bluuebunny/crossref_metadata_2025 huggingface dataset:
Donor pulmonary intravascular nonclassical monocytes recruit recipient neutrophils and mediate primary lung allograft dysfunction
Authors: Zheng Zhikun , Chiu Stephen , Akbarpour Mahzad , Sun Haiying , Reyfman Paul A. , Anekalla Kishore R. , Abdala-Valencia Hiam , Edgren Daphne , Li Wenjun , Kreisel Daniel , Korobova Farida V. , Fernandez Ramiro , McQuattie-Pimentel Alexandra , Zhang Zheng J. , Perlman Harris , Misharin Alexander V. , Scott Budinger G. R. , Bharat Ankit
Published: August 2017

Donor nonclassical monocytes mediate primary lung allograft dysfunction by recruiting neutrophils via MyD88-dependent production of CXCL2.
Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS
Authors: Ross Sarah J. , Revenko Alexey S. , Hanson Lyndsey L. , Ellston Rebecca , Staniszewska Anna , Whalley Nicky , Pandey Sanjay K. , Revill Mitchell , Rooney Claire , Buckett Linda K. , Klein Stephanie K. , Hudson Kevin , Monia Brett P. , Zinda Michael , Blakey David C. , Lyne Paul D. , Macleod A. Robert
Published: August 2017

AZD4785 is a therapeutic antisense oligonucleotide targeting KRAS mRNA with promising preclinical antitumor activity and a favorable safety profile.
Intrinsic Maturational Neonatal Immune Deficiencies and Susceptibility to Group B Streptococcus Infection
Authors: Korir Michelle L. , Manning Shannon D. , Davies H. Dele
Published: August 2017

Although a normal member of the gastrointestinal and vaginal microbiota, group B
Streptococcus
(GBS) can also occasionally be the cause of highly invasive neonatal disease and is an emerging pathogen in both elderly and immunocompromised adults. Neonatal GBS infections are typically transmitted from mother to baby either
in utero
or during passage through the birth canal and can lead to pneumonia, sepsis, and meningitis within the first few months of life. Compared to the adult immune system, the neonatal immune system has a number of deficiencies, making neonates more susceptible to infection. Recognition of GBS by the host immune system triggers an inflammatory response to clear the pathogen. However, GBS has developed several mechanisms to evade the host immune response. A comprehensive understanding of this interplay between GBS and the host immune system will aid in the development of new preventative measures and therapeutics.
A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs
Authors: Wang Zeng , Yang Huanliang , Chen Yan , Tao Shiyu , Liu Liling , Kong Huihui , Ma Shujie , Meng Fei , Suzuki Yasuo , Qiao Chuanling , Chen Hualan
Published: August 2017

Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains.

IMPORTANCE
Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by increasing virus affinity for human-type receptors. In this study, we explored the genetic basis of the transmissibility difference between two Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses in guinea pigs and found that the amino acid glutamic acid at position 225 in the HA1 protein plays a critical role in the transmission of EAH1N1 virus by increasing the efficiency of viral assembly and budding.
Mutation of the Putative Immunosuppressive Domain of the Retroviral Envelope Glycoprotein Compromises Infectivity
Authors: Eksmond Urszula , Jenkins Bryony , Merkenschlager Julia , Mothes Walther , Stoye Jonathan P. , Kassiotis George
Published: August 2017

The envelope glycoprotein of diverse endogenous and exogenous retroviruses is considered inherently immunosuppressive. Extensive work mapped the immunosuppressive activity to a highly conserved domain, termed the immunosuppressive domain (ISD), in the transmembrane (TM) subunit of the envelope glycoprotein and identified two naturally polymorphic key residues that afford immunosuppressive activity to distinct envelope glycoproteins. Concurrent mutation of these two key residues (E14R and A20F) in the envelope glycoprotein of the Friend murine leukemia virus (F-MLV) ISD has been reported to abolish its immunosuppressive activity, without affecting its fusogenicity, and to weaken the ability of the virus to replicate specifically in immunocompetent hosts. Here, we show that mutation of these key residues did, in fact, result in a substantial loss of F-MLV infectivity, independently of host immunity, challenging whether associations exist between the two. Notably, a loss of infectivity incurred by the F-MLV mutant with the E14R and A20F double ISD mutation was conditional on expression of the ecotropic envelope receptor murine cationic amino acid transporter-1 (mCAT1) in the virus-producing cell. Indeed, the F-MLV mutant retained infectivity when it was produced by human cells, which naturally lack mCAT1 expression, but not by murine cells. Furthermore, mCAT1 overexpression in human cells impaired the infectivity of both the F-MLV double mutant and the wild-type F-MLV strain, suggesting a finely tuned relationship between the levels of mCAT1 in the producer cell and the infectivity of the virions produced. An adverse effect on this relationship, rather than disruption of the putative ISD, is therefore more likely to explain the loss of F-MLV infectivity incurred by mutations in key ISD residues E14 and A20.

