bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotine might have a protective effect in the etiology of multiple sclerosis
Authors: Hedström AK , Hillert J , Olsson T , Alfredsson L 
Published: January 2013

Objective: The use of moist snuff is common in Sweden and leads to exposure to high doses of nicotine. Recent studies indicate that exposure to nicotine could modulate immune responses. The aim of this study was to investigate the influence of snuff use on the risk of developing multiple sclerosis (MS), taking smoking habits into consideration. Methods: In two Swedish population-based, case-control studies (7883 cases, 9437 controls), subjects with different snuff use habits were compared regarding MS risk, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). Results: Snuff-takers have a decreased risk of developing MS compared with those who have never used moist snuff (OR 0.83, 95% CI 0.75–0.92), and we found clear evidence of an inverse dose-response correlation between cumulative dose of snuff use and the risk of developing the disease. We further observed that subjects who combined smoking and snuff use had a significantly lower risk for MS than smokers who had never used moist snuff, also after adjustment for amount of smoking. Conclusions: Our results add evidence to the hypothesis that nicotine exerts anti-inflammatory and immune-modulating effects in a way that might decrease the risk of developing MS.
Early brain pseudoatrophy while on natalizumab therapy is due to white matter volume changes
Authors: Vidal-Jordana Angela , Sastre-Garriga Jaume , Pérez-Miralles Francisco , Tur Carmen , Tintoré Mar , Horga Alejandro , Auger Cristina , Río Jordi , Nos Carlos , Edo Mari C , Arévalo María J , Castilló Joaquín , Rovira Alex , Montalban Xavier 
Published: January 2013

Background: Investigation of atrophy data from a pivotal natalizumab trial has demonstrated an increased rate of volume loss, compared to placebo, after the first year of therapy. It was considered to be probably due to a pseudoatrophy effect. Objective: To assess grey and white matter volume changes and their relation to global brain volume changes and to baseline inflammation, for patients under natalizumab therapy. Methods: We selected 45 patients on natalizumab therapy for at least 24 months, with magnetic resonance imaging (MRI) scans at baseline, 12 and 24 months. We calculated the percentage brain volume change (PBVC) for the first and second year, using SIENA software. Grey and white matter fractions (GMF and WMF, respectively) for the first year were calculated with SPM5, using lesion masks. After quality checks, six patients were excluded. We studied the predictive variables of change in brain volumes. Results: The PBVC decrease was faster during the first year (−1.10% ± 1.43%), as compared to the second (−0.51% ± 0.96%) ( p = 0.037). These differences were more marked in patients with baseline gadolinium-enhancing lesions ( p = 0.005). Mean GMF and WMF changes during the first year of treatment were +1.15% (n.s.) and −1.72% ( p = 0.017), respectively. The presence of active lesions at baseline MRI predicted PBVC ( p = 0.022) and WMF change ( p = 0.026) during the first year of treatment, after adjusting for age and corticosteroid treatment. No predictors were found for GMF volume changes. Conclusion: Early brain volume loss during natalizumab therapy is mainly due to WMF volume loss and it is related to the inflammatory activity present at the onset of therapy. We found that the pseudoatrophy effect is mostly due to white matter volume changes.
Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy
Authors: Hsieh Yao-Te , Gang Eun Ji , Geng Huimin , Park Eugene , Huantes Sandra , Chudziak Doreen , Dauber Katrin , Schaefer Paul , Scharman Carlton , Shimada Hiroyuki , Shojaee Seyedmehdi , Klemm Lars , Parameswaran Reshmi , Loh Mignon , Kang Eun-Suk , Koo Hong Hoe , Hofmann Wolf-Karsten , Andrade Jacob , Crooks Gay M. , Willman Cheryl L. , Müschen Markus , Papayannopoulou Thalia , Heisterkamp Nora , Bönig Halvard , Kim Yong-Mi 
Published: January 2013

Key Points
We evaluated interference with integrin alpha4–mediated stromal adhesion as a new acute lymphoblastic leukemia treatment. Integrin alpha4 blockade using natalizumab in combination with chemotherapy sensitizes pre-B acute lymphoblastic leukemia to chemotherapy.
Both Kdr and Flt1 play a vital role in hypoxia-induced Src-PLD1-PKCγ-cPLA2 activation and retinal neovascularization
Authors: Singh Nikhlesh K. , Hansen Dale E. , Kundumani-Sridharan Venkatesh , Rao Gadiparthi N. 
Published: January 2013

