bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nectin-4-Dependent Measles Virus Spread to the Cynomolgus Monkey Tracheal Epithelium: Role of Infected Immune Cells Infiltrating the Lamina Propria
Authors: Frenzke Marie , Sawatsky Bevan , Wong Xiao X. , Delpeut Sébastien , Mateo Mathieu , Cattaneo Roberto , von Messling Veronika 
Published: December 2012

ABSTRACT

After the contagion measles virus (MV) crosses the respiratory epithelium within myeloid cells that express the primary receptor signaling lymphocytic activation molecule (SLAM), it replicates briskly in SLAM-expressing cells in lymphatic organs. Later, the infection spreads to epithelia expressing nectin-4, an adherens junction protein expressed preferentially in the trachea, but how it gets there is not understood. To characterize the mechanisms of spread, we infected groups of 5 or 6 cynomolgus monkeys (
Macaca fascicularis
) with either a wild-type MV or its “N4-blind” derivative, which is unable to enter nectin-4-expressing cells because of the targeted mutation of two hemagglutinin residues. As expected, both viruses caused similar levels of immunosuppression, as monitored by reductions in white blood cell counts and lymphocyte proliferation activity. However, monkeys infected with the N4-blind MV cleared infection more rapidly. Wild-type virus-infected monkeys secreted virus, while marginal virus titers were detected in tracheal lavage fluid cells of N4-blind MV-infected hosts. Analyses of tracheal rings obtained at necropsy (day 12) documented widespread infection of individual cells or small cell clusters in the subepithelial lamina propria of monkeys infected with either virus. However, only wild-type MV spread to the epithelium, forming numerous infectious centers comprised of many contiguous columnar cells. Infected CD11c
+
myeloid (macrophage or dendritic) cells were frequently observed in the lamina propria below epithelial infectious centers. Thus, MV may use myeloid cells as vehicles not only immediately after contagion but also to infect epithelia of tissues expressing nectin-4, including the trachea.
Prion Propagation and Toxicity Occur
In Vitro
with Two-Phase Kinetics Specific to Strain and Neuronal Type
Authors: Hannaoui Samia , Maatouk Layal , Privat Nicolas , Levavasseur Etienne , Faucheux Baptiste A. , Haïk Stéphane 
Published: December 2012

ABSTRACT

Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative disorders that occur in humans and animals. The neuropathological hallmarks of TSEs are spongiosis, glial proliferation, and neuronal loss. The only known specific molecular marker of TSEs is the abnormal isoform (PrP
Sc
) of the host-encoded prion protein (PrP
C
), which accumulates in the brain of infected subjects and forms infectious prion particles. Although this transmissible agent lacks a specific nucleic acid component, several prion strains have been isolated. Prion strains are characterized by differences in disease outcome, PrP
Sc
distribution patterns, and brain lesion profiles at the terminal stage of the disease. The molecular factors and cellular mechanisms involved in strain-specific neuronal tropism and toxicity remain largely unknown. Currently, no cellular model exists to facilitate
in vitro
studies of these processes. A few cultured cell lines that maintain persistent scrapie infections have been developed, but only two of them have shown the cytotoxic effects associated with prion propagation. In this study, we have developed primary neuronal cultures to assess
in vitro
neuronal tropism and toxicity of different prion strains (scrapie strains 139A, ME7, and 22L). We have tested primary neuronal cultures enriched in cerebellar granular, striatal, or cortical neurons. Our results showed that (i) a strain-specific neuronal tropism operated
in vitro
; (ii) the cytotoxic effect varied among strains and neuronal cell types; (iii) prion propagation and toxicity occurred in two kinetic phases, a replicative phase followed by a toxic phase; and (iv) neurotoxicity peaked when abnormal PrP accumulation reached a plateau.
The Highly Conserved Layer-3 Component of the HIV-1 gp120 Inner Domain Is Critical for CD4-Required Conformational Transitions
Authors: Désormeaux Anik , Coutu Mathieu , Medjahed Halima , Pacheco Beatriz , Herschhorn Alon , Gu Christopher , Xiang Shi-Hua , Mao Youdong , Sodroski Joseph , Finzi Andrés 
Published: December 2012