IMPORTANCE
Retroviruses can interact with their hosts in ways that, although not entirely understood, can greatly influence their pathogenic potential. One such example is a putative immunosuppressive activity, which has been mapped to a conserved domain of the retroviral envelope glycoprotein of several exogenous as well as endogenous retroviruses. In this study, mutations naturally found in some envelope glycoproteins lacking immunosuppressive activity were shown to affect retrovirus infectivity only if the host cell that produced the retrovirus also expressed the cellular entry receptor. These findings shed light on a novel role for this conserved domain in providing the necessary stability to the envelope glycoprotein in order to withstand the interaction with the cellular receptor during virus formation. This function of the domain is critical for further elucidation of the mechanism of immunosuppression mediated by the retroviral envelope glycoprotein.
Baculovirus Molecular Evolution via Gene Turnover and Recurrent Positive Selection of Key Genes
Authors: Hill Tom , Unckless Robert L.
Published: August 2017

Hosts and viruses are locked in an evolutionary arms race. Hosts are constantly evolving to suppress virulence and replication, while viruses, which are reliant on host machinery for survival and reproduction, develop counterstrategies to escape this immune defense. Viruses must also adapt to novel conditions while establishing themselves in a host species. Both processes provide strong selection for viral adaptation. Understanding adaptive evolution in insect viruses can help us to better understand adaptive evolution in general and is important due to the use of these viruses as biocontrol agents and for protecting ecologically or economically important species from outbreaks. Here we examine the molecular evolution of baculoviruses and nudiviruses, a group of insect-infecting viruses with key roles in biocontrol. We looked for signatures of selection between genomes of baculoviruses infecting a range of species and within a population of baculoviruses. Both analyses found only a few strong signatures of positive selection, primarily in replication- and transcription-associated genes and several structural protein genes. In both analyses, we detected a conserved complex of genes, including the helicase gene, showing consistently high levels of adaptive evolution, suggesting that they may be key in antagonistic coevolution to escape host suppression. These genes are integral to the baculovirus life cycle and may be good focal genes for developing baculoviruses as effective biocontrol agents or for targeting baculoviruses infecting ecologically relevant species. Recombination and complex genomes make evolution in these double-stranded DNA viruses more efficient than that in smaller RNA viruses with error-prone replication, as seen via signatures of selection in specific genes within a population of baculoviruses.

IMPORTANCE
Most viral evolutionary studies focus on RNA viruses. While these viruses cause many human and animal diseases, such studies leave us with a lesser understanding of how DNA viruses adapt to hosts and how the host responds to these pathogens. In this paper, we focus on the evolution of baculoviruses, a group of insect-infecting DNA viruses, many of which have been used in biocontrol. We find that most of the genome is under purifying selection, with only a few key genes evolving adaptively. Our results provide a glimpse into how DNA viruses differ from RNA viruses in their evolutionary dynamics and identify genes that are key to DNA virus adaptation, improving our understanding of how this group of pathogens evolves.
Deletion of Cytoplasmic Double-Stranded RNA Sensors Does Not Uncover Viral Small Interfering RNA Production in Human Cells
Authors: Schuster Susan , Tholen Lotte E. , Overheul Gijs J. , van Kuppeveld Frank J. M. , van Rij Ronald P.
Published: August 2017

The contribution of the RNA interference (RNAi) pathway in antiviral immunity in vertebrates has been widely debated. It has been proposed that RNAi possesses antiviral activity in mammalian systems but that its antiviral effect is masked by the potent antiviral interferon response in differentiated mammalian cells. In this study, we show that inactivation of the interferon response is not sufficient to uncover antiviral activity of RNAi in human epithelial cells infected with three wild-type positive-sense RNA viruses.
Hospitalisation of preterm infants with pertussis in the context of a maternal vaccination programme in England
Authors: Byrne Lisa , Campbell Helen , Andrews Nick , Ribeiro Sonia , Amirthalingam Gayatri
Published: August 2017

Aims

To assess whether preterm infants are at increased risk of pertussis infection and whether this increased following introduction of a maternal pertussis vaccination in England, while examining characteristics of infants associated with more severe disease.

Methods

Infants aged <60 days admitted between 1 April 2009 and 31 March 2016 with a pertussis diagnosis code were extracted from Hospital Episode Statistics (HES) data. HES data were reconciled with existing surveillance systems to capture maternal vaccination status where available. Cases were compared preimplementation and postimplementation of the maternal programme with respect to demography, preterm or full-term birth and coinfection. Survival analysis was undertaken to assess the impact of variables on duration of hospital stay.

Results

The proportion of hospitalised preterm infants (138/1309, 10.6%) was higher than population estimates (7.4%), increasing from 9.8% (83/847) to 12.1% (56/462) following implementation of the maternal programme. Longer duration of hospital stay was associated with prematurity, younger age, additional respiratory illnesses and mothers unvaccinated in pregnancy. Of 13 deaths, 5 were preterm (38.5%) and 11 (84.6%) were female. A larger proportion of full-term infants’ (49/188, 26.1%) mothers had been vaccinated in pregnancy than preterm infants (7/49, 14.3%), with 14.3% of mothers of full-term cases vaccinated after 35 weeks.

Conclusions

Preterm infants are over-represented in hospitalised pertussis cases and have less benefit from the maternal pertussis vaccination programme in England due to reduced opportunity for maternal vaccination.
Mothers’ knowledge and attitudes to sudden infant death syndrome risk reduction messages: results from a UK survey
Authors: Pease Anna S , Blair Peter S , Ingram Jenny , Fleming Peter J
Published: August 2017

Objective

To investigate mothers’ knowledge of reducing the risks for sudden infant death syndrome (SIDS) and attitudes towards safer sleep practices.

