bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic, Transcriptomic, and Lipidomic Profiling Highlights the Role of Inflammation in Individuals With Low High-density Lipoprotein Cholesterol
Authors: Laurila Pirkka-Pekka , Surakka Ida , Sarin Antti-Pekka , Yetukuri Laxman , Hyötyläinen Tuulia , Söderlund Sanni , Naukkarinen Jussi , Tang Jing , Kettunen Johannes , Mirel Daniel B. , Soronen Jarkko , Lehtimäki Terho , Ruokonen Aimo , Ehnholm Christian , Eriksson Johan G. , Salomaa Veikko , Jula Antti , Raitakari Olli T. , Järvelin Marjo-Riitta , Palotie Aarno , Peltonen Leena , Orešič Matej , Jauhiainen Matti , Taskinen Marja-Riitta , Ripatti Samuli 
Published: February 2013

Objective—
Low high-density lipoprotein cholesterol (HDL-C) is associated with cardiometabolic pathologies. In this study, we investigate the biological pathways and individual genes behind low HDL-C by integrating results from 3 high-throughput data sources: adipose tissue transcriptomics, HDL lipidomics, and dense marker genotypes from Finnish individuals with low or high HDL-C (n=450).

Approach and Results—

In the pathway analysis of genetic data, we demonstrate that genetic variants within inflammatory pathways were enriched among low HDL-C associated single-nucleotide polymorphisms, and the expression of these pathways upregulated in the adipose tissue of low HDL-C subjects. The lipidomic analysis highlighted the change in HDL particle quality toward putatively more inflammatory and less vasoprotective state in subjects with low HDL-C, as evidenced by their decreased antioxidative plasmalogen contents. We show that the focal point of these inflammatory pathways seems to be the
HLA
region with its low HDL-associated alleles also associating with more abundant local transcript levels in adipose tissue, increased plasma vascular cell adhesion molecule 1 (VCAM1) levels, and decreased HDL particle plasmalogen contents, markers of adipose tissue inflammation, vascular inflammation, and HDL antioxidative potential, respectively. In a population-based look-up of the inflammatory pathway single-nucleotide polymorphisms in a large Finnish cohorts (n=11 211), no association of the
HLA
region was detected for HDL-C as quantitative trait, but with extreme HDL-C phenotypes, implying the presence of low or high HDL genes in addition to the population-genomewide association studies–identified HDL genes.

Conclusions—

Our study highlights the role of inflammation with a genetic component in subjects with low HDL-C and identifies novel
cis
-expression quantitative trait loci (
cis
-eQTL) variants in
HLA
region to be associated with low HDL-C.
Clarifying Differences Among Thrombolysis in Cerebral Infarction Scale Variants
Authors: Suh Sang Hyun , Cloft Harry J. , Fugate Jennifer E. , Rabinstein Alejandro A. , Liebeskind David S. , Kallmes David F. 
Published: February 2013

Background and Purpose—
Although thrombolysis in cerebral infarction (TICI) 2b/3 has been regarded as a successful angiographic outcome, the definition or subclassification of TICI 2 has differed between the original (o-TICI) and modified TICI (m-TICI). We sought to compare interobserver variability for both scores and analyze the subgroups of the TICI 2.

Methods—
Five readers interpreted angiographies independently using a 6-point scale as follows: grade 0, no antegrade flow; grade 1, flow past the initial occlusion without tissue reperfusion; grade 2, partial reperfusion in <50% of the affected territory; grade 3, partial reperfusion in 50% to 66%; grade 4, partial reperfusion in ≥67%; grade 5, complete perfusion. Readings using this scale were then converted into o-TICI and m-TICI score. Statistical analysis was performed according to TICI 2 subgroups.

Results—
Interobserver agreement was good for the o-TICI and m-TICI scores (intraclass correlation coefficient, 0.73 and 0.67, respectively). Our grade 3 (partial perfusion with 50% to 66%) occupied 19% of total readings, which would have been classified as grade 2a in o-TICI, but as 2b in m-TICI. The m-TICI was more likely to predict good clinical outcome than o-TICI (odds ratio, 2.01 versus 1.63, in reads with TICI 2b/3 versus 0/2a).