ABSTRACT
The trimeric envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) mediates virus entry into host cells. CD4 engagement with the gp120 exterior envelope glycoprotein subunit represents the first step during HIV-1 entry. CD4-induced conformational changes in the gp120 inner domain involve three potentially flexible topological layers (layers 1, 2, and 3). Structural rearrangements between layer 1 and layer 2 have been shown to facilitate the transition of the envelope glycoprotein trimer from the unliganded to the CD4-bound state and to stabilize gp120-CD4 interaction. However, our understanding of CD4-induced conformational changes in the gp120 inner domain remains incomplete. Here, we report that a highly conserved element of the gp120 inner domain, layer 3, plays a pivot-like role in these allosteric changes. In the unliganded state, layer 3 modulates the association of gp120 with the Env trimer, probably by influencing the relationship of the gp120 inner and outer domains. Importantly, layer 3 governs the efficiency of the initial gp120 interaction with CD4, a function that can also be fulfilled by filling the Phe43 cavity. This work defines the functional importance of layer 3 and completes a picture detailing the role of the gp120 inner domain in CD4-induced conformational transitions in the HIV-1 Env trimer.
Impact of prior probabilities of MRSA as an infectious agent on the accuracy of the emerging molecular diagnostic tests: a model simulation
Authors: Zilberberg Marya D , Shorr Andrew F 
Published: December 2012

ObjectivesTraditional microbiology identification takes 48–72 h to complete. This lag forces clinicians to rely on broad-spectrum empiric coverage. To address this gap, manufacturers are developing rapid molecular diagnostics (RMD). We hypothesised that RMD's accuracy is more dependent upon population risk of harbouring the culprit pathogen than to their sensitivity and specificity.DesignA mathematical model.Setting and participantsWe used the range of risks (5–50%) for methicillin-resistantStaphylococcus aureus(MRSA) among patients hospitalised with complicated skin and skin structure infections (cSSSI), pneumonia or sepsis.Main outcome measuresWe modelled the impact of changing a test's characteristics on its positive (PPV) and negative (NPV) predictive values, and hence the risk of overtreatment or undertreatment, within strata of an organism's population prevalence. MRSA diagnostics provided assumptions for the test sensitivity and specificity (95–99%). Scenarios with low sensitivity and specificity (90%), and best-case and worst-case scenarios normalised to the annual universe of populations of interest, were examined.ResultsWith a low prevalence (5%) and high test specificity, the PPV was 84%. Conversely, with 50% prevalence and 95% test specificity the PPV rose to ≥95%. Even when the test's specificity and sensitivity were both 90%, in a high-risk population both PPV and NPV were ∼90%. In the worst-case scenario, 150 000 patients with cSSSI, pneumonia and sepsis annually were at risk for inappropriate treatment, 91% of these at risk for over-treatment. In the best-case scenario, 81% of 18 000 patients at risk for inappropriate coverage were subject to overtreatment.ConclusionsAlthough promising for limiting exposure to excessive antimicrobial coverage, RMDs alone will not solve the issue of inappropriate, and particularly overtreatment. Increasing pretest probability as a strategy to minimise antibiotic abuse results in more accurate patient classification than does developing a test with near-perfect characteristics. The healthcare community must build robust evidence and information technology infrastructure to guide appropriate use of such testing.
Home-based cardiac rehabilitation is an attractive alternative to no cardiac rehabilitation for elderly patients with coronary heart disease: results from a randomised clinical trial
Authors: Oerkild Bodil , Frederiksen Marianne , Hansen Jorgen Fischer , Prescott Eva 
Published: December 2012

