bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence Diversity in the
pe_pgrs
Genes of Mycobacterium tuberculosis Is Independent of Human T Cell Recognition
Authors: Copin Richard , Coscollá Mireia , Seiffert Salome N. , Bothamley Graham , Sutherland Jayne , Mbayo Georgetta , Gagneux Sebastien , Ernst Joel D. 
Published: January 2014

ABSTRACT

The
Mycobacterium tuberculosis
genome includes the large family of
pe_pgrs
genes, whose functions are unknown. Because of precedents in other pathogens in which gene families showing high sequence variation are involved in antigenic variation, a similar role has been proposed for the
pe_pgrs
genes. However, the impact of immune selection on
pe_pgrs
genes has not been examined. Here, we sequenced 27
pe_pgrs
genes in 94 clinical strains from five phylogenetic lineages of the
M. tuberculosis
complex (MTBC). We found that
pe_pgrs
genes were overall more diverse than the remainder of the MTBC genome, but individual members of the family varied widely in their nucleotide diversity and insertion/deletion (indel) content: some were more, and others were much less, diverse than the genome average. Individual
pe_pgrs
genes also differed in the ratio of nonsynonymous to synonymous mutations, suggesting that different selection pressures act on individual
pe_pgrs
genes. Using bioinformatic methods, we tested whether sequence diversity in
pe_pgrs
genes might be selected by human T cell recognition, the major mechanism of adaptive immunity to MTBC. We found that the large majority of predicted human T cell epitopes were confined to the conserved PE domain and experimentally confirmed the antigenicity of this domain in tuberculosis patients. In contrast, despite being genetically diverse, the PGRS domains harbored few predicted T cell epitopes. These results indicate that human T cell recognition is not a significant force driving sequence diversity in
pe_pgrs
genes, which is consistent with the previously reported conservation of human T cell epitopes in the MTBC.

IMPORTANCE
Recognition of
Mycobacterium tuberculosis
antigens by T lymphocytes is known to be important for immune protection against tuberculosis, but it is unclear whether human T cell recognition drives antigenic variation in
M. tuberculosis
. We previously discovered that the known human T cell epitopes in the
M. tuberculosis
complex are highly conserved, but we hypothesized that undiscovered epitopes with naturally occurring sequence variants might exist. To test this hypothesis, we examined the
pe_pgrs
genes, a large family of genes that has been proposed to function in immune evasion by
M. tuberculosis
. We found that the
pe_pgrs
genes exhibit considerable sequence variation, but the regions containing T cell epitopes and the regions of variation are distinct. These findings confirm that the majority of human T cell epitopes of
M. tuberculosis
are highly conserved and indicate that selection forces other than T cell recognition drive sequence variation in the
pe_pgrs
genes.
Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3
Authors: Arbuckle Jesse H. , Kristie Thomas M. 
Published: January 2014

ABSTRACT
Upon infection, the genome of herpes simplex virus is rapidly incorporated into nucleosomes displaying histone modifications characteristic of heterochromatic structures. The initiation of infection requires complex viral-cellular interactions that ultimately circumvent this repression by utilizing host cell enzymes to remove repressive histone marks and install those that promote viral gene expression. The reversion of repression and activation of viral gene expression is mediated by the cellular coactivator HCF-1 in association with histone demethylases and methyltransferases. However, the mechanisms and the components that are involved in the initial repression remain unclear. In this study, the chromatin remodeler chromodomain helicase DNA binding (CHD3) protein is identified as an important component of the initial repression of the herpesvirus genome. CHD3 localizes to early viral foci and suppresses viral gene expression. Depletion of CHD3 results in enhanced viral immediate early gene expression and an increase in the number of transcriptionally active viral genomes in the cell. Importantly, CHD3 can recognize the repressive histone marks that have been detected in the chromatin associated with the viral genome and this remodeler is important for ultimately reducing the levels of accessible viral genomes. A model is presented in which CHD3 represses viral infection in opposition to the actions of the HCF-1 coactivator complex. This dynamic, at least in part, determines the initiation of viral infection.

