bluuebunny/crossref_metadata_2025 huggingface dataset:
Maturity‐associated variation in total and depot‐specific body fat in children and adolescents
Authors: Staiano Amanda E. , Broyles Stephanie T. , Gupta Alok K. , Malina Robert M. , Katzmarzyk Peter T.
Published: April 2013

Objectives

This study considered the association between sexual maturation and adiposity in children and adolescents, and examined the contribution of sexual maturation to ethnic differences in total and depot‐specific body fat.

Methods

The sample included 382 White and African American 5–18‐year‐olds. Body mass index (BMI), waist circumference (WC) and sexual maturity status (breast/genital and pubic hair stage) were assessed in a clinical setting. Total body fat (TBF) was measured by dual‐energy X‐ray absorptiometry and abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) were measured by magnetic resonance imaging. Analysis of covariance adjusted for age was used to examine the association between sexual maturity status and adiposity, and linear regression adjusted for age was used to examine the influence of sexual maturation on ethnic differences in adiposity. Analysis of VAT also controlled for TBF. Significance was accepted at P < 0.05.

Results

Breast/genital stage was significantly associated with BMI, WC, TBF, and SAT in girls of both ethnic groups and in White boys. Breast stage was associated with VAT. Stage of pubic hair was significantly associated with TBF and VAT in White girls only. In girls, sexual maturation attenuated the ethnic effects on BMI and WC, but the ethnic effect in VAT persisted. In boys, sexual maturation did not attenuate ethnic differences on VAT and did not predict WC or SAT. Sexual maturity status independently explained variance in adiposity in girls only.

Conclusions

Sexual maturity status is an important determinant of pediatric adiposity and attenuates ethnic differences in girls' adiposity. Am. J. Hum. Biol. 25:473–479, 2013. © 2013 Wiley Periodicals, Inc.
Bioactive conformations of two seminal delta opioid receptor penta‐peptides inferred from free‐energy profiles
Authors: Scarabelli Guido , Provasi Davide , Negri Ana , Filizola Marta
Published: April 2013

Delta‐opioid (DOP) receptors are members of the G protein‐coupled receptor (GPCR) sub‐family of opioid receptors, and are evolutionarily related, with homology exceeding 70%, to cognate mu‐opioid (MOP), kappa‐opioid (KOP), and nociceptin opioid (NOP) receptors. DOP receptors are considered attractive drug targets for pain management because agonists at these receptors are reported to exhibit strong antinociceptive activity with relatively few side effects. Among the most potent analgesics targeting the DOP receptor are the linear and cyclic enkephalin analogs known as DADLE (Tyr‐D‐Ala‐Gly‐Phe‐D‐Leu) and DPDPE (Tyr‐D‐Pen‐Gly‐Phe‐D‐Pen), respectively. Several computational and experimental studies have been carried out over the years to characterize the conformational profile of these penta‐peptides with the ultimate goal of designing potent peptidomimetic agonists for the DOP receptor. The computational studies published to date, however, have investigated only a limited range of timescales and used over‐simplified representations of the solvent environment. We provide here a thorough exploration of the conformational space of DADLE and DPDPE in an explicit solvent, using microsecond‐scale molecular dynamics and bias‐exchange metadynamics simulations. Free‐energy profiles derived from these simulations point to a small number of DADLE and DPDPE conformational minima in solution, which are separated by relatively small energy barriers. Candidate bioactive forms of these peptides are selected from identified common spatial arrangements of key pharmacophoric points within all sampled conformations. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 21–27, 2014.
Baseline characteristics of the patient population in the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus (SAVOR)‐TIMI 53 trial
Authors: Mosenzon O. , Raz I. , Scirica B. M. , Hirshberg B. , Stahre C. I. , Steg P. G. , Davidson J. , Ohman P. , Price D. L. , Frederich B. , Udell J. A. , Braunwald E. , Bhatt D. L.
Published: April 2013

Background and aims

SAVOR‐TIMI 53 was designed to study the effects of the DPP‐4 inhibitor saxagliptin on cardiovascular outcomes in high risk type 2 diabetes patients with diverse levels of diabetes control and background anti‐diabetic drugs. The goal of this article is to describe the baseline characteristics of this hypothesis driven study.

