI, 2.00–10.55],p < 0.001) for overall survival. Also in vitro results demonstrated that knockdown of FOXO1 was associated with decreased cell viability, migration, and colony formation.ConclusionsThis study revealed that high expression of FOXO1/PAX3 is an indicator of poor prognosis in EOC. Our results suggest the promising potential of FOXO1 and PAX3 as prognostic and therapeutic markers. The possible link between biological functions of FOXO1 and PAX3 in EOC warrants further studies.