bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous Space–Time Artificial Neural Networks for Space–Time Series Prediction
Authors: Deng Min , Yang Wentao , Liu Qiliang , Jin Rui , Xu Feng , Zhang Yunfei 
Published: October 2017

AbstractSpace–time series prediction plays a key role in the domain of geographic data mining and knowledge discovery. In general, the existing methods of space–time series prediction can be divided into two main categories: statistical machine learning methods. Comparatively, machine leaning methods have obvious advantages with respect to handling nonlinear problems. However, space–time dependence and the heterogeneity of space–time data are not well addressed by the existing machine learning methods. Because of this limitation, an accurate prediction of a space–time series is still a challenging problem. Therefore, in this study, both space–time dependence and heterogeneity are incorporated into the feedback artificial neural network, and heterogeneous space–time artificial neural networks (HSTANNs) are developed for space–time series prediction. First, to handle spatial heterogeneity, space–time series clustering is used to divide the study area into a set of homogeneous sub‐areas. Then, a space–time autocorrelation analysis is employed to explore the space–time dependence structure of the dataset. Finally, a HSTANN is established for each sub‐area. Further, HSTANNs are applied to predict the concentrations of fine particulate matter (PM2.5) in Beijing–Tianjin–Hebei. The experimental results show that when compared with other methods, the accuracy of the forecasting results is considerably improved by using HSTANNs.
The de minimis threshold in international trade: The costs of being too low
Authors: Latipov Olim , McDaniel Christine , Schropp Simon 
Published: October 2017

AbstractWith tariffs largely negotiated away, trade facilitation issues such as custom delays and border costs are one of the next key barriers for trade policymakers to address. One important trade facilitation issue is the de minimis threshold (DMT)—a valuation ceiling for imports below which no duty or tax is charged and the clearance procedures are minimal. Customs assessments are costly and low thresholds can hinder trade flows. We offer a detailed analytical approach to assess the direct economic effects of raising theDMT. We focus on Canada, which has one of the lowestDMTs among developed countries. We utilise a unique data set and find that raising Canada'sDMTwould have positive effects for consumers and businesses, particularly small businesses because the cost saving for smaller entities is disproportionately large. For the government, foregone duty and tax revenues are outweighed by the cost saving, resulting in a fiscally neutral or even positive effect for government revenues.
Infectious Laryngotracheitis Virus Viral Chemokine-Binding Protein Glycoprotein G Alters Transcription of Key Inflammatory Mediators
In Vitro
and
In Vivo
Authors: Coppo Mauricio J. C. , Devlin Joanne M. , Legione Alistair R. , Vaz Paola K. , Lee Sang-Won , Quinteros José A. , Gilkerson James R. , Ficorilli Nino , Reading Patrick C. , Noormohammadi Amir H. , Hartley Carol A. 
Published: October 2017

ABSTRACT

Infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that infects chickens, causing upper respiratory tract disease and significant losses to poultry industries worldwide. Glycoprotein G (gG) is a broad-range viral chemokine-binding protein conserved among most alphaherpesviruses, including ILTV. A number of studies comparing the immunological parameters between infection with gG-expressing and gG-deficient ILTV strains have demonstrated that expression of gG is associated with increased virulence, modification of the amount and the composition of the inflammatory response, and modulation of the immune responses toward antibody production and away from cell-mediated immune responses. The aims of the current study were to examine the establishment of infection and inflammation by ILTV and determine how gG influences that response to infection.
In vitro
infection studies using tracheal organ tissue specimen cultures and blood-derived monocytes and
in vivo
infection studies in specific-pathogen-free chickens showed that leukocyte recruitment to the site of infection is an important component of the induced pathology and that this is influenced by the expression of ILTV gG and changes in the transcription of the chicken orthologues of mammalian CXC chemokine ligand 8 (CXCL8), chicken CXCLi1 and chicken CXCLi2, among other cytokines and chemokines. The results from this study demonstrate that ILTV gG interferes with chemokine and cytokine transcription at different steps of the inflammatory cascade, thus altering inflammation, virulence, and the balance of the immune response to infection.