Design and setting

A cross-sectional survey was carried out in deprived areas of Bristol, UK. Recruitment took place in 2014 at local health visitor-led baby clinics.

Participants

Of 432 mothers approached, 400 (93%) completed the face-to-face survey. Participants with infants at ‘higher’ risk of SIDS (using an algorithm based on a previous observational study) were compared with those at ‘lower’ risk.

Main outcome measures

The survey asked participants to recall three SIDS risk reduction strategies (unprompted), and scored responses to 14 SIDS risk-related infant sleep scenarios (prompted).

Results

Overall, 48/400 (12%) mothers were classified as higher risk. Mothers in the higher risk group were less likely to breast feed (multivariate OR=3.59(95% CI 1.46 to 8.86)), less likely to be able to cite two or more unprompted correct SIDS risk reduction strategies (multivariate OR=2.05(95% CI 1.02 to 4.13)) and scored lower on prompted safer sleep scenarios overall.

Notably, only 206/400 (52%) of all mothers surveyed (33% in the higher risk group) from these deprived areas in Bristol identified infant sleep position as a risk reduction strategy for SIDS, despite 25 years of campaigns.

Conclusions

Mothers in the higher risk group were disadvantaged when it came to some aspects of knowledge of SIDS risk reduction and attitudes to safer sleep. The initial ‘Back-to Sleep’ message that dramatically reduced these deaths a generation ago needs more effective promotion for today’s generation of mothers.
Comparing glaucomatous disc change using stereo disc viewing and the MatchedFlicker programme in glaucoma experts and trainees
Authors: Schaefer Jamie L , Meyer Alissa M , Rodgers Cooper D , Rosenberg Nicole C , Leoncavallo Anthony J , Lukowski Zachary L , Greer Anthony B , Martorana Gina M , Zou Baiming , Shuster Jonathan J , Jay Katz L , Schuman Joel S , Kass Michael A , Sherwood Mark B
Published: August 2017

Background/aims

The objective of this study is to evaluate the accuracy and speed of trainees and experienced glaucoma specialists using the MatchedFlicker software against the manual examination of stereoscopic disc photographs for detecting glaucomatous optic disc change.

Methods

Three experienced glaucoma specialists, two resident ophthalmologists and one glaucoma fellow from multiple institutions independently evaluated the same 140 image pairs from 100 glaucomatous/ocular hypertensive eyes using a handheld stereo viewer and the MatchedFlicker programme. Fifty had progression to glaucoma as determined by the Ocular Hypertension Treatment Study (OHTS) Optic Disc Reading Group and endpoint committee, and 50 more were negative controls for progression with photos taken a few minutes apart. Twenty photo pairs from each of the two groups were duplicated for reviewer variability analysis. The initial viewing method was randomised and then alternated for each group of 70 image pairs. Reviewer accuracy and evaluation time for each method were measured.

Results

Evaluators averaged 8.6 s faster per image pair (26%) with the MatchedFlicker programme than with the stereo viewer (p=0.0007). Evaluators correctly identified more image pairs when using the MatchedFlicker software over the stereo viewer (p=0.0003). There was no significant difference between the expert and trainee group in speed or overall accuracy for either method. Experts were significantly more consistent than trainees with the duplicate image pairs (p=0.029). Trainees appeared more reluctant to designate eyes as showing glaucoma progression than experts.

Conclusions

Both expert glaucoma specialists and ophthalmologists in various stages of training had greater accuracy and speed with the MatchedFlicker programme than with a handheld stereoscopic viewer.
Long-term outcomes with as-needed aflibercept in diabetic macular oedema: 2-year outcomes of the ENDURANCE extension study
Authors: Wykoff Charles C , Ou William C , Khurana Rahul N , Brown David M , Lloyd Clark W , Boyer David S
Published: August 2017

Background/aims

To evaluate the efficacy and safety of individualised 2.0 mg intravitreal aflibercept retreatment for diabetic macular oedema (DME) through the fifth year of management.

Methods

This is a phase IV, 2-year, open-label extension study. Sixty patients completing the 3-year VISTA DME (Study of Intravitreal Aflibercept Injection in Patients With Diabetic Macular Edema) phase III trial enrolled in the ENDURANCE (Long-Term Efficacy and Safety of Intravitreal Aflibercept for the Treatment of DME in Subjects Who Completed the VISTA DME Trial) extension study. All patients received aflibercept in the presence of clinically relevant DME. Intervals between visits were prescribed according to disease activity. The main outcome measure was mean aflibercept injections given through 2 years.

Results

A mean of 7.7 aflibercept injections were administered through 2 years. Fifteen (25%) patients required no retreatment and 48% (n=29) of patients received five or fewer injections through 2 years. Among patients who received at least one aflibercept retreatment during ENDURANCE, the mean number of injections through 2 years was 9.5. The mean visual acuity and central retinal thickness gains achieved during VISTA DME were maintained and stable during ENDURANCE. The most notable safety signal was progression of diabetic retinopathy. Six (10%) patients converted from non-proliferative to proliferative diabetic retinopathy (PDR), and a total of eight patients experienced PDR events occurring at a mean of 387 days following the previous aflibercept treatment.