ObjectiveTo compare home-based cardiac rehabilitation (CR) with usual care (control group with no rehabilitation) in elderly patients who declined participation in centre-based CR.DesignRandomised clinical trial with 12 months follow-up and mortality data after 5.5 years (mean follow-up 4½ years).SettingRehabilitation unit, Department of Cardiology, Copenhagen, Denmark.ParticipantsElderly patients ≥65 years with coronary heart disease.InterventionA physiotherapist made home visits in order to develop an individualised exercise programme that could be performed at home and surrounding outdoor area. Risk factor intervention, medical adjustment, physical and psychological assessments were offered at baseline and after 3, 6 and 12 months.Main outcome measurementsThe primary outcome was 6 min walk test (6MWT). Secondary outcomes were blood pressure, body composition, cholesterol profile, cessation of smoking, health-related quality of life (HRQoL), anxiety and depression.Results40 patients participated. The study population was characterised by high age (median age 77 years, range 65–92 years) and high level of comorbidity. Patients receiving home-based CR had a significant increase in the primary outcome 6MWT of 33.5 m (95% CI: 6.2 to 60.8, p=0.02) at 3 months, whereas the usual care group did not significantly improve, but with no significant differences between the groups. At 12 months follow-up, there was a decline in 6MWT in both groups; −55.2 m (95% CI: 18.7 to 91.7, p<0.01) in the home group and −52.1 m (95% CI: −3.0 to 107.1, p=0.06) in the usual care group. There were no significant differences in blood pressure, body composition, cholesterol profile, cessation of smoking or HRQoL after 3, 6 and 12 months follow-up.ConclusionsParticipation in home-based CR improved exercise capacity among elderly patients with coronary heart disease, but there was no significant difference between the home intervention and the control group. In addition, no significant difference was found in the secondary outcomes. When intervention ceased, the initial increase in exercise capacity was rapidly lost.
Family meals can help children reach their 5 A Day: a cross-sectional survey of children's dietary intake from London primary schools
Authors: Christian Meaghan S , Evans Charlotte E L , Hancock Neil , Nykjaer Camilla , Cade Janet E 
Published: December 2012

BackgroundThis study aims to explore how the home food environment and parental attitudes and values affect children's fruit and vegetable (F&V) intake.MethodsThe sample consists of 2383 children with a mean age of 8.3 years (95% CI 8.2 to 8.3) attending 52 primary schools in London. These children are taking part in two randomised controlled trials to evaluate a school gardening programme. Diet was assessed using a validated 24-h food tick list, the Child And Diet Evaluation Tool (CADET).ResultsThe CADET tool found that children consumed on average 293 g F&V (95% CI 287 to 303) per day. Clustered (by school) multilevel regression models with total F&V as the primary outcome were conducted to explore how the home environment affects children's F&V intake. Children of families who reported ‘always’ eating a family meal together at a table had 125 g (95% CI 92 to 157; p=<0.001) more F&V than families who never ate a meal together. Daily consumption of F&V by parents was associated with higher F&V (88 g, 95% CI 37 to 138) intake in children compared with rarely/never consumption of F&V by parents. Cutting up fruit and vegetables for children was associated with higher consumption. Families who reported always cutting up F&V for their children had 44 g (95% CI 18 to 71) more F&V than families who never cut up F&V.ConclusionsThis study identified that cutting up F&V and family consumption of F&V facilitates children's intake. Eating a family meal together regularly could increase children's F&V intake and help them achieve the recommended intake.Trial registrationISRCTN11396528.
Prevalence of antibodies to prothrombin in solid phase (aPT) and to phosphatidylserine-prothrombin complex (aPS/PT) in patients with and without lupus anticoagulant
Authors: Sciascia Savino , Murru Veronica , Garcia-Fernandez Cesar , Sanna Giovanni , Khamashta Munther , Bertolaccini Maria Laura 
Published: December 2012

SummaryAntibodies to prothrombin in solid phase (aPT) and those to phosphatidiyserine- prothrombin complex (aPS/PT) have been suggested to strongly correlate with the presence of lupus anticoagulant (LA). As their clinical diagnostic value and true relationship with the LA remains elusive, we designed this study to evaluate the prevalence and significance of aPT and aPS/PT in a large cohort of patients with and without LA. Samples from 257 patients were included. aPT and aPS/PT were tested by ELISA. LA was tested as per the current criteria from the ISTH Subcommittee on LA-Phospholipid-dependent antibodies. aPS/PT and aPT were found in 51% and 32% of LA-positive (LA+ve) patients and in 22% and 28% of LA-negative (LA-ve) patients, respectively. Thrombosis, particularly venous thrombosis was associated with IgG aPT in the LA+ve group (p=0.0006) and in the LA-ve group (p=0.017). Antibodies to phosphatidylserine-prothrombin, either IgG and IgM were associated with thrombosis in general (p=0.0003) in particularly with venous thrombosis in the LA+ve group (p<0.0001 for IgG and p=0.025 for IgM; respectively) and the LA-ve group (p=0.028, 0.02 and 0.001, respectively). Further multivariate logistic regression analysis showed that LA and of IgG and/or IgM aPS/PT were independent risk factors for thrombosis and pregnancy loss. In conclusion, aPS/PT, but not aPT, are more frequently found in patients with LA. Their association with thrombosis seems to be independent of the presence of LA.
Evaluating the clinical usefulness of platelet function testing: Considerations for the proper application and interpretation of performance measures
Authors: Price Matthew J. , Parise Helen , Gurbel Paul A. , Dahlen Jeffrey R. 
Published: December 2012

SummaryVarious diagnostic and prognostic performance measures have been used to describe the clinical usefulness of platelet function testing in the evaluation and management of patients taking P2Y12 inhibitors, which reduce the risk for thrombosis due to their action on the platelet P2Y12 receptor. Platelet function tests are used to confirm the presence of an antiplatelet effect of a P2Y12 inhibitor, and confirmation that the pharmacodynamic effect is associated with a reduction in the rate of thrombosis. Despite this clear association, enthusiasm for the clinical usefulness of platelet function testing has been tempered based on observed sensitivity, specificity, and positive predictive value for the detection of future thrombotic events. However, evaluating the prognostic utility of a test based on diagnostic performance indicators is not appropriate because prognostic tests are not used to diagnose which patients will have events; instead, they are used to assist in risk stratification. Therefore, when evaluating the usefulness of platelet function testing, diagnostic performance measures such as sensitivity, specificity, and predictive values should focus on diagnostic performance in identifying a pharmacodynamic effect, and prognostic performance should be evaluated using prognostic performance measures such as hazard ratios and net reclassification improvement, which are comparable to other well-established risk factors for cardiovascular events.
Percutaneous Hemodynamic Support With Impella 2.5 During Scar-Related Ventricular Tachycardia Ablation (PERMIT 1)
Authors: Miller Marc A. , Dukkipati Srinivas R. , Chinitz Jason S. , Koruth Jacob S. , Mittnacht Alexander J. , Napolitano Craig , d’Avila Andre , Reddy Vivek Y. 
Published: December 2012

Background—
Percutaneous left ventricular assist devices (pLVADs) are increasingly being used to facilitate ablation of unstable ventricular tachycardia (VT), but the safety profile and hemodynamic benefits of these devices have not been described in a systematic, prospective manner.

Methods and Results—

Twenty patients with scar VT underwent ablation with a pLVAD. Neuromonitoring using cerebral oximetry was performed to evaluate a cerebral desaturation threshold to guide the duration of activation/entrainment mapping. The efficacy of pLVAD support was tested in a controlled manner with simulated VT. Complete procedural success was achieved in 50% (n=8) of patients, who were initially inducible for sustained VT, and partial procedural success in 37% (n=6). Using a cerebral desaturation level of 55% as a lower safety limit to guide the duration of sustained VT, 3 patients (15%) developed mild acute kidney injury (all resolved), and 1 (5%) patient developed mild cognitive dysfunction. During fast simulated VT (300 ms), cerebral desaturation to ≤55% occurred in more than half (53%) of patients tested without pLVAD support, compared with only 5% with full pLVAD support (
P
=0.003).

Conclusions—
In a consecutive series of patients with severe left ventricular dysfunction, pLVAD-supported scar VT ablation was safe and feasible. During fast simulated VT, a miniaturized axial flow pump imparted a more favorable hemodynamic profile compared with pharmacological agents alone. Cerebral oximetry is a complimentary monitoring modality during scar VT ablation, and avoidance of cerebral desaturations below a threshold of 55% may safely guide the duration of mapping during unstable VT.
Early and nonreversible decrease of CD161++/MAIT cells in HIV infection
Authors: Cosgrove Cormac , Ussher James E. , Rauch Andri , Gärtner Kathleen , Kurioka Ayako , Hühn Michael H. , Adelmann Krista , Kang Yu-Hoi , Fergusson Joannah R. , Simmonds Peter , Goulder Philip , Hansen Ted H. , Fox Julie , Günthard Huldrych F. , Khanna Nina , Powrie Fiona , Steel Alan , Gazzard Brian , Phillips Rodney E. , Frater John , Uhlig Holm , Klenerman Paul 
Published: December 2012