IMPORTANCE
Infectious laryngotracheitis virus is an alphaherpesvirus that expresses gG, a conserved broad-range viral chemokine-binding protein known to interfere with host immune responses. However, little is known about how gG modifies virulence and influences the inflammatory signaling cascade associated with infection. Here, data from
in vitro
and
in vivo
infection studies are presented. These data show that gG has a direct impact on the transcription of cytokines and chemokine ligands
in vitro
(such as chicken CXCL8 orthologues, among others), which explains the altered balance of the inflammatory response that is associated with gG during ILTV infection of the upper respiratory tract of chickens. This is the first report to associate gG with the dysregulation of cytokine transcription at different stages of the inflammatory cascade triggered by ILTV infection of the natural host.
Selective Proteomic Analysis of Antibiotic-Tolerant Cellular Subpopulations inPseudomonas aeruginosaBiofilms
Authors: Babin Brett M. , Atangcho Lydia , van Eldijk Mark B. , Sweredoski Michael J. , Moradian Annie , Hess Sonja , Tolker-Nielsen Tim , Newman Dianne K. , Tirrell David A. 
Published: October 2017

ABSTRACTBiofilm infections exhibit high tolerance against antibiotic treatment. The study of biofilms is complicated by phenotypic heterogeneity; biofilm subpopulations differ in their metabolic activities and their responses to antibiotics. Here, we describe the use of the bio-orthogonal noncanonical amino acid tagging (BONCAT) method to enable selective proteomic analysis of aPseudomonas aeruginosabiofilm subpopulation. Through controlled expression of a mutant methionyl-tRNA synthetase, we targeted BONCAT labeling to cells in the regions of biofilm microcolonies that showed increased tolerance to antibiotics. We enriched and identified proteins synthesized by cells in these regions. Compared to the entire biofilm proteome, the labeled subpopulation was characterized by a lower abundance of ribosomal proteins and was enriched in proteins of unknown function. We performed a pulse-labeling experiment to determine the dynamic proteomic response of the tolerant subpopulation to supra-MIC treatment with the fluoroquinolone antibiotic ciprofloxacin. The adaptive response included the upregulation of proteins required for sensing and repairing DNA damage and substantial changes in the expression of enzymes involved in central carbon metabolism. We differentiated the immediate proteomic response, characterized by an increase in flagellar motility, from the long-term adaptive strategy, which included the upregulation of purine synthesis. This targeted, selective analysis of a bacterial subpopulation demonstrates how the study of proteome dynamics can enhance our understanding of biofilm heterogeneity and antibiotic tolerance.IMPORTANCEBacterial growth is frequently characterized by behavioral heterogeneity at the single-cell level. Heterogeneity is especially evident in the physiology of biofilms, in which distinct cellular subpopulations can respond differently to stresses, including subpopulations of pathogenic biofilms that are more tolerant to antibiotics. Global proteomic analysis affords insights into cellular physiology but cannot identify proteins expressed in a particular subpopulation of interest. Here, we report a chemical biology method to selectively label, enrich, and identify proteins expressed by cells within distinct regions of biofilm microcolonies. We used this approach to study changes in protein synthesis by the subpopulation of antibiotic-tolerant cells throughout a course of treatment. We found substantial differences between the initial response and the long-term adaptive strategy that biofilm cells use to cope with antibiotic stress. The method we describe is readily applicable to investigations of bacterial heterogeneity in diverse contexts.
Anti-MAG antibodies in 202 patients: clinicopathological and therapeutic features
Authors: Svahn Juliette , Petiot Philippe , Antoine Jean-Christophe , Vial Christophe , Delmont Emilien , Viala Karine , Steck Andreas J , Magot Armelle , Cauquil Cecile , Zarea Aline , Echaniz-Laguna Andoni , Iancu Ferfoglia Ruxandra , Gueguen Antoine , Magy Laurent , Léger Jean-Marc , Kuntzer Thierry , Ferraud Karine , Lacour Arnaud , Camdessanché Jean-Philippe 
Published: October 2017