Conclusion

The need for aflibercept retreatment was substantially reduced in the fourth and fifth years of aflibercept dosing for DME following initiation of therapy in the VISTA DME trial. While vision gains achieved during the 3-year VISTA DME trial were maintained through ENDURANCE with a reduced treatment burden, clinically relevant worsening of diabetic retinopathy was observed with progression to PDR in 10% of the eyes.

Trial registration number

NCT02299336
Does use of point-of-care testing improve cost-effectiveness of the NHS Health Check programme in the primary care setting? A cost-minimisation analysis
Authors: El-Osta Austen , Woringer Maria , Pizzo Elena , Verhoef Talitha , Dickie Claire , Ni Melody Z , Huddy Jeremy R , Soljak Michael , Hanna George B , Majeed Azeem
Published: August 2017

Objective

To determine if use of point of care testing (POCT) is less costly than laboratory testing to the National Health Service (NHS) in delivering the NHS Health Check (NHSHC) programme in the primary care setting.

Design

Observational study and theoretical mathematical model with microcosting approach.

Setting

We collected data on NHSHC delivered at nine general practices (seven using POCT; two not using POCT).

Participants

We recruited nine general practices offering NHSHC and a pathology services laboratory in the same area.

Methods

We conducted mathematical modelling with permutations in the following fields: provider type (healthcare assistant or nurse), type of test performed (total cholesterol with either lab fasting glucose or HbA1c), cost of consumables and variable uptake rates, including rate of non-response to invite letter and rate of missed [did not attend (DNA)] appointments. We calculated total expected cost (TEC) per 100 invites, number of NHSHC conducted per 100 invites and costs for completed NHSHC for laboratory and POCT-based pathways. A univariate and probabilistic sensitivity analysis was conducted to account for uncertainty in the input parameters.

Main outcome measures

We collected data on cost, volume and type of pathology services performed at seven general practices using POCT and a pathology services laboratory. We collected data on response to the NHSHC invitation letter and DNA rates from two general practices.

Results

TEC of using POCT to deliver a routine NHSHC is lower than the laboratory-led pathway with savings of £29 per 100 invited patients up the point of cardiovascular disease risk score presentation. Use of POCT can deliver NHSHC in one sitting, whereas the laboratory pathway offers patients several opportunities to DNA appointment.

Conclusions

TEC of using POCT to deliver an NHSHC in the primary care setting is lower than the laboratory-led pathway. Using POCT minimises DNA rates associated with laboratory testing and enables completion of NHSHC in one sitting.
Empirical treatment of bacterial keratitis: an international survey of corneal specialists
Authors: Austin Ariana , Schallhorn Julie , Geske Mike , Mannis Mark , Lietman Tom , Rose-Nussbaumer Jennifer
Published: August 2017

Background/aims

New antibiotic agents and changing susceptibility patterns may have changed the empirical treatment of bacterial keratitis. Our objective in this study was to survey cornea specialists’ practice patterns in the initial treatment of bacterial ulcers.

Methods

This study consisted of a short online survey emailed to members of the Cornea Society listserv for an international sample of cornea specialists. Data collection began July 2014 and ended October 2014.

Results

A total of 1009 surveys were emailed, and we received 140 (14%) responses. The majority of US clinicians surveyed (n=83, 80%) chose fortified antibiotics empirically, with 55% (n=57) selecting fortified vancomycin and 16% (n=17) using fluoroquinolone alone. International respondents were twice as likely to use fluoroquinolone monotherapy (31%, n=11, p=0.07) and less likely to use fortified vancomycin (33%, n=12, p=0.03). Forty-five per cent (n=46) of US respondents reported that their initial antibiotic choice covered methicillin-resistantStaphylococcus aureus, compared with 22% (n=8) of international respondents (p<0.01). Overall, respondents who were concerned about availability of antibiotics and toxicity were 20.86 (p<0.001) and 7.48 (p<0.001) times more likely to choose fluoroquinolone monotherapy, respectively. If respondents’ primary considerations were broad spectrum coverage or antibiotic resistance they had 7.10 (p<0.001) and 12.51 (p<0.001) times the odds of using fortified vancomycin, respectively.

Conclusion

Practice patterns for the initial treatment of bacterial keratitis vary with clinicians in the USA being more likely to use fortified antibiotics versus fluoroquinolone monotherapy and more concerned with resistant organisms than their international peers.
Early prediction of hospital admission for emergency department patients: a comparison between patients younger or older than 70 years
Authors: Lucke Jacinta A , de Gelder Jelle , Clarijs Fleur , Heringhaus Christian , de Craen Anton J M , Fogteloo Anne J , Blauw Gerard J , Groot Bas de , Mooijaart Simon P
Published: August 2017

Objective

The aim of this study was to develop models that predict hospital admission to ED of patients younger and older than 70 and compare their performance.

Methods

Prediction models were derived in a retrospective observational study of all patients≥18 years old visiting the ED of a university hospital during the first 6 months of 2012. Patients were stratified into two age groups (<70 years old and ≥70 years old). Multivariable logistic regression analysis was used to identify predictors of hospital admission among factors available immediately after patient arrival to the ED. Validation of the prediction models was performed on patients presenting to the ED during the second half of the year 2012.