Key PointsBoth VEGFA and VEGFB and their receptors, Kdr and Flt1, are involved in retinal neovascularization.
Clonal architecture of chronic myelomonocytic leukemias
Authors: Itzykson Raphaël , Kosmider Olivier , Renneville Aline , Morabito Margot , Preudhomme Claude , Berthon Céline , Adès Lionel , Fenaux Pierre , Platzbecker Uwe , Gagey Olivier , Rameau Philippe , Meurice Guillaume , Oréar Cédric , Delhommeau François , Bernard Olivier A. , Fontenay Michaela , Vainchenker William , Droin Nathalie , Solary Eric 
Published: January 2013

Key Points
Early clonal dominance may distinguish chronic myelomonocytic leukemia from other chronic myeloid neoplasms with similar gene mutations. Early dominance of TET2-mutated cells in the hematopoietic tissue promotes myeloid differentiation skewing toward the granulomonocytic line.
Genome-wide identification of alternate bearing-associated microRNAs (miRNAs) in olive (Olea europaeaL.)
Authors: Yanik Huriye , Turktas Mine , Dundar Ekrem , Hernandez Pilar , Dorado Gabriel , Unver Turgay 
Published: January 2013

Abstract

Background
Alternate bearing is a widespread phenomenon among crop plants, defined as the tendency of certain fruit trees to produce a high-yield crop one year ("on-year"), followed by a low-yield or even no crop the following year ("off-year"). Several factors may affect the balance between such developmental phase-transition processes. Among them are the microRNA (miRNA), being gene-expression regulators that have been found to be involved as key determinants in several physiological processes.

Results
Six olive (Olea europaea L. cv. Ayvalik variety) small RNA libraries were constructed from fruits (ripe and unripe) and leaves (”on year” and ”off year” leaves in July and in November, respectively) and sequenced by high-throughput Illumina sequencing. The RNA was retrotranscribed and sequenced using the high-throughput Illumina platform. Bioinformatics analyses of 93,526,915 reads identified 135 conserved miRNA, belonging to 22 miRNA families in the olive. In addition, 38 putative novel miRNAs were discovered in the datasets. Expression of olive tree miRNAs varied greatly among the six libraries, indicating the contribution of diverse miRNA in balancing between reproductive and vegetative phases. Predicted targets of miRNA were categorized into 108 process ontology groups with significance abundance. Among those, potential alternate bearing-associated processes were found, such as development, hormone-mediated signaling and organ morphogenesis. The KEGG analyses revealed that the miRNA-targeted genes are involved in seven main pathways, belonging to carbohydrate metabolism and hormone signal-transduction pathways.

Conclusion
A comprehensive study on olive miRNA related to alternate bearing was performed. Regulation of miRNA under different developmental phases and tissues indicated that control of nutrition and hormone, together with flowering processes had a noteworthy impact on the olive tree alternate bearing. Our results also provide significant data on the miRNA-fruit development interaction and advance perspectives in the miRNA profile of the olive tree.
A study of two Chinese patients with tetrasomy and pentasomy 15q11q13 including Prader-Willi/Angelman syndrome critical region present with developmental delays and mental impairment
Authors: Yang Jing , Yang Yongchen , Huang Yi , Hu Yan , Chen Xi , Sun Hengjuan , Lv Zhibao , Cheng Qian , Bao Liming 
Published: January 2013

Abstract

Background
The proximal chromosome 15q is prone to unequal crossover, leading to rearrangements. Although 15q11q13 duplications are common in patients with developmental delays and mental impairment, 15q aneusomies resulting in greater or equal to 4 copies of 15q11q13 are rare and no pentasomy 15q11q13 has been reported in the literature. Thus far, all reported high copy number 15q11q13 cases are from the West populations and no such study in Chinese patients have been documented. Dosage-response pattern of high copy number 15q11q13 on clinical presentations is still a subject for further study.

