bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Percutaneous Coronary Intervention on Viable Myocardium and Heart Function of Diabetic Patients With Chronic Total Occlusion
Authors: Zhou Guowei , Yang Wenyi , Li Liang 
Published: April 2017

Objective
The aim of this study was to compare the effects of percutaneous coronary intervention (PCI) on coronary chronic total occlusion patients with (DM) or without (NDM) diabetes mellitus.

Methods
A total of 78 patients were divided into DM group and NDM group according to whether the patient has DM. The results of PCI were analyzed using quantitative coronary analysis. In addition, all the patients underwent 99mTc-MIBI (methoxyisobutylisonitrile) single-photon emission computed tomography (SPECT) and ultrasonic cardiogram in the first week and the sixth month after PCI to evaluate PCI results. During the 6-month follow-up, major adverse cardiac event (MACE) was recorded and analyzed as well.

Results
The first and second classes of collateral circulation between the 2 groups have significant differences (P < 0.05). Left ventricular end-diastolic volume index and left ventricular end-systolic volume index were decreased at the sixth month compared with those at the first week. Left ventricular ejection fraction was significantly increased. In both groups, the defect size significantly reduced, and percentage of radionuclide scintigraphic count significantly increased between rest and nitroglycerin interventional SPECT. After 6 months, both groups repeated nitroglycerin interventional SPECT, which showed that defect size was significantly reduced, and the percentage of radionuclide scintigraphic count was significantly increased compared with those of the first week. During the 6-month follow-up, the incidence of MACE between the 2 groups had no significant difference.

Conclusions
Percutaneous coronary intervention has beneficial effects on heart functions and MACE when performed on chronic total occlusion patients with and without DM.
Postoperative Morbidity After Radical Resection of Primary Retroperitoneal Sarcoma
Authors: MacNeill Andrea J. , Gronchi Alessandro , Miceli Rosalba , Bonvalot Sylvie , Swallow Carol J. , Hohenberger Peter , Van Coevorden Frits , Rutkowski Piotr , Callegaro Dario , Hayes Andrew J. , Honoré Charles , Fairweather Mark , Cannell Amanda , Jakob Jens , Haas Rick L. , Szacht Milena , Fiore Marco , Casali Paolo G. , Pollock Raphael E. , Barretta Francesco , Raut Chandrajit P. , Strauss Dirk C. 
Published: April 2017

Objective:
To investigate the safety of radical resection for retroperitoneal sarcoma (RPS).

Background:
The surgical management of RPS frequently involves complex multivisceral resection. Improved oncologic outcomes have been demonstrated with this approach compared to marginal excision, but the safety of radical resection has not been shown in a large study population.

Methods:
The Transatlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaborative of sarcoma centers. A combined experience of 1007 consecutive resections for primary RPS from January 2002 to December 2011 was studied retrospectively with respect to adverse events. A weighted organ score was devised to account for differences in surgical complexity. Univariate and multivariate logistic regression analyses were performed to investigate associations between adverse events and number and patterns of organs resected. Associations between adverse events and overall survival, local recurrence, and distant metastases were investigated.

Results:
Severe postoperative adverse events (Clavien-Dindo ≥3) occurred in 165 patients (16.4%) and 18 patients (1.8%) died within 30 days. Significant predictors of severe adverse events were age (P = 0.003), transfusion requirements (P < 0.001), and resected organ score (P = 0.042). Resections involving pancreaticoduodenectomy, major vascular resection, and splenectomy/pancreatectomy were found to entail higher operative risk (odds ratio >1.5). There was no impact of postoperative adverse events on overall survival, local recurrence, or distant metastases.

Conclusions:
A radical surgical approach to RPS is safe when carried out at a specialist sarcoma center. High-risk resections should be carefully considered on an individual basis and weighed against anticipated disease biology. There appears to be no association between surgical morbidity and long-term oncologic outcomes.
A Longitudinal Investigation of Inflammatory Markers in Colorectal Cancer Patients Perioperatively Demonstrates Benefit in Serial Remeasurement
Authors: Chan Joseph C. Y. , Diakos Connie I. , Chan David L. H. , Engel Alexander , Pavlakis Nick , Gill Anthony , Clarke Stephen J. 
Published: April 2017

Objective:
To characterize the longitudinal course of the systemic inflammatory response (SIR) throughout the perioperative period. To investigate whether postoperative changes in the neutrophil-to-lymphocyte ratio (NLR) or lymphocyte-to-monocyte ratio (LMR) when compared with preoperative levels (‘conversion’) are associated with survival differences in colorectal cancer patients undergoing resection.