Results

10 807 patients were included in the derivation and 10 480 in the validation cohorts. The strongest independent predictors of hospital admission among the 8728 patients <70 years old were age, sex, triage category, mode of arrival, performance of blood tests, chief complaint, ED revisit, type of specialist, phlebotomised blood sample and all vital signs. The area under the curve (AUC) of the validation cohort for those <70 years old was 0.86 (95% CI 0.85 to 0.87). Among the 2079 patients ≥70 years, the same factors were predictive, except for gender, type of specialist and heart rate; the AUC was 0.77 (95% CI 0.75 to 0.79). The prediction models could identify a group of 10% of patients with the highest risk in whom hospital admission was predicted at ED triage, with a positive predictive value (PPV) of 71% (95% CI 68% to 74%) in younger patients and PPV of 87% (95% CI 81% to 92%) in older patients.

Conclusion

Demographic and clinical factors readily available early in the ED visit can be useful in identifying patients who are likely to be admitted to the hospital. While the model for the younger patients had a higher AUC, the model for older patients had a higher PPV in identifying the patients at highest risk for admission. Of note, heart rate was not a useful predictor in the older patients.
Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach
Authors: Choi Eunyoung , Lantz Tyler L , Vlacich Gregory , Keeley Theresa M , Samuelson Linda C , Coffey Robert J , Goldenring James R , Powell Anne E
Published: August 2017

Objective

Lrig1 is a marker of proliferative and quiescent stem cells in the skin and intestine. We examined whether Lrig1-expressing cells are long-lived gastric progenitors in gastric glands in the mouse stomach. We also investigated how the Lrig1-expressing progenitor cells contribute to the regeneration of normal gastric mucosa by lineage commitment to parietal cells after acute gastric injury in mice.

Design

We performed lineage labelling using Lrig1-CreERT2/+;R26R-YFP/+ (Lrig1/YFP) or R26R-LacZ/+ (Lrig1/LacZ) mice to examine whether the Lrig1-YFP-marked cells are gastric progenitor cells. We studied whether Lrig1-YFP-marked cells give rise to normal gastric lineage cells in damaged mucosa using Lrig1/YFP mice after treatment with DMP-777 to induce acute injury. We also studied Lrig1-CreERT2/CreERT2 (Lrig1 knockout) mice to examine whether the Lrig1 protein is required for regeneration of gastric corpus mucosa after acute injury.

Results

Lrig1-YFP-marked cells give rise to gastric lineage epithelial cells both in the gastric corpus and antrum, in contrast to published results that Lgr5 only marks progenitor cells within the gastric antrum. Lrig1-YFP-marked cells contribute to replacement of damaged gastric oxyntic glands during the recovery phase after acute oxyntic atrophy in the gastric corpus. Lrig1 null mice recovered normally from acute gastric mucosal injury indicating that Lrig1 protein is not required for lineage differentiation. Lrig1+ isthmal progenitor cells did not contribute to transdifferentiating chief cell lineages after acute oxyntic atrophy.

Conclusions

Lrig1 marks gastric corpus epithelial progenitor cells capable of repopulating the damaged oxyntic mucosa by differentiating into normal gastric lineage cells in mouse stomach.
Clinical features and prognosis of patients with isolated severe aortic stenosis and valve area less than 1.0 cm2
Authors: Mehrotra Praveen , Jansen Katrijn , Tan Timothy C , Flynn Aidan , Hung Judy W
Published: August 2017

Objective

Current guidelines define severe aortic stenosis (AS) as an aortic valve area (AVA)≤1.0 cm2, but some authors have suggested that the AVA cut-off be decreased to 0.8 cm2. The aim of this study was, therefore, to better describe the clinical features and prognosis of patients with an AVA of 0.8–0.99 cm2.

Methods

Patients with isolated, severe AS and ejection fraction ≥55% with an AVA of 0.8–0.99 cm2 (n=105) were compared with those with an AVA<0.8 cm2 (n=155) and 1.0–1.3 cm2 (n=81). The endpoint of this study was a combination of death from any cause or aortic valve replacement at or before 3 years.

Results

Patients with an AVA of 0.8–0.99 cm2 group comprised predominantly normal-flow, low-gradient (NFLG) AS, while high gradients and low flow were more often observed with an AVA<0.8 cm2. The frequency of symptoms was not significantly different between an AVA of 0.8–0.99 cm2 and 1.0–1.3 cm2. The combined endpoint was achieved in 71%, 52% and 21% of patients with an AVA of 0.8 cm2, 0.8–0.99 cm2and 1.0–1.3 cm2, respectively (p<0.001). Among patients with an AVA of 0.8–0.99 cm2, NFLG AS was associated with a lower hazard (HR=0.40, 95% CI 0.23 to 0.68, p=0.001) of achieving the combined endpoint with outcomes similar to moderate AS in the first 1.5 years of follow-up. Patients with high-gradient or low-flow AS with an AVA of 0.8–0.99 cm2 had outcomes similar to those with an AVA<0.8 cm2. The sensitivity for the combined endpoint was 61% for an AVA cut-off of 0.8 cm2 and 91% for a cut-off of 1.0 cm2.