Case Presentation
In this study, we characterized two Han Chinese patients with high copy number 15q11q13. Using chromosome banding, high resolution SNP-based cytogenomic array, Fluorescence in situ hybridization, and PCR-based microsatellite analysis, we identified two patients with tetrasomy 15q11q13 and pentasomy 15q11q13. Both 15q11q13 aneusomies resulted from a maternally inherited supernumerary marker chromosome 15, and each was composed of two different sized 15q11q13 segments covering the Prader-Willi/Angelman critical region: one being about 10 Mb with breakpoints at BP1 and BP5 regions on 15q11 and 15q13, respectively, and another about 8 Mb in size with breakpoints at BP1 and BP4 regions on 15q. Both patients presented with similar clinical features that included neurodevelopmental delays, mental impairment, speech and autistic behavior, and mild dysmorphism. The patient with pentasomy 15q11q13 was more severely affected than the patient with tetrasomy 15q11q13. Low birth weight was noted in patient with pentasomy 15q1q13.

Conclusions
To the best of our knowledge, this is the first case of pentasomy 15q11q13 and the first study of high copy number 15q11q13 in Han Chinese patients. Our findings demonstrate that patients with tetrasomy and pentasomy of chromosome 15q11q13 share similar spectrum of phenotypes reported in other high copy number 15q11q13 patients in the West, and positive correlation between 15q11q13 copy number and degree of severity of clinical phenotypes. Low birth weight observed in the pentasomy 15q11q13 patient was not reported in other patients with high copy number 15q11q13. Additional studies would be necessary to further characterize high copy number 15q11q13 aneusomies.
A pri-miR-218variant and risk of cervical carcinoma in Chinese women
Authors: Shi Ting-Yan , Chen Xiao-Jun , Zhu Mei-Ling , Wang Meng-Yun , He Jing , Yu Ke-Da , Shao Zhi-Ming , Sun Meng-Hong , Zhou Xiao-Yan , Cheng Xi , Wu Xiaohua , Wei Qingyi 
Published: January 2013

Abstract

Background
MicroRNA (miRNA)-related single nucleotide polymorphisms (SNPs) may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma.

Methods
In this case–control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women.

Results
We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015). However, this association was not observed for the miR-218 binding site SNP (rs2566) on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma.

Conclusions
The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.
Similar decline in mortality rate of older persons with and without type 2 diabetes between 1993 and 2004 the Icelandic population-based Reykjavik and AGES-Reykjavik cohort studies
Authors: Olafsdottir Elin , Aspelund Thor , Sigurdsson Gunnar , Benediktsson Rafn , Thorsson Bolli , Harris Tamara B , Launer Lenore J , Eiriksdottir Gudny , Gudnason Vilmundur 
Published: January 2013

Abstract

Background
A decline in mortality rates due to cardiovascular diseases and all-cause mortality has led to increased life expectancy in the Western world in recent decades. At the same time, the prevalence of type 2 diabetes, a disease associated with a twofold excess risk of cardiovascular disease and mortality, has been increasing. The objective of this study was to estimate the secular trend of cardiovascular and all-cause mortality rates in two population-based cohorts of older persons, with and without type 2 diabetes, examined 11 years apart.

Methods
1506 participants (42% men) from the population-based Reykjavik Study, examined during 1991–1996 (median 1993), mean age 75.0 years, and 4814 participants (43% men) from the AGES-Reykjavik Study, examined during 2002–2006 (median 2004), mean age 77.2 years, age range in both cohorts 70–87 years. The main outcome measures were age-specific mortality rates due to cardiovascular disease and all causes, over two consecutive 5.7- and 5.3-year follow-up periods.

Results
A 32% decline in cardiovascular mortality rate and a 19% decline in all-cause mortality rate were observed between 1993 and 2004. The decline was greater in those with type 2 diabetes, as illustrated by the decline in the adjusted hazard ratio of cardiovascular mortality in individuals with diabetes compared to those without diabetes, from 1.88 (95% CI 1.24-2.85) in 1993 to 1.46 (95% CI 1.11-1.91) in 2004. We also observed a concurrent decrease in major cardiovascular risk factors in both those with and without diabetes. A higher proportion of persons with diabetes received glucose-lowering, hypertensive and lipid-lowering medication in 2004.