Conclusions—
Both TICI scales showed good agreement among readers. However, the variability in partial perfusion thresholds leads to different grading in ≈20% of cases and may result in significantly different rates of accurate outcome prediction.
A Risk Factor-based Predictive Model of Outcomes in Carotid Endarterectomy
Authors: Bekelis Kimon , Bakhoum Samuel F. , Desai Atman , Mackenzie Todd A. , Goodney Philip , Labropoulos Nicos 
Published: February 2013

Background and Purpose—
Accurate knowledge of individualized risks and benefits is crucial to the surgical management of patients undergoing carotid endarterectomy (CEA). Although large randomized trials have determined specific cutoffs for the degree of stenosis, precise delineation of patient-level risks remains a topic of debate, especially in real world practice. We attempted to create a risk factor-based predictive model of outcomes in CEA.

Methods—
We performed a retrospective cohort study involving patients who underwent CEAs from 2005 to 2010 and were registered in the American College of Surgeons National Quality Improvement Project database.

Results—
Of the 35 698 patients, 20 015 were asymptomatic (56.1%) and 15 683 were symptomatic (43.9%). These patients demonstrated a 1.64% risk of stroke, 0.69% risk of myocardial infarction, and 0.75% risk of death within 30 days after CEA. Multivariate analysis demonstrated that increasing age, male sex, history of chronic obstructive pulmonary disease, myocardial infarction, angina, congestive heart failure, peripheral vascular disease, previous stroke or transient ischemic attack, and dialysis were independent risk factors associated with an increased risk of the combined outcome of postoperative stroke, myocardial infarction, or death. A validated model for outcome prediction based on individual patient characteristics was developed. There was a steep effect of age on the risk of myocardial infarction and death.

Conclusions—
This national study confirms that that risks of CEA vary dramatically based on patient-level characteristics. Because of limited discrimination, it cannot be used for individual patient risk assessment. However, it can be used as a baseline for improvement and development of more accurate predictive models based on other databases or prospective studies
Symptom overlap in anxiety and multiple sclerosis
Authors: Ó Donnchadha Seán , Burke Teresa , Bramham Jessica , O’Brien Marie Claire , Whelan Robert , Reilly Richard , Kiiski Hanni , Lonergan Róisín , Kinsella Katie , Kelly Siobhán , McGuigan Christopher , Hutchinson Michael , Tubridy Niall 
Published: February 2013

Background: The validity of self-rated anxiety inventories in people with multiple sclerosis (pwMS) is unclear. However, the appropriateness of self-reported depression scales has been widely examined. Given somatic symptom overlap between depression and MS, research emphasises caution when using such scales. Objective: This study evaluates symptom overlap between anxiety and MS in a group of 33 individuals with MS, using the Beck Anxiety Inventory (BAI). Methods: Participants underwent a neurological examination and completed the BAI. Results: A novel procedure using hierarchical cluster analysis revealed three distinct symptom clusters. Cluster one (‘wobbliness’ and ‘unsteady’) grouped separately from all other BAI items. These symptoms are well-recognised MS-related symptoms and we question whether their endorsement in pwMS can be considered to reflect anxiety. A modified 19-item BAI (mBAI) was created which excludes cluster one items. This removal reduced the number of MS participants considered ‘anxious’ by 21.21% (low threshold) and altered the level of anxiety severity for a further 27.27%. Conclusion: Based on these data, it is suggested that, as with depression measures, researchers and clinicians should exercise caution when using brief screening measures for anxiety in pwMS.
Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo
Authors: McGoldrick Suzanne M. , Bleakley Marie E. , Guerrero Abraham , Turtle Cameron J. , Yamamoto Tori N. , Pereira Shalini E. , Delaney Colleen S. , Riddell Stanley R. 
Published: February 2013

Key PointsPriming of CMV-specific CD4+ and CD8+ T cells occurs as early as day 42 in patients undergoing UCBT. Lack of CMV control in UCBT patients could be related to low absolute frequency of T cells and lack of in vivo expansion of T cells.
A highly expressed miR-101 isomiR is a functional silencing small RNA
Authors: Llorens Franc , Bañez-Coronel Mónica , Pantano Lorena , del Río Jose Antonio , Ferrer Isidre , Estivill Xavier , Martí Eulàlia 
Published: February 2013