Background:
Recent evidence suggests that preoperative measurements of markers of the SIR including the NLR and LMR are prognostic. However, a few data exist evaluating longitudinal changes in the SIR especially in regards to their association with surgical interventions, optimal timing of assessment, and their effect on patient survival.

Methods:
Data from 6 hospitals from January 1998 to December 2012 were retrospectively collected. We examined 2280 patients with complete data. For the subgroup analysis investigating conversion, we examined 587 patients with full preoperative and postoperative data from 21 to 56 days postoperative. Patients were stratified into 4 groups for analysis of conversion in a multivariate Cox-regression model.

Results:
A longitudinal profile for the perioperative NLR and LMR was clearly characterized identifying an optimal period of remeasurement at 21 to 56 days postoperation. In multivariate analysis both NLR change group (P < 0.001) and LMR change group (P < 0.001) were independently associated with overall survival. For both biomarkers, patients with both a low preoperative and postoperative inflammatory state had the best survival. A change from the preoperative to postoperative inflammatory state was associated with a survival difference.

Conclusions:
This study characterizes the perioperative SIR profile and provides evidence for the remeasurement of SIR biomarkers postoperatively at 21 to 56 days for further prognostication.
Cured into Destitution: Catastrophic Health Expenditure Risk Among Uninsured Trauma Patients in the United States
Authors: Scott John W. , Raykar Nakul P. , Rose John A. , Tsai Thomas C. , Zogg Cheryl K. , Haider Adil H. , Salim Ali , Meara John G. , Shrime Mark G. 
Published: April 2017

Objective:
To characterize the economic hardship for uninsured patients admitted for trauma using catastrophic health expenditure (CHE) risk.

Background:
Medical debts are the greatest cause of bankruptcies in the United States. Injuries are often unpredictable, expensive to treat, and disproportionally affect uninsured patients. Current measures of economic hardship are insufficient and exclude those at greatest risk.

Methods:
We performed a retrospective review, using data from the 2007–2011 Nationwide Inpatient Samples of all uninsured nonelderly adults (18—64 yrs) admitted with primary diagnoses of trauma. We used US Census data to estimate annual postsubsistence income and inhospital charges for trauma-related admission. Our primary outcome measure was catastrophic health expenditure risk, defined as any charges ≥40% of annual postsubsistence income.

Results:
Our sample represented 579,683 admissions for uninsured nonelderly adults over the 5-year study period. Median estimated annual income was $40,867 (interquartile range: $21,286–$71.733). Median inpatient charges were $27,420 (interquartile range: $15,196–$49,694). Overall, 70.8% (95% posterior confidence interval: 70.7%–71.1%) of patients were at risk for CHE. The risk of CHE was similar across most demographic subgroups. The greatest risk, however, was concentrated among patients from low-income communities (77.5% among patients in the lowest community income quartile) and among patients with severe injuries (81.8% among those with ISS ≥ 16).

Conclusions:
Over 7 in 10 uninsured patients admitted for trauma are at risk of catastrophic health expenditures. This analysis is the first application of CHE to a US trauma population and will be an important measure to evaluate the effectiveness of health care and coverage strategies to improve financial risk protection.
Surgeon Age in Relation to Prognosis After Esophageal Cancer Resection
Authors: Markar Sheraz R. , Mackenzie Hugh , Lagergren Pernilla , Lagergren Jesper 
Published: April 2017

Objective:
It was hypothesized that patient survival improves with increasing surgeon age up to an age where it then decreases.

Background:
Experience, physical and psychological abilities required for esophagectomy may change with increasing surgeon age.

Methods:
This population-based cohort study included all patients having undergone esophagectomy for esophageal cancer in Sweden in 1987 to 2010, with follow-up until 2016. Risk-adjusted cumulative sum (RA-CUSUM) analysis was performed to estimate the relation between surgeon age and 90-day mortality, all-cause, and disease-specific 5-year mortality. Change-points in surgeon age identified by the RA-CUSUM were then analyzed in relation to mortality using multivariable Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for age, sex, comorbidity, tumor stage, tumor histology, neoadjuvant therapy, surgeon volume, and calendar year.