ObjectiveTo assess the clinicopathological and therapeutic features of patients with low (≥1000 to <10 000 Bühlmann Titre Units) (BTU), medium (10 000–70 000) or high (≥70 000) anti-myelin-associated glycoprotein (anti-MAG) antibody titres.MethodsWe retrospectively and prospectively analysed standardised report forms and medical records of 202 patients from 14 neuromuscular centres.ResultsMean age at onset and mean time between symptom onset to last follow-up were respectively 62.6 years (25–91.4) and 8.4 years (0.3–33.3). Anti-MAG antibody titres at diagnosis were low, medium or high in 11%, 51% and 38% of patients. Patients presented with monoclonal gammopathy of undetermined significance in 68% of cases. About 17% of patients presented with ‘atypical’ clinical phenotype independently of anti-MAG titres, including acute or chronic sensorimotor polyradiculoneuropathies (12.4%), and asymmetric or multifocal neuropathy (3%). At the most severe disease stage, 22.4% of patients were significantly disabled. Seventy-eight per cent of patients received immunotherapies. Transient clinical worsening was observed in 12% of patients treated with rituximab (11/92). Stabilisation after rituximab treatment during the 7–12-month follow-up period was observed in 29% of patients. Clinical response to rituximab during the 6-month and/or 7–12-month follow-up period was observed in 31.5% of patients and correlated with anti-MAG titre ≥10 000 BTU.ConclusionOur study highlights the extended clinical spectrum of patients with anti-MAG neuropathy, which appears unrelated to antibody titre. Besides, it may also suggest beneficial use of rituximab in the early phase of anti-MAG neuropathy.
Perceived intentional transmission of HIV infection, sustained viral suppression and psychosocial outcomes among men who have sex with men living with HIV: a cross-sectional assessment
Authors: Brown Monique J , Serovich Julianne M , Kimberly Judy A 
Published: October 2017

ObjectiveHIV continues to be a global and national public health challenge, and men who have sex with men (MSM) are disproportionately affected in the USA. Transmission of HIV is intentional if the person living with HIV knows about his/her serostatus, acts with the intention to and actually transmits HIV. Research on intentional transmission of HIV infections is lacking, and the relationships between perceived intentional transmission, viral suppression and psychosocial outcomes have not been assessed. The objective of this study was to investigate the association between perceived intentional transmission of HIV, sustained viral suppression and psychosocial outcomes.MethodsData were obtained from 338 MSM living with HIV who participated in a disclosure intervention study. Logistic and linear regression models were used to assess the associations between perceived intentional transmission and viral suppression, condomless anal intercourse in the past 30 days, being at risk for clinical depression, substance use, self-efficacies for condom use, HIV disclosure and negotiation of safer sex practices, and sexual compulsivity.Results44% of the study population reported perceiving intentional HIV transmission. After adjusting for sociodemographic characteristics, men who thought that they were infected intentionally had 69% higher odds (adjusted OR: 1.69; 95% CI 1.01 to 2.83) of being at risk for clinical depression, and on average, scored approximately 3 points and 4 points higher on depressive symptoms and sexual compulsivity, respectively (adjusted β: 3.29; 95% CI 0.42 to 6.15; adjusted β: 3.74; 95% CI 1.32 to 6.17) compared with men who did not think that they were intentionally infected. After adjusting for confounders, there was no statistically significant association between perceived intentional transmission and viral suppression.ConclusionsIntervention programmes for MSM living with HIV who thought they were infected intentionally are warranted and should aim to attenuate depressive symptoms and sexual compulsivity.
Treatment of chlamydia and gonorrhoea, compliance with treatment guidelines and factors associatedwith non-compliant prescribing: findings form a cross-sectional study
Authors: Tisler-Sala Anna , Ojavee Sven-Erik , Uusküla Anneli 
Published: October 2017