Materials and methods

A total of 16 496 diabetic patients from North America (31.9%), Western Europe (26.0%), Eastern Europe (17.3%), Latin America (16.4%) and Asia (8.3%), with either established cardiovascular disease (78.3%) or with ≥two additional cardiovascular risk factors (21.7%) were randomised to saxagliptin or placebo. Biomarkers of inflammation and insulin resistance were taken at baseline and 2 years later in order to correlate saxagliptin effect on cardiovascular outcome to its effect on inflammation and insulin resistance.

Results

Mean [+/−standard deviation (SD)] age was 65.0 (+/−8.6) years, 66.9% were male, body mass index was 31.2 kg/m2 (+/−5.6), mean diabetes duration was 11.9 years (+/−8.9) and the mean HbA1c 8.0% (+/−1.4%). HbA1c < 7% was most prevalent among North Americans (30.8%) and least among Asians (15.1%), whereas HbA1c > 9% was 30.7% in Latin America 27.0% in Asia and 15.1% in North America. Diabetic retinopathy was reported in 12.3% of patients, nephropathy in 17.7% and amputation in 2.5%. Diabetic treatments categories were as follows: no medication (5.4%), 1 oral anti‐diabetic drug (OAD) (25.0%), ≥2 OAD (27.7%) and/or insulin (40.9%). The prevalence of micro‐albuminuria was twice as high among insulin users compared with users of ≥2 OAD. Baseline statin use (78.3% overall) varied by region.

Conclusion

The SAVOR‐TIMI 53 patient population, with differing background diabetes control and anti‐diabetic treatment, provides global representation of diabetic patients with established cardiovascular disease or at high risk for cardiovascular disease and is well‐positioned to determine the effect of saxagliptin on cardiovascular events. Copyright © 2013 John Wiley & Sons, Ltd.
Plasma follistatin is elevated in patients with type 2 diabetes: relationship to hyperglycemia, hyperinsulinemia, and systemic low‐grade inflammation
Authors: Hansen J. , Rinnov A. , Krogh‐Madsen R. , Fischer C. P. , Andreasen A. S. , Berg R. M. G. , Møller K. , Pedersen B. K. , Plomgaard P.
Published: April 2013

Background

Plasma follistatin is elevated in patients with low‐grade inflammation and insulin resistance as observed with polycystic ovary syndrome. In the present study, we evaluated plasma follistatin in patients with type 2 diabetes characterised by low‐grade inflammation and assessed the acute effects of hyperglycemia, hyperinsulinemia and LPS on plasma follistatin.

Methods

Baseline plasma follistatin and inflammatory biomarkers were measured in a cross‐sectional study that involved 95 patients with type 2 diabetes and 103 matched controls. To determine the acute effect of hyperglycemia and hyperinsulinemia on follistatin, hyperglycemic and hyperinsulinemic‐euglycemic clamps were performed in five healthy males. Furthermore, 15 patients with type 2 diabetes and 22 healthy controls were challenged with low‐dose LPS to determine the effect on follistatin.

Results

Patients with type 2 diabetes have higher HOMA2‐IR values mean [95% CI] 1.64 [1.40–1.93] versus mean 0.86 [0.75–0.99], p < 0.001 and inflammatory markers compared with controls. Baseline plasma follistatin is elevated in patients with type 2 diabetes compared with controls mean 1564 [1456–1680] versus mean 1328 [1225–1440] ng/L, p = 0.003 and correlates with fasting glucose levels (r = 0.44, p < 0.0001), 2 h glucose (r = 0.48, p < 0.0001), HbA1c (r = 0.41, p < 0.0001), triacylglycerol (r = 0.28, p = 0.008) and total cholesterol (r = 0.33, p = 0.004) in patients but not in controls. No correlation exists between plasma follistatin and inflammatory biomarkers in either of the groups. Neither hyperglycemia, hyperinsulinemia nor LPS increase plasma follistatin.