Results:
Among 139 surgeons performing 1761 esophagectomies, RA-CUSUM analysis of 90-day mortality showed change-points at 43 years (downward deflection) and at 56 years (upward deflection). Both all-cause and disease-specific 5-year mortality had corresponding change-points at 52 years and 56 years. Compared with surgeon age 52 to 55 years, surgeon age ≤51 years was associated with increased 90-day mortality (HR = 1.71, 95% CI 1.01–2.90) and 5-year all-cause mortality (HR = 1.21, 95% CI 1.02–1.43), and surgeon age ≥56 years showed increased 90-day mortality (HR = 2.38, 95% CI 1.38–4.13), 5-year all-cause mortality (HR = 1.29, 95% CI 1.08–1.55), and disease-specific 5-year mortality (HR = 1.18, 95% CI 1.01–1.42).

Conclusions:
Surgeon age ≤51 and ≥56 years may increase short- and long-term mortality after esophagectomy for cancer.
Medial prefrontal cortical NMDA receptors regulate depression-like behavior and dictate limbic thalamus innervation
Authors: Miller Oliver H. , Bruns Andreas , Ammar Imen Ben , Mueggler Thomas , Hall Benjamin J. 
Published: April 2017

AbstractDepression is a pervasive and debilitating neuropsychiatric disorder. A single, low dose of the NMDA receptor (NMDAR) antagonist ketamine elicits a long-lasting antidepressant response in patients with treatment-resistant major depressive disorder. Developing mechanistic understanding of how NMDAR antagonism alters synapse and circuit function is pivotal to developing translatable, circuit-based therapies for depression. Here using viral vectors, anatomical tracing, fMRI, and optogenetic-assisted circuit analysis, we assessed the role of the NMDAR subunit GluN2B in regulating cellular, synaptic, and circuit-level function and depression-related behavior. We demonstrate that post-developmental deletion of GluN2B from pyramidal neurons in medial prefrontal cortex enhances action potential output in a synaptic activity-dependent manner. GluN2B deletion dictates functional connectivity between mPFC and limbic thalamus but not ventral hippocampus and elicits antidepressant-like behavior. Our findings demonstrate that postsynaptic GluN2B exerts input-specific control of pyramidal neuron innervation, and identify a novel circuit for regulating depression-like behaviors in mice.
Decoding the functional Fes kinase signaling network topology in a lymphocyte model
Authors: Helbig Andreas O. , Kofler Michael , Gish Gerald , Sriraja Lourdes , Lorenzen Kristina , Tucholska Monika , Zhang Cunjie , Roth Frederick P. , Pawson Tony , Colwill Karen , Petsalaki Evangelia 
Published: April 2017

SummaryThe c-Fes protein tyrosine kinase is a proto-oncogene that can also act as a tumor suppressor. We implemented an unbiased phosphoproteomics-based analysis that establishes cognate kinase-substrate associations, and revealed that c-Fes directly phosphorylates Dok1, Ptpn18 and Sts1, facilitating recruitment of the Src inhibitory kinase Csk to these substrates. These interactions resulted in modulation of Src signaling following B-cell receptor (BCR) stimulation and subsequent alteration of the protein levels of CD19, a membrane-localized BCR co-receptor and emerging key protein affecting the development of B- and plasma cell-lymphoma. Strikingly, manipulating c-Fes expression levels drove opposing biological outcomes. Low-level exogenous c-Fes expression led to a strong increase in CD19 protein levels while high c-Fes expression abolished CD19 protein levels. Thus, we propose that a balance of c-Fes and Src signaling can regulate receptor maintenance, which may influence cellular outcome such as tumorigenesis or tumor suppression.
16S rRNA gene sequencing reveals site-specific signatures of the upper and lower airways of cystic fibrosis patients
Authors: Lucas Sarah K. , Yang Robert , Dunitz Jordan M. , Boyer Holly C. , Hunter Ryan C. 
Published: April 2017