Key PointsThe frequency of CD161++ MAIT cells is dramatically decreased in the blood of HIV-infected patients, and they are nonrecoverable with HAART. Gut sequestration and apoptosis in response to bacterial signals may, amongst others, be mechanisms that contribute to this.
Forssman expression on human erythrocytes: biochemical and genetic evidence of a new histo-blood group system
Authors: Svensson Lola , Hult Annika K. , Stamps Robert , Ångström Jonas , Teneberg Susann , Storry Jill R. , Jørgensen René , Rydberg Lennart , Henry Stephen M. , Olsson Martin L. 
Published: December 2012

Key PointsA new histo-blood group system was discovered, based on the identification of Forssman glycolipid antigen on human red blood cells. A newly described polymorphism in the GBGT1 gene activates the encoded enzyme to synthesize Forssman antigen.
MicroRNAs and essential components of the microRNA processing machinery are not encoded in the genome of the ctenophore Mnemiopsis leidyi
Authors: Maxwell Evan K , Ryan Joseph F , Schnitzler Christine E , Browne William E , Baxevanis Andreas D 
Published: December 2012

Abstract

Background
MicroRNAs play a vital role in the regulation of gene expression and have been identified in every animal with a sequenced genome examined thus far, except for the placozoan Trichoplax. The genomic repertoires of metazoan microRNAs have become increasingly endorsed as phylogenetic characters and drivers of biological complexity.

Results
In this study, we report the first investigation of microRNAs in a species from the phylum Ctenophora. We use short RNA sequencing and the assembled genome of the lobate ctenophore Mnemiopsis leidyi to show that this species appears to lack any recognizable microRNAs, as well as the nuclear proteins Drosha and Pasha, which are critical to canonical microRNA biogenesis. This finding represents the first reported case of a metazoan lacking a Drosha protein.

Conclusions
Recent phylogenomic analyses suggest that Mnemiopsis may be the earliest branching metazoan lineage. If this is true, then the origins of canonical microRNA biogenesis and microRNA-mediated gene regulation may postdate the last common metazoan ancestor. Alternatively, canonical microRNA functionality may have been lost independently in the lineages leading to both Mnemiopsis and the placozoan Trichoplax, suggesting that microRNA functionality was not critical until much later in metazoan evolution.
Transcriptome analysis of Sacha Inchi (Plukenetia volubilis L.) seeds at two developmental stages
Authors: Wang Xiaojuan , Xu Ronghua , Wang Ruling , Liu Aizhong 
Published: December 2012

Abstract

Background
Sacha Inchi (Plukenetia volubilis L., Euphorbiaceae) is a potential oilseed crop because the seeds of this plant are rich in unsaturated fatty acids (FAs). In particular, the fatty acid composition of its seed oil differs markedly in containing large quantities of α-linolenic acid (18C:3, a kind of ω-3 FAs). However, little is known about the molecular mechanisms responsible for biosynthesis of unsaturated fatty acids in the developing seeds of this species. Transcriptome data are needed to better understand these mechanisms.

Results
In this study, de novo transcriptome assembly and gene expression analysis were performed using Illumina sequencing technology. A total of 52.6 million 90-bp paired-end reads were generated from two libraries constructed at the initial stage and fast oil accumulation stage of seed development. These reads were assembled into 70,392 unigenes; 22,179 unigenes showed a 2-fold or greater expression difference between the two libraries. Using this data we identified unigenes that may be involved in de novo FA and triacylglycerol biosynthesis. In particular, a number of unigenes encoding desaturase for formation of unsaturated fatty acids with high expression levels in the fast oil accumulation stage compared with the initial stage of seed development were identified.

Conclusions
This study provides the first comprehensive dataset characterizing Sacha Inchi gene expression at the transcriptional level. These data provide the foundation for further studies on molecular mechanisms underlying oil accumulation and PUFA biosynthesis in Sacha Inchi seeds. Our analyses facilitate understanding of the molecular mechanisms responsible for the high unsaturated fatty acids (especially α-linolenic acid) accumulation in Sacha Inchi seeds.