Conclusions

Plasma follistatin is moderately elevated in patients with type 2 diabetes. Our findings suggest that this is not likely caused by hyperglycemia, hyperinsulinemia or systemic low‐grade inflammation. Copyright © 2013 John Wiley & Sons, Ltd.
Testosterone levels and fecundity in the hermaphroditic aquatic snail Lymnaea stagnalis exposed to testosterone and endocrine disruptors
Authors: Giusti Arnaud , Ducrot Virginie , Joaquim-Justo Célia , Lagadic Laurent
Published: April 2013

Endocrine disruptors are known to alter endogenous free and esterified levels of androgenic and estrogenic steroid hormones in aquatic mollusks. The origin of steroids in these animals, however, remains controversial. In the present study, free and esterified testosterone concentrations were measured in the hermaphroditic aquatic gastropod Lymnaea stagnalis exposed to molecules known for their androgenic (testosterone and tributyltin), anti-androgenic (cyproterone-acetate), and estrogenic (chlordecone) properties, by reference to their mode of action in vertebrates. In parallel, snail oviposition and fecundity were followed over a 21-d exposure period. Testosterone exposure resulted in increased esterified testosterone levels, whereas free testosterone concentrations remained stable. In contrast, cyproterone-acetate significantly increased the free form of testosterone with no changes in the esterified form, whereas chlordecone showed a tendency to reduce (though not significantly) esterified testosterone concentrations without changing free testosterone levels. Finally, tributyltin did not alter testosterone homeostasis. The production of egg clutches and eggs was significantly reduced only in the snails exposed to the highest concentrations of chlordecone (19.6 µg/L) and tributyltin (94.2 ng Sn/L). Overall, the present study demonstrates that uptake of testosterone from the exposure medium occurs in L. stagnalis. Moreover, it shows that cyproterone-acetate and, to a lesser extent, chlordecone can alter endogenous testosterone levels in this freshwater snail. However, the relationship between hormonal changes and snail reproduction has not been established. Environ Toxicol Chem 2013;32:1740–1745. © 2013 SETAC
An effects addition model based on bioaccumulation of metals from exposure to mixtures of metals can predict chronic mortality in the aquatic invertebrate hyalella azteca
Authors: Norwood Warren P. , Borgmann Uwe , Dixon D. George
Published: April 2013

Chronic toxicity tests of mixtures of 9 metals and 1 metalloid (As, Cd, Co, Cr, Cu, Mn, Ni, Pb, Tl, and Zn) at equitoxic concentrations over an increasing concentration range were conducted with the epibenthic, freshwater amphipod Hyalella azteca. The authors conducted 28-d, water-only tests. The bioaccumulation trends changed for 8 of the elements in exposures to mixtures of the metals compared with individual metal exposures. The bioaccumulation of Co and Tl were affected the most. These changes may be due to interactions between all the metals as well as interactions with waterborne ligands. A metal effects addition model (MEAM) is proposed as a more accurate method to assess the impact of mixtures of metals and to predict chronic mortality. The MEAM uses background-corrected body concentration to predict toxicity. This is important because the chemical characteristics of different waters can greatly alter the bioavailability and bioaccumulation of metals, and interactions among metals for binding at the site of action within the organism can affect body concentration. The MEAM accurately predicted toxicity in exposures to mixtures of metals, and predicted results were within a factor of 1.1 of the observed data, using 24-h depurated body concentrations. The traditional concentration addition model overestimated toxicity by a factor of 2.7. Environ Toxicol Chem 2013;32:1672–1681. © 2013 SETAC
Azimuthal anisotropy at Valhall: The Helmholtz equation approach
Authors: Mordret Aurélien , Shapiro Nikolai M. , Singh Satish , Roux Philippe , Montagner Jean‐Paul , Barkved Olav. I.
Published: April 2013