ObjectivesProper antibiotic treatment of STI reduces transmission, antimicrobial resistance and serious disease complications. In this study, we assessed compliance with STI treatment guidelines for genital gonorrhoea and chlamydia infections in Estonia.MethodsPrescription data from the Estonian Health Insurance Fund on 7556 treatment episodes of 6499 patients treated for gonorrhoea or chlamydia during 2012–2014 were analysed to assess compliance with the guidelines and factors associated with it.ResultsBetween 1 January 2012 and 31 December 2014, a total of 6074 patients were treated for chlamydia and 425 for gonorrhoea in Estonia. Among all prescriptions, 48.6% were non-compliant with gonorrhoea treatment guidelines and 3.8% for chlamydia. Non-compliant antibiotic treatment for gonorrhoea was associated with patient gender (female (adjusted OR (AOR)) 3.0, 95% CI 1.6 to 5.9), region (east AOR 3.3, 95% CI 1.3 to 8.2; west AOR 6.5, 95% CI 2.2 to 19.7) and prescribing physician specialty (general healthcare doctors: AOR 5.6, 95% CI 2.3 to 13.8; gynaecologists: AOR 5.9, 95% CI 2.8 to 12.4). Non-compliant antibiotic treatment for chlamydia was associated with younger patient age (15–24 AOR 0.5, 95% CI 0.4 to 0.7), region (north AOR 1.9, 95% CI 1.4 to 2.6; west AOR 2.3, 95% CI 1.5 to 3.4) and multiple treatment episodes (AOR 2.7, 95% CI 2.1 to 3.9). Approximately 14% of prescriptions were multiple treatments for the same patient for the same infection over the 3-year period (6.1% for gonorrhoea and 14.5% for chlamydia).ConclusionThere are significant differences in terms of compliance with treatment guidelines for gonorrhoea and chlamydia, and several factors associated with non-compliance that can potentially be targeted with interventions. Future research should explore reasons clinicians do not follow guidelines and examine ways to improve practice among doctors and patients and assess factors associated with multiple treatments, particularly multiple treatments for the same STI.
PQR309 Is a Novel Dual PI3K/mTOR Inhibitor with Preclinical Antitumor Activity in Lymphomas as a Single Agent and in Combination Therapy
Authors: Tarantelli Chiara , Gaudio Eugenio , Arribas Alberto J. , Kwee Ivo , Hillmann Petra , Rinaldi Andrea , Cascione Luciano , Spriano Filippo , Bernasconi Elena , Guidetti Francesca , Carrassa Laura , Pittau Roberta Bordone , Beaufils Florent , Ritschard Reto , Rageot Denise , Sele Alexander , Dossena Barbara , Rossi Francesca Maria , Zucchetto Antonella , Taborelli Monica , Gattei Valter , Rossi Davide , Stathis Anastasios , Stussi Georg , Broggini Massimo , Wymann Matthias P. , Wicki Andreas , Zucca Emanuele , Cmiljanovic Vladimir , Fabbro Doriano , Bertoni Francesco 
Published: October 2017

AbstractPurpose: Activation of the PI3K/mTOR signaling pathway is recurrent in different lymphoma types, and pharmacologic inhibition of the PI3K/mTOR pathway has shown activity in lymphoma patients. Here, we extensively characterized the in vitro and in vivo activity and the mechanism of action of PQR309 (bimiralisib), a novel oral selective dual PI3K/mTOR inhibitor under clinical evaluation, in preclinical lymphoma models.Experimental Design: This study included preclinical in vitro activity screening on a large panel of cell lines, both as single agent and in combination, validation experiments on in vivo models and primary cells, proteomics and gene-expression profiling, and comparison with other signaling inhibitors.Results: PQR309 had in vitro antilymphoma activity as single agent and in combination with venetoclax, panobinostat, ibrutinib, lenalidomide, ARV-825, marizomib, and rituximab. Sensitivity to PQR309 was associated with specific baseline gene-expression features, such as high expression of transcripts coding for the BCR pathway. Combining proteomics and RNA profiling, we identified the different contribution of PQR309-induced protein phosphorylation and gene expression changes to the drug mechanism of action. Gene-expression signatures induced by PQR309 and by other signaling inhibitors largely overlapped. PQR309 showed activity in cells with primary or secondary resistance to idelalisib.Conclusions: On the basis of these results, PQR309 appeared as a novel and promising compound that is worth developing in the lymphoma setting. Clin Cancer Res; 24(1); 120–9. ©2017 AACR.
Inflammatory Biomarkers Interleukin‐6 and C‐Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial
Authors: Held Claes , White Harvey D. , Stewart Ralph A. H. , Budaj Andrzej , Cannon Christopher P. , Hochman Judith S. , Koenig Wolfgang , Siegbahn Agneta , Steg Philippe Gabriel , Soffer Joseph , Weaver W. Douglas , Östlund Ollie , Wallentin Lars ,   on behalf of the STABILITY Investigators
Published: October 2017

Background
Evaluation of cardiovascular prognosis in patients with stable coronary heart disease is based on clinical characteristics and biomarkers indicating dysglycemia, dyslipidemia, renal dysfunction, and possibly cardiac dysfunction. Inflammation plays a key role in atherosclerosis, but the association between inflammatory biomarkers and clinical outcomes is less studied in this population.

Methods and Results

Overall, 15 828 patients with coronary heart disease in the
STABILITY
(Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial were randomized to treatment with darapladib or placebo and observed for a median of 3.7 years. In 14 611 patients, levels of interleukin‐6 (
IL
‐6) and high‐sensitivity C‐reactive protein were measured in plasma samples: median levels were 2.1 (interquartile range, 1.4–3.2) ng/L and 1.3 (interquartile range, 0.6–3.1) mg/L, respectively. Associations between continuous levels or quartile groups and adjudicated outcomes were evaluated by spline graphs and Cox regression adjusted for clinical factors and cardiovascular biomarkers.
IL
‐6 was associated with increased risk of major adverse cardiovascular events (quartile 4 versus quartile 1 hazard ratio [
HR
], 1.60; 95% confidence interval [CI], 1.30–1.97;
P
<0.0001); cardiovascular death (
HR
, 2.15; 95% CI, 1.53–3.04;
P
<0.0001); myocardial infarction (
HR
, 1.53; 95% CI, 1.14–2.04;
P
<0.05); all‐cause mortality (
HR
, 2.11; 95% CI, 1.62–2.76;
P
<0.0001); and risk of hospitalization for heart failure (
HR
, 2.28; 95% CI, 1.34–3.89;
P
<0.001). Cancer death was doubled in the highest
IL
‐6 quartile group (
HR
, 2.34; 95% CI, 1.20–4.53;
P
<0.05). High‐sensitivity C‐reactive protein was associated with both cardiovascular and non‐cardiovascular events in the unadjusted model, but these did not remain after multivariable adjustments.

Conclusions

IL
‐6, an upstream inflammatory marker, was independently associated with the risk of major adverse cardiovascular events, cardiovascular and all‐cause mortality, myocardial infarction, heart failure, and cancer mortality in patients with stable coronary heart disease. IL‐6 might reflect a pathophysiological process involved in the development of these events.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00799903.
Cumulative Exposure to High‐Sensitivity C‐Reactive Protein Predicts the Risk of Cardiovascular Disease
Authors: Wang Aitian , Liu Jie , Li Chunguang , Gao Jingli , Li Xiaolan , Chen Shuohua , Wu Shouling , Ding Hui , Fan Haojun , Hou Shike 
Published: October 2017

Background

One measurement of hs‐CRP (high‐sensitivity C‐reactive protein) is associated with increased risk of cardiovascular disease (
CVD
). The objective of this study was to characterize the association of cumulative exposure to increased hs‐
CRP
with incident cardiovascular events.

Methods and Results

We included 53 065 participants with hs‐
CRP
measured at 3 examinations in 2006, 2008, and 2010. Cumulative exposure to hs‐
CRP
was calculated as the weighted sum of the average hs‐
CRP
level for each time interval (level×time). Participants were classified into nonexposed group (hs‐
CRP
<3.0 mg/L in all 3 examinations), 1‐exposed group (hs‐
CRP
≥3.0 mg/L in 1 of the 3 examinations), 2‐exposed group (hs‐
CRP
≥3.0 mg/L in 2 of the 3 examinations), and 3‐exposed group (hs‐
CRP
≥3.0 mg/L in 3 examinations). Cox proportional hazards models were used to assess the association of cumulative hs‐
CRP
with incident
CVD
. The study showed a dose‐response pattern with risk of
CVD
and myocardial infarction as the number of years of exposure to hs‐
CRP
increases. Participants in the 3‐exposed group had significantly increased
CVD
risk with hazard ratio (95% confidence interval) of 1.38 (1.11–1.72), in comparison with 1.28 (1.07–1.52) for participants in the 2‐exposed group and 1.13 (0.97–1.31) for those in the 1‐exposed group (
P
<0.05); meanwhile, the similar and significant associations were also observed for myocardial infarction with respective hazard ratio (95% confidence interval) of 2.13 (1.42–3.18), 1.60 (1.12–2.27), and 1.57 (1.17–2.10). The associations between stroke and cumulative hs‐
CRP
were not statistically significant (
P
=0.360).

Conclusions

Cumulative exposure to hs‐
CRP
was dose dependently associated with a subsequent increased risk of
CVD
and myocardial infarction.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/
. Unique identifier: ChiCTR‐TNC‐11001489.