bluuebunny/crossref_metadata_2025_split huggingface dataset:
Panel 2: Eustachian Tube, Middle Ear, and Mastoid—Anatomy, Physiology, Pathophysiology, and Pathogenesis
Authors: Swarts J. Douglas , Alper Cuneyt M. , Luntz Michal , Bluestone Charles D. , Doyle William J. , Ghadiali Samir N. , Poe Dennis S. , Takahashi Haruo , Tideholm Bo 
Published: March 2013

ObjectiveThis report reviews the literature to identify the advances in our understanding of the middle ear (ME)–Eustachian tube (ET) system during the past 4 years and, on that basis, to determine whether the short‐term goals elaborated in the last report were achieved and propose updated goals to guide future otitis media (OM) research.Data SourcesDatabases searched included PubMed, Web of Science (1945‐present), Medline (1950 to present), Biosis Previews (1969‐present), and the Zoological Record (1978 to present). The initial literature search covered the time interval from January 2007 to June 2011, with a supplementary search completed in February 2012.Review MethodsThe panel topic was subdivided; each contributor performed a literature search and provided a preliminary report. Those reports were consolidated and discussed when the panel met on June 9, 2011. At that meeting, the progress was evaluated and new short‐term goals proposed.ConclusionsProgress was made on 16 of the 19 short‐term goals proposed in 2007. Significant advances were made in the characterization of ME gas exchange pathways, modeling ET function, and preliminary testing of treatments for ET dysfunction.Implications for PracticeIn the future, imaging technologies should be developed to noninvasively assess ME/ET structure and physiology with respect to their role in OM pathogenesis. The new data derived from form/function experiments should be integrated into the finite element models and used to develop specific hypotheses concerning OM pathogenesis and persistence. Finally, rigorous studies of treatments, medical or surgical, of ET dysfunction should be undertaken.
Charting changes in commitment
Authors: Dailey René M. , Brody Nicholas , LeFebvre Leah , Crook Brittani 
Published: March 2013

The present study examined how turning points reported by individuals in on-again/off-again (on–off) relationships reflected relationship trajectories. Participants ( N = 581) completed an online Retrospective Interview Technique asking them to report on up to 10 turning points. Participants indicated their commitment level at each turning point. Based on the variations in commitment across turning points, five trajectories emerged. Trajectory groups were compared regarding relational stability factors. Results suggest that on–off partners with a steady-low commitment trajectory reported less stability than individuals with steady-high commitment. Additionally, partners in the fluctuating trajectory, which would seemingly represent less stability, reported moderate perceptions of their relationships, faring better than the low-steady commitment group. Overall, findings add to an understanding of how to best characterize on–off relationships.
Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells
Authors: van Balkom Bas W. M. , de Jong Olivier G. , Smits Michiel , Brummelman Jolanda , den Ouden Krista , de Bree Petra M. , van Eijndhoven Monique A. J. , Pegtel D. Michiel , Stoorvogel Willem , Würdinger Thomas , Verhaar Marianne C. 
Published: March 2013

Key Points
Endothelial cells secrete exosomes containing miR-214, which suppress senescence and stimulates an angiogenic program in target cells. Exosomal miR-214 regulates ataxia telangiectasia mutated expression in recipient endothelial cells.
Computing minimal nutrient sets from metabolic networks via linear constraint solving
Authors: Eker Steven , Krummenacker Markus , Shearer Alexander G , Tiwari Ashish , Keseler Ingrid M , Talcott Carolyn , Karp Peter D 
Published: March 2013

Abstract

Background
As more complete genome sequences become available, bioinformatics challenges arise in how to exploit genome sequences to make phenotypic predictions. One type of phenotypic prediction is to determine sets of compounds that will support the growth of a bacterium from the metabolic network inferred from the genome sequence of that organism.