ABSTRACTRationaleChronic rhinosinusitis (CRS) is an inflammatory disorder of the sinonasal mucosa associated with microbial colonization. Metastasis of sinus microbiota into the lower airways is thought have significant implications in the development of chronic respiratory disease. However, this dynamic has not been thoroughly investigated in cystic fibrosis (CF) patients, where lower airway infections are the primary driver of patient mortality. Given the high prevalence of CRS in CF patients and the proposed infection dynamic between the upper and lower airways, a better understanding of sinus-lung continuum is warranted.ObjectiveTo compare the microbiome of matched sinus mucus and lung sputum samples from CF subjects undergoing functional endoscopic sinus surgery (FESS) for treatment of CRS.MethodsMucus was isolated from the sinuses and lungs of twelve CF patients undergoing FESS. 16S ribosomal RNA gene sequencing was then performed to compare bacterial communities of the CF lung and sinus niches. Finally, functional profiling was performed to predict bacterial metagenomes from the 16S dataset, and was used to compare pathogenic bacterial phenotypes between the upper and lower airways.Measurements and Main ResultsBacterial richness was comparable between airway sites, though sinus and lung environments differed in community evenness, with the sinuses harboring a higher prevalence of dominant microorganisms. Beta diversity metrics also revealed that samples clustered more consistently by airway niche rather than by individual. Finally, predicted metagenomes showed that anaerobic metabolism was enriched in the lung environment, while genes associated with both biofilm formation and Gram identity were not variable between sites.ConclusionsSinus and lung microbiomes are distinct with respect to richness and evenness, while sinus communities have a higher incidence of a dominant taxon. Additionally, ordination analyses point to sinus and lung environments as being stronger determinants of microbial community structure than the individual patient. Finally, BugBase-predicted metagenomes revealed anaerobic phenotypes to be in higher abundance in the lung relative to the sinuses. Our findings indicate that while the paranasal sinuses and lungs may still comprise a unified airway in which lower airways are seeded by sinus microbiota, these discrete airway microenvironments harbor distinct bacterial communities.
Strain-resolved microbiome sequencing reveals mobile elements that drive bacterial competition on a clinical timescale
Authors: Bishara Alex , Moss Eli L. , Tkachenko Ekaterina , Kang Joyce B. , Zlitni Soumaya , Culver Rebecca N. , Andermann Tessa M. , Weng Ziming , Wood Christina , Handy Christine , Ji Hanlee , Batzoglou Serafim , Bhatt Ami S. 
Published: April 2017

AbstractAlthough shotgun short-read sequencing has facilitated the study of strain-level architecture within complex microbial communities, existing metagenomic approaches often cannot capture structural differences between closely related co-occurring strains. Recent methods, which employ read cloud sequencing and specialized assembly techniques, provide significantly improved genome drafts and show potential to capture these strain-level differences. Here, we apply this read cloud metagenomic approach to longitudinal stool samples from a patient undergoing hematopoietic cell transplantation. The patient’s microbiome is profoundly disrupted and is eventually dominated by Bacteroides caccae. Comparative analysis of B. caccae genomes obtained using read cloud sequencing together with metagenomic RNA sequencing allows us to predict that particular mobile element integrations result in increased antibiotic resistance, which we further support using in vitro antibiotic susceptibility testing. Thus, we find read cloud sequencing to be useful in identifying strain-level differences that underlie differential fitness.
K-mer similarity, networks of microbial genomes and taxonomic rank
Authors: Bernard Guillaume , Greenfield Paul , Ragan Mark A. , Chan Cheong Xin 
Published: April 2017

AbstractAlignment-free (AF) methods have recently been adopted to infer phylogenetic trees. However, the evolutionary relationships among microbes, impacted by common phenomena such as lateral genetic transfer and rearrangement, cannot be adequately captured in a strictly tree-like structure. Bacterial and archaeal genomes consist of highly conserved regions, e.g. ribosomal RNA genes (commonly used as phylogenetic markers), more-variable regions and extrachromosomal elements, i.e. plasmids (that contain genes critical under a selective condition e.g. antibiotic resistance). The impact of these elements on genome-scale inference of microbial phylogeny remains little known. Here, using an AF approach, we inferred phylogenomic networks of microbial life based on 2785 completely sequenced bacterial and archaeal genomes, and systematically assessed the impact of ribosomal RNA genes and plasmid sequences in this network. Our results indicate that k-mer similarity can correlate with taxonomic rank of microbes. Using a relational database approach, we linked the implicatedk-mers to annotated genomic regions (thus functions), and defined core functions in specific phyletic groups and genera. We found that, in most phyla, highly conserved functions are often related to Amino acid metabolism and transport, and Energy production and conversion. Our findings indicate that AF phylogenomics can be used to infer reticulate relationships in a scalable manner and provide new perspective into microbial biology and evolution.
Integrated design, execution, and analysis of arrayed and pooled CRISPR genome editing experiments
Authors: Canver Matthew C. , Haeussler Maximilian , Bauer Daniel E. , Orkin Stuart H. , Sanjana Neville E. , Shalem Ophir , Yuan Guo-Cheng , Zhang Feng , Concordet Jean-Paul , Pinello Luca 
Published: April 2017

