bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon-α sensitizes HBx-expressing hepatocarcinoma cells to chemotherapeutic drugs through inhibition of HBx-mediated NF-κB activation
Authors: Liu Yanning , Lou Guohua , Wu Wei , Shi Yu , Zheng Min , Chen Zhi 
Published: May 2013

Abstract

Background
Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) is characterized by high chemotherapy resistance; however, the underlying mechanism has not been fully clarified. In addition, HBx protein has been reported to play a key role in virus-mediated hepatocarcinogenesis. Therefore, the present study aims to investigate the role of HBx in the drug-resistance of HBV-related HCC and examine whether such drug-resistance can be reversed by IFN-α treatment.

Methods
We established HBx-expressing cells by liposome-mediated transfection of HBx into the Huh7 cell line. MTT, Annexin V/PI, and cell cycle assay were used for determining the cellular growth inhibition, apoptosis, and growth arrest, respectively, after treatment with chemical drug. We further used tumor-bearing mice model to compare the tumor growth inhibition efficacy of ADM and 5-FU between the Huh7-HBx group and the control group, as well as the ADM + IFN-α or ADM + IMD treated group and the ADM treated group. SQ-Real time-PCR was performed to analyze the expression of MDR-associated genes and anti-apoptotic genes. Moreover, immunofluorescence and Western blotting were used to determine the subcellular localization of p65 and the phosphorylation of IκBα.

Results
The IC50 values of Huh7-HBx cells against ADM and Amn were 2.317 and 1.828-folds higher than those of Huh7-3.1 cells, respectively. The apoptosis ratio and growth arrest was significantly lower in Huh7-HBx cells after treatment with ADM. The in vivo experiment also confirmed that the Huh7-HBx group was much more resistant to ADM or 5-FU than the control. Furthermore, the expression of MDR-associated genes, such as MDR1, MRP1, LRP1, and ABCG2, were significantly up-regulated in Huh7-HBx cells, and the NF-κB pathway was activated after HBx gene transfection in Huh7 cells. However, combined with IFN-α in ADM treatment, the HBx induced drug-resistance in Huh7-HBx cells can be partly abolished in in vitro and in vivo models. Moreover, we found that the NF-κB canonical pathway was affected by IFN-α treatment, and the expression of anti-apoptotic genes, such as Gadd45β, Survivin, and c-IAP-1 was down-regulated by IFN-α treatment in a dose-dependent manner.

Conclusions
HBx protein can induce MDR of HBV-related HCC by activating the NF-κB pathway, which can be partly abolished by IFN-α treatment.
‘Honeycomb appearance’ on three-dimensional transthoracic echocardiography as the landmark of left ventricular non-compaction: two case reports
Authors: Konishi Takao , Nagai Tomoo , Hamabe Akira , Arakawa Junko , Hisadome Hideki , Yoshida Mikoto , Tabata Hirotsugu 
Published: May 2013

Abstract

Introduction
Left ventricular non-compaction is a rare congenital heart disease, and is most commonly diagnosed via two-dimensional echocardiography according to echocardiographic criteria. Recently, transthoracic three-dimensional echocardiography has become available in the clinical setting.

Case presentation
We present two isolated cases of left ventricular non-compaction from Japan (in an 84-year-old woman and 47-year-old man) that were confirmed by two-dimensional echocardiography, contrast-enhanced two-dimensional echocardiography, three-dimensional echocardiography and cardiac magnetic resonance imaging. In both cases, three-dimensional echocardiography successfully demonstrated the trabecular meshwork of the left ventricle, referred to as a ‘honeycomb appearance’.

Conclusions
Three-dimensional echocardiography has the advantage of visualizing an en-face view of the trabecular meshwork, which is not possible with two-dimensional echocardiography. We further emphasize the clinical utility of three-dimensional echocardiography, which is not limited to just the observation of the trabeculations and inter-trabecular recesses, but can also visualize the trabecular meshwork with a ‘honeycomb appearance’.
Effect of salts on the Co-fermentation of glucose and xylose by a genetically engineered strain of Saccharomyces cerevisiae
Authors: Casey Elizabeth , Mosier Nathan S , Adamec Jiri , Stockdale Zachary , Ho Nancy , Sedlak Miroslav 
Published: May 2013

Abstract

Background
A challenge currently facing the cellulosic biofuel industry is the efficient fermentation of both C5 and C6 sugars in the presence of inhibitors. To overcome this challenge, microorganisms that are capable of mixed-sugar fermentation need to be further developed for increased inhibitor tolerance. However, this requires an understanding of the physiological impact of inhibitors on the microorganism. This paper investigates the effect of salts on Saccharomyces cerevisiae 424A(LNH-ST), a yeast strain capable of effectively co-fermenting glucose and xylose.