Results
We present a method for computationally determining alternative growth media for an organism based on its metabolic network and transporter complement. Our method predicted 787 alternative anaerobic minimal nutrient sets for Escherichia coli K-12 MG1655 from the EcoCyc database. The program automatically partitioned the nutrients within these sets into 21 equivalence classes, most of which correspond to compounds serving as sources of carbon, nitrogen, phosphorous, and sulfur, or combinations of these essential elements. The nutrient sets were predicted with 72.5% accuracy as evaluated by comparison with 91 growth experiments. Novel aspects of our approach include (a) exhaustive consideration of all combinations of nutrients rather than assuming that all element sources can substitute for one another(an assumption that can be invalid in general) (b) leveraging the notion of a machinery-duplicating constraint, namely, that all intermediate metabolites used in active reactions must be produced in increasing concentrations to prevent successive dilution from cell division, (c) the use of Satisfiability Modulo Theory solvers rather than Linear Programming solvers, because our approach cannot be formulated as linear programming, (d) the use of Binary Decision Diagrams to produce an efficient implementation.

Conclusions
Our method for generating minimal nutrient sets from the metabolic network and transporters of an organism combines linear constraint solving with binary decision diagrams to efficiently produce solution sets to provided growth problems.
Genetic variants in PARP1 (rs3219090) and IRF4(rs12203592) genes associated with melanoma susceptibility in a Spanish population
Authors: Peña-Chilet Maria , Blanquer-Maceiras Maite , Ibarrola-Villava Maider , Martinez-Cadenas Conrado , Martin-Gonzalez Manuel , Gomez-Fernandez Cristina , Mayor Matias , Aviles Juan Antonio , Lluch Ana , Ribas Gloria 
Published: March 2013

Abstract

Background
Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS) have been the ideal strategy to identify new common, low-penetrance susceptibility loci. In this case–control study, we try to validate in our population nine melanoma associated markers selected from published GWAS in melanoma predisposition.

Methods
We genotyped the 9 markers corresponding to 8 genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and 347 controls from a Spanish population using KASPar probes. Genotypes were analyzed by logistic regression and adjusted by phenotypic characteristics.

Results
We confirm the protective role in MM of the rs3219090 located on the PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4 gene was associated with protection to develop MM for the dominant model (p-value 0.037). We have also observed an association of this SNP with both lentigines (p-value 0.014) and light eye color (p-value 3.76 × 10-4). Furthermore, we detected a novel association with rs1485993, located on the CCND1 gene, and dark eye color (p-value 4.96 × 10-4). Finally, rs1801516, located on the ATM gene, showed a trend towards a protective role in MM similar to the one firstly described in a GWAS study.

Conclusions
To our knowledge, this is the first time that these SNPs have been associated with MM in a Spanish population. We confirmed the proposed role of rs3219090, located on the PARP1 gene, and rs12203592, located on the IRF4 gene, as protective to MM along the same lines as have previous genome-wide associated works. Finally, we have seen associations between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming previous results for the IRF4 gene and presenting novel data for the last two, suggesting that pigmentation characteristics correlated with eye color are potential mediators between PARP1 and MM protection.
A novel panel of biomarkers in distinction of small well-differentiated HCC from dysplastic nodules and outcome values
Authors: Jin Guang-Zhi , Dong Hui , Yu Wen-Long , Li Yan , Lu Xin-Yuan , Yu Hua , Xian Zhi-Hong , Dong Wei , Liu Yin-Kun , Cong Wen-Ming , Wu Meng-Chao 
Published: March 2013

Abstract

Background
Differential diagnosis of high-grade dysplastic nodules (HGDN) and well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to experienced hepatic clinicians, radiologists and hepatopathologists.

Methods
The expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were assessed by immunohistochemistry. The differential diagnostic performances of these three markers alone and in combination for HGDN and WDHCC were investigated by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses in an independent set of 500 patients.

Results
ACY1, SQSTM1 and GPC3 were differentially expressed in each group. For the differential diagnosis of WDHCC from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 + GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set, which were higher than any of the three two-marker combinations. The validities of the four diagnostic models were further confirmed in an independent test set, and corresponding good sensitivity and specificity were observed. Interestingly, GPC3 expression in HCC tissues combined with serum α-fetoprotein (AFP) was found to be an independent predictor for overall survival and time to recurrence.

