bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Prevalence of Metabolic Syndrome and Adipocytokine Levels in a Psoriatic Arthritis Cohort
Authors: Feld Joy , Nissan Sarit , Eder Lihi , Rahat Michal Amit , Elias Muna , Rimar Doron , Laor Arie , Bitterman Haim , Zisman Devy 
Published: February 2018

ObjectiveThe aims of this study were to evaluate the prevalence of metabolic syndrome (MetS) in psoriatic arthritis (PsA) patients according to the most recent definition in a Mediterranean population and to determine its association with biomarkers of inflammation and serum adipocytokine levels.MethodsDemographic, clinical, and laboratory data were collected on 74 patients with PsA and 82 control subjects. The presence of MetS was determined according to the current “harmonization” definition. Serum adipocytokines were analyzed. Continuous variables were compared byttest and discrete variables by χ2test. Multivariate regression models compared the association between the presence of MetS and the blood levels of adipocytokines.ResultsThe prevalence of MetS was higher in PsA patients compared with the control group: 54.8% versus 36.6%, respectively (P= 0.02; odds ratio, 2.33; 95% confidence interval, 1.16–4.69). The main difference between the 2 groups was waist circumference. No association was found between MetS and parameters of articular and skin disease activity or treatment. Leptin levels and leptin/adiponectin ratio were higher in PsA patients compared with control subjects: 83.4 versus 51.7 ng/mL (P= 0.001) and 6.3 × 10−3versus 4.1 × 10−3(P= 0.015), respectively. There was no significant difference in the adiponectin levels between the groups.ConclusionsThe prevalence of MetS was higher in PsA patients compared with non-PsA control subjects in this Mediterranean population. Clinicians caring for PsA patients ought to be aware of the increased risk of MetS in PsA patients, confirmed in different regions worldwide. The increased MetS seems to be linked to central obesity in these patients, and appropriate treatment recommendations are advised.
Breakthrough Reactions to Gadobenate Dimeglumine
Authors: Bhatti Zeeshaan S. , Mervak Benjamin M. , Dillman Jonathan R. , Davenport Matthew S. 
Published: February 2018

Purpose
The aim of this study was to determine the severity of breakthrough reactions to gadobenate dimeglumine in patients premedicated with a 13-hour premedication regimen.

Methods
Institutional review board approval was obtained and informed consent waived for this Health Insurance Portability and Accountability Act–compliant retrospective cohort study. All acute allergic-like reactions to gadobenate dimeglumine from 11/1/2008 to 1/31/2016 were identified. Of these, 19 allergic-like reactions followed 13-hour premedication: 150 mg prednisone and 50 mg diphenhydramine (ie, “breakthrough reactions”). Reasons for premedication, risk factors, index reaction characteristics, and breakthrough reaction characteristics were catalogued. Reaction severities were assigned using American College of Radiology guidelines. Severities of breakthrough (n = 19) and nonbreakthrough reactions (n = 97) were compared with the Cochran-Armitage test for trend.

Results
Premedication was most commonly given (63% [12/19]) for a previous allergic-like reaction to gadolinium-based contrast material (GBCM); in 37% (7/19), it was given for a different risk factor. In those premedicated for a previous allergic-like reaction to GBCM of known severity (n = 9), the breakthrough reaction severity was the same as index reaction severity in 56% (5/9), less severe in 11% (1/9), and of greater severity in 33% (3/9). Two severe breakthrough reactions occurred; both were in subjects premedicated for risk factors other than a previous GBCM reaction. No subjects died. Five subjects were reexposed to GBCM a total of 9 times; no repeat breakthrough reactions occurred. Breakthrough reactions were more severe than nonbreakthrough reactions (P = 0.046), but the level of significance was borderline.

Conclusion
Premedication does not eliminate severe reactions to gadobenate dimeglumine. Breakthrough reactions to gadobenate dimeglumine can be of greater severity than index reactions.
CD44 Deficiency in Mice Protects the Heart Against Angiotensin Ii-Induced Cardiac Fibrosis
Authors: Yang Li-Wang , Qin Dong-Ze , James Erskine , McKallip Robert J. , Wang Ning-Ping , Zhang Wei-Wei , Zheng Rong-Hua , Han Qing-Hua , Zhao Zhi-Qing 
Published: February 2018