Conclusions

The outcomes of patients with AS with an AVA of 0.8–0.99 cm2 are variable and are more precisely defined by flow-gradient status. Our findings support the current AVA cut-off of 1.0 cm2.
Influence of arterial stiffness on cardiovascular outcome in patients without high blood pressure
Authors: Ichikawa Keishi , Sakuragi Satoru , Nishihara Takahiro , Tsuji Masahiro , Mori Atsushi , Yokohama Fumi , Wada Tadashi , Hasegawa Daiji , Kawamoto Kenji , Tanakaya Machiko , Katayama Yusuke , Ito Hiroshi
Published: August 2017

Objective

Although blood pressure (BP) is a major determinant of arterial stiffness, whether high pulse wave velocity (PWV) adversely influences cardiac parameters and cardiovascular (CV) outcome in patients without high BP remains unclear.

Methods

Outpatients without high BP (n=320), defined as systolic BP ≥140 mm Hg, were enrolled in this retrospective study. At baseline, all patients underwent echocardiography and multidetector CT to determine the coronary artery calcification (CAC) score. Arterial stiffness was assessed based on brachial-ankle PWV (baPWV), from which patients were classified into two groups: those with high (≥18 m/s, n=89) and low baPWV (<18 m/s, n=231). Cardiac parameters and CV event incidence during the follow-up period were compared between these groups.

Results

In multivariable linear regression analysis, baPWV was significantly associated with CAC score and serum N-terminal pro-brain natriuretic peptide hormone level, after adjustment for confounding factors. In multivariable logistic regression analysis, baPWV ≥18 m/s was significantly associated with CAC score ≥400 (OR 2.466, 95% CI 1.012 to 6.009, p=0.0471). Kaplan-Meier analysis showed that the high-baPWV group experienced more CV events during the 575 days of follow-up (20% vs 6%, p=0.0003).

Conclusions

High baPWV was associated with greater CAC and a high risk of a future CV event, especially coronary artery disease, even in patients without high BP.
Fetal-type gastrointestinal adenocarcinoma: a morphologically distinct entity with unfavourable prognosis
Authors: Arora Kshitij , Bal Munita , Shih Angela , Moy Andrea , Zukerberg Lawerence , Brown Ian , Liu Xiuli , Kelly Paul , Oliva Esther , Mullen John , Ahn Soomin , Kim Kyoung-Mee , Deshpande Vikram
Published: August 2017

Aims

This multi-institutional study and a re-evaluation of the TCGA cohort explores the morphological spectrum, genetics and outcome of GI (gastrointestinal) hepatoid tumours, tumours expressing alpha-fetoprotein (AFP) and fetal-type (FT) GI adenocarcinomas.

Methods

44 tumours with evidence of hepatocellular differentiation were evaluated for morphology as well as by immunohistochemistry for AFP, HepPar1, glypican-3 and arginase-1 and by in situ hybridisation for albumin. Three categories were defined: type I (hepatoid: morphological evidence of hepatocellular differentiation), type II (FT GI adenocarcinoma: tubular profiles and subnuclear vacuolisation, resembling fetal intestine) and type III: positive for at least two hepatocyte-specific markers but lacking morphological evidence of hepatocellular differentiation. GI adenocarcinomas in the TCGA cohort were also evaluated (n=829).

Results

18 cases were classified as type I, 19 as FT GI adenocarcinomas and 7 as type III (resembling conventional gastrointestinal carcinomas). Serum AFP was elevated in 92% of cases. 93% of tumours were positive for glypican-3, 90% for albumin and 89% for AFP. Arginase-1 was restricted to 35% of type 1 tumours. TCGA gastric tumours with elevated AFP expression showed morphological features of FT GI adenocarcinoma (70%) and were exclusively MSI stable. TCGA gastric adenocarcinomas with high AFP expression showed inferior survival on univariate and multivariate analysis.

Conclusions

FT GI adenocarcinomas show a distinctive morphological and immunohistochemical profile. Gastric adenocarcinomas with elevated expression of AFP morphologically resemble FT GI adenocarcinomas, demonstrate aggressive behaviour, independent of grade and stage, and a distinct genetic profile.
Propofol attenuates BV2 microglia inflammation via NMDA receptor inhibition
Authors: Wu Qichao , Zhao Yanjun , Chen Xiangyuan , Zhu Minmin , Miao Changhong
Published: August 2017

Activated microglia, involved in the occurrence and improvement of sepsis-associated encephalopathy, can induce the expression of pro-inflammatory cytokines and pro-inflammatory enzymes, resulting in inflammation-mediated neuronal cell death. It was reported that propofol could inhibit lipopolysaccharide (LPS) induced pro-inflammatory cytokine and pro-inflammatory enzyme expression in BV2 and primary microglial cells. However, the underlying mechanism is not well known. In the present study, we investigated whether and how propofol inhibited LPS-induced the expression of pro-inflammatory cytokines and pro-inflammatory enzymes in BV2 cells. LPS induced pro-inflammatory cytokine and pro-inflammatory enzyme expression, NF-κB, extracellular regulated kinase 1/2 (ERK), calcium (Ca2+)/calmodulin-dependent protein kinase II (CaMK II) phosphorylation, and BV2 cell Ca2+ accumulation. Propofol could reverse these effects induced by LPS. MK801, an inhibitor of the NMDA receptor, could attenuate LPS-induced Ca2+ accumulation, the expression of pro-inflammatory cytokines and pro-inflammatory enzymes, and phosphorylation of NF-κB, ERK, and CaMK II, which was similar to propofol. Moreover, these effects of propofol could be counteracted by rapastinel, an activator of the NMDA receptor. The present study suggested that propofol, via inhibiting the NMDA receptor, attenuating Ca2+ accumulation, and inhibiting CaMK II, ERK1/2, and NF-κB phosphorylation, down-regulated LPS-induced pro-inflammatory cytokine and pro-inflammatory enzyme expression.
Spiking Neural P Systems with Communication on Request
Authors: Pan Linqiang , Păun Gheorghe , Zhang Gexiang , Neri Ferrante
Published: August 2017