We used 6 h of continuous vertical records from 2320 sensors of the Valhall Life of Fields Seismic network to compute 2,690,040 cross‐correlation functions between the full set of sensor pair combinations. We applied the “Helmholtz tomography” approach combined with the ambient noise correlation method to track the wave front across the network with every station considered as a virtual source. The gradient of the interpolated phase travel time gives us an estimate of the local phase speed and of the direction of wave propagation. By combining the individual measurements for every station, we estimated the distribution of Scholte's wave phase speeds with respect to azimuth. The observed cosine pattern indicates the presence of azimuthal anisotropy. The elliptic shape of the fast anisotropy direction is consistent with results of previous shear wave splitting studies and reflects the strong seafloor subsidence due to the hydrocarbon reservoir depletion at depth and is in good agreement with geomechanical modeling.
Highly time-variable exposure to chemicals—toward an assessment strategy
Authors: Ashauer Roman , Brown Colin D
Published: April 2013

Organisms in the environment experience fluctuating, pulsed, or intermittent exposure to pollutants. Accounting for effects of such exposures is an important challenge for environmental risk assessment, particularly given the simplified design of standard ecotoxicity tests. Dynamic simulation using toxicokinetic-toxicodynamic (TK-TD) models describes the processes that link exposure with effects in an organism and provides a basis for extrapolation to a range of exposure scenarios. In so doing, TK-TD modeling makes the risk assessment more robust and aids use and interpretation of experimental data. Toxicokinetic-toxicodynamic models are well-developed for predicting survival of individual organisms and are increasingly applied to sublethal endpoints. In the latter case particularly, linkage to individual-based models (IBMs) allows extrapolation to population level as well as accounting for differences in effects of toxicant exposure at different stages in the life cycle. Extrapolation between species remains an important constraint because there is currently no systematic understanding of species traits that cause differences in the relevant processes. Toxicokinetic-toxicodynamic models allow interrogation of exposure profiles to determine intrinsic toxicity potential rather than using absolute maximum concentrations or time-weighted averages as surrogates. A decision scheme is proposed to guide selection of risk assessment approaches using dose extrapolation based on Haber's Law, TK-TD models, and/or IBMs depending on the nature of toxic effect and timing in relation to life history. Integr Environ Assess Manag 2013;9:e27–e33. © 2013 SETAC
Draft DG SANCO document: Addressing the new challenges for risk assessment—an industry perspective
Authors: Campbell Peter , Dohmen Peter
Published: April 2013

The draft European Commission's Directorate General for Health and Consumer Policy (DG SANCO) document represents the state of the art in environmental risk assessment (ERA) including new trends and combining high level environmental protection and realism. Using the ecosystem services concept, it offers a promising approach to determine which impact may be tolerable, where, and when. Established ERA uses a stepwise approach starting with standardized internationally accepted studies combined with appropriate assessment factors (AFs) and where needed followed by higher tier assessments and respective adjusted AFs. The draft SANCO document follows this approach and presents additional refinements to improve the realism of risk assessment, which is desirable; however, that such additional data becomes a standard requirement without a clear need must be avoided. The idea of additional AFs presented in parts of this article should accordingly first consider risks and benefits in line with this approach and only be requested if data indicates their necessity. In addition, the suggested focus on uncertainty analysis without any obvious according benefits in terms of reduced assessment factors where uncertainty is reduced, is still a challenge. The requirement for science- and/or data-based relevant concerns before requesting more data, and the list of requirements for new innovative approaches that should be met before such approaches can be used in regulatory ecological risk assessments, is well-founded and strongly supported. Modeling has been included in ERA to allow extrapolation of risk assessments without the need of excessive (animal) testing; it will also address uncertainties more quantitatively. However, this should be done in an overall realistic ecological assessment; simply adding up various individual uncertainties and worst-case assumptions must be avoided, as this is counterproductive for the use of this valuable tool. The need for expert judgment should be low at the lower tiers of ERA; however, more complex and less standard ERA will still require significant expertise. Integr Environ Assess Manag 2013;9:e81–e84. © 2013 SETAC
Electrospun PLGA/gelatin fibrous tubes for the application of biodegradable intestinal stent in rat model
Authors: Son So‐Ra , Franco Rose‐Ann , Bae Sang‐Ho , Min Young‐Ki , Lee Byong‐Taek
Published: April 2013