ABSTRACT
This study tested the hypothesis that CD44 is involved in the development of cardiac fibrosis via angiotensin II (Ang II) AT1 receptor-stimulated TNFα/NFκB/IκB signaling pathways. Study was conducted in C57BL/6 wild type and CD44 knockout mice subjected to Ang II infusion (1,000 ng/kg/min) using osmotic minipumps up to 4 weeks or with gastric gavage administration of the AT1 receptor blocker, telmisartan at a dose of 10 mg/kg/d. Results indicated that Ang II enhances expression of the AT1 receptor, TNFα, NFκB, and CD44 as well as downregulates IκB. Further analyses revealed that Ang II increases macrophage migration, augments myofibroblast proliferation, and induces vascular/interstitial fibrosis. Relative to the Ang II group, treatment with telmisartan significantly reduced expression of the AT1 receptor and TNFα. These changes occurred in coincidence with decreased NFκB, increased IκB, and downregulated CD44 in the intracardiac vessels and intermyocardium. Furthermore, macrophage migration and myofibroblast proliferation were inhibited and fibrosis was attenuated. Knockout of CD44 did not affect Ang II-stimulated AT1 receptor and modulated TNFα/NFκB/IκB signaling, but significantly reduced macrophage/myofibroblast-mediated fibrosis as identified by less extensive collagen-rich area. These results suggest that the AT1 receptor is involved in the development of cardiac fibrosis by stimulating TNFα/NFκB/IκB-triggered CD44 signaling pathways. Knockout of CD44 blocked Ang II-induced cell migration/proliferation and cardiac fibrosis. Therefore, selective inhibition of CD44 may be considered as a potential therapeutic target for attenuating Ang II-induced deleterious cardiovascular effects.
Antibodies and the brain: anti-N-methyl-d-aspartate receptor antibody and the clinical effects in patients with systemic lupus erythematosus
Authors: Arinuma Yoshiyuki 
Published: February 2018

Purpose of review
Neuropsychiatric manifestations are one of the fatal complications in patients with systemic lupus erythematosus (SLE). However, the diagnosis and monitoring of that aspect of SLE is still challenging, as there are no reliable biomarkers linked to central nervous system (CNS) damage. This review emphasizes potential candidate autoantibodies that appear to be associated with development of behavioral and psychiatric manifestations in SLE patients.

Recent findings
Developments in the pathogenesis in SLE, not surprising for this immune disorder, point to specific, autoantibody toxicity. Namely, the discovery of an antibody which reacts with DNA and with the extracellular domain of N-methyl-d-aspartate (NMDA) receptor subunit GluN2A and 2B (anti-NMDA), an important receptor on neurons that is ubiquitous in the CNS, may lead to new insights into the behavioral and psychiatric manifestations in SLE. These anti-NMDA antibodies induce neuronal apoptosis and degeneration of surviving neurons in murine models. This functional antibody is also detected in SLE patients who have behavioral and psychiatric manifestations. The presence of anti-NMDA in cerebrospinal fluid but not in serum is associated significantly with overwhelming CNS abnormalities, suggesting importance of direct access of autoantibodies to brain dysfunction.

Summary
As anti-NMDA autoantibodies are present in patients who develop psychiatric manifestations in SLE, it is possible that novel therapeutic approaches will depend on altering the activity of these autoantibodies.
Sensitivity of a Reduced EEG Montage for Seizure Detection in the Neurocritical Care Setting
Authors: Ma Brandy B. , Johnson Emily L. , Ritzl Eva K. 
Published: February 2018

Introduction:
Neurocritical care units commonly implement the double-distance reduced EEG montage in postoperative neurosurgic patients who have structural barriers that hinder the placement of a standard 10-20 system array. Despite its widespread use, its sensitivity has not been adequately addressed. We evaluated the sensitivity and specificity of this montage for seizure detection.

Methods:
One hundred fifty-five full-montage continuous EEGs (cEEGs) completed in the Johns Hopkins University neurocritical care unit containing unequivocal electrographic seizures, status epilepticus, or other abnormalities were selected, comprising 73 ictal and 82 nonictal EEGs. EEGs were reformatted to the reduced montage, and 2-hour clips were reviewed independently by 2 epileptologists who documented the presence of seizures, status, or background abnormalities.

Results:
The sensitivity and specificity of the reduced montage for electrographic seizure detection was 81% and 92% with substantial interrater agreement (kappa 0.71). The sensitivity for status epilepticus was lower at 69%, but specificity remained high at 97% (kappa 0.67). Several EEGs miscategorized as nonictal were labeled as rather having rhythmic activity or periodic discharges. Evaluation of background patterns on the ictal–interictal continuum resulted in sensitivities ranging from 68% to 83%.