Abstract

Background
MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression usually producing translational repression and gene silencing. High-throughput sequencing technologies have revealed heterogeneity at length and sequence level for the majority of mature miRNAs (IsomiRs). Most isomiRs can be explained by variability in either Dicer1 or Drosha cleavage during miRNA biogenesis at 5’ or 3’ of the miRNA (trimming variants). Although isomiRs have been described in different tissues and organisms, their functional validation as modulators of gene expression remains elusive. Here we have characterized the expression and function of a highly abundant miR-101 5’-trimming variant (5’-isomiR-101).

Results
The analysis of small RNA sequencing data in several human tissues and cell lines indicates that 5’-isomiR-101 is ubiquitously detected and a highly abundant, especially in the brain. 5’-isomiR-101 was found in Ago-2 immunocomplexes and complementary approaches showed that 5’-isomiR-101 interacted with different members of the silencing (RISC) complex. In addition, 5’-isomiR-101 decreased the expression of five validated miR-101 targets, suggesting that it is a functional variant. Both the binding to RISC members and the degree of silencing were less efficient for 5’-isomiR-101 compared with miR-101. For some targets, both miR-101 and 5’-isomiR-101 significantly decreased protein expression with no changes in the respective mRNA levels. Although a high number of overlapping predicted targets suggest similar targeted biological pathways, a correlation analysis of the expression profiles of miR-101 variants and predicted mRNA targets in human brains at different ages, suggest specific functions for miR-101- and 5’-isomiR-101.

Conclusions
These results suggest that isomiRs are functional variants and further indicate that for a given miRNA, the different isomiRs may contribute to the overall effect as quantitative and qualitative fine-tuners of gene expression.
A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-β signaling pathways
Authors: Jia Luoqi , Jin Hongyan , Zhou Jiayi , Chen Lianghua , Lu Yiling , Ming Yanlin , Yu Yinhua 
Published: February 2013

Abstract

Background

Phyllanthus niruri L. is a well-known hepatoprotective and antiviral medicinal herb. Recently, we identified Corilagin as a major active component with anti-tumor activity in this herbal medicine. Corilagin is a member of the tannin family that has been discovered in many medicinal plants and has been used as an anti-inflammatory agent. However, there have been few reports of the anti-tumor effects of Corilagin, and its anti-tumor mechanism has not been investigated clearly. The aim of the present study is to investigate the anticancer properties of Corilagin in ovarian cancer cells.

Methods
The ovarian cancer cell lines SKOv3ip, Hey and HO-8910PM were treated with Corilagin and analyzed by Sulforhodamine B (SRB) cell proliferation assay, flow cytometry, and reverse phase protein array (RPPA). Corilagin was delivered intraperitoneally to mice bearing SKOv3ip xenografts.

Results
Corilagin inhibited the growth of the ovarian cancer cell lines SKOv3ip and Hey, with IC50 values of less than 30 μM, while displaying low toxicity against normal ovarian surface epithelium cells, with IC50 values of approximately 160 μM. Corilagin induced cell cycle arrest at the G2/M stage and enhanced apoptosis in ovarian cancer cells. Immunoblotting assays demonstrated that Cyclin B1, Myt1, Phospho-cdc2 and Phospho-Weel were down-regulated after Corilagin treatment. Xenograft tumor growth was significantly lower in the Corilagin-treated group compared with the untreated control group (P <0.05). More interestingly, Corilagin inhibited TGF-β secretion into the culture supernatant of all tested ovarian cancer cell lines and blocked the TGF-β-induced stabilization of Snail. In contrast, a reduction of TGF-β secretion was not observed in cancer cells treated with the cytotoxic drug Paclitaxel, suggesting that Corilagin specifically targets TGF-β secretion. Corilagin blocked the activation of both the canonical Smad and non-canonical ERK/AKT pathways.

