bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZEB Proteins in Leukemia: Friends, Foes, or Friendly Foes?
Authors: Soen Bieke , Vandamme Niels , Berx Geert , Schwaller Jürg , Van Vlierberghe Pieter , Goossens Steven 
Published: May 2018

AbstractZEB1 and ZEB2 play pivotal roles in solid cancer metastasis by allowing cancer cells to invade and disseminate through the transcriptional regulation of epithelial‐to‐mesenchymal transition. ZEB expression is also associated with the acquisition of cancer stem cell properties and therapy resistance. Consequently, expression levels of ZEB1/2 and of their direct target genes are widely seen as reliable prognostic markers for solid tumor aggressiveness and cancer patient outcome.Recent loss‐of‐function mouse models demonstrated that both ZEBs are also essential hematopoietic transcription factors governing blood lineage commitment and fidelity. Interestingly, both gain‐ and loss‐of‐function mutations have been reported in multiple hematological malignancies. Combined with emerging functional studies, these data suggest that ZEB1 and ZEB2 can act as tumor suppressors and/or oncogenes in blood borne malignancies, depending on the cellular context. Here, we review these novel insights and discuss how balanced expression of ZEB proteins may be essential to safeguard the functionality of the immune system and prevent leukemia.
FIVE-YEAR OUTCOMES OF INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH PATHOLOGIC MYOPIA
Authors: Onishi Yuka , Yokoi Tae , Kasahara Kaori , Yoshida Takeshi , Nagaoka Natsuko , Shinohara Kosei , Kaneko Yuichiro , Suga Mitsuki , Uramoto Kengo , Ohno-Tanaka Akiko , Ohno-Matsui Kyoko 
Published: May 2018

Purpose:
To determine the 5-year outcome of intravitreal ranibizumab (IVR) for myopic choroidal neovascularization (CNV).

Method:
We retrospectively analyzed the medical records of 51 eyes of 51 consecutive patients with myopic CNV who had been treated with IVR with a minimum follow-up period of 5 years after the initial IVR injection. The factors that predicted the best-corrected visual acuity (BCVA) at 5 years after IVR were determined by multiple regression analysis.

Results:
The mean age of the subjects was 63.6 years, and the mean axial length was 29.4 mm. The mean number of IVR was 1.6, and 34 eyes (66.7%) had only a single IVR. At the baseline and at the 1-year, 2-year, 4-year, and 5-year period, the mean BCVAs were 20/49, 20/37, 20/41, 20/45, and 20/42, respectively. Stepwise multiple regression analysis showed that the BCVA at 5-year period was significantly correlated with the baseline BCVA, the number of IVR injections, and the size of the CNV-related macular atrophy.

Conclusion:
Intravitreal ranibizumab provide a 5-year visual benefit in eyes with myopic CNV compared with the natural course. A lack of enlargement of the CNV-related macular atrophy, a better baseline BCVA, and a minimum number of IVR injections were associated with better visual outcomes.
Effect of Diabetes Mellitus and Metformin on Central Corneal Endothelial Cell Density in Eye Bank Eyes
Authors: Chocron Isaac M. , Rai Dinesh K. , Kwon Ji-Won , Bernstein Nicole , Hu Jimmy , Heo Moonseong , Lee Jimmy K. , Gore Patrick K. , McCartney Mitchell D. , Chuck Roy S. 
Published: May 2018

Purpose:
To determine whether metformin use and diabetes mellitus (DM) affect central corneal endothelial cell density (ECD) by examining an eye bank corneal donor database.

Methods:
The Lions Eye Institute corneal donor database, which consists of 38,318 corneal samples, was examined. Associations of ECD with metformin use and DM were tested by mixed effects linear models that account for correlations of outcomes between eyes within subjects adjusting for age, intraocular lens status, and glaucoma. Subjects (N = 17,056) with observed ECD counts for both eyes are included for analysis.

Results:
Average donor age was 56.3 (SD = 15.0). ECD was not associated with metformin use (mean ± SE = 2592 ± 11.9 (N = 1014) versus nonuse [2592 ± 3.0 (N = 16,042), P = 0.302]; further analysis showed that ECD was not significantly associated with metformin use in patients with diabetes. However, metformin use was significantly associated with lower ECD among patients with glaucoma: [2658 ± 50.7 (N = 27) for use versus 2789 ± 19.0 (N = 164) for nonuse, P = 0.018]. The presence of DM was significantly associated with lower ECD 2581 ± 5.6 (N = 4766) for DM versus 2595 ± 3.4 (N = 12,290) for non-DM, P = 0.031).

