bluuebunny/crossref_metadata_2025_split huggingface dataset:
A North American H7N3 Influenza Virus Supports Reassortment with 2009 Pandemic H1N1 and Induces Disease in Mice without Prior Adaptation
Authors: Williams Graham D. , Pinto Amelia K. , Doll Brittany , Boon Adrianus C. M. 
Published: March 2016

ABSTRACT

Reassortment between H5 or H9 subtype avian and mammalian influenza A viruses (IAV) can generate a novel virus that causes disease and transmits between mammals. Such information is currently not available for H7 subtype viruses. We evaluated the ability of a low-pathogenicity North American avian H7N3 virus (A/shorebird/Delaware/22/2006) to reassort with mammalian or avian viruses using a plasmid-based competition assay. In addition to genome segments derived from an avian H7N9 virus, the H7N3 virus reassorted efficiently with the PB2, NA, and M segments from the 2009 pandemic H1N1 (
P
H1N1) virus.
In vitro
and
in vivo
evaluation of the H7N3:
P
H1N1 (7 + 1) reassortant viruses revealed that the PB2, NA, or M segments from
P
H1N1 largely do not attenuate the H7N3 virus, whereas the PB1, PA, NP, or NS genome segments from
P
H1N1 do. Additionally, we assessed the functionality of the H7N3:
P
H1N1 7 + 1 reassortant viruses by measuring the inflammatory response
in vivo
. We found that infection with wild-type H7N3 resulted in increased inflammatory cytokine production relative to that seen with the
P
H1N1 strain and that the increase was further exacerbated by substitution of
P
H1N1 PB2 but not NA or M. Finally, we assessed if any adaptations occurred in the individually substituted segments after
in vivo
inoculation and found no mutations, suggesting that
P
H1N1 PB2, NA, and M are genetically stable in the background of this H7N3 virus. Taking the data together, we demonstrate that a North American avian H7N3 IAV is genetically and functionally compatible with multiple gene segments from the 2009 pandemic influenza virus strain without prior adaptation.

IMPORTANCE
The 2009 pandemic H1N1 virus continues to circulate and reassort with other influenza viruses, creating novel viruses with increased replication and transmission potential in humans. Previous studies have found that this virus can also reassort with H5N1 and H9N2 avian influenza viruses. We now show that several genome segments of the 2009 H1N1 virus are also highly compatible with a low-pathogenicity avian H7N3 virus and that these reassortant viruses are stable and not attenuated in an animal model. These results highlight the potential for reassortment of H1N1 viruses with avian influenza virus and emphasize the need for continued surveillance of influenza viruses in areas of cocirculation between avian, human, and swine viruses.
Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery
Authors: van Dongen Helena M. , Masoumi Niala , Witwer Kenneth W. , Pegtel D. Michiel 
Published: March 2016

SUMMARY

Extracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, being involved in a wide array of key biological processes. Eukaryotic cells, and also bacteria, actively release heterogeneous subtypes of EVs into the extracellular space, where their contents reflect their (sub)cellular origin and the physiologic state of the parent cell. Within the past 20 years, presumed subtypes of EVs have been given a rather confusing diversity of names, including exosomes, microvesicles, ectosomes, microparticles, virosomes, virus-like particles, and oncosomes, and these names are variously defined by biogenesis, physical characteristics, or function. The latter category, functions, in particular the transmission of biological signals between cells
in vivo
and how EVs control biological processes, has garnered much interest. EVs have pathophysiological properties in cancer, neurodegenerative disorders, infectious disease, and cardiovascular disease, highlighting possibilities not only for minimally invasive diagnostic applications but also for therapeutic interventions, like macromolecular drug delivery. Yet, in order to pursue therapies involving EVs and delivering their cargo, a better grasp of EV targeting is needed. Here, we review recent progress in understanding the molecular mechanisms underpinning EV uptake by receptor-ligand interactions with recipient cells, highlighting once again the overlap of EVs and viruses. Despite their highly heterogeneous nature, EVs require common viral entry pathways, and an unanticipated specificity for cargo delivery is being revealed. We discuss the challenges ahead in delineating specific roles for EV-associated ligands and cellular receptors.
Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies
Authors: Barber Amelia E. , Norton J. Paul , Wiles Travis J. , Mulvey Matthew A. 
Published: March 2016