Conclusions
Corilagin extracted from Phyllanthus niruri L. acts as a natural, effective therapeutic agent against the growth of ovarian cancer cells via targeted action against the TGF-β/AKT/ERK/Smad signaling pathways.
On the formation of blisters in annealed hydrogenated a-Si layers
Authors: Serényi Miklós , Frigeri Cesare , Szekrényes Zsolt , Kamarás Katalin , Nasi Lucia , Csik Attila , Khánh Nguyen Quoc 
Published: February 2013

Abstract
Differently hydrogenated radio frequency-sputtered a-Si layers have been studied by infrared (IR) spectroscopy as a function of the annealing time at 350°C with the aim to get a deeper understanding of the origin of blisters previously observed by us in a-Si/a-Ge multilayers prepared under the same conditions as the ones applied to the present a-Si layers. The H content varied between 10.8 and 17.6 at.% as measured by elastic recoil detection analysis. IR spectroscopy showed that the concentration of the clustered (Si-H)
n
groups and of the (Si-H2)
n
(n ≥ 1) polymers increased at the expense of the Si-H mono-hydrides with increasing annealing time, suggesting that there is a corresponding increase of the volume of micro-voids whose walls are assumed from literature to be decorated by the clustered mono-hydride groups and polymers. At the same time, an increase in the size of surface blisters was observed. Also, with increasing annealing time, the total concentration of bonded H of any type decreases, indicating that H is partially released from its bonds to Si. It is argued that the H released from the (Si-H)
n
complexes and polymers at the microvoid surfaces form molecular H2 inside the voids, whose size increases upon annealing because of the thermal expansion of the H2 gas, eventually producing plastic surface deformation in the shape of blisters.
Treatment with an anti-CD11d integrin antibody reduces neuroinflammation and improves outcome in a rat model of repeated concussion
Authors: Shultz Sandy R , Bao Feng , Weaver Lynne C , Cain Donald P , Brown Arthur 
Published: February 2013

AbstractBackgroundConcussions account for the majority of traumatic brain injuries (TBI) and can result in cumulative damage, neurodegeneration, and chronic neurological abnormalities. The underlying mechanisms of these detrimental effects remain poorly understood and there are presently no specific treatments for concussions. Neuroinflammation is a major contributor to secondary damage following more severe TBI, and recent findings from our laboratory suggest it may be involved in the cumulative properties of repeated concussion. We previously found that an anti-CD11d monoclonal antibody that blocks the CD11d/CD18 integrin and adhesion molecule interaction following severe experimental TBI reduces neuroinflammation, oxidative activity, and tissue damage, and improves functional recovery. As similar processes may be involved in repeated concussion, here we studied the effects of the anti-CD11d treatment in a rat model of repeated concussion.MethodsRats were treated 2 h and 24 h after each of three repeated mild lateral fluid percussion injuries with either the CD11d antibody or an isotype-matched control antibody, 1B7. Injuries were separated by a five-day inter-injury interval. After the final treatment and either an acute (24 to 72 h post-injury) or chronic (8 weeks post-injury) recovery period had elapsed, behavioral and pathological outcomes were examined.ResultsThe anti-CD11d treatment reduced neutrophil and macrophage levels in the injured brain with concomitant reductions in lipid peroxidation, astrocyte activation, amyloid precursor protein accumulation, and neuronal loss. The anti-CD11d treatment also improved outcome on tasks of cognition, sensorimotor ability, and anxiety.ConclusionsThese findings demonstrate that reducing inflammation after repeated mild brain injury in rats leads to improved behavioral outcomes and that the anti-CD11d treatment may be a viable therapy to improve post-concussion outcomes.
Congenital nasal pyriform aperture stenosis: diagnosis and management
Authors: Sesenna Enrico , Leporati Massimiliano , Brevi Bruno , Oretti Gabriele , Ferri Andrea 
Published: February 2013

Abstract

Background
Congenital nasal pyriform aperture stenosis is a rare and potentially lethal form of airway obstruction in newborns. Immediate recognition and appropriate therapy are mandatory for this potentially life-threating condition. This anomaly may present as an isolated malformation or may be associated with other cranial-facial anomalies. Clinically, CNPS shows unspecific symptoms of nasal airway obstruction such as apnoic crisis, episodic cyanosis and inability to nurse. The purpose of this report is to present author's experience in the surgical management of this rare pathology in 3 patients.