Conclusions:
Lower ECD was associated with DM. Lower ECD was not associated with metformin use except in a subgroup of patients with glaucoma, in which subgroup analysis showed lower ECD. The differences in ECD observed were small and unlikely to affect the suitability for transplantation of donor corneas.
Intravenous Hypertonic Saline to Lower Intraocular Pressure in Ocular Hypertension and Primary Open-angle and Exfoliation Glaucoma
Authors: Inborr Pia Katriina , Harju Mika , Kivelä Tero T. 
Published: May 2018

Purpose:
The purpose of this article was to quantitate the effect of intravenous hypertonic saline (IVHTS) on elevated intraocular pressure (IOP) among 3 groups of glaucoma patients or suspects.

Materials and Methods:
Among the forty-four patients with IOP 24 to 30 mm Hg included in this study, 13 had ocular hypertension (OHT), 14 primary open-angle glaucoma (POAG), and 17 exfoliation glaucoma (ExG). Participants received a bolus of 23.4% IVHTS (1.0 mmol/kg) through an antecubital vein. We measured IOP, heart rate, and blood pressure before the bolus, thereafter every minute for 10 minutes, and less frequently for 2 hours.

Results:
The median baseline IOP was 24 mm Hg (range, 24 to 30 mm Hg), 26.5 mm Hg (range, 24 to 30 mm Hg), and 26 mm Hg (range, 24 to 30 mm Hg) in OHT, POAG, and ExG patients, respectively. Sixteen minutes after the bolus, IOP was a median of 9 mm Hg (range, 4 to 12 mm Hg), 10 mm Hg (range, 6 to 12 mm Hg), and 10 mm Hg (range, 4 to 14 mm Hg) lower in OHT, POAG, and ExG groups (P=0.70), respectively. After 1 hour, the median IOP reduction was similar between ExG (9 mm Hg; range, 4 to 14 mm Hg) and POAG patients (9.5 mm Hg; range, 6 to 12 mm Hg) but lower in OHT patients (6 mm Hg; range, 2 to 9 mm Hg; P=0.006). Heart rate decreased by a median of 7 beats/min. Blood pressure increased within 3 minutes (median, mm Hg; 15 systolic; 5 diastolic), but returned to baseline at 10 minutes. Within 1 to 3 minutes of treatment, 36 (82%) patients felt pain in the infusion arm, and 29 (66%) reported a feeling of warmth in their head.

Conclusions:
IVHTS reduced IOP effectively in all groups.
Referral to Low Vision Services for Glaucoma Patients: Referral Criteria and Barriers
Authors: Kaleem Mona A. , West Sheila K. , Im Lily , Swenor Bonnielin K. 
Published: May 2018

Purpose:
To determine what criteria are being used by glaucoma specialists to refer patients to low vision services (LVS) and to identify potential barriers to LVS referral.

Methods:
A survey was emailed to members of the American Glaucoma Society (AGS). The number and percentage of responses to each survey question were examined.

Results:
Reported criteria for referral included difficulty performing activities related to vision (78%), degree of visual field loss (63%), and difficulty with orientation and mobility (27%). Reported barriers to LVS referral included patients not expressing difficulty with activities related to vision (34%), not having enough time to counsel patients during clinic visits (32%), and perceiving that patients would not be able to afford LVS even if they were referred (31%).

Conclusions:
Among glaucoma specialists, patient-reported difficulties with vision-related activities were the most common criteria used for LVS referral. Reported barriers to LVS referral, including perceived patient economic restraints and insufficient time to counsel patients during clinic visits, need to be addressed through appropriate interventions.
Endogenous pain modulation in chronic orofacial pain: a systematic review and meta-analysis
Authors: Moana-Filho Estephan J. , Herrero Babiloni Alberto , Theis-Mahon Nicole R. 
Published: May 2018