Results
In this study, we show that salts can be significant inhibitors of S. cerevisiae. All 6 pairs of anions (chloride and sulfate) and cations (sodium, potassium, and ammonium) tested resulted in reduced cell growth rate, glucose consumption rate, and ethanol production rate. In addition, the data showed that the xylose consumption is more strongly affected by salts than glucose consumption at all concentrations. At a NaCl concentration of 0.5M, the xylose consumption rate was reduced by 64.5% compared to the control. A metabolomics study found a shift in metabolism to increased glycerol production during xylose fermentation when salt was present, which was confirmed by an increase in extracellular glycerol titers by 4 fold. There were significant differences between the different cations. The salts with potassium cations were the least inhibitory. Surprisingly, although salts of sulfate produced twice the concentration of cations as compared to salts of chloride, the degree of inhibition was the same with one exception. Potassium salts of sulfate were less inhibitory than potassium paired with chloride, suggesting that chloride is more inhibitory than sulfate.

Conclusions
When developing microorganisms and processes for cellulosic ethanol production, it is important to consider salt concentrations as it has a significant negative impact on yeast performance, especially with regards to xylose fermentation.
Changing trends in surgery for Graves’ disease: A cohort comparison of those having surgery intended to preserve thyroid function with those having ablative surgery
Authors: Al-Adhami Ahmed , Snaith Ailsa C , Craig Wendy L , Krukowski Zygmunt H 
Published: May 2013

Background Surgery for Graves’ disease may be performed with the intent of preserving thyroid function (subtotal thyroidectomy) or ablating thyroid function (total thyroidectomy). This study examines the evolving practice in a specialist endocrine surgical unit. Method Longitudinal cohort study of patients undergoing surgery for Graves’ disease between 1986 and 2008. Outcome measures were thyroid failure, recurrent toxicity, recurrent laryngeal nerve (RLN) palsy, early reoperation and hypocalcaemia. Time to thyroid failure was analysed by potential predictors. Results Of 149 patients (129 female), 78 (52.3 percent) underwent subtotal thyroidectomy with the intention to preserve function (PF) and 71 (47.6 percent) total thyroidectomy with the intention to ablate thyroid function (AF). Mean duration of follow-up was 11.1 years; 14.8 years and 7.0 years respectively. Of 78 PF procedures: six (7.7 percent) patients suffered recurrent toxicity; 68 (87.2 percent) developed thyroid failure (four after treatment for recurrent toxicity); and eight (10 percent) remained euthyroid without replacement. Male gender and remnant gland weight were significant predictors of failure (P = 0.021 and 0.022 respectively). One patient developed permanent RLN palsy and one permanent hypocalcaemia. Of 71 AF procedures: one developed acute airway obstruction; one permanent RLN palsy; four permanent hypocalcaemia; and none developed recurrent toxicity. There were no deaths within a year of surgery. There was no statistically significant difference in complication rates. Conclusion Most PF resections resulted in eventual thyroid failure. The shift to ablative surgery virtually eliminated the need for lifelong specialist follow-up, albeit with an insignificant rise in permanent hypocalcaemia.
A genome scale metabolic network for rice and accompanying analysis of tryptophan, auxin and serotonin biosynthesis regulation under biotic stress
Authors: Dharmawardhana Palitha , Ren Liya , Amarasinghe Vindhya , Monaco Marcela , Thomason Jim , Ravenscroft Dean , McCouch Susan , Ware Doreen , Jaiswal Pankaj 
Published: May 2013

Abstract

Background
Functional annotations of large plant genome projects mostly provide information on gene function and gene families based on the presence of protein domains and gene homology, but not necessarily in association with gene expression or metabolic and regulatory networks. These additional annotations are necessary to understand the physiology, development and adaptation of a plant and its interaction with the environment.

Results
RiceCyc is a metabolic pathway networks database for rice. It is a snapshot of the substrates, metabolites, enzymes, reactions and pathways of primary and intermediary metabolism in rice. RiceCyc version 3.3 features 316 pathways and 6,643 peptide-coding genes mapped to 2,103 enzyme-catalyzed and 87 protein-mediated transport reactions. The initial functional annotations of rice genes with InterPro, Gene Ontology, MetaCyc, and Enzyme Commission (EC) numbers were enriched with annotations provided by KEGG and Gramene databases. The pathway inferences and the network diagrams were first predicted based on MetaCyc reference networks and plant pathways from the Plant Metabolic Network, using the Pathologic module of Pathway Tools. This was enriched by manually adding metabolic pathways and gene functions specifically reported for rice. The RiceCyc database is hierarchically browsable from pathway diagrams to the associated genes, metabolites and chemical structures. Through the integrated tool OMICs Viewer, users can upload transcriptomic, proteomic and metabolomic data to visualize expression patterns in a virtual cell. RiceCyc, along with additional species-specific pathway databases hosted in the Gramene project, facilitates comparative pathway analysis.

Conclusions
Here we describe the RiceCyc network development and discuss its contribution to rice genome annotations. As a case study to demonstrate the use of RiceCyc network as a discovery environment we carried out an integrated bioinformatic analysis of rice metabolic genes that are differentially regulated under diurnal photoperiod and biotic stress treatments. The analysis of publicly available rice transcriptome datasets led to the hypothesis that the complete tryptophan biosynthesis and its dependent metabolic pathways including serotonin biosynthesis are induced by taxonomically diverse pathogens while also being under diurnal regulation. The RiceCyc database is available online for free access at http://www.gramene.org/pathway/.
A tale of two systems: poisoning management in Iran and the United States
Authors: Mehrpour Omid , Zamani Nasim , Brent Jeffrey , Abdollahi Mohammad 
Published: May 2013

AbstractPoisoning morbidity and mortality is high in the developing world. Systems for care of poisoned patients differ markedly between countries. In this paper a comparison of two very different systems for the care of poisoned patients, is presented. Specifically, the role of poison centers and poison treatment centers in the US and Iran are contrasted. A systematic literature search was undertaken utilizing the PubMed, Scopus, and Google Scholar and the keywords “poison centers”, “treatment” “Iran” “United States of America” and 100 publications were identified. From these, relevant data were found in 23 publications. The information was double-checked and data were summarized herein.We find that the system of the care of poisoned patients relies heavily on certified poison centers in the US and that only a few hospitals have well developed medical toxicology services. In contrast, in Iran, the poison center system is somehow less developed and the care of poisoned patients is provided in centralized high volume hospital poison units.Although both the US and Iran have highly developed systems for the care of poisoned patients they are distinctly different. Comparative studies based on these systems could provide important data for developing countries with more rudimentary poison control and treatment facilities.
Aging phenotypes in cultured normal human mammary epithelial cells are correlated with decreased telomerase activity independent of telomere length
Authors: Sputova Klara , Garbe James C , Pelissier Fanny A , Chang Eric , Stampfer Martha R , LaBarge Mark A 
Published: May 2013

Background
Shortening of telomeres, which are essential for maintenance of genomic integrity, is a mechanism commonly associated with the aging process. Here we ascertained whether changes in telomere lengths or telomerase activity correlated with age in normal human mammary epithelial cells (HMEC), or with phenotypes of aging in breast. Accordingly, flow cytometry fluorescence in situ hybridization (flowFISH) was used to determine relative telomere lengths (RTL), and telomerase activity was measured by the telomeric repeat amplification protocol (TRAP), in a collection of 41 primary HMEC strains established from women aged 16 to 91 years.

Results
RTL measurements of HMEC strains that were heterogeneous with respect to lineage composition revealed no significant associations between telomere length with age, maximum observed population doublings, or with lineage composition of the strains. However, within strains, luminal epithelial and cKit-expressing epithelial progenitor cells that were flow cytometry-enriched from individual HMEC strains exhibited significantly shorter telomeres relative to isogenic myoepithelial cells (P < 0.01). In unsorted strains, detectable telomerase activity did not correlate with RTL. Telomerase activity declined with age; the average age of strains that exhibited TRAP activity was 29.7 ± 3.9y, whereas the average age of strains with no detectable TRAP activity was 49.0 ± 4.9y (P < 0.01). Non-detectable TRAP activity also was correlated with phenotypes of aging previously described in HMEC strains; increased proportions of CD227-expressing luminal epithelial cells (P < 0.05) and cKit-expressing progenitor cells (P < 0.05).

Conclusions
Telomere shortening did not correlate with the chronological ages of HMEC strains, whereas decreased telomerase activity correlated with age and with lineage distribution phenotypes characteristic of aging.
Increased mitochondrial activity in a novel IDH1-R132H mutant human oligodendroglioma xenograft model: in situ detection of 2-HG and α-KG
Authors: Navis Anna C , Niclou Simone P , Fack Fred , Stieber Daniel , van Lith Sanne , Verrijp Kiek , Wright Alan , Stauber Jonathan , Tops Bastiaan , Otte-Holler Irene , Wevers Ron A , van Rooij Arno , Pusch Stefan , von Deimling Andreas , Tigchelaar Wikky , van Noorden Cornelis JF , Wesseling Pieter , Leenders William PJ 
Published: May 2013

Abstract

Background
Point mutations in genes encoding NADP+-dependent isocitrate dehydrogenases (especially IDH1) are common in lower grade diffuse gliomas and secondary glioblastomas and occur early during tumor development. The contribution of these mutations to gliomagenesis is not completely understood and research is hampered by the lack of relevant tumor models. We previously described the development of the patient-derived high-grade oligodendroglioma xenograft model E478 that carries the commonly occurring IDH1-R132H mutation. We here report on the analyses of E478 xenografts at the genetic, histologic and metabolic level.

Results
LC-MS and in situ mass spectrometric imaging by LESA-nano ESI-FTICR revealed high levels of the proposed oncometabolite D-2-hydroxyglutarate (D-2HG), the product of enzymatic conversion of α-ketoglutarate (α-KG) by IDH1-R132H, in the tumor but not in surrounding brain parenchyma. α-KG levels and total NADP+-dependent IDH activity were similar in IDH1-mutant and -wildtype xenografts, demonstrating that IDH1-mutated cancer cells maintain α-KG levels. Interestingly, IDH1-mutant tumor cells in vivo present with high densities of mitochondria and increased levels of mitochondrial activity as compared to IDH1-wildtype xenografts. It is not yet clear whether this altered mitochondrial activity is a driver or a consequence of tumorigenesis.

Conclusions
The oligodendroglioma model presented here is a valuable model for further functional elucidation of the effects of IDH1 mutations on tumor metabolism and may aid in the rational development of novel therapeutic strategies for the large subgroup of gliomas carrying IDH1 mutations.
The consequences of measurement error when estimating the impact of obesity on income
Authors: O’Neill Donal , Sweetman Olive 
Published: May 2013

AbstractThis paper examines the consequences of using self-reported measures of BMI when estimating the effect of BMI on income for women using both Irish and US data. We find that self-reported BMI is subject to substantial measurement error and that this error deviates from classical measurement error. These errors cause the traditional least squares estimator to overestimate the relationship between BMI and income. We show that neither the conditional expectation estimator nor the instrumental variables approach adequately address the bias and briefly discuss alternative approaches that could be considered when faced with non-classical measurement error.JEL codesC13, C26, I14
Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers
Authors: Valentini Gabriele , Marcoccia Antonella , Cuomo Giovanna , Vettori Serena , Iudici Michele , Bondanini Francesco , Santoriello Carlo , Ciani Aldo , Cozzolino Domenico , De Matteis Giovanni Maria , Cappabianca Salvatore , Vitelli Filiberto , Spanò Alberto 
Published: May 2013

Abstract
Introduction
Early systemic sclerosis (SSc) is characterized by Raynaud's phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Whether early SSc patients with only marker autoantibodies or capillaroscopic positivity differ in any aspect at presentation is unclear.

Methods
Seventy-one consecutive early SSc patients were investigated for preclinical cardiopulmonary alterations. Out of these, 44 patients and 25 controls affected by osteoarthritis or primary fibromyalgia syndrome were also investigated for serum markers of fibroblast (carboxyterminal propeptide of collagen I), endothelial (soluble E-selectin) and T-cell (soluble IL-2 receptor alpha) activation.

Results
Thirty-two of the 71 patients (45.1%) had both a marker autoantibody and a capillaroscopic scleroderma pattern (subset 1), 16 patients (22.5%) had only a marker autoantibody (subset 2), and 23 patients (32.4%) had only a capillaroscopic scleroderma pattern (subset 3). Patients with marker autoantibodies (n = 48, 67.6%) had a higher prevalence of impaired diffusing lung capacity for carbon monoxide (P = 0.0217) and increased serum levels of carboxyterminal propeptide of collagen I (P = 0.0037), regardless of capillaroscopic alterations. Patients with a capillaroscopic scleroderma pattern (n = 55, 77.5%) had a higher prevalence of puffy fingers (P = 0.0001) and increased serum levels of soluble E-selectin (P = 0.0003) regardless of marker autoantibodies.

Conclusion
These results suggest that the autoantibody and microvascular patterns in early SSc may each be related to different clinical-preclinical features and circulating activation markers at presentation. Longitudinal studies are warranted to investigate whether these subsets undergo a different disease course over time.
Treatment of Muckle-Wells syndrome: analysis of two IL-1-blocking regimens
Authors: Kuemmerle-Deschner Jasmin B , Wittkowski Helmut , Tyrrell Pascal N , Koetter Ina , Lohse Peter , Ummenhofer Katharina , Reess Fabian , Hansmann Sandra , Koitschev Assen , Deuter Christoph , Bialkowski Anja , Foell Dirk , Benseler Susanne M 
Published: May 2013

Abstract
Objectives
Muckle-Wells syndrome (MWS) is an autoinflammatory disease characterized by excessive interleukin-1 (IL-1) release, resulting in recurrent fevers, sensorineural hearing loss, and amyloidosis. IL-1 inhibition with anakinra, an IL-1 receptor antagonist, improves clinical symptoms and inflammatory markers. Subclinical disease activity is commonly observed. Canakinumab, a fully human IgG1 anti-IL-1β monoclonal antibody, can abolish excess IL-1β. The study aim was to analyze the efficacy and safety of these two anti-IL-1 therapies.

Methods
Two cohorts of patients with severe MWS and confirmed NLRP3 mutation were treated with anakinra and/or canakinumab. Clinical and laboratory features including ESR, CRP, SAA, and the neutrophil marker S100A12 were determined serially. Disease activity was captured by MWS disease activity scores (MWS-DAS). Remission was defined as MWS-DAS ≤5 plus normal CRP and SAA. Treatment efficacy and safety were analyzed.

Results
The study included 12 anakinra- and 14 canakinumab-treated patients; the median age was 33.5 years (3.0 years to 72.0 years); 57% were female patients. Both treatment regimens led to a significant reduction of clinical disease activity and inflammatory markers. At last follow-up, 75% of anakinra-treated and 93% of canakinumab-treated patients achieved remission. During follow-up, S100A12 levels mirrored recurrence of disease activity. Both treatment regimens had favorable safety profiles.

Conclusions
IL-1 blockade is an effective and safe treatment in MWS patients. MWS-DAS in combination with MWS inflammatory markers provides an excellent monitoring tool set. Canakinumab led to a sustained control of disease activity even after secondary failure of anakinra therapy. S100A12 may be a sensitive marker to detect subclinical disease activity.
Chronic pain in survivors of critical illness: a retrospective analysis of incidence and risk factors
Authors: Battle Ceri E , Lovett Simon , Hutchings Hayley 
Published: May 2013

Abstract
Introduction
Chronic pain has been reported in survivors of critical illness for many years after discharge from hospital. This study investigates the incidence and site of chronic pain in survivors of critical illness between 6 months and 1 year after hospitalization, including ICU admission. A retrospective analysis of the risk factors for chronic pain in this patient group was also completed.

Methods
A questionnaire method was used to investigate the incidence of chronic pain and the specific body parts affected. A retrospective study and multivariable analysis were used to investigate the risk factors for chronic pain in this patient group. All survivors of a general intensive care unit (ICU) in South Wales in a 6-month period were included in this study.

Results
Chronic pain was reported in 44% of all respondents. The shoulder was the most commonly reported joint affected by pain (22%). Risk factors for chronic pain between 6 months and 1 year after ICU discharge were increasing patient age and severe sepsis.

Conclusions
Chronic pain is a problem in survivors of critical illness, especially in the shoulder joint, and further studies are needed investigating therapeutic interventions that address this long-term problem.