Conclusions
A decline in cardiovascular and all-cause mortality rates was observed in older persons during the period 1993–2004, in both those with and without type 2 diabetes. This decline may be partly explained by improvements in cardiovascular risk factors and medical treatment over the period studied. However, type 2 diabetes still persists as an independent risk factor for cardiovascular mortality.
Glycemic variability is associated with subclinical atherosclerosis in Chinese type 2 diabetic patients
Authors: Mo Yifei , Zhou Jian , Li Mei , Wang Yuwei , Bao Yuqian , Ma Xiaojing , Li Ding , Lu Wei , Hu Cheng , Li Minghua , Jia Weiping 
Published: January 2013

Abstract

Background
The contribution of glycemic variability to macrovascular complications remains unclear. We therefore investigated the association between glycemic variability and cervical and/or intracranial atherosclerosis in Chinese type 2 diabetic patients.

Methods
We conducted a cross-sectional study in 216 type 2 diabetic patients with a hemoglobin A1c of 8.3 ± 1.7% and a median diabetes duration of 9.0 years. The standard deviation of blood glucose values (SDBG) and the mean amplitude of glycemic excursion (MAGE) were calculated from continuous glucose monitoring system data for assessing glycemic variability while 24h mean blood glucose (MBG) was calculated for measuring overall blood glucose level. Magnetic resonance angiography (MRA) was used to detect cervical and/or intracranial plaque, and ultrasonography was used to quantify carotid intima-media thickness (IMT) as an index of subclinical atherosclerosis.

Results
One hundred and fifty-three patients (70.8%) presented with cervical and/or intracranial lesions on MRA among 216 patients in the study. Elder age, increased systolic blood pressure, increased MBG and elevated low density lipoprotein cholesterol were independent contributors to plaque formation. In patients without stenosis (n = 63), SDBG (r = 0.412, P = 0.001) and MAGE (r = 0.365, P = 0.005) were both correlated with carotid IMT and these relationships remained significant in multiple linear regression analysis (multiple R

2
= 0.314 for the model including SDBG and multiple R

2
= 0.268 for the model including MAGE). However, SDBG and MAGE were not significantly different among patients with different stenosis degrees.

Conclusions
Glycemic variability is associated with subclinical atherosclerosis in Chinese type 2 diabetic patients.
MEK inhibition induced downregulation of MRP1 and MRP3 expression in experimental hepatocellular carcinoma
Authors: Lin Shibo , Hoffmann Katrin , Xiao Zhi , Jin Nan , Galli Uwe , Mohr Elvira , Büchler Markus W , Schemmer Peter 
Published: January 2013

Abstract

Background
Hepatocellular carcinoma (HCC) exhibits strong intrinsic and acquired drug resistance which is the main obstacle to chemotherapy. Overexpression of ATP binding cassette (ABC) proteins correlates with activation of mitogen activated protein kinase (MAPK) pathway in HCC. Here, we systematically investigated the inhibition of MAPK pathway and its role in regulating HCC cell growth as well as ABC proteins MRP1 and MRP3 expression.

Methods
The Raf1 kinase inhibitor (GW5074) and different MEK inhibitors (U0126 and AZD6244) were used to treat HCC cells to identify their effects on HCC cell growth and ABC proteins expression in vitro. Cell viability tests were performed after the treatment of MAPK pathway inhibitors and in combination with gemcitabine or doxorubicin. Western blot was applied to assess the changes of MAPK pathway and protein expression of MRP1 and MRP3. Flow cytometry was used to measure intracellular doxorubicin accumulation after the treatment of MEK inhibitors.

Results
Both Raf1 inhibitor (GW5074) and MEK inhibitors (U0126 and AZD6244) suppressed HCC cell growth in a dose dependent manner. Pre-treatment of MEK inhibitor U0126 or AZD6244 sensitized HCC cells to gemcitabine or doxorubicin based chemotherapy. Raf1 inhibitor GW5074 had no effect on MRP1 and MRP3 protein expression. Treatment of gemcitabine or doxorubicin activated phosphorylated ERK and induced the upregulation of MRP1 and MRP3. MEK inhibitors U0126 and AZD6244 deactivated phosphorylated ERK, decreased endogenous MRP1 expression, reversed gemcitabine or doxorubicin induced MRP1 and MRP3 upregulation, and increased the intracellular doxorubicin accumulation.