Abstract
Abnormal endogenous pain modulation was suggested as a potential mechanism for chronic pain, ie, increased pain facilitation and/or impaired pain inhibition underlying symptoms manifestation. Endogenous pain modulation function can be tested using psychophysical methods such as temporal summation of pain (TSP) and conditioned pain modulation (CPM), which assess pain facilitation and inhibition, respectively. Several studies have investigated endogenous pain modulation function in patients with nonparoxysmal orofacial pain (OFP) and reported mixed results. This study aimed to provide, through a qualitative and quantitative synthesis of the available literature, overall estimates for TSP/CPM responses in patients with OFP relative to controls. MEDLINE, Embase, and the Cochrane databases were searched, and references were screened independently by 2 raters. Twenty-six studies were included for qualitative review, and 22 studies were included for meta-analysis. Traditional meta-analysis and robust variance estimation were used to synthesize overall estimates for standardized mean difference. The overall standardized estimate for TSP was 0.30 (95% confidence interval: 0.11-0.49; P = 0.002), with moderate between-study heterogeneity (Q [df = 17] = 41.8, P = 0.001; I2 = 70.2%). Conditioned pain modulation's estimated overall effect size was large but above the significance threshold (estimate = 1.36; 95% confidence interval: −0.09 to 2.81; P = 0.066), with very large heterogeneity (Q [df = 8] = 108.3, P < 0.001; I2 = 98.0%). Sensitivity analyses did not affect the overall estimate for TSP; for CPM, the overall estimate became significant if specific random-effect models were used or if the most influential study was removed. Publication bias was not present for TSP studies, whereas it substantially influenced CPM's overall estimate. These results suggest increased pain facilitation and trend for pain inhibition impairment in patients with nonparoxysmal OFP.
Incidental Detection of Meningioma by 18F-FMAU PET/CT in a Patient With Suspected Prostate Cancer
Authors: Varghese Bino , Velez Erik , Desai Bhushan , Jadvar Hossein 
Published: May 2018

Abstract
We report on an incidental detection of a meningioma on [18F]-2′-fluoro-5-methyl-1-beta-d-arabinofuranosyluracil (18F-FMAU) PET/CT scan that was performed during a prospective investigation of 18F-FMAU PET/CT for targeted biopsy of potential sites of tumor in men with suspected prostate cancer based on elevated prostate-specific antigen level. Neither prostate multiparamteric MRI nor 18F-FMAU PET/CT localized small volume Gleason 3 + 3 tumor deposits. However, an incidental focal high accumulation of 18F-FMAU was observed in high right parietal lobe that displayed characteristics of a meningioma on a subsequent brain MRI.
Unicentric Castleman’s Disease Revealed by 18F-FDG PET/CT and Somatostatin Receptor Scintigraphy With 99mTc-HYNIC-TOC
Authors: Luo Yaping , Wang Ling , Pan Qingqing , Ma Yanru , Li Fang 
Published: May 2018

Abstract
A 51-year-old woman with a history of hypertension and abdominal pain was found with a retroperitoneal mass. The mass had intense enhancement in contrast-enhanced CT, and it showed a moderate degree of increased FDG uptake in PET/CT. The mass was also positive in somatostatin receptor scintigraphy with 99mTc-HYNIC-TOC, but it was negative in 131I-MIBG scan. The histopathological result after surgical resection of the mass confirmed the diagnosis of Castleman’s disease, the hyaline vascular variant.
Systematic Identification and Analysis of Expression Profiles of mRNAs and Incrnas in Macrophage Inflammatory Response
Authors: Li Lei , Zhang Yimei , Luo Haihua , Huang Chenyang , Li Shan , Liu Aihua , Jiang Yong 
Published: May 2018