Conclusions
ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry. Meanwhile, low GPC3 staining combined with positive serum AFP may play a practical role in predicting poor postoperative outcome and high tumor recurrence risk.
Enhanced transgene expression in rice following selection controlled by weak promoters
Authors: Zhou Jie , Yang Yong , Wang Xuming , Yu Feibo , Yu Chulang , Chen Juan , Cheng Ye , Yan Chenqi , Chen Jianping 
Published: March 2013

Abstract

Background
Techniques that enable high levels of transgene expression in plants are attractive for the commercial production of plant-made recombinant pharmaceutical proteins or other gene transfer related strategies. The conventional way to increase the yield of desired transgenic products is to use strong promoters to control the expression of the transgene. Although many such promoters have been identified and characterized, the increase obtainable from a single promoter is ultimately limited to a certain extent.

Results
In this study, we report a method to magnify the effect of a single promoter by using a weak promoter-based selection system in transgenic rice. tCUP1, a fragment derived from the tobacco cryptic promoter (tCUP), was tested for its activity in rice by fusion to both a β-glucuronidase (GUS) reporter and a hygromycin phosphotransferase (HPT) selectable marker. The tCUP1 promoter allowed the recovery of transformed rice plants and conferred tissue specific expression of the GUS reporter, but was much weaker than the CaMV 35S promoter in driving a selectable marker for growth of resistant calli. However, in the resistant calli and regenerated transgenic plants selected by the use of tCUP1, the constitutive expression of green fluorescent protein (GFP) was dramatically increased as a result of the additive effect of multiple T-DNA insertions. The correlation between attenuated selection by a weak promoter and elevation of copy number and foreign gene expression was confirmed by using another relatively weak promoter from nopaline synthase (Nos).

Conclusions
The use of weak promoter derived selectable markers leads to a high T-DNA copy number and then greatly increases the expression of the foreign gene. The method described here provides an effective approach to robustly enhance the expression of heterogenous transgenes through copy number manipulation in rice.
Prokinetic and laxative effects of the crude methanolic extract of Viola betonicifolia whole plant in rodents
Authors: Muhammad Naveed , Rehman Najeeb ur , Khan Haroon , Saeed Muhammad , Gilani Anwarul-Hassan 
Published: March 2013

Abstract

Background
The present study was aimed to provide ethnopharmacological basis for the medicinal use of Viola betonicifolia whole plant in indigestion and constipation.

Methods
Mice were used in in-vivo prokinetic and laxative studies while in-vitro experiments were conducted on isolated tissues of rabbit and guinea-pig gut preparations suspended in a tissue bath to measure isotonic contractions.

Results
The crude methanolic extract of Viola betonicifolia (VBME) showed partially atropine-sensitive prokinetic (50 and 100 mg/kg) and laxative (30 and 100 mg/kg) activities in mice. When tested in isolated rabbit jejunum and guinea-pig ileum, VBME caused dose-dependent contractions at 0.01-0.3 mg/mL and 0.03-5 mg/mL, respectively. The spasmogenic effect was partially sensitive to atropine, while the presence of pyrilamine, SB203186 or hexamethonium had no effect in both gut preparations. VBME partially inhibited acetylcholinesterase enzyme (19%) in the in-vitro assay. The spasmodic effect of VBME was more efficacious in guinea-pig ileum than rabbit jejunum preparation. The phytochemical analysis of the crude methanolic extract for total alkaloids and saponins revealed that the VBME is a rich source of alkaloids and saponins.

Conclusions
This study showed the prokinetic and laxative effects of Viola betonicifolia in mice, partially mediated through cholinergic action. The in-vitro spasmodic effect of the plant extract was also partially sensitive to atropine indicating more than one mechanisms in the gut stimulant effect. This study provides a rationale for the medicinal use of Viola betonicifolia in indigestion and constipation.
Type 1 diabetes mellitus abrogates compensatory augmentation of myocardial neuregulin-1β/ErbB in response to myocardial infarction resulting in worsening heart failure
Authors: Odiete Oghenerukevwe , Konik Ewa A , Sawyer Douglas B , Hill Michael F 
Published: March 2013

Abstract

Background
Diabetes mellitus (DM) patients surviving myocardial infarction (MI) exhibit a substantially higher incidence of subsequent heart failure (HF). Neuregulin (NRG)-1 and erythroblastic leukemia viral oncogene homolog (ErbB) receptors have been shown to play a critical role in maintenance of cardiac function. However, whether myocardial NRG-1/ErbB is altered during post-MI HF associated with DM remains unknown. The aim of this study was to determine the impact of type 1 DM on the myocardial NRG-1/ErbB system following MI in relation to residual left ventricular (LV) function.

Methods
Type 1 DM was induced in rats via administration of streptozotocin (65 mg/kg, i.p.). Control rats were injected with citrate buffer (vehicle) only. Two weeks after induction of type 1 DM, MI was produced in DM and non-DM rats by ligation of the left coronary artery. Sham MI rats underwent the same surgical procedure with the exception that the left coronary artery was not ligated. At 4 weeks after surgery, residual in vivo LV function was assessed via echocardiography. Myocardial protein expression of NRG-1β, ErbB2 and ErbB4 receptors, and MDM2 (a downstream signaling pathway induced by NRG-1 that has been implicated in cell survival) was assessed in the remaining, viable LV myocardium by Western blotting. Changes in ErbB receptor localization in the surviving LV myocardium of diabetic and non-diabetic post-MI rats was determined using immunohistochemistry techniques.

Results
At 4 weeks post-MI, echocardiography revealed that LV fractional shortening (FS) and LV ejection fraction (EF) were significantly lower in the DM + MI group compared to the MI group (LVFS: 17.9 ± 0.7 vs. 25.2 ± 2.2; LVEF: 35.5 ± 1.4 vs. 47.5 ± 3.5, respectively; P < 0.05), indicating an increased functional severity of HF among the DM + MI rats. Up-regulation of NRG-1β and ErbB2 protein expression in the MI group was abrogated in the DM + MI group concurrent with degradation of MDM2, a downstream negative regulator of p53. ErbB2 and ErbB4 receptors re-localized to cardiac myocyte nuclei in failing type 1 diabetic post-MI hearts.

Conclusions
Type 1 DM prevents compensatory up-regulation of myocardial NRG-1/ErbB after MI coincident with an increased severity of HF.
Comparing the angiogenic potency of naïve marrow stromal cells and Notch-transfected marrow stromal cells
Authors: Dao Mo , Tate Ciara C , McGrogan Michael , Case Casey C 
Published: March 2013

Abstract

Background
Angiogenesis is a critical part of the endogenous repair process in brain injury and disease, and requires at least two sequential steps. First, angiogenic sprouting of endothelial cells occurs, which entails the initial proliferation of endothelial cells and remodeling of the surrounding extracellular matrix. Second, vessel stabilization is necessary to prevent vascular regression, which relies on vascular smooth muscle recruitment to surround the young vessels. Marrow stromal cells (MSCs) have been shown to promote revascularization after hindlimb ischemia, cardiac ischemia, and stroke. SB623 cells are derived from marrow stromal cells by transfection with a Notch1 intracellular domain (NICD)-expressing plasmid and are known to elicit functional improvement in experimental stroke. These cells are currently used in human clinical testing for treatment of chronic stroke. In the current study, the angiogenic property of SB623 cells was investigated using cell-based assays.

Methods
Angiogenic paracrine factors secreted by SB623 cells and the parental MSCs were identified using the Qantibody Human Angiogenesis Array. To measure the angiogenic activity of conditioned medium from SB623 cells and MSCs, endothelial tube formation in the human umbilical vein endothelial cell (HUVEC) assay and endothelial cell sprouting and branching in the rodent aortic ring assay were quantified. To validate the angiogenic contribution of VEGF in conditioned medium, endothelial cells and aortic rings were treated with SU5416, which inhibits VEGFR2 at low dose.

Results
Conditioned medium from SB623 cells promoted survival and proliferation of endothelial cells under serum-deprived conditions and supports HUVEC vascular tube formation. In a rodent aortic ring assay, there was enhanced endothelial sprouting and branching in response to SB623-derived conditioned medium. SU5416 treatment partially reversed the effect of conditioned medium on endothelial cell survival and proliferation while completely abrogate HUVEC tube formation and endothelial cell sprouting and branching in aortic ring assays.