Patients and Methods
Three cases of congenital nasal pyriform aperture stenosis were reviewed for presentation of the disorder, management and effectiveness of the surgical treatment.

Results
All the patients underwent a surgical correction of the pyriform aperture stenosis using a sublabial approach followed by nasal stenting. During the follow-up no cases of restenosis, respiratory failure or cyanosis were detected.

Conclusions
Congenital pyriform aperture stenosis should be suspected in newborns with clinical signs of severe nasal obstruction associated with a difficulty to pass a small catheter though the anterior nasal valve. Timely recognition is mandatory to prevent a potential deadly outcome. Surgical correction of the stenosis though a sublabial approach followed by a nasal stenting revealed to be most effective treatment for these patients.
Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery
Authors: Zuleger Nikolaj , Boyle Shelagh , Kelly David A , de las Heras Jose I , Lazou Vassiliki , Korfali Nadia , Batrakou Dzmitry G , Randles K Natalie , Morris Glenn E , Harrison David J , Bickmore Wendy A , Schirmer Eric C 
Published: February 2013

Abstract
Background
Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified.

Results
To search for such proteins, 23 nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells.

Conclusions
The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning.
Sepsis otopathy: experimental sepsis leads to significant hearing impairment due to apoptosis and glutamate excitotoxicity in murine cochlea
Authors: Schmutzhard Joachim , Glueckert Rudolf , Pritz Christian , Blumer Michael J. F. , Bitsche Mario , Lackner Peter , Fille Manfred , Riechelmann Herbert , Harkamp Matthias , Sitthisak Thongrong , Schrott-Fischer Annelies 
Published: February 2013

SummaryHearing loss is frequent in intensive care patients and can be due to several causes. However, sepsis has not been examined as a possible cause. The aim of this study is to assess the influence of experimental sepsis on hearing thresholds and to evaluate pathological changes in the cochlea. The cecal ligation puncture technique was used to induce sepsis in 18 mice. Results were compared with those from 13 sham-operated and 13 untreated control mice. The hearing thresholds of the animals were evaluated with auditory evoked brainstem responses prior to the induction of sepsis and again at the peak of the disease. Immediately after the second measurement, the mice were sacrificed and the inner ears harvested and prepared for further evaluation. The cochleae were examined with light microscopy, electron microscopy and immunohistochemistry for Bax, cleaved caspase-3 and Bcl-2. The mice with sepsis showed a significant hearing loss but not the control groups. Induction of apoptosis could be shown in the supporting cells of the organ of Corti. Furthermore, excitotoxicity could be shown at the basal pole of the inner hair cells. In this murine model, sepsis leads to significant hearing impairment. The physiological alteration could be linked to apoptosis in the supporting cells of the organ of Corti and to a disturbance of the synapses of the inner hair cells.
The fracture behavior of birch and spruce in the radial-tangential crack propagation direction at the scale of the growth ring
Authors: Tukiainen Pekka , Hughes Mark 
Published: February 2013

Abstract
Crack-tip displacement fields have been computed based on digital image correlation for spruce (Picea abies [L.] Karst.) and birch (Betula pendula Roth.) wood, which were submitted to pure mode I loading in the RT-direction under both green and air-dried conditions. Moreover, crack propagation was modeled based on both linear elastic fracture mechanics (LEFM) and nonlinear fracture mechanics, relying on the fictitious crack model (FCM). The measured and modeled load versus the crack-mouth opening displacement (CMOD) curves and displacement fields were compared. In the case of spruce, the load-CMOD curves simulated by the FCM coincide well with the measured ones. On the contrary, measured near crack-tip displacement fields in both green and air-dried spruce are better comparable with the LEFM predictions than with the FCM predictions. In the case of green birch, the simulated FCM curve follows the measured curve quite well, but in air-dried birch the simulated FCM curve has a better fit than the LEFM-curve only before maximum load. In birch, the FCM predicts the displacement fields better than the LEFM. In both species, moisture content has a big effect on the softening behavior. In both spruce and birch, the FCM overestimates the displacements ahead of crack tip, whereas the LEFM model underestimates the displacements.