ABSTRACT
Long noncoding RNAs (lncRNAs), once thought to be transcriptional noise, have been recently shown to regulate a variety of biological processes. However, their roles in the inflammatory response are largely unexplored. In this study, we performed high-throughput sequencing to identify the profiles of mRNA and lncRNA transcriptomes in response to lipopolysaccharide (LPS) stimulation, followed by a comprehensive bioinformatics analysis. We found a total of 325 lncRNAs and 1,187 mRNAs to be significantly dysregulated in RAW264.7 cells stimulated with LPS (fold change >4.0 or <0.25, false discovery rate <0.01). Further validation with qRT-PCR demonstrated that Cd40 and Traf1 mRNAs were significantly upregulated, whereas Slc43a2 and Ccnd1 were downregulated in RAW264.7 cells treated with LPS. Gene ontology (GO) analysis indicated that the altered mRNAs and lncRNAs were mainly involved in the immune response, inflammation response, chemokine receptor binding, protein binding, and regulation of cytokine production. KEGG pathway analysis showed that altered lncRNAs and mRNAs were significantly enriched in immune- and inflammation-related signaling pathways, such as Herpes simplex infection, cytokine–cytokine receptor interaction, and TNF, PI3K-Akt, MAPK, NF-κB, and JAK-STAT signaling pathways. lncRNA-mRNA network analysis showed that the coexpression network profile for mRNAs and lncRNAs from the immune category consisted of 93 network nodes and 145 connections among 70 differentially expressed mRNAs and 23 dysregulated lncRNAs, suggesting that lncRNAs play an important role in the regulation of functional mRNA expression in LPS-induced inflammation.
Integrative analysis of 5-methyl- and 5-hydroxymethylcytosine indicates a role for 5-hydroxymethylcytosine as a repressive epigenetic mark
Authors: Schlosberg Christopher E. , Edwards John R. 
Published: May 2018

ABSTRACTSince the discovery of 5-hydroxymethylcytosine (5hmC) as a prominent DNA base modification found in mammalian genomes, an emergent question has been what role this mark plays in gene regulation. 5hmC is hypothesized to function as an intermediate in the demethylation of 5-methylcytosine (5mC) and also in reactivation of silenced regulatory elements, including promoters and enhancers. Further, weak positive correlations have been observed between gene body 5hmC and gene expression. We previously demonstrated that ME-Class, which uses a high-resolution model of whole-genome bisulfite sequencing data, is an effective tool to understand relationships between 5mC and expression. In this work, we present ME-Class2, a machine-learning based tool to perform integrative 5mCG, 5hmCG and expression analysis. Using ME-Class2 we analyze whole-genome single-base resolution 5mC and 5hmC datasets from 20 primary tissue and cell samples to uncover relationships between 5hmC and expression. The addition of 5hmC improves model performance for tissues with high-levels of 5hmC such as the brain. Our analysis further indicates that conversion of 5mC to 5hmC within 2kb of the transcription start site associates with distinct functions depending on the summed level of 5mC + 5hmC. Unchanged levels of 5mC + 5hmC (i.e. conversion from 5mC to stable 5hmC) associate with repression. Meanwhile, decreases in 5mC + 5hmC (i.e. 5hmC-mediated demethylation) associate with gene activation. As more large-scale, genome-wide, differential DNA methylation studies become available, tools such as ME-Class2 will prove invaluable to interpret epigenomic data and guide mechanistic studies into the function of 5hmC.
Modeling gene expression networks to predict interchromosomal organization during human embryonic stem cell differentiation
Authors: Laster Kyle V. , Garza-Gongora Arturo G. , Daley Elizabeth , Terskikh Alexey , Kiskinis Evangelos , Smith Erica D. , Kosak Steven T. 
Published: May 2018

AbstractCellular differentiation occurs through the regulation of lineage-specific gene expression networks that are facilitated by the spatial organization of the genome. Although techniques based on the chromatin conformation capture (3C) approach have yielded intrachromosomal genome-wide interaction maps, strategies to identify non-random interchromosomal associations is lacking. Therefore, we modeled the genomic organization of chromosomes based on the regulatory networks involved in the differentiation of pluripotent human embryonic stem cells (hESCs) to committed neuronal precursor cells (cNPCs). Importantly, transcriptional regulation has been demonstrated to be a driving force in non-random genome organization. Thus, we constructed coarse-grainedin siliconetworks using gene expression data to identify potential physical associations among chromosomes occurringin situand then analyzed the three-dimensional (3D) distribution of these chromosomes, assessing how their associations contribute to nuclear organization. Our analysis suggests that coordinate regulation of differentially expressed genes is correlated with the 3D organization of chromosomes in hESC nuclei induced to differentiate to cNPCs.Author SummaryThe cellular commitment and differentiation of stem cells is a hallmark of metazoan development. The ultimate fate of a stem cell is defined by the synergistic modulation of key gene regulatory networks within the nucleus. In our work, we formulate anin silicomodel describing how the similarity in the expression profile of differentially regulated gene networks is correlated with the higher-order organization of chromosomes during differentiation from human embryonic stem cells (hESCs) to committed neuronal precursor cells (cNPCs). Using graph statistics, we observe that the genome networks generated using thein silicomodel exhibit properties similar to real-world networks. In addition to modeling how gene expression relates to dynamic changes in chromosome organization, we test the model by calculating the relative proximity of multiple chromosome pairs using 3D fluorescencein situhybridization (FISH). While various chromosomal properties, including gene density and overall length, have been attributed to chromosome organization, our previous work has identified the emergence of cell-type specific chromosomal topologies related to coordinate gene regulation during cellular differentiation. Here we extend these findings by determining whether ourin silicomodel can predict chromosome association based upon coordinate gene expression. Our work supports the idea that gene co-regulation, in addition to inherent organizational constraints of the nucleus, influences three-dimensional chromosome organization.
Bone remodeling: A tissue-level process emerging from cell-level molecular algorithms
Authors: Arias Clemente F. , Herrero Miguel A. , Echeverri Luis F. , Oleaga Gerardo E. , López José M. 
Published: May 2018

AbstractHuman skeleton undergoes constant remodeling during the whole life. By means of such process, which occurs at a microscopic scale, worn out bone is replaced by new, fully functional one. Multiple bone remodeling events occur simultaneously and independently throughout the body, so the whole skeleton is completely renewed about every ten years.Bone remodeling is performed by groups of cells called Bone Multicellular Units (BMU). BMUs consist of different cell types; some are specialized in destroying old bone, whereas others produce new bone to replace the former. The whole process is tightly regulated so that the amount of new bone produced exactly balances that of old one removed and bone microscopic structure is maintained.To date, many regulatory molecules involved in bone remodeling have been identified, but the precise mechanism of BMU operation remains to be fully elucidated. Given the complexity of the signaling pathways already known, the question arises of ascertaining whether such complexity is an inherent requirement of the process, or a consequence of operational redundancy.In this work we propose a minimal model of BMU function which involves a small number of signals and accounts for fully functional BMU operation. Our main assumptions are i) at any given time, any cell within a BMU can select only one among a reduced choice of decisions: divide, die, migrate or differentiate, ii) such decision is irreversibly determined by depletion of an appropriate internal inhibitor and iii) the dynamics of any such inhibitor is coupled to that of a few external mediators. It is shown that efficient BMU operation then unfolds as an emergent property, which results from individual decisions taken by cells in the BMU unit in the absence of any external planning.Author summaryOur skeleton is a living organ that is being renewed throughout our life. This task is accomplished by teams of bone cells termed as Bone Multicellular Units (BMUs) that are recruited when and where needed, to operate at places where bone has lost functionality either for an excess of mechanical stress or because loss of activity. Once assembled, BMU remove old bone and replace it by new one, and disband as soon as their mission has been accomplished. No single bone evades BMU screening, so that the whole human skeleton is completely renewed approximately every ten years.It is natural to wonder how such robust and fascinating process is regulated. Many signaling pathways involved in bone remodeling have been identified so far, but whether all of them are necessary for BMU operation remains unclear. In this work we show that just a reduced number of such signals could suffice for that purpose. This suggests that a large degree of redundancy might have been kept in place, perhaps as a consequence of different convergent strategies developed in the course of evolution.
Temporal dynamics of endogenous attentional modulation without cue awareness
Authors: Osako Yuma , Murai Shota , Shimpaku Jun , Kobayasi Kohta I. 
Published: May 2018

ABSTRACTInvisible visual stimuli can regulate our broad cognitive performance in the pursuit of current goals. Endogenous spatial attention is an important modulator of cognitive performance, and it can be triggered by unconscious cues. However, how its effect changes with time remains unclear. Here, we show that endogenous attention was triggered by an arrow-cue whose direction participants reported being unaware of but which affected the task performance in a time-dependent manner. Participants were asked to remember the directions of eight Landolt c rings (target memory array) after arrow-cue presentation, which was designed to orient their attention to a certain c ring. Then, we applied a delay, ranging from 83 ms to 1000 ms, between the arrow-cue and the target memory array presentation (the possible delays were equally spaced on a logarithmic scale). The attentional effect was greater for the 83, 183, 250 and 333 ms delays than the other six possible delays. In contrast, its effect was maintained irrespective of the delay when the participants reported being aware of the cue direction. Thus, awareness of arrow-cue direction was necessary to maintain endogenous attentional modulation, and its modulation without arrow-cue direction awareness was limited in a time-dependent manner.