Conclusions:
Although the specificity of the reduced array is good, epileptologists should remain vigilant when monitoring patients using this montage, given its reduced sensitivity for epileptic activity, especially status epilepticus.
MicroRNA-132 provides neuroprotection for tauopathies via multiple signaling pathways
Authors: Fatimy Rachid El , Li Shaomin , Chen Zhicheng , Mushannen Tasnim , Gongala Sree , Wei Zhiyun , Balu Darrick T. , Rabinovsky Rosalia , Cantlon Adam , Elkhal Abdallah , Selkoe Dennis J. , Sonntag Kai C. , Walsh Dominic M. , Krichevsky Anna M. 
Published: February 2018

AbstractMicroRNAs (miRNA) regulate fundamental biological processes, including neuronal plasticity, stress response, and survival. Here we describe a neuroprotective function of miR-132, the miRNA most significantly down-regulated in Alzheimer’s disease. miR-132 protects mouse and human wild-type neurons and more vulnerable Tau-mutant primary neurons against amyloid β-peptide (Aβ) and glutamate excitotoxicity. It lowers the levels of total, phosphorylated, acetylated, and cleaved forms of Tau implicated in tauopathies, promotes neurite elongation and branching, and reduces neuronal death. Similarly, miR-132 attenuates PHF Tau pathology and neurodegeneration and enhances long-term potentiation in the P301S Tau transgenic mice. The neuroprotective effects are mediated by direct regulation of the Tau modifiers acetyltransferase EP300, kinase GSK3β, RNA-binding protein Rbfox1, and proteases Calpain 2 and Caspases 3/7. These data suggest miR-132 as a master regulator of neuronal health and indicate that miR-132 supplementation could be of therapeutic benefit for the treatment of Tau-associated neurodegenerative disorders.
Citius, Fortius? Cohort, inflammation and trajectories of gait speed and grip strength in older Britons
Authors: Tampubolon Gindo , Fajarini Maria 
Published: February 2018

AbstractAlthough the cost of long term care of physical disabilities is considerable, little is known about individual trajectories of physical function (measured by gait speed and grip strength) that preceded the process of disablement. Moreover, studies on trajectories of health function have often ignored cohort composition, precluding evidence of secular improvement. And few have explored the role of chronic inflammation on older people’s physical function trajectories. Using the English Longitudinal Study of Ageing 2004–2013 we derived trajectories of gait speed and grip strength of Britons aged ≥ 50 years and investigated the effect of inflammation. Then we drew trajectories for different cohorts to seek evidence of secular improvement. We uncovered a complex gradient of improvement in trajectories of physical function that depends on sex and maximum versus normal capacity. In conclusion, accounting for the cohort composition of older people can materially modify the future cost of long term care.
Trends in CRP, D-dimer and fibrinogen during therapy for HIV associated multidrug resistant tuberculosis
Authors: Cudahy Patrick G. T. , Warren Joshua L. , Cohen Ted , Wilson Doug 
Published: February 2018

ABSTRACTBackgroundHIV positive adults on treatment for multidrug-resistant tuberculosis (MDR-TB) experience high mortality. Biomarkers of HIV/MDR-TB treatment response may enable earlier treatment modifications that improve outcomes.MethodsTo determine whether trends in C-reactive protein (CRP), D-dimer and fibrinogen predict treatment outcome among those with HIV/MDR-TB co-infection we studied 20 HIV positive participants initiating therapy for MDR-TB. Serum CRP, fibrinogen, and D-dimer were measured at baseline and serially while on treatment. Results: At baseline, all biomarkers were elevated with median CRP 86.15 mg/L (IQR 29.25-149.32), D-dimer 0.85 μg/mL (IQR 0.34-1.80) and fibrinogen 4.11 g/L (IQR 3.75-6.31). CRP decreased significantly within 10 days of treatment initiation and fibrinogen within 28 days; D-dimer did not change significantly. 5 (25%) participants died. Older age (median age of 38y among survivors and 54y among deceased, p=0.008) and higher baseline fibrinogen (3.86 g/L among survivors and 6.37 g/L among deceased, p=0.02) were significantly associated with death. Higher CRP concentrations at the beginning of each measurement interval were significantly associated with a higher risk of death during that interval.ConclusionTrends in fibrinogen and CRP may be useful for evaluating early response to treatment among individuals with HIV/MDR-TB co-infection.
Cell type-dependent control of p53 transcription and enhancer activity by p63
Authors: Uzunbas Gizem Karsli , Ahmed Faraz , Sammons Morgan A. 
Published: February 2018

ABSTRACTTranscriptional activation by p53 provides powerful, organism-wide tumor suppression. In this work, we demonstrate that the p53-induced transcriptome varies based on cell type, reflects cell type-specific activities, and is considerably more broad than previously anticipated. This behavior is strongly influenced by p53 engagement with differentially active cell type-specific enhancers and promoters. In epithelial cell types, p53 activity is dependent on the p53 family member p63, which displays widespread enhancer binding. Notably, we demonstrate that p63 is required for epithelial enhancer identity including enhancers used by p53 during stress-dependent signaling. Loss of p63, but not p53, leads to site-specific depletion of enhancer-associated chromatin modifications, suggesting that p63 functions as an enhancer maintenance factor in epithelial cells. Additionally, a subset of epithelial-specific enhancers is dependent on the activity of p63 providing a direct link between lineage determination and enhancer structure. These data suggest a broad, cell-intrinsic mechanism for regulating the p53-dependent cellular response to stress through differential regulation ofcis-regulatory elements.
ADAR1 A-to-I RNA editing alters codon usage
Authors: Brachova Pavla , Alvarez Nehemiah S. , Hong Xiaoman , Vincent Kailey A. , Latham Keith E. , Christenson Lane K. 
Published: February 2018

AbstractBackgroundFully grown mammalian oocytes and eggs are transcriptionally quiescent, and therefore have a unique RNA environment in which cellular processes depend on post-transcriptional regulation. RNA editing of adenosines into inosines (A-to-I) by adenosine deaminases acting on RNA (ADARs) is a common post-transcriptional gene regulatory mechanism, yet it has not been systematically studied in oocytes.ResultsA genome-wide RNA editing analysis of transcriptionally active growing oocytes from postnatal day 12 (PND12) mice, fully grown germinal vesicle (GV) oocytes, and transcriptionally quiescent metaphase II (MII) eggs indicates an abundant amount of A-to-I editing of mRNA transcripts. Editing of mRNA was greatest in GV oocyte and MII eggs compared to the PND12 immature oocytes, this was consistent with ADAR1 levels within these cells. Compared to somatic tissues, oocytes exhibited a different pattern of RNA editing, with a high proportion of RNA edits occurring in the coding regions. These edits resulted in nucleotide substitutions that were enriched at the third nucleotide of the codon (wobble position). Codon usage can affect mRNA stability and translation efficiency.ConclusionsRNA editing in mouse oocytes is distinct from RNA editing in somatic cells due to increased frequencies of coding sequence RNA edits. We provide evidence in support of a previously unreported phenomenon of selective ADAR1 editing of the codon wobble position. Editing of the wobble position has the potential to fine tune post-transcriptional gene regulation through altering codon usage. This important observation advances our current understanding of RNA editing in mammalian cells.
ViDGER: An R package for integrative interpretation of differential gene expression results of RNA-seq data
Authors: McDermaid Adam , Monier Brandon , Zhao Jing , Ma Qin 
Published: February 2018

AbstractDifferential gene expression (DGE) is one of the most common applications of RNA-sequencing (RNA-seq) data. This process allows for the elucidation of differentially expressed genes (DEGs) across two or more conditions. Interpretation of the DGE results can be non-intuitive and time consuming due to the variety of formats based on the tool of choice and the numerous pieces of information provided in these results files. Here we present an R package,ViDGER(Visualization of Differential Gene Expression Results using R), which contains nine functions that generate information-rich visualizations for the interpretation of DGE results from three widely-used tools,Cuffdiff,DESeq2, andedgeR.
SeqStruct: A New Amino Acid Similarity Matrix Based on Sequence Correlations and Structural Contacts Yields Sequence-Structure Congruence
Authors: Jia Kejue , Jernigan Robert L. 
Published: February 2018

SUMMARYProtein sequence matching does not properly account for some well-known features of protein structures: surface residues being more variable than core residues, the high packing densities in globular proteins, and does not yield good matches of sequences of many proteins known to be close structural relatives. There are now abundant protein sequences and structures to enable major improvements to sequence matching. Here, we utilize structural frameworks to mount the observed correlated sequences to identify the most important correlated parts. The rationale is that protein structures provide the important physical framework for improving sequence matching. Combining the sequence and structure data in this way leads to a simple amino acid substitution matrix that can be readily incorporated into any sequence matching. This enables the incorporation of allosteric information into sequence matching and transforms it effectively from a 1-D to a 3-D procedure. The results from testing in over 3,000 sequence matches demonstrate a 37% gain in sequence similarity and a loss of 26% of the gaps when compared with the use of BLOSUM62. And, importantly there are major gains in the specificity of sequence matching across diverse proteins. Specifically, all known cases where protein structures match but sequences do not match well are resolved.
Endothelia extrude apoptotic cells to maintain a constant barrier
Authors: Mleynek Tara M. , Redd Michael , Chan Aubrey , Gu Yapeng , Li Dean Y , Rosenblatt Jody 
Published: February 2018

AbstractThe vascular system is lined with endothelial cells that, although only existing in a single monolayer, are key in the regulation of vascular barrier function. One of the major challenges these cells face is a routine exposure to environmental stressors that can induce apoptosis. Uncontrolled apoptosis in the endothelial monolayer threatens the ability of the cells to maintain their barrier function, resulting in vascular dysfunction. Therefore, we sought to identify ways in which endothelia maintain a cohesive monolayer during apoptotic events. We found that endothelial cells fated die will undergo a process of apoptotic cellular extrusion, similar to what has been described in the epithelium. We further show that endothelial extrusion uses a conserved S1P-S1PR2-RhoA signaling pathway in order to induce the formation of an actin ring that contracts closed, forcing the dying cell out of the monolayer while simultaneously filling in the gap left behind. Thus, endothelial extrusion successfully removes an apoptotic cell before it compromises the monolayer, preserving the barrier function.
Intergenerational epigenetic inheritance in reef-building corals
Authors: Liew Yi Jin , Howells Emily J. , Wang Xin , Michell Craig T. , Burt John A. , Idaghdour Youssef , Aranda Manuel 
Published: February 2018

MainThe notion that intergenerational or transgenerational inheritance operates solely through genetic means is slowly being eroded: epigenetic mechanisms have been shown to induce heritable changes in gene activity in plants1,2and metazoans1,3. Inheritance of DNA methylation provides a potential pathway for environmentally induced phenotypes to contribute to evolution of species and populations1–4. However, in basal metazoans, it is unknown whether inheritance of CpG methylation patterns occurs across the genome (as in plants) or as rare exceptions (as in mammals)4. Here, we demonstrate genome-wide intergenerational transmission of CpG methylation patterns from parents to sperm and larvae in a reef-building coral. We also show variation in hypermethylated genes in corals from distinct environments, indicative of responses to variations in temperature and salinity. These findings support a role of DNA methylation in the transgenerational inheritance of traits in corals, which may extend to enhancing their capacity to adapt to climate change.
An immortalised mesenchymal stem cell line maintains mechano-responsive behaviour and can be used as a reporter of substrate stiffness
Authors: Galarza Torre Asier , Shaw Joshua E. , Wood Amber , Gilbert Hamish T. J. , Dobre Oana , Genever Paul , Brennan Keith , Richardson Stephen M. , Swift Joe 
Published: February 2018

AbstractThe mechanical environment can influence cell behaviour, including changes to transcriptional and proteomic regulation, morphology and, in the case of stem cells, commitment to lineage. However, current tools for characterizing substrates’ mechanical properties, such as atomic force microscopy (AFM), often do not fully recapitulate the length and time scales over which cells ‘feel’ substrates. Here, we show that an immortalised, clonal line of human mesenchymal stem cells (MSCs) maintained responsiveness to substrate mechanics observed in primary cells, and could be used as a reporter of stiffness. MSCs were cultured on soft and stiff polyacrylamide hydrogels. In both primary and immortalised MSCs, stiffer substrates promoted increased cell spreading, expression of lamin-A/C and translocation of mechano-sensitive proteins YAP1 and MKL1 to the nucleus. Stiffness was also found to regulate transcriptional markers of lineage. A GFP-YAP / RFP-H2B reporter construct was designed and virally delivered to the immortalised MSCs for in situ detection of substrate stiffness. MSCs with stable expression of the reporter showed GFP-YAP to be increasingly co-localized with nuclear RFP-H2B on stiffer substrates, enabling development of a cellular reporter of substrate stiffness. This will facilitate mechanical characterisation of new materials developed for applications in tissue engineering and regenerative medicine.