Spiking Neural [Formula: see text] Systems are Neural System models characterized by the fact that each neuron mimics a biological cell and the communication between neurons is based on spikes. In the Spiking Neural [Formula: see text] systems investigated so far, the application of evolution rules depends on the contents of a neuron (checked by means of a regular expression). In these [Formula: see text] systems, a specified number of spikes are consumed and a specified number of spikes are produced, and then sent to each of the neurons linked by a synapse to the evolving neuron.

[Formula: see text]In the present work, a novel communication strategy among neurons of Spiking Neural [Formula: see text] Systems is proposed. In the resulting models, called Spiking Neural [Formula: see text] Systems with Communication on Request, the spikes are requested from neighboring neurons, depending on the contents of the neuron (still checked by means of a regular expression). Unlike the traditional Spiking Neural [Formula: see text] systems, no spikes are consumed or created: the spikes are only moved along synapses and replicated (when two or more neurons request the contents of the same neuron).

[Formula: see text]The Spiking Neural [Formula: see text] Systems with Communication on Request are proved to be computationally universal, that is, equivalent with Turing machines as long as two types of spikes are used. Following this work, further research questions are listed to be open problems.
Stable maps of genus zero in the space of stable vector bundles on a curve
Authors: Chung Kiryong , Lee Sanghyeon
Published: August 2017

Let [Formula: see text] be a smooth projective curve with genus [Formula: see text]. Let [Formula: see text] be the moduli space of stable rank two vector bundles on [Formula: see text] with a fixed determinant [Formula: see text] for [Formula: see text]. In this paper, as a generalization of Kiem and Castravet’s works, we study the stable maps in [Formula: see text] with genus [Formula: see text] and degree [Formula: see text]. Let [Formula: see text] be a natural closed subvariety of [Formula: see text] which parametrizes stable vector bundles with a fixed subbundle [Formula: see text] for a line bundle [Formula: see text] on [Formula: see text]. We describe the stable map space [Formula: see text]. It turns out that the space [Formula: see text] consists of two irreducible components. One of them parameterizes smooth rational cubic curves and the other parameterizes the union of line and smooth conics.
The impact of intelligent vehicles on a two-route system with a work zone
Authors: Xiao Wen , Chen Yu-Guang , Yang Ya-Ping , Yang Chao
Published: August 2017

By the cellular automaton (CA) model, traffic behaviors of an intelligent two-route system with a work zone are studied. In the model, the two-route system consists of a double-lane (DL) and a single-lane (SL). Supposing a work zone exists on DL, a big traffic jam will be formed. For improving the system traffic flow, an intelligent vehicle (IV) which can change driving strategy on the basis of received real-time information has been introduced into the model. The simulation results indicate that the traffic condition can be improved and the area of the traffic jam can be reduced effectively if there are enough IVs. Moreover, if all of the vehicles are IVs, the traffic jam may disappear, and the system will be in free flow state.
Extremely low frequency band gaps of beam-like inertial amplification metamaterials
Authors: Hou Mingming , Wu Jiu Hui , Cao Songhua , Guan Dong , Zhu Yanwei
Published: August 2017

In this paper, extremely low frequency band gaps of beam-like inertial amplification metamaterials are investigated based on local resonance theory. Inertial amplification mechanism is proposed to obtain extremely low frequency band gaps by altering geometry parameters of the beam-like structures rather than modulating material properties, which allow first lower band gap (BG) to be attained easily compared to traditional local resonance structures. Band structures, frequency response functions (FRFs) plots and vibration modes of the beam-like structures are calculated and analyzed by employing finite element method. Numerical results show that first BG of the structure ranges from 23 Hz to 21 Hz. FRFs are in accordance with the dispersion relationship. It is found that interaction between inertial amplification and traveling wave modes in the proposed structure are responsible for formation of the first BG. This type of beam-like inertial amplification metamaterials has many potential applications in the field of low frequency vibration and noise reduction.
Classification of book representations of K6
Authors: Rowland Dana
Published: August 2017

A book representation of a graph is a particular way of embedding a graph in three-dimensional space so that the vertices lie on a circle and the edges are chords on disjoint topological disks. We describe a set of operations on book representations that preserves ambient isotopy, and apply these operations to [Formula: see text], the complete graph with six vertices. We prove there are exactly 59 distinct book representations for [Formula: see text], and we identify the number and type of knotted and linked cycles in each representation. We show that book representations of [Formula: see text] contain between one and seven links, and up to nine knotted cycles. Furthermore, all links and cycles in a book representation of [Formula: see text] have crossing number at most four.
A possible analogy between the dynamics of a skydiver and a scalar field: Cosmological consequences
Authors: Costa F. E. M.
Published: August 2017