Conclusion
This study provides evidence that MEK inhibitors sensitize HCC cells to chemotherapy by increasing intracellular chemodrug accumulation. MEK inhibirors U0126 and AZD6244 reduced MRP1 as well as MRP3 expression, and may contribute partially to the sensitization. The combination of MEK inhibitor and conventional chemotherapy may offer new therapeutic option for the treatment of resistant HCC.
Waist circumference vs body mass index in association with cardiorespiratory fitness in healthy men and women: a cross sectional analysis of 403 subjects
Authors: Dagan Shiri Sherf , Segev Shlomo , Novikov Ilya , Dankner Rachel 
Published: January 2013

Abstract

Objective
Body mass index (BMI) is more commonly used than waist circumference as a measure of adiposity in clinical and research settings. The purpose of this study was to compare the associations of BMI and waist circumference with cardiorespiratory fitness.

Methods
In a cross-sectional study of 403 healthy men and women aged 50 ± 8.8 years, BMI and waist circumference were measured. Cardiorespiratory fitness was assessed from estimated maximal O2 uptake (VO2max), as calculated from a maximal fitness test.

Results
Mean BMI (kg/m2) was 27.8 ± 3.7 and 25.5 ± 4.6; and mean waist circumference (cm) 94.1 ± 9.7 and 84.3 ± 10.4 for men and women, respectively. Both men and women reported an average of 2.5 hours of weekly sports related physical activity, and 18% were current smokers. Correlation coefficients between both BMI and waist circumference, and VO2max were statistically significant in men (r = −0.280 and r = −0.377, respectively, p > 0.05 for both) and in women (r = −0.514 and r = −0.491, respectively, p > 0.05 for both). In women, the contribution of BMI to the level of VO2max in a regression model was greater, while in men waist circumference contributed more to the final model. In these models, age, hours of training per week, and weekly caloric expenditure in sport activity, significantly associated with VO2max, while smoking did not.

Conclusion
The differences observed between the sexes in the associations of BMI and waist circumference with VO2max support the clinical use of both obesity measures for assessment of cardiorespiratory fitness.
Bioenergetics of murine lungs infected with respiratory syncytial virus
Authors: Alsuwaidi Ahmed R , Benedict Sheela , Kochiyil Jose , Mustafa Farah , Hartwig Stacey M , Almarzooqi Saeeda , Albawardi Alia , Rizvi Tahir A , Varga Steven M , Souid Abdul-Kader 
Published: January 2013

Abstract

Background
Cellular bioenergetics (cellular respiration and accompanying ATP synthesis) is a highly sensitive biomarker of tissue injury and may be altered following infection. The status of cellular mitochondrial O2 consumption of the lung in pulmonary RSV infection is unknown.

Methods
In this study, lung fragments from RSV-infected BALB/c mice were evaluated for cellular O2 consumption, ATP content and caspase activity. The disease was induced by intranasal inoculation with the RSV strain A2 and lung specimens were analyzed on days 2–15 after inoculation. A phosphorescence O2 analyzer that measured dissolved O2 concentration as a function of time was used to monitor respiration. The caspase-3 substrate analogue N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin (Ac-DEVD-AMC) was used to monitor intracellular caspases.

Results
O2 concentration declined linearly with time when measured in a sealed vial containing lung fragment and glucose as a respiratory substrate, revealing its zero-order kinetics. O2 consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Cellular respiration increased by 1.6-fold (p<0.010) and ATP content increased by 3-fold in the first week of RSV infection. Both parameters returned to levels found in uninfected lungs in the second week of RSV infection. Intracellular caspase activity in infected lungs was similar to uninfected lungs throughout the course of disease.

Conclusions
Lung tissue bioenergetics is transiently enhanced in RSV infection. This energy burst, triggered by the virus or virus-induced inflammation, is an early biomarker of the disease and may be targeted for therapy.
Response to Dr. Roger’s letter: further studies are necessary in order to conclude a causal association between the consumption of monosodium L-glutamate (MSG) and the prevalence of metabolic syndrome in the rural Thai population
Authors: Insawang Tonkla , Selmi Carlo , Cha’on Ubon , Gershwin M Eric , Yongvanit Puangrat , Prasongwattana Vitoon 
Published: January 2013

Abstract
See related article: http://www.nutritionandmetabolism.com/content/10/1/14