A biodegradable fibrous tube was fabricated by electrospinning method using a combination of Poly(lactic‐co‐glycolic acid) (PLGA) and gelatin dissolved in trifluoroethanol (TFE). Different ratios of the two polymers (PLGA/Gelatin: 1/9, 3/7, 5/5) were used for electrospinning to determine the optimum condition appropriate for intestinal stent application. Fiber morphology was visualized and analyzed using a scanning electron microscope (SEM). Characterizations of physical properties were done according to its tensile strength, surface hydrophilicity, swelling ability, and biodegradability. Biocompatibility of the scaffolds was investigated in vitro using IEC‐18 (Rat intestinal epithelial cell). Cell proliferation was quantified using MTT assay and cell adhesion behavior was visualized by SEM and confocal laser scanning microscope. PLGA/Gelatin (5/5) was determined to have adequate material properties and sufficient in vitro biocompatibility. This was then implanted in a male Sprague‐Dawley rat for 14 days to determine in vivo behavior of the sample. Histological examination on the intestinal tissue surrounding the graft showed normal morphology comparable to non‐implanted intestine. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
Radiographic and retrieval wear analyses of the first generation highly cross‐linked polyethylene cup against a ceramic femoral head
Authors: Oonishi Hiroyuki , Kyomoto Masayuki , Iwamoto Mikio , Ueno Masaru , Oonishi Hironobu
Published: April 2013

In this study, the in vivo wear of highly cross‐linked polyethylene (CLPE) cups against alumina ceramic femoral heads was evaluated by radiographic and retrieval analysis. The radiographic wear of six ethylene oxide gas‐sterilized (i.e., non‐cross‐linked) conventional polyethylene (PE) cups with the mean follow‐up of 20.9 years and 60 CLPE cups with the mean follow‐up of 7.4 years was measured. The retrieved 16 PE cups with clinical use for mean 21.5 years and 10 CLPE cups with clinical use for mean 2.9 years was evaluated as a retrieval analysis. In the radiographic analysis, the linear wear of CLPE cups was significantly lower (99% reduction) compared to conventional polyethylene cups. The results of retrieval analyses for both cups were similar to those of radiographic analyses. Even when third‐body wear occurred during clinical use, no surface damage was observed on the surface of ceramic femoral heads. The surface is not sensitive to third‐body wear, and hence, the ceramic femoral head has a great advantage in terms of the wear of CLPE under third‐body wear conditions. In conclusion, CLPE cups used with alumina ceramic femoral heads in total hip arthroplasty should have favorable wear resistance in several in vivo situations. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 101B: 1594–1601, 2013.
Changes in Physical Properties of Soils with Land Use Time in the Brazilian Savanna Environment
Authors: Trabaquini Kleber , Formaggio Antônio Roberto , Galvão Lênio Soares
Published: April 2013