IMPORTANCE
Chromatin modulation of herpesvirus infection is a dynamic process involving regulatory components that mediate suppression and those that promote viral gene expression and the progression of infection. The mechanisms by which the host cell employs the assembly and modulation of chromatin as an antiviral defense strategy against an invading herpesvirus remain unclear. This study defines a critical cellular component that mediates the initial repression of infecting HSV genomes and contributes to understanding the dynamics of this complex interplay between host cell and viral pathogen.
Reliability and validity of a new French-language triage algorithm: the ELISA scale
Authors: Jobé Jerôme , Ghuysen Alexandre , Gérard Paul , Hartstein Gary , D'Orio Vincent 
Published: January 2014

ObjectiveOvercrowding in emergency departments (ED) leads to reductions in quality of care. Consequently, several different triage tools have been developed to prioritise patient intake. Differences in emergency medical services in different countries have limited the generalisation of pre-existing triage systems; for this reason, specific algorithms corresponding to local characteristics are needed. Accordingly, we developed a specific French-language triage system named Echelle Liégeoise d'Index de Sévérité à l'Admission (ELISA). This study tested its validity and efficiency.MethodsELISA is a five-category nursing triage algorithm. Intrarater agreement was tested by comparing triage levels attributed to the same clinical scenarios at two different times. Interrater agreement was investigated by comparing triage categories attributed to clinical cases by different triage nurses. Finally, validity was estimated by studying the correlations between the triage ranking assigned by the nurse and actual resource consumption and patient outcome.ResultsThe distribution of the difference between nurse classification at the two times was statistically unrelated to which nurse carried out the evaluation. Regarding interrater agreement, assigned classifications were compared to the reference assignment. Cohen's κ coefficient revealed an almost perfect agreement between classification by nurses and the reference. Finally, statistical analysis revealed a strong relation between ELISA and the overall need for supplementary clinical testing. Outcomes were also significantly correlated with ELISA.ConclusionsThe need for a specific, French-language triage tool in our ED led us to develop a new triage scale. This study demonstrates that the scale is a valid triage tool with high interrater and intrarater agreement and considerable efficiency.
Genomic Analysis of Head and Neck Squamous Cell Carcinoma Cell Lines and Human Tumors: A Rational Approach to Preclinical Model Selection
Authors: Li Hua , Wawrose John S. , Gooding William E. , Garraway Levi A. , Lui Vivian Wai Yan , Peyser Noah D. , Grandis Jennifer R. 
Published: January 2014

Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide. The increasing amount of genomic information on human tumors and cell lines provides more biologic data to design preclinical studies. We and others previously reported whole-exome sequencing data of 106 HNSCC primary tumors. In 2012, high-throughput genomic data and pharmacologic profiling of anticancer drugs of hundreds of cancer cell lines were reported. Here, we compared the genomic data of 39 HNSCC cell lines with the genomic findings in 106 HNSCC tumors. Amplification of eight genes (PIK3CA, EGFR, CCND2, KDM5A, ERBB2, PMS1, FGFR1, and WHSCIL1) and deletion of five genes (CDKN2A, SMAD4, NOTCH2, NRAS, and TRIM33) were found in both HNSCC cell lines and tumors. Seventeen genes were only mutated in HNSCC cell lines (&gt;10%), suggesting that these mutations may arise through immortalization in tissue culture. Conversely, 11 genes were only mutated in &gt;10% of human HNSCC tumors. Several mutant genes in the EGF receptor (EGFR) pathway are shared both in cell lines and in tumors. Pharmacologic profiling of eight anticancer agents in six HNSCC cell lines suggested that PIK3CA mutation may serve as a predictive biomarker for the drugs targeting the EGFR/PI3K pathway. These findings suggest that a correlation of gene mutations between HNSCC cell lines and human tumors may be used to guide the selection of preclinical models for translational research.
Implications: These findings suggest that a correlation of gene mutations between HNSCC cell lines and human tumors may be used to guide the selection of preclinical models for translational research.
Visual Overview: http://mcr.aacrjournals.org/content/12/4/571/F1.large.jpg.
Mol Cancer Res; 12(4); 571–82. ©2014 AACR.
Development of a Technique for Left Ventricular Endocardial Pacing via Puncture of the Interventricular Septum
Authors: Betts Tim R. , Gamble James H.P. , Khiani Raj , Bashir Yaver , Rajappan Kim 
Published: January 2014

Background—
Left ventricular (LV) pacing through the coronary sinus is the standard approach for cardiac resynchronization therapy. When this route is unavailable, the alternatives have major limitations. LV endocardial pacing through the interventriuclar septum may offer a simpler solution. We describe an initial case series to demonstrate technical feasibility and to describe our refinement of the puncture technique.