ABSTRACTCRISPR genome editing experiments offer enormous potential for the evaluation of genomic loci using arrayed single guide RNAs (sgRNAs) or pooled sgRNA libraries. Numerous computational tools are available to help design sgRNAs with optimal on-target efficiency and minimal off-target potential. In addition, computational tools have been developed to analyze deep sequencing data resulting from genome editing experiments. However, these tools are typically developed in isolation and oftentimes not readily translatable into laboratory-based experiments. Here we present a protocol that describes in detail both the computational and benchtop implementation of an arrayed and/or pooled CRISPR genome editing experiment. This protocol provides instructions for sgRNA design with CRISPOR, experimental implementation, and analysis of the resulting high-throughput sequencing data with CRISPResso. This protocol allows for design and execution of arrayed and pooled CRISPR experiments in 4-5 weeks by non-experts as well as computational data analysis in 1-2 days that can be performed by both computational and non-computational biologists alike.
Enterococcus faecalismodulates immune activation and slows healing during wound infection
Authors: Long Chong Kelvin Kian , Tay Wei Hong , Janela Baptiste , Adeline Yong Mei Hui , Liew Tze Horng , Madden Leigh , Keogh Damien , Sebastian Barkham Timothy Mark , Ginhoux Florent , Becker David Laurence , Kline Kimberly A. 
Published: April 2017

ABSTRACTEnterococcus faecalisis one of most frequently isolated bacterial species in wounds yet little is known about its pathogenic mechanisms in this setting. Here, we used a mouse wound excisional model to characterize the infection dynamics ofE. faecalisand show that infected wounds result in two different states depending on the initial inoculum. Low dose inocula were associated with short term, low titer colonization whereas high dose inocula were associated with acute bacterial replication and long term persistence. High dose infection and persistence were also associated with immune cell infiltration, despite suppression of some inflammatory cytokines and delayed wound healing. During high dose infection, the multiple peptide resistance factor (MprF) which is involved in resisting immune clearance, contributes toE. faecalisfitness. These results comprehensively describe a mouse model for investigatingE. faecaliswound infection determinants, and suggest that both immune modulation and resistance contribute to persistent, non-healing wounds.
Linking dendroecology and association genetics: Stress responses archived in tree rings associate with SNP genotypes inAbies alba (Mill.)
Authors: Heer Katrin , Behringer David , Piermattei Alma , Bässler Claus , Fady Bruno , Jehl Hans , Liepelt Sascha , Lorch Sven , Piotti Andrea , Vendramin Giovanni Guiseppe , Weller Max , Ziegenhagen Birgit , Büntgen Ulf , Opgenoorth Lars 
Published: April 2017

SummaryGenetic association studies in forest tress would greatly benefit from information on tree response to environmental stressors over time. Dendroecology can close this gap by providing such time series measurements. Here, we jointly analyzed dendroecological and genetic data to explore the genetic basis of resistance, recovery and resilience to episodic stress in silver fir.We used individual level tree-ring data to characterize the growth patterns of surviving silver fir (Abies alba) during the forest dieback in the 1970s and 1980s in Central Europe and associated them with SNPs in candidate genes.Most trees at our study sites in the Bavarian Forest experienced severe growth decline from 1974 until the mid-1980s, which peaked during the drought year of 1976. Using the machine learning algorithm random forest, we identified 15 candidate genes that were associated with the variance in resistance, resilience and recovery among trees in this period.With our study we show that the unique possibility of phenotypic time series archived in tree-rings are a powerful resource in genetic association studies. We call for a closer collaboration of dendroceologists and forest geneticists to focus on integrating individual tree level signals in genetic association studies in long lived trees.