Soils from central Brazil have been intensively used over the last decades because of the rapid conversion of savannas (Cerrado) into corn/soybean fields. The objective of this work is to study modifications in the physical properties of soils in the Rio Verde watershed, as a function of the land use time for agriculture, determined from classification of Landsat satellite images between 1980 and 2010. Soil samples were collected at surface (0–20 cm) and subsurface (20–40 cm) horizons for the different classes of land use time (<10, 10–20, 20–30, and >30 years). The following physical properties were measured: bulk density (BD), air permeability (Ka), penetration resistance (PR), microporosity (MI), macroporosity (MA), and total porosity (TP). Results showed a strong expansion with time of agriculture that occupied 35·3% (1980), 37·4% (1990), 51·3% (2000), and 60·9% (2010) of the watershed area. When properties were compared with those from the reference areas (preserved soils under native vegetation), significant differences were observed for all the physical attributes of soils for a land use time higher than 20 years. Overall, BD and PR increased with land use time, and the opposite was verified for Ka, MA, and TP. Some physical properties presented values (e.g., 1·54 g cm−3 for BD and 0.06 cm3 cm−3 for MA) close to the critical ones reported to affect crop development, but they were not still impacting on local soybean yield. Copyright © 2013 John Wiley & Sons, Ltd.
Interpreting Oral Pathology at Machu Picchu, Peru
Authors: Turner B. L.
Published: April 2013

This study analyzes oral pathological conditions—caries, antemortem tooth loss, and occlusal macrowear—among adults (N = 70) interred at Machu Picchu, Peru. Previous isotopic diet reconstructions at Machu Picchu suggest substantial early‐life variation that may have narrowed somewhat by the last decade of life. This study seeks to further elucidate the intersection of diet, sex, and health at Machu Picchu by analyzing oral pathological conditions with existing carbon and nitrogen isotopic data. Observed caries prevalence is corrected to control for age and tooth loss, and is described for both anterior and posterior teeth; wear data are scored and reported for individual tooth types. Results indicate caries prevalence consistent with carbohydrate‐rich diets and no significant difference between males and females. However, no significant isotopic parameters are associated with caries prevalence in young adult males, while caries prevalence is significantly associated only with enamel carbonate δ13C in older adult males. Dietary protein sources, but not C4 resources, are associated with caries prevalence in young adult females, and to a lesser degree in older adult females. Significant associations between occlusal wear and caries exist among young adult males and young adult females, but involving different tooth types. These findings suggest differential protein consumption at Machu Picchu between males and females, and separate masticatory and physiological processes shaping caries prevalence between the sexes at the site. This study therefore underscores the role that gender roles may have played in diet variation among this population and the need to account for sex in analyzing oral pathology. Copyright © 2013 John Wiley & Sons, Ltd.
Capillary effect on water table fluctuations in unconfined aquifers
Authors: Kong Jun , Shen Cheng‐Ji , Xin Pei , Song Zhiyao , Li Ling , Barry D. A. , Jeng D.‐S. , Stagnitti F. , Lockington D. A. , Parlange J.‐Y.
Published: April 2013

Key Points

A new governing equation of watertable dynamics was derived.

A new analytical solution for watertable fluctuations was derived.

The effect of finite unsaturated zone thickness was examined.
A fast simulation method for uncertainty quantification of subsurface flow and transport
Authors: Meyer Daniel W. , Tchelepi Hamdi A. , Jenny Patrick
Published: April 2013

Key Points

new polar Markovian velocity processes (PMVPs) to model macro‐dispersion

generalization of PMVPs for inhomogeneous cases with conductivity measurements

validation of PMVP with Monte Carlo, CPU‐time PMVP = CPU‐time MC / 1000
Circular dichroism calculation for natural products
Authors: Nugroho Alfarius Eko , Morita Hiroshi
Published: April 2013

Determination of the absolute configuration (AC) is often a challenging aspect in the structure elucidation of natural products. When chiral compounds possess appropriate chromophore(s), electronic circular dichroism (ECD) may provide a powerful approach to the determination of their absolute configuration. Recently, ECD calculations by time-dependent density functional theory (TDDFT) have come to be used more commonly. In the present review, we give several examples of recent studies using TDDFT-calculated ECD spectra for the AC determination of natural products.
Vaginal hysterectomy in women with a history of 2 or more cesarean deliveries
Authors: Sheth Shirish S.
Published: April 2013

Objective

To perform vaginal hysterectomy (VH) safely in women with a history of 2 or more cesarean deliveries (CDs).