SUMMARY

Urinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are a source of substantial morbidity among otherwise healthy women. UTIs can be caused by a variety of microbes, but the predominant etiologic agent of these infections is uropathogenic
Escherichia coli
(UPEC). An especially troubling feature of UPEC-associated UTIs is their high rate of recurrence. This problem is compounded by the drastic increase in the global incidence of antibiotic-resistant UPEC strains over the past 15 years. The need for more-effective treatments for UTIs is driving research aimed at bettering our understanding of the virulence mechanisms and host-pathogen interactions that occur during the course of these infections. Surrogate models of human infection, including cell culture systems and the use of murine, porcine, avian, teleost (zebrafish), and nematode hosts, are being employed to define host and bacterial factors that modulate the pathogenesis of UTIs. These model systems are revealing how UPEC strains can avoid or overcome host defenses and acquire scarce nutrients while also providing insight into the virulence mechanisms used by UPEC within compromised individuals, such as catheterized patients. Here, we summarize our current understanding of UTI pathogenesis while also giving an overview of the model systems used to study the initiation, persistence, and recurrence of UTIs and life-threatening sequelae like urosepsis. Although we focus on UPEC, the experimental systems described here can also provide valuable insight into the disease processes associated with other bacterial pathogens both within the urinary tract and elsewhere within the host.
Adaptation and validation of the Distress Scale for Mexican patients with type 2 diabetes and hypertension: a cross-sectional survey
Authors: Martinez-Vega Ingrid Patricia , Doubova Svetlana V , Aguirre-Hernandez Rebeca , Infante-Castañeda Claudia 
Published: March 2016

ObjectivesThe aim of this study was to adapt and validate the Distress Scale for Mexican patients with type 2 diabetes and hypertension (DSDH17M).SettingTwo family medicine clinics affiliated with the Mexican Institute of Social Security.Participants722 patients with type 2 diabetes and/or hypertension (235 patients with diabetes, 233 patients with hypertension and 254 patients with both diseases).DesignA cross-sectional survey.MethodsThe validation procedures included: (1) content validity using a group of experts, (2) construct validity from exploratory factor analysis, (3) internal consistency using Cronbach's α, (4) convergent validity between DSDH17M and anxiety and depression using the Spearman correlation coefficient, (5) discriminative validity through the Wilcoxon rank-sum test and (6) test–retest reliability using intraclass correlation coefficient.ResultsThe DSDH17M has 17 items and three factors explaining 67% of the total variance. Cronbach α ranged from 0.83 to 0.91 among factors. The first factor of ‘Regime-related Distress and Emotional Burden’ moderately correlated with anxiety and depression scores. Discriminative validity revealed that patients with obesity, those with stressful events and those who did not adhere to pharmacological treatment had significantly higher distress scores in all DSDH17M domains. Test–retest intraclass correlation coefficient for DSDH17M ranged from 0.92 to 0.97 among factors.ConclusionsDSDH17M is a valid and reliable tool to identify distress of patients with type 2 diabetes and hypertension.
Discovering untapped relationship potential with patients in telehealth: a qualitative interview study
Authors: Heckemann Birgit , Wolf Axel , Ali Lilas , Sonntag Steffen Mark , Ekman Inger 
Published: March 2016

ObjectivesTo explore factors that influence relationship building between telehealth professionals and patients with chronic illness over a distance, from a telehealth professional's perspective.Design4 focus group interviews were conducted in June 2014. Digital recordings were transcribed verbatim and qualitative content analysis was performed using an iterative process of 3 coding rounds.Participants20 telehealth professionals.SettingA telehealth service centre in the south of Germany that provided care for 12 000 patients with chronic heart failure across Germany.ResultsNon-video telehealth technology creates an atmosphere that fosters sharing of personal information and a non-judgemental attitude. This facilitates the delivery of fair and equal healthcare. A combination of a protocol-driven service structure along with shared team and organisational values provide a basis for establishing long-term healthcare relationships. However, each contact between a telehealth professional and a patient has an uncertain outcome and requires skilful negotiation of the relationship. Although care provision was personalised, there was scope to include the patients as ‘experts on their own illness’ to a greater extent as advocated by person-centred care. Currently, provision of person-centred care is not sufficiently addressed in telehealth professional training.ConclusionsTelehealth offers a viable environment for the delivery of person-centred care for patients with long-standing disease. Current telehealth training programmes may be enhanced by teaching person-centred care skills.
Socioeconomic deprivation and barriers to live-donor kidney transplantation: a qualitative study of deceased-donor kidney transplant recipients
Authors: Bailey Phillippa K , Ben-Shlomo Yoav , Tomson Charles R V , Owen-Smith Amanda 
Published: March 2016