Conclusions
These data indicate that SB623 cell-secreted angiogenic factors promoted several aspects of angiogenesis, which likely contribute to promoting recovery in the injured brain.
Impact of diuretic therapy-associated electrolyte disorders present on admission to the emergency department: a cross-sectional analysis
Authors: Arampatzis Spyridon , Funk Georg-Christian , Leichtle Alexander Benedikt , Fiedler Georg-Martin , Schwarz Christoph , Zimmermann Heinz , Exadaktylos Aristomenis Konstantinos , Lindner Gregor 
Published: March 2013

Abstract

Background
Diuretics are among the most commonly prescribed medications and, due to their mechanisms of action, electrolyte disorders are common side effects of their use. In the present work we investigated the associations between diuretics being taken and the prevalence of electrolyte disorders on admission as well as the impact of electrolyte disorders on patient outcome.

Methods
In this cross sectional analysis, all patients presenting between 1 January 2010 and 31 December 2011 to the emergency room (ER) of the Inselspital, University Hospital Bern, Switzerland were included. Data on diuretic medication, baseline characteristics and laboratory data including electrolytes and renal function parameters were obtained from all patients. A multivariable logistic regression model was performed to assess the impact of factors on electrolyte disorders and patient outcome.

Results
A total of 8.5% of patients presenting to the ER used one diuretic, 2.5% two, and 0.4% three or four. In all, 4% had hyponatremia on admission and 12% hypernatremia. Hypokalemia was present in 11% and hyperkalemia in 4%. All forms of dysnatremia and dyskalemia were more common in patients taking diuretics. Loop diuretics were an independent risk factor for hypernatremia and hypokalemia, while thiazide diuretics were associated with the presence of hyponatremia and hypokalemia. In the Cox regression model, all forms of dysnatremia and dyskalemia were independent risk factors for in hospital mortality.

Conclusions
Existing diuretic treatment on admission to the ER was associated with an increased prevalence of electrolyte disorders. Diuretic therapy itself and disorders of serum sodium and potassium were risk factors for an adverse outcome.
Protective and therapeutic potency of N-acetyl-cysteine on propionic acid-induced biochemical autistic features in rats
Authors: Aldbass Abeer M , Bhat Ramesa Shafi , El-Ansary Afaf 
Published: March 2013

Abstract

Background
The investigation of the environmental contribution for developmental neurotoxicity is very critical. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations towards identifying either environmental toxicants that cause or drugs that protect from neurotoxicity and may help in treatment of neurodevelopmental disorders.

Objective
To study both the protective and therapeutic effects of N-acetyl cysteine on brain intoxication induced by propionic acid (PPA) in rats.

Methods
Twenty-eight young male Western Albino rats were enrolled in the present study. They were grouped into four equal groups, each of 7 animals. Group 1: control group, orally received only phosphate buffered saline; Group 2: PPA-treated group, received a neurotoxic dose of of PPA of 250 mg/kg body weight/day for 3 days; Group 3: protective group, received a dose of 50 mg/kg body weight/day N-acetyl-cysteine for one week followed by a similar dose of PPA for 3 days; and Group 4: therapeutic group, treated with the same dose of N-acetyl cysteine after being treated with the toxic dose of PPA. Serotonin, interferon gamma (IFN-γ), and glutathione-s-transferase activity, together with Comet DNA were assayed in the brain tissue of rats in all different groups.

Results
The obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of serotonin (5HT), increase in IFN-γ and inhibition of glutathione-s-transferase activity as three biomarkers of brain dysfunction. Additionally Comet DNA assay showed remarkably higher tail length, tail DNA % damage and tail moment. N-acetyl-cysteine was effective in counteracting the neurotoxic effects of PPA.

Conclusions
The low dose and the short duration of N-acetyl-cysteine treatment tested in the present study showed much more protective rather than therapeutic effects on PPA-induced neurotoxicity in rats, as there was a remarkable amelioration in the impaired biochemical parameters representing neurochemical, inflammatory, detoxification and DNA damage processes.