The cosmological consequences of a slow-rolling scalar field with constant kinetic term in analogy to the vertical movement of a skydiver after reaching terminal velocity are investigated. In this approach, the scalar field potential is given by a quadratic function of the field. This model provides solutions in which the universe was dominated in the past by a mixture of baryons and dark matter, is currently accelerating (as indicated by type Ia supernovae data), but will be followed by a contraction phase. The theoretical predictions of this model are consistent with current observations, therefore, a terminal scalar field is a viable candidate to dark energy.
Improved Quality View Selection for Analytical Query Performance Enhancement Using Particle Swarm Optimization
Authors: Kumar Amit , Vijay Kumar T. V.
Published: August 2017

A data warehouse, which is a central repository of the detailed historical data of an enterprise, is designed primarily for supporting high-volume analytical processing in order to support strategic decision-making. Queries for such decision-making are exploratory, long and intricate in nature and involve the summarization and aggregation of data. Furthermore, the rapidly growing volume of data warehouses makes the response times of queries substantially large. The query response times need to be reduced in order to reduce delays in decision-making. Materializing an appropriate subset of views has been found to be an effective alternative for achieving acceptable response times for analytical queries. This problem, being an NP-Complete problem, can be addressed using swarm intelligence techniques. One such technique, i.e., the similarity interaction operator-based particle swarm optimization (SIPSO), has been used to address this problem. Accordingly, a SIPSO-based view selection algorithm (SIPSOVSA), which selects the Top-[Formula: see text] views from a multidimensional lattice, has been proposed in this paper. Experimental comparison with the most fundamental view selection algorithm shows that the former is able to select relatively better quality Top-[Formula: see text] views for materialization. As a result, the views selected using SIPSOVSA improve the performance of analytical queries that lead to greater efficiency in decision-making.
System Risk Importance Analysis Using Bayesian Networks
Authors: Noroozian Ali , Kazemzadeh Reza Baradaran , Niaki Seyed Taghi Akhavan , Zio Enrico
Published: August 2017

Importance measures (IMs) are used for risk-informed decision making in system operations, safety, and maintenance. Traditionally, they are computed within fault tree (FT) analysis. Although FT analysis is a powerful tool to study the reliability and structural characteristics of systems, Bayesian networks (BNs) have shown explicit advantages in modeling and analytical capabilities. In this paper, the traditional definitions of IMs are extended to BNs in order to have more capability in terms of system risk modeling and analysis. Implementation results on a case study illustrate the capability of finding the most important components in a system.
Quasilinear parabolic problem with variable exponent: Qualitative analysis and stabilization
Authors: Giacomoni Jacques , Rădulescu Vicenţiu , Warnault Guillaume
Published: August 2017

We discuss the existence and uniqueness of the weak solution of the following nonlinear parabolic problem: [Formula: see text] which involves a quasilinear elliptic operator of Leray–Lions type with variable exponents. Next, we discuss the global behavior of solutions and in particular the convergence to a stationary solution as [Formula: see text].
An Ambrosetti–Prodi-type problem for the (p,q)-Laplacian operator
Authors: Junges Miotto Taísa , Miotto Márcio Luís
Published: August 2017

This work has objective to obtain results of existence and multiplicity of solutions for an Ambrosetti–Prodi-type problem for the [Formula: see text] operator. Moreover, it was proved a continuity result for the parameter which limits the existence of solutions in relation of the parameter [Formula: see text].
Bounded solutions for general time interval BSDEs with quadratic growth coefficients and stochastic conditions
Authors: Luo Huan-Huan , Fan Sheng-Jun
Published: August 2017

This paper deals with bounded solutions for general time interval one-dimensional backward stochastic differential equations (BSDEs for short) with quadratic growth coefficients and stochastic conditions. Several general results of existence, uniqueness, stability and comparison for the bounded solutions are put forward and established, which improve considerably some existing works, even though for the case of finite time interval. Some new ideas are also developed to establish these results.
Automorphism groups and invariant theory on ℙN
Authors: de Faria João Alberto , Hutz Benjamin
Published: August 2017

Let [Formula: see text] be a field and [Formula: see text] a morphism. There is a natural conjugation action on the space of such morphisms by elements of the projective linear group [Formula: see text]. The group of automorphisms, or stabilizer group, of a given [Formula: see text] for this action is known to be a finite group. In this paper, we apply methods of invariant theory to automorphism groups by addressing two mainly computational problems. First, given a finite subgroup of [Formula: see text], determine endomorphisms of [Formula: see text] with that group as a subgroup of its automorphism group. In particular, we show that every finite subgroup occurs infinitely often and discuss some associated rationality problems. Inversely, given an endomorphism, determine its automorphism group. In particular, we extend the Faber–Manes–Viray fixed-point algorithm for [Formula: see text] to endomorphisms of [Formula: see text]. A key component is an explicit bound on the size of the automorphism group depending on the degree of the endomorphism.
Classification of a modified de Sitter metric by variational symmetries and conservation laws
Authors: Beesham A. , Gadjagboui B. B. I. , Kara A. H.
Published: August 2017

Variational symmetries and conservation laws of a modified de Sitter metric are classified. The resulting Noether symmetries in each case are compared with conservation laws given by Killing vectors.