ObjectivesSocioeconomically deprived individuals with renal disease are less likely to receive a live-donor kidney transplant than less-deprived individuals. This qualitative study aimed to identify reasons for the observed socioeconomic disparity in live-donor kidney transplantation.DesignA qualitative study using face-to-face in-depth semistructured interviews.SettingA UK tertiary renal referral hospital and transplant centre.ParticipantsPurposive sampling was used to select deceased-donor transplant recipients from areas of high socioeconomic deprivation (SED) (19 participants), followed by a low SED comparison group (13 participants), aiming for maximum diversity in terms of age, gender, ethnicity, primary renal disease and previous renal replacement therapy.MethodsParticipants were interviewed following their routine transplant clinic review. Interviews were digitally audio-recorded and transcribed verbatim. Transcripts were coded using NVivo software and analysed using the constant comparison method described in Grounded Theory.ResultsThemes common and distinct to each socioeconomic group emerged. 6 themes appeared to distinguish between individuals from areas of high and low SED. 4 themes were distinct to participants from areas of high SED: (1) Passivity, (2) Disempowerment, (3) Lack of social support and (4) Short-term focus. 2 themes were distinct to the low SED group: (1) Financial concerns and (2) Location of donor.ConclusionsSeveral of the emerging themes from the high SED individuals relate to an individual's lack of confidence and skill in managing their health and healthcare; themes that are in keeping with low levels of patient activation. Inadequate empowerment of socioeconomically deprived individuals by healthcare practitioners was also described. Financial concerns did not emerge as a barrier from interviews with the high SED group. Interventions aiming to redress the observed socioeconomic inequity should be targeted at both patients and clinical teams to increase empowerment and ensure shared decision-making.
Teamwork evaluation during emergency medicine residents’ high-fidelity simulation
Authors: Innocenti Francesca , Angeli Elena , Alesi Andrea , Scorpiniti Margherita , Pini Riccardo 
Published: March 2016

BackgroundTeamwork training has been included in several emergency medicine (EM) curricula; the aim of this study was to compare different scales’ performance in teamwork evaluation during simulation for EM residents.MethodsIn the period October 2013–June 2014, we performed bimonthly high-fidelity simulation sessions, with novice (I–III year, group 1 (G1)) and senior (IV–V year, group 2 (G2)) EM residents; scenarios were designed to simulate management of critical patients. Videos were assessed by three independent raters with the following scales: Emergency Team Dynamics (ETD), Clinical Teamwork Scale (CTS) and Team Emergency Assessment Measure (TEAM). In the period March–June, after each scenario, participants completed the CTS and ETD.ResultsThe analysis based on 18 sessions showed good internal consistency and good to fair inter-rater reliability for the three scales (TEAM, CTS, ETD: Cronbach's α 0.954, 0.954, 0.921; Intraclass Correlation Coefficients (ICC), 0.921, 0.917, 0.608). Single CTS items achieved highly significant ICC results, with 12 of the total 13 comparisons achieving ICC results ≥0.70; a similar result was confirmed for 4 of the total 11 TEAM items and 1 of the 8 total ETD items. Spearman's r was 0.585 between ETD and CTS, 0.694 between ETD and TEAM, and 0.634 between TEAM and CTS (scales converted to percentages, all p<0.0001). Participants gave themselves a better evaluation compared with external raters (CTS: 101±9 vs 90±9; ETD: 25±3 vs 20±5, all p<0.0001).ConclusionsAll examined scales demonstrated good internal consistency, with a slightly better inter-rater reliability for CTS compared with the other tools.
Counting of oscillatory modes of valence quarks forming q–q̄ mesons
Authors: Kabana Sonia , Minkowski Peter 
Published: March 2016