Methods

A 4‐step method was followed to safeguard the bladder, access the vesicouterine peritoneum (VUP), and perform VH in 312 patients with a history of 2 or more CDs. If access to the VUP did not occur at the end of step 2, step 3 and, if necessary, step 4 were implemented.

Results

Hysterectomy was performed vaginally in 311 patients, and the abdominal route was resorted to in 1 patient because of hemorrhage. Only 1 patient incurred bladder trauma, which was promptly repaired.

Conclusion

In the absence of contraindications, the 4‐step VH method described and the surgical techniques involved are safe to implement in women with a history of 2 or more CDs who need a hysterectomy.
A comprehensive approach in hospice shared care in Taiwan: Nonelderly patients have more physical, psychosocial and spiritual suffering
Authors: Yang Chiu‐Hsien , Chiu Yu‐Wen , Huang Chia‐Tsuan , Haung Yu‐Wen , Chuang Hung‐Yi
Published: April 2013

While symptomatic differences exist between younger and older advanced cancer patients, few studies have examined the differences in their care with respect to age. Our goals were to examine the influences of age differences on physical, psychosocial and spiritual distress among advanced cancer patients. Advanced cancer patients who resided in Kaohsiung Medical University Hospital during 2007–2008 were recruited. Data were collected through professional consultants. The influences of age variations on physical, psychosocial and spiritual distress in nonelderly (<60 years old) and elderly (≧60 years old) patients were analyzed. A total of 1013 advanced cancer patients were included in the analyses with 467 nonelderly patients and 546 elderly patients. Nonelderly patients were identified to have a higher baseline pain level (4.0 vs. 2.8, p < 0.001), breakthrough pain (19.3% vs. 9.9%, p < 0.01), insomnia (6.4% vs. 2.7%, p = 0.006), emotional distress (69.0% vs. 60.6%, p = 0.013), and unwillingness to pass away because of concern for loved ones (18.8% vs. 11.9%, p = 0.003) with significant difference. Elderly ones were concerned about unfulfilled wishes (29.7% vs. 18.4%, p < 0.001) in spiritual concerns. After adjustments in regression models, nonelderly age (<60 years old) still revealed significant positive or negative impact on all categories of distress. Patients aged under 60 years have more physical, psychosocial and spiritual suffering. This study suggested that professional practitioners should provide intensive care for vulnerable terminally ill cancer patients.
Bimodal quantitative relationships between histone modifications for X-linked and autosomal loci
Authors: Sadreyev Ruslan I. , Yildirim Eda , Pinter Stefan F. , Lee Jeannie T.
Published: April 2013

Gene expression is controlled by coordinated action of many epigenetic mechanisms including covalent histone modifications. Although numerous recurrent patterns of colocalized histone modifications have been associated with specific gene expression states, interrelationships between individual modifications are largely unknown. Here, we analyze quantitative relationships between colocalized histone marks during embryonic stem cell (ESC) differentiation and find that, for autosomal genes, these densities follow bimodal patterns. Analysis of repressive H3K27me3 and activating H3K4me3 modifications reveals the expected anticorrelation between them at active promoters but an unexpected positive correlation at inactive promoters. The two trends connect in a region corresponding to bivalent genes. Interestingly, this region is characterized by maximal H3K27 methylation. Resolving gene bivalency during ESC differentiation does not conform to the expected model of two marks as counteracting and competing forces. Although activated genes acquire H3K4me3 and lose H3K27me3, repressed genes lose H3K4me3 without gaining H3K27me3. The behavior of X-linked genes also deviates from expected models. Allele-specific analysis of chromatin modifications during X-chromosome inactivation (XCI) suggests that the silencing machinery focuses on active genes and depletion of H3K4me3 and that H3K27me3 is most significant during establishment of gene silencing. Our analysis reveals nontrivial relationships between H3K4me3 and H3K27me3, reveals unique aspects of gene bivalency, and demonstrates that XCI does not conform neatly to autosomal models.
tmVar: a text mining approach for extracting sequence variants in biomedical literature
Authors: Wei Chih-Hsuan , Harris Bethany R. , Kao Hung-Yu , Lu Zhiyong
Published: April 2013

Motivation: Text-mining mutation information from the literature becomes a critical part of the bioinformatics approach for the analysis and interpretation of sequence variations in complex diseases in the post-genomic era. It has also been used for assisting the creation of disease-related mutation databases. Most of existing approaches are rule-based and focus on limited types of sequence variations, such as protein point mutations. Thus, extending their extraction scope requires significant manual efforts in examining new instances and developing corresponding rules. As such, new automatic approaches are greatly needed for extracting different kinds of mutations with high accuracy.

Results: Here, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society. By doing so, we cover several important types of mutations that were not considered in past studies. Using a novel CRF label model and feature set, our method achieves higher performance than a state-of-the-art method on both our corpus (91.4 versus 78.1% in F-measure) and their own gold standard (93.9 versus 89.4% in F-measure). These results suggest that tmVar is a high-performance method for mutation extraction from biomedical literature.

Availability: tmVar software and its corpus of 500 manually curated abstracts are available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/pub/tmVar.

Contact:  zhiyong.lu@nih.gov
LibSBMLSim: a reference implementation of fully functional SBML simulator
Authors: Takizawa Hiromu , Nakamura Kazushige , Tabira Akito , Chikahara Yoichi , Matsui Tatsuhiro , Hiroi Noriko , Funahashi Akira
Published: April 2013

Motivation: The Systems Biology Markup Language (SBML) is currently supported by >230 software tools, among which 160 support numerical integration of ordinary differential equation (ODE) models. Although SBML is a widely accepted standard within this field, there is still no language-neutral library that supports all features of SBML for simulating ODE models. Therefore, a demand exists for a simple portable implementation of a numerical integrator that supports SBML to enhance the development of a computational platform for systems biology.

Results: We implemented a library called libSBMLSim, which supports all the features of SBML and confirmed that the library passes all tests in the SBML test suite including those for SBML Events, AlgebraicRules, ‘fast’ attribute on Reactions and Delay. LibSBMLSim is implemented in the C programming language and does not depend on any third-party library except libSBML, which is a library to handle SBML documents. For the numerical integrator, both explicit and implicit methods are written from scratch to support all the functionality of SBML features in a straightforward implementation. We succeeded in implementing libSBMLSim as a platform-independent library that can run on most common operating systems (Windows, MacOSX and Linux) and also provides several language bindings (Java, C#, Python and Ruby).

Availability: The source code of libSBMLSim is available from http://fun.bio.keio.ac.jp/software/libsbmlsim/. LibSBMLSim is distributed under the terms of LGPL.

Contact:  funa@bio.keio.ac.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
Network predicting drug’s anatomical therapeutic chemical code
Authors: Wang Yong-Cui , Chen Shi-Long , Deng Nai-Yang , Wang Yong
Published: April 2013

Motivation: Discovering drug’s Anatomical Therapeutic Chemical (ATC) classification rules at molecular level is of vital importance to understand a vast majority of drugs action. However, few studies attempt to annotate drug’s potential ATC-codes by computational approaches.

Results: Here, we introduce drug-target network to computationally predict drug’s ATC-codes and propose a novel method named NetPredATC. Starting from the assumption that drugs with similar chemical structures or target proteins share common ATC-codes, our method, NetPredATC, aims to assign drug’s potential ATC-codes by integrating chemical structures and target proteins. