bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunologic Rejection Episodes After Deep Anterior Lamellar Keratoplasty: Incidence and Risk Factors
Authors: Gonzalez Andres , Price Marianne O. , Feng Matthew T. , Lee Christopher , Arbelaez Juan G. , Price Francis W. 
Published: April 2017

Purpose:
To assess the rejection episode rate after deep anterior lamellar keratoplasty (DALK) and to identify associated risk factors.

Methods:
This retrospective review of 251 primary DALK procedures performed by 14 surgeons at a single center between February 2008 and November 2015 evaluated the rejection episode rate and associated risk factors using Kaplan–Meier survival and proportional hazards analyses, which took the length of follow-up into consideration.

Results:
Transplant indications were keratoconus or ectasia after laser refractive surgery (n = 170, 68%), corneal opacity (n = 72, 28%), and other anterior corneal disease (n = 9, 4%). The median recipient age was 46 years. The overall rejection episode rate was 14% with 18-month median follow-up and a 7-week median postoperative corticosteroid duration. In univariate analysis, increased risk of rejection episodes was associated with younger recipient age [relative risk (RR): 2.1, 95% confidence interval (CI): 1.4–5.2], African American race (RR: 2.1, 95% CI: 1.1–4.1), and use of manual trephination (compared with the femtosecond laser) for the side-cut incisions (RR: 2.7, 95% CI: 1.4–5.2). In multivariate analysis, the combined effect of patient age and race (P = 0.0012) and the side-cut method (P = 0.021) were each significant risk factors.

Conclusions:
This study demonstrates the substantial rate of rejection episodes that can be induced by corneal stroma in DALK and suggests that postoperative topical corticosteroids should be continued longer than the study's 7-week median and that young African Americans need higher-dose, longer-duration topical corticosteroids. The association between the side-cut method and rejection risk merits further investigation.
Comparison of Daptomycin and Linezolid in the Treatment of Vancomycin-Resistant Enterococcus faecium in the Absence of Endocarditis
Authors: Suleyman Geehan , Mahan Meredith , Zervos Marcus J. 
Published: April 2017

Background
Although linezolid and daptomycin are frequently used for the management of vancomycin-resistant Enterococcus (VRE) bloodstream infection, optimal treatment is undefined.

Methods
We conducted a retrospective cohort study from January 2010 to December 2013 of patients with VRE faecium (VREF) bloodstream infection in the absence of endocarditis treated with daptomycin or linezolid at a single 802-bed teaching hospital in Detroit, Mich. Ninety-day all-cause mortality, length of stay, bacteremia duration, antibiotic duration, and recurrence at 30 days were evaluated. Multivariable analysis was performed to determine the effect of treatment selection on mortality.

Results
One hundred eighteen patients were included. Seventy-four patients received daptomycin and 44 linezolid. There was no significant difference in baseline characteristics between the 2 groups with the exception of nursing home residence (P = 0.007), intensive care unit admission (P = 0.049), receipt of chemotherapy (P = 0.013), and neutropenia (P = 0.007). Ninety-day all-cause mortality was 46% and 27% (odds ratio = 2.27; 95% confidence interval, 1.1–5.07; P = 0.044) and mean bacteremia duration was 3.6 and 2.6 days (odds ratio = 2.52; 95% confidence interval, 1.17–5.42; P = 0.037) for daptomycin and linezolid, respectively. There was no significant difference in mean length of stay, mean antibiotic duration, and recurrence between the 2 groups. Moreover, there were no significant differences in mortality between the 2 groups after controlling for variables such as chemotherapy, neutropenia, and renal replacement therapy that were associated with increased mortality.

Conclusions
Our study showed that there was no significant difference in mortality between linezolid and daptomycin for therapy of VRE bacteremia in the absence of endocarditis after controlling for other variables that were associated with increased mortality.
Pyogenic Liver Abscess
Authors: Jaiswal Shubham Suresh , Nanjappa Sowmya , Greene John N. 
Published: April 2017

Abstract
Pyogenic liver abscess (PLA) is an uncommon but potentially lethal disease affecting humans worldwide. Despite the improvement in diagnostic imaging techniques and therapeutic modalities, the case fatality rate of PLA in patients with an underlying malignancy is high. There is little microbiological data available regarding PLA in patients with cancer. We found that the single most common organism isolated from PLAs was Escherichia coli (26.31%), followed by Enterococcus faecium (10.52%) and Pseudomonas aeruginosa (10.52%). More than half the cases were polymicrobial (20/38, 52.63%). Our data suggest that polymicrobial PLAs are common in patients with cancer. Further information is needed to determine how these trends might optimize prevention and treatment strategies for PLA in patients with cancer.
Transcriptional circuits in B cell transformation
Authors: Hu Yeguang , Yoshida Toshimi , Georgopoulos Katia 
Published: April 2017

Purpose of review
Loss of IKAROS in committed B cell precursors causes a block in differentiation while at the same time augments aberrant cellular properties, such as bone marrow stromal adhesion, self-renewal and resistance to glucocorticoid-mediated cell death. B cell acute lymphoblastic leukaemias originating from these early stages of B cell differentiation and associated with IKAROS mutations share a high-risk cellular phenotype suggesting that deregulation of IKAROS-based mechanisms cause a highly malignant disease process.

Recent studies
Recent studies show that IKAROS is critical for the activity of super-enhancers at genes required for pre-B cell receptor (BCR) signalling and differentiation, working either downstream of or in parallel with B cell master regulators such as EBF1 and PAX5. IKAROS also directly represses a cryptic regulatory network of transcription factors prevalent in mesenchymal and epithelial precursors that includes YAP1, TEAD1/2, LHX2 and LMO2, and their targets, which are not normally expressed in lymphocytes. IKAROS prevents not only expression of these ‘extra-lineage’ transcription factors but also their cooperation with endogenous B cell master regulators, such as EBF1 and PAX5, leading to the formation of a de novo for lymphocytes super-enhancer network. IKAROS coordinates with the Polycomb repression complex (PRC2) to provide stable repression of associated genes during B cell development. However, induction of regulatory factors normally repressed by IKAROS starts a feed-forward loop that activates de-novo enhancers and elevates them to super-enhancer status, thereby diminishing PRC2 repression and awakening aberrant epithelial-like cell properties in B cell precursors.

Summary
Insight into IKAROS-based transcriptional circuits not only sets new paradigms for cell differentiation but also provides new approaches for classifying and treating high-risk human B-ALL that originates from these early stages of B cell differentiation.
Adiponectin, lipids and atherosclerosis
Authors: Katsiki Niki , Mantzoros Christos , Mikhailidis Dimitri P. 
Published: April 2017

Purpose of review
Adiponectin is an adipokine with anti-inflammatory, antioxidant, antiatherogenic, pro-angiogenic, vasoprotective and insulin-sensitizing properties. Several factors may influence adiponectin levels, such as genetic polymorphisms, obesity / body fat distribution, diet and exercise as well as cardiovascular risk factors such as sleep deprivation and smoking as well as medications. Adiponectin has been proposed as a potential prognostic biomarker and a therapeutic target in patients with cardiometabolic diseases.

Recent findings
This narrative review discusses the associations of adiponectin with obesity-related metabolic disorders (metabolic syndrome, nonalcoholic fatty liver disease, hyperuricaemia and type 2 diabetes mellitus). We also focus on the links between adiponectin and lipid disorders and with coronary heart disease and noncardiac vascular diseases (i.e. stroke, peripheral artery disease, carotid artery disease, atherosclerotic renal artery stenosis, abdominal aortic aneurysms and chronic kidney disease). Further, the effects of lifestyle interventions and drug therapy on adiponectin levels are briefly reviewed.

Summary
Based on available data, adiponectin represents a multifaceted biomarker that may beneficially affect atherosclerosis, inflammation and insulin resistance pathways. However, there are conflicting results with regard to the associations between adiponectin levels and the prevalence and outcomes of cardiometabolic diseases. Further research on the potential clinical implications of adiponectin in the diagnosis and treatment of such diseases is needed.
Emergence and Spread of Neisseria gonorrhoeae Isolates With Decreased Susceptibility to Extended-Spectrum Cephalosporins in Argentina, 2009 to 2013
Authors: Gianecini Ricardo , Romero Maria de las Mercedes , Oviedo Claudia , Vacchino Martin , Galarza Patricia 
Published: April 2017

Background
The emergence of Neisseria gonorrhoeae strains with decreased susceptibility to cephalosporins represents a major concern globally. The aim of this study was to examine the phenotypic and molecular characteristics of N. gonorrhoeae isolates with decreased susceptibility to ceftriaxone and cefixime in Argentina.

Methods
A total of 1987 isolates were collected during 2009 and 2013. The susceptibility to penicillin G, tetracycline, ciprofloxacin, cefixime, ceftriaxone, and azithromycin was determined using the agar dilution method. The major extended-spectrum cephalosporin resistance determinants (penA, mtrR, and porB1b) were sequenced in 42 N. gonorrhoeae isolates that showed decreased susceptibility to ceftriaxone (minimum inhibitory concentration [MIC], 0.06–0.125 mg/L) and cefixime (MIC, 0.125–0.25 mg/L). Genotyping by N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed.

Results
Between 2009 and 2013, there was a shift in the modal MICs for ceftriaxone. Among the 42 isolates exhibiting decreased susceptibility to ceftriaxone and cefixime, 95.2% were resistant to penicillin G, 95.2% to tetracycline, 97.6% to ciprofloxacin, and 33.3% to azithromycin. Thirty-five (83.3%) of the 42 isolates had a mosaic penA allele XXXIV, which has been previously associated with resistance to ceftriaxone and cefixime as well as treatment failures. The isolates that contained the mosaic penicillin-binding protein 2 (PBP2) XXXIV were associated with NG-MAST ST1407 or closely related genotypes.

Conclusions
In Argentina, N. gonorrhoeae isolates with decreased susceptibility to cefixime and ceftriaxone have now emerged, mostly due to the introduction of the internationally spread multidrug-resistant NG-MAST ST1407.
Impact of Number of Human Papillomavirus Vaccine Doses on Genital Warts Diagnoses Among a National Cohort of U.S. Adolescents
Authors: Perkins Rebecca B. , Lin Mengyun , Wallington Sherrie F. , Hanchate Amresh 
Published: April 2017

Background
The impact of fewer than 3 doses of human papillomavirus (HPV) vaccine on genital warts is uncertain.

Methods
Using the Truven Health Analytics Marketscan administrative database, we compared rates of genital warts among women receiving 0, 1, 2, or 3 doses of HPV vaccine. Females aged 9 to 18 years on January 1, 2007, who were continuously enrolled in the database through December 31, 2013, were included. Patients were assigned an HPV dose state (0, 1, 2, or 3) based on the last recorded dose. The exposure period began on January 1, 2007, or the date of the final HPV dose, and lasted until the first diagnosis of genital warts or December 31, 2013. Multivariable Poisson regression was performed to determine the risk of genital warts associated with vaccine doses.

Results
Among 387,906 subjects, mean age and exposure period were 14.73 and 5.64 years, respectively. The proportions of doses received were: 52.1%, 7.8%, 9.4%, and 30.7% for 0, 1, 2, and 3 doses, respectively. The rate of genital warts was 1.97/1000 person-years. Receipt of 0 or 1 dose was associated with more genital warts than 3 doses. The effectiveness of 2 doses following current Centers for Disease Control and Prevention guidelines was similar to 3 doses. The risk of genital warts rose with age.

Conclusions
Prevention of genital warts is higher with completion of 3 vaccine doses than with 1 dose, though 2-dose recommendations appear to provide similar protection. Prospective effectiveness studies of recommended 2-dose schedules against clinical endpoints including persistent infection, genital warts, and cervical dysplasia are necessary to ensure long-term protection of vaccinated cohorts.
Advanced MRI of the Optic Nerve
Authors: Hoch Michael J. , Bruno Mary T. , Shepherd Timothy M. 
Published: April 2017

Background:
Clinical orbital MRI protocols are routinely used to study the optic nerves and exclude compressive lesions, infarctions, or inflammation. However, the small caliber and divergent oblique orientations of the optic nerves make it challenging to characterize them well with conventional MRI, especially since adjacent air-filled bony structures distort the MRI signal and motion is a problem even in cooperative, healthy volunteers.

Evidence Acquisition:
Over the past 3 years we have experimented with multiple novel MRI approaches and sequences to better characterize the optic nerves. The perfect MRI protocol would be quantitative and sensitive to subtle optic nerve pathologic changes, provide high spatial resolution, be rapidly acquired, and resistant to motion degradation.

Results:
This review provides an update of recent MRI sequence innovations for the optic nerves being currently translated into clinical practice. Methods discussed include rapid MRI with compressed sensing or simultaneous multislice approaches, postprocessing techniques for quantitative T2 mapping or track density imaging, and multiple MRI sequences for measuring diffusion in the optic nerves.

Conclusions:
Recently-developed orbit-specific MRI coils, quantitative sequences, and rapid acquisition techniques can improve our future ability to study optic nerve pathologies noninvasively. As advanced MRI becomes more proficient at characterizing the optic nerves, its role in the clinical management of patients should increase.
Encoding and Decoding Dynamic Sensory Signals with Recurrent Neural Networks: An Application of Conceptors to Birdsongs
Authors: Gast Richard , Faion Patrick , Standvoss Kai , Suckro Andrea , Lewis Brian , Pipa Gordon 
Published: April 2017

AbstractIn a constantly changing environment the brain has to make sense of dynamic patterns of sensory input. These patterns can refer to stimuli with a complex and hierarchical structure which has to be inferred from the neural activity of sensory areas in the brain. Such areas were found to be locally recurrently structured as well as hierarchically organized within a given sensory domain. While there is a great body of work identifying neural representations of various sensory stimuli at different hierarchical levels, less is known about the nature of these representations. In this work, we propose a model that describes a way to encode and decode sensory stimuli based on the activity patterns of multiple, recurrently connected neural populations with different receptive fields. We demonstrate the ability of our model to learn and recognize complex, dynamic stimuli using birdsongs as exemplary data. These birdsongs can be described by a 2-level hierarchical structure, i.e. as sequences of syllables. Our model matches this hierarchy by learning single syllables on a first level and sequences of these syllables on a top level. Model performance on recognition tasks is investigated for an increasing number of syllables or songs to recognize and compared to state-of-the-art machine learning approaches. Finally, we discuss the implications of our model for the understanding of sensory pattern processing in the brain. We conclude that the employed encoding and decoding mechanisms might capture general computational principles of how the brain extracts relevant information from the activity of recurrently connected neural populations.
An experimental approach to understanding elevation limits in a montane terrestrial salamander,plethodon montanus
Authors: Caruso Nicholas M. , Jacobs Jeremy F. , Rissler Leslie J. 
Published: April 2017

AbstractUnderstanding the abiotic and biotic factors that determine the limits to species’ range is an essential goal in ecology, biogeography, evolutionary biology, and conservation biology. Moreover, predictions of shifts in species’ distributions under future changes in climate can be improved through understanding the spatial variation in survival, growth, and reproduction. A long-standing hypothesis postulates that, for Northern Hemisphere species, abiotic factors like temperature limit northern and/or higher elevation extents, while biotic factors like competition limit the southern and/or lower elevation range edges; though amphibians may not follow this general trend. Therefore, we combined environmental suitability models and a reciprocal transplant experiment across an elevational gradient to explore the role of the abiotic environment on the range limits of a montane salamander (Plethodon montanus). We first determined suitability of the abiotic environment forP. montanus, under current (1960 – 2000) and future (2050) climate scenarios. Second, we collected juveniles from each of three elevations and transplanted them within mesocosms such that each origin population was represented within each transplant location and vice-versa. We found that environmental suitability in 2050 decreased throughout the range compared to current predictions, especially at lower elevations. Additionally, we found that individuals’ starting body condition and transplant location were important predictors of survival, growth, and reproduction condition; importantly, individuals transplanted to low elevation had lower survival and growth rates compared to those moved to mid or high elevations. Our study provides experimental support that the abiotic environment limits the lower elevation distribution ofP. montanusand, unfortunately, our results also paint a possible bleak future for this species and likely other montane terrestrial plethodontids. The abiotic environment, which will become increasingly limited under future changes in climate, was found to have more influence on survival and growth than population identity.
TGFβ mediated structural remodeling facilitates optic fissure fusion and the necessity of BMP antagonism in this process
Authors: Knickmeyer Max D. , Mateo Juan L. , Eckert Priska , Roussa Eleni , Rahhal Belal , Zuniga Aimee , Krieglstein Kerstin , Wittbrodt Joachim , Heermann Stephan 
Published: April 2017

AbstractThe optic fissure is a transient gap in the developing vertebrate eye, which must be closed as development proceeds. A persisting optic fissure, coloboma, is a major cause for blindness in children. Multiple factors are genetically linked to coloboma formation. However, especially the process of optic fissure fusion is still largely elusive on a cellular and molecular basis.We found a coloboma phenotype in mice with a targeted inactivation of the transforming growth factor 2 (TGFβ2). Here the optic fissure margins got in touch, however, failed to fuse. Transcriptomic analyses indicated TGFβ mediated ECM remodeling during optic fissure fusion. For functional analyses, we switched model systems and made use of zebrafish. We found TGFβ ligands expressed in the developing zebrafish eye, and the ligand binding receptor in the optic fissure. Using a new in vivo TGFβ signaling reporter, we also found active TGFβ signaling in the margins of the optic fissure. We addressed the function of Cadherin 6 (cdh6), one of the TGFβ regulated genes, by knock down experiments in zebrafish and found a prominent coloboma phenotype.Cdh6was often found involved in processes of epithelial to mesenchymal transition (EMT), strengthening our hypothesis that an EMT-like process is also necessary for optic fissure fusion. Furthermore, we found Gremlin 2b (grem2b) and Follistatin a (fsta), homologs of TGFβ regulated bone morphogenetic protein (BMP) antagonists, expressed in the optic fissure margins, indicating the necessity of a localized inhibition of BMP signaling. Finally, we show that induced BMP expression is sufficient to inhibit optic fissure fusion. Together with our previous findings this indicates a dual role of BMP signaling during optic fissure closure.Summary statementTGFβ is crucial for optic fissure fusion, involvingcdh6. TGFβ mediated optic fissure fusion is potentially hampered by BMP signaling, which is blocked by TGFβ induced BMP antagonists within the optic fissure margins.
GTC: a novel attempt to maintenance of huge genome collections compressed
Authors: Danek Agnieszka , Deorowicz Sebastian 
Published: April 2017

AbstractMotivationResultsWe present GTC, a novel compressed data structure for representation of huge collections of genetic variation data. GTC significantly outperforms existing solutions in terms of compression ratio and time of answering various types of queries. We show that the largest of publicly available database of about 60 thousand haplotypes at about 40 million SNPs can be stored in less than 4 Gbytes, while the queries related to variants are answered in a fraction of a second.AvailabilityGTC can be downloaded fromhttps://github.com/refresh-bio/GTCorhttp://sun.aei.polsl.pl/REFRESH/GTC.Contactsebastian.deorowicz@polsl.pl
Genome-scale detection of positive selection in 9 primates predicts human-virus evolutionary conflicts
Authors: der Lee Robin van , Wiel Laurens , van Dam Teunis J.P. , Huynen Martijn A. 
Published: April 2017

AbstractHotspots of rapid genome evolution hold clues about human adaptation. Here, we present a comparative analysis of nine whole-genome sequenced primates to identify high-confidence targets of positive selection. We find strong statistical evidence for positive selection acting on 331 protein-coding genes (3%), pinpointing 934 adaptively evolving codons (0.014%). Our stringent procedure and quality control of alignments and evolutionary inferences reveal substantial artefacts (20% of initial predictions) that have inflated previous estimates of positive selection, the large majority relating to transcript definitions (61%) or gene models (38%). Our final set of 331 positively selected genes (PSG) are strongly enriched for innate and adaptive immune functions, secreted and cell membrane proteins (e.g. pattern recognition, complement, cytokine pathways, defensins, immune receptors, MHC, Siglecs). We also find evidence for positive selection in reproduction, chromosome segregation and meiosis (e.g. centromere-associatedCENPO, CENPT), apolipoproteins, smell/taste receptors, and proteins interacting with mitochondrial-encoded molecules. Focusing on the virus-host interaction, we retrieve most evolutionary conflicts known to influence antiviral activity (e.g.TRIM5,MAVS,SAMHD1, tetherin) and predict 70 novel cases through integration with virus-host interaction data (virus-human PPIs, immune cell expression, infection screens). Protein structure analysis identifies positive selection in the interaction interfaces between viruses and their human cellular receptors (CD4– HIV;CD46[MCP] – measles, adenoviruses;CD55[DAF] – picornaviruses). Finally, the primate PSG consistently show high sequence variation in human exomes, suggesting ongoing evolution. Our curated dataset of positively selected genes and positions, available athttp://www.cmbi.umcn.nl/∼rvdlee/positive_selection/, is a rich source for studying the genetics underlying human (antiviral) phenotypes.