We present the unique properties of oscillatory modes of valence quarks [Formula: see text] and antiquarks in mesons and the mass spectrum of associated mesons. The mesonic multiplets are shown to emerge from the picture of oscillating quarks and antiquarks in three space dimensions in the center of mass system of the mesons. All oscillatory modes are fully relativistic with a finite number of oscillators and this is forming the unique harmonic oscillator with these properties. The density of states as a function of masssquare is calculated. Since it is known that there are missing states of unobserved hadrons this estimate is of relevance for the accounting of the latter, as the here estimated mesonic multiplets include both the observed and the unobserved (or “missing”) hadrons. The estimate is conceptually different from Hagedorn’s model and is based on field theory of QCD.
Site preferences and effects of X (X = Mn, Fe, Co, Cu) on the properties of NiAl: A first-principles study
Authors: Li Hongshan , Cao Yong , Zhou Shenggang , Zhu Peixian , Zhu Jingchuan 
Published: March 2016

The site preference of X (X = Mn, Fe, Co, Cu) in NiAl and its effects on structural, electronic and elastic properties were investigated by performing first-principles calculations using density functional theory (DFT). Formation enthalpy calculations show that adding X increases the formation enthalpy of NiAl, indicating that X addition reduces the stability of system. The site preference was investigated by calculating the transfer energy of NiAl alloys with X. The results further exhibit that Mn, Fe and Cu show no site preference, but Co tends to occupy Ni site. By analyzing electronic density of states, Mulliken population, overlap population and valence charge density, the electronic property and bond characters were discussed. The elastic property calculation shows that only substitution of Ni by Cu increased the plasticity of alloy, while in the other cases the plasticity was decreased.
FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma
Authors: Koole Koos , Brunen Diede , van Kempen Pauline M.W. , Noorlag Rob , de Bree Remco , Lieftink Cor , van Es Robert J.J. , Bernards René , Willems Stefan M. 
Published: March 2016

Abstract
Purpose: FGFR1 is a promising therapeutic target in multiple types of solid tumors, including head and neck squamous cell carcinoma (HNSCC). FGFR inhibitors have shown great therapeutic value in preclinical models. However, resistance remains a major setback. In this study, we have investigated the prognostic value of FGFR1 expression in HNSCC, the therapeutic relevance of targeting FGFR with AZD4547, and potential resistant mechanisms.
Experimental Design: IHC and FISH were applied on tissue microarrays to investigate FGFR1 protein expression and FGFR1 gene copy numbers in 452 HNSCCs. The sensitivity of HNSCC cell lines to AZD4547, either as single or combination treatment with the EGFR inhibitor gefitinib, was assessed using long-term colony formation assays, short-term viability assays, and biochemical analysis.
Results: FGFR1 protein overexpression occurred in 82% (36/44) of human papillomavirus (HPV)–positive HNSCC and 75% (294/392) of HPV-negative HNSCC and relates with poor overall survival and disease-free survival in HPV-negative HNSCC [HR, 3.07; 95% confidence interval (CI), 1.74–6.90; P = 0.001 and HR, 1.53; 95% CI, 1.04–2.39; P = 0.033]. Moreover, the FGFR1 gene was amplified in 3% (3/110) of HPV-negative HNSCC. Treatment of the high FGFR1-expressing cell line CCL30 with AZD4547 reduced cell proliferation and FGFR signaling. Two FGFR-amplified cell lines, SCC147 and BICR16, were resistant to AZD4547 treatment due to EGFR signaling. Combined AZD4547 and gefitinib treatment synergistically inhibited the proliferation of resistant cell lines.
Conclusions: Here, we identify high FGFR1 expression as a candidate prognostic biomarker in HPV-negative HNSCC. Furthermore, we provide a rationale for treating FGFR1-expressing HNSCC with the FGFR inhibitor AZD4547 and for combining AZD4547 and gefitinib in FGFR inhibitor–resistant HNSCC patients. Clin Cancer Res; 22(15); 3884–93. ©2016 AACR.
Methionine and Kynurenine Activate Oncogenic Kinases in Glioblastoma, and Methionine Deprivation Compromises Proliferation
Authors: Palanichamy Kamalakannan , Thirumoorthy Krishnan , Kanji Suman , Gordon Nicolaus , Singh Rajbir , Jacob John R. , Sebastian Nikhil , Litzenberg Kevin T. , Patel Disha , Bassett Emily , Ramasubramanian Brinda , Lautenschlaeger Tim , Fischer Steven M. , Ray-Chaudhury Abhik , Chakravarti Arnab 
Published: March 2016

Abstract
Purpose: We employed a metabolomics-based approach with the goal to better understand the molecular signatures of glioblastoma cells and tissues, with an aim toward identifying potential targetable biomarkers for developing more effective and novel therapies.
Experimental Design: We used liquid chromatography coupled with mass spectrometry (LC-MS/Q-TOF and LC-MS/QQQ) for the discovery and validation of metabolites from primary and established glioblastoma cells, glioblastoma tissues, and normal human astrocytes.
Results: We identified tryptophan, methionine, kynurenine, and 5-methylthioadenosine as differentially regulated metabolites (DRM) in glioblastoma cells compared with normal human astrocytes (NHAs). Unlike NHAs, glioblastoma cells depend on dietary methionine for proliferation, colony formation, survival, and to maintain a deregulated methylome (SAM:SAH ratio). In methylthioadenosine phosphorylase (MTAP)-deficient glioblastoma cells, expression of MTAP transgene did not alter methionine dependency, but compromised tumor growth in vivo. We discovered that a lack of the kynurenine-metabolizing enzymes kynurenine monooxygenase and/or kynureninase promotes the accumulation of kynurenine, which triggers immune evasion in glioblastoma cells. In silico analysis of the identified DRMs mapped the activation of key oncogenic kinases that promotes tumorigenesis in glioblastoma. We validated this result by demonstrating that the exogenous addition of DRMs to glioblastoma cells in vitro results in oncogene activation as well as the simultaneous downregulation of Ser/Thr phosphatase PP2A.
Conclusions: We have connected a four-metabolite signature, implicated in the methionine and kynurenine pathways, to the promotion and maintenance of glioblastoma. Together, our data suggest that these metabolites and their respective metabolic pathways serve as potential therapeutic targets for glioblastoma. Clin Cancer Res; 22(14); 3513–23. ©2016 AACR.
ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer
Authors: Gao Shuai , Ye Huihui , Gerrin Sean , Wang Hongyun , Sharma Ankur , Chen Sen , Patnaik Akash , Sowalsky Adam G. , Voznesensky Olga , Han Wanting , Yu Ziyang , Mostaghel Elahe A. , Nelson Peter S. , Taplin Mary-Ellen , Balk Steven P. , Cai Changmeng 
Published: March 2016

Abstract
Purpose: ErbB2 signaling appears to be increased and may enhance androgen receptor (AR) activity in a subset of patients with castration-resistant prostate cancer (CRPC), but agents targeting ErbB2 have not been effective. This study was undertaken to assess ErbB2 activity in abiraterone-resistant prostate cancer and to determine whether it may contribute to AR signaling in these tumors.
Experimental Design: AR activity and ErbB2 signaling were examined in the radical prostatectomy specimens from a neoadjuvant clinical trial of leuprolide plus abiraterone and in the specimens from abiraterone-resistant CRPC xenograft models. The effect of ErbB2 signaling on AR activity was determined in two CRPC cell lines. Moreover, the effect of combination treatment with abiraterone and an ErbB2 inhibitor was assessed in a CRPC xenograft model.
Results: We found that ErbB2 signaling was elevated in residual tumor following abiraterone treatment in a subset of patients and was associated with higher nuclear AR expression. In xenograft models, we similarly demonstrated that ErbB2 signaling was increased and associated with AR reactivation in abiraterone-resistant tumors. Mechanistically, we show that ErbB2 signaling and subsequent activation of the PI3K/AKT signaling stabilizes AR protein. Furthermore, concomitantly treating CRPC cells with abiraterone and an ErbB2 inhibitor, lapatinib, blocked AR reactivation and suppressed tumor progression.
Conclusions: ErbB2 signaling is elevated in a subset of patients with abiraterone-resistant prostate cancer and stabilizes AR protein. Combination therapy with abiraterone and ErbB2 antagonists may be effective for treating the subset of CRPC with elevated ErbB2 activity. Clin Cancer Res; 22(14); 3672–82. ©2016 AACR.