Methods and Results—
Ten patients with previous failed coronary sinus lead implant or with nonresponse to cardiac resynchronization therapy and a suboptimal LV lead position were selected. All patients were anticoagulated. Left ventriculography and coronary angiography were performed to identify LV borders and septal vessels. Subclavian vein access was used for a superior approach ventricular transseptal puncture under fluoroscopic guidance, using a steerable sheath and a standard transseptal needle, radiofrequency needle, or radiofrequency energy delivered through a guidewire. An active-fixation pacing lead was successfully delivered to the endocardial wall of the lateral LV in all patients (9 men; age, 62±10 years). LV lead implant procedure time shortened with experience. The use of radiofrequency energy delivered through a guidewire was the most effective technique. Mean threshold and R wave at implant were 0.8±0.3 V and 10.8±3.9 mV. At follow-up (mean, 8.7 months; minimum, 0; and maximum 19), thresholds were stable, and there were no thromboembolic events. Of 9 patients, 8 were classed as clinical responders (1 had inadequate follow-up to assess response).

Conclusions—
LV endocardial pacing through a ventricular septal puncture is a feasible approach for cardiac resynchronization therapy.
Risk Stratification for Long-Term Mortality After Percutaneous Coronary Intervention
Authors: Wu Chuntao , Camacho Fabian T. , King Spencer B. , Walford Gary , Holmes David R. , Stamato Nicholas J. , Berger Peter B. , Sharma Samin , Curtis Jeptha P. , Venditti Ferdinand J. , Jacobs Alice K. , Hannan Edward L. 
Published: January 2014

Background—
A simple risk score to predict long-term mortality after percutaneous coronary intervention (PCI) using preprocedural risk factors is currently not available. In this study, we created one by simplifying the results of a Cox proportional hazards model.

Methods and Results—
A total of 11 897 patients who underwent PCI from October through December 2003 in New York State were randomly divided into derivation and validation samples. Patients’ vital statuses were tracked using the National Death Index through the end of 2008. A Cox proportional hazards model was fit to predict death after PCI using the derivation sample, and a simplified risk score was created. The Cox model identified 12 separate risk factors for mortality including older age, extreme body mass indexes, multivessel disease, a lower ejection fraction, unstable hemodynamic state or shock, several comorbidities (cerebrovascular disease, peripheral vascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, and renal failure), and a history of coronary artery bypass graft surgery. The C statistics of this model when applied to the validation sample were 0.787, 0.785, and 0.773 for risks of death within 1, 3, and 5 years after PCI, respectively. In addition, the point-based risk score demonstrated good agreement between patients’ observed and predicted risks of death.

Conclusions—
A simple risk score created from a more complicated Cox proportional hazards model can be used to accurately predict a patient’s risk of long-term mortality after PCI.
Incidences, Predictors, and Clinical Outcomes of Acute and Late Stent Malapposition Detected by Optical Coherence Tomography After Drug-Eluting Stent Implantation
Authors: Im Eui , Kim Byeong-Keuk , Ko Young-Guk , Shin Dong-Ho , Kim Jung-Sun , Choi Donghoon , Jang Yangsoo , Hong Myeong-Ki 
Published: January 2014

Background—
We investigated the incidences, predictors, and clinical outcomes of acute and late stent malapposition detected by optical coherence tomography (OCT) after drug-eluting stent implantation.

Methods and Results—

We analyzed the OCT images from 351 patients with 356 lesions who received poststent and follow-up OCT examinations. Acute stent malapposition was observed in 62% of lesions. Approximately half of the acute stent malappositions were located within the edges of the stents. Severe diameter stenosis, calcified lesions, and long stents were independent predictors of acute stent malapposition. Follow-up OCT examinations were performed 175±60 days after drug-eluting stent implantation. Thirty-one percent of lesions with acute stent malapposition remained malapposed (late-persistent stent malapposition) and were typically (72%) located within the edges of the stent. The location within the stent edges and the volume of acute stent malapposition were independent predictors of late-persistent stent malapposition. Acute stent malapposition with a volume >2.56 mm
3
differentiated late-persistent stent malapposition from resolved acute stent malapposition. Late-acquired stent malapposition was detected in 15% of all lesions and was usually (61%) located within the stent body. Late-acquired stent malapposition was more frequently associated with plaque/thrombus prolapse on poststent OCT images (70% versus 42%;
P
<0.001). Clinical events, including cardiovascular death, nonfatal myocardial infarction, and stent thrombosis, did not occur in patients with late stent malapposition during the follow-up period of 28.6±10.3 months after drug-eluting stent implantation.

Conclusions—
Acute, late-persistent, and late-acquired stent malapposition had relatively high incidences but different predictors. The clinical outcome of stent malapposition was favorable.
Causes of Short-Term Readmission After Percutaneous Coronary Intervention
Authors: Wasfy Jason H. , Strom Jordan B. , O’Brien Cashel , Zai Adrian H. , Luttrell Jennifer , Kennedy Kevin F. , Spertus John A. , Zelevinsky Katya , Normand Sharon-Lise T. , Mauri Laura , Yeh Robert W. 
Published: January 2014

Background—
Rehospitalization within 30 days after an admission for percutaneous coronary intervention (PCI) is common, costly, and a future target for Medicare penalties. Causes of readmission after PCI are largely unknown.

Methods and Results—
To illuminate the causes of PCI readmissions, patients with PCI readmitted within 30 days of discharge between 2007 and 2011 at 2 hospitals were identified, and their medical records were reviewed. Of 9288 PCIs, 9081 (97.8%) were alive at the end of the index hospitalization. Of these, 893 patients (9.8%) were readmitted within 30 days of discharge and included in the analysis. Among readmitted patients, 341 patients (38.1%) were readmitted for evaluation of recurrent chest pain or other symptoms concerning for angina, whereas 59 patients (6.6%) were readmitted for staged PCI without new symptoms. Complications of PCI accounted for 60 readmissions (6.7%). For cases in which chest pain or other symptoms concerning for angina prompted the readmission, 21 patients (6.2%) met criteria for myocardial infarction, and repeat PCI was performed in 54 patients (15.8%). The majority of chest pain patients (288; 84.4%) underwent ≥1 diagnostic imaging test, most commonly coronary angiography, and only 9 (2.6%) underwent target lesion revascularization.

Conclusions—
After PCI, readmissions within 30 days were seldom related to PCI complications but often for recurrent chest pain. Readmissions with recurrent chest pain infrequently met criteria for myocardial infarction but were associated with high rates of diagnostic testing.
Sodium Excretion and Risk of Developing Coronary Heart Disease
Authors: Joosten Michel M. , Gansevoort Ron T. , Mukamal Kenneth J. , Lambers Heerspink Hiddo J. , Geleijnse Johanna M. , Feskens Edith J.M. , Navis Gerjan , Bakker Stephan J.L. 
Published: January 2014

Background—
Despite compelling evidence for sodium’s adverse effects on blood pressure, it remains uncertain whether excess sodium intake is a risk factor for coronary heart disease (CHD) in the overall population and in potentially more susceptible subgroups.

Methods and Results—

We prospectively followed 7543 adults aged 28 to 75 years and free of cardiovascular and kidney disease in 1997/1998 of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. Sodium excretion was measured in two 24-hour urine collections at baseline. Potential susceptibility factors were blood pressure and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP). Median 24-hour sodium excretion was 137 mmol (Q1–Q3, 106–171 mmol). During a median follow-up of 10.5 (Q1–Q3: 9.9–10.8) years, 452 CHD events occurred. In the entire cohort, there was no association between each 1-g/d (43 mmol/24 h) increment in sodium excretion and CHD risk (adjusted hazard ratio, 1.07; 95% confidence interval, 0.98–1.18;
P
=0.15). However, the association of sodium excretion with CHD risk tended to be modified by mean arterial pressure (
P
interaction
=0.08) and was modified by NT-proBNP (
P
interaction
=0.002). When stratified, each 1-g/d increment in sodium excretion was associated with an increased risk for CHD in subjects with hypertension (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01–1.28; n=2363) and in subjects with NT-proBNP concentrations above the sex-specific median (adjusted hazard ratio, 1.16; 95% confidence interval, 1.03–1.30; n=3771).

Conclusions—
Overall, there was no association between sodium excretion and risk of CHD. The association between sodium excretion and CHD risk was modified by NT-proBNP. Higher sodium excretion was associated with an increased CHD risk among subjects with increased NT-proBNP concentrations or with hypertension.
Impaired Cerebral Autoregulation Is Associated With Vasospasm and Delayed Cerebral Ischemia in Subarachnoid Hemorrhage
Authors: Otite Fadar , Mink Susanne , Tan Can Ozan , Puri Ajit , Zamani Amir A. , Mehregan Aujan , Chou Sherry , Orzell Susannah , Purkayastha Sushmita , Du Rose , Sorond Farzaneh A. 
Published: January 2014

Background and Purpose—
Cerebral autoregulation may be impaired in the early days after subarachnoid hemorrhage (SAH). The purpose of this study was to examine the relationship between cerebral autoregulation and angiographic vasospasm (aVSP) and radiographic delayed cerebral ischemia (DCI) in patients with SAH.

Methods—
Sixty-eight patients (54±13 years) with a diagnosis of nontraumatic SAH were studied. Dynamic cerebral autoregulation was assessed using transfer function analysis (phase and gain) of the spontaneous blood pressure and blood flow velocity oscillations on days 2 to 4 post-SAH. aVSP was diagnosed using a 4-vessel conventional angiogram. DCI was diagnosed from CT. Decision tree models were used to identify optimal cut-off points for clinical and physiological predictors of aVSP and DCI. Multivariate logistic regression models were used to develop and validate a risk scoring tool for each outcome.

Results—

Sixty-two percent of patients developed aVSP, and 19% developed DCI. Patients with aVSP had higher transfer function gain (1.06±0.33 versus 0.89±0.30;
P
=0.04) and patients with DCI had lower transfer function phase (17.5±39.6 versus 38.3±18.2;
P
=0.03) compared with those who did not develop either. Multivariable scoring tools using transfer function gain >0.98 and phase <12.5 were strongly predictive of aVSP (92% positive predictive value; 77% negative predictive value; area under the receiver operating characteristic curve, 0.92) and DCI (80% positive predictive value; 91% negative predictive value; area under the curve, 0.94), respectively.

Conclusions—
Dynamic cerebral autoregulation is impaired in the early days after SAH. Including autoregulation as part of the initial clinical and radiographic assessment may enhance our ability to identify patients at a high risk for developing secondary complications after SAH.
Gradual Lesion Expansion and Brain Shrinkage Years After Stroke
Authors: Seghier Mohamed L. , Ramsden Sue , Lim Louise , Leff Alex P. , Price Cathy J. 
Published: January 2014

Background and Purpose—
Lesioned brains of patients with stroke may change through the course of recovery; however, little is known about their evolution in the chronic phase. Here, we aimed to quantify the extent of lesion volume change and brain atrophy in the chronic poststroke brain using magnetic resonance imaging.

Methods—
Optimized T1-weighted scans were collected more than once (time between visits=2 months to 6 years) in 56 patients (age=36–90 years; time poststroke=3 months to 20 years). Volumetric changes attributable to lesion growth and atrophy were quantified with automated procedures. We looked at how volumetric changes related to time between visits, using nonparametric statistics, after controlling for age, time poststroke, and brain and lesion size at the earlier time.

Results—

Lesions expanded more in patients who had longer time-intervals between their imaging sessions (partial rank correlation ρ=0.56;
P
<0.001). The median rate of lesion growth was 1.59 cm
3
per year. Across patients, the whole-brain atrophy rate was 0.95% per year, with accelerated atrophy in the ipsilesional hemisphere.

Conclusions—
We show gradual lesion expansion many years after stroke, beyond that expected by normal aging and after controlling for other variables. Future studies need to understand how structural reorganization enables long-term recovery even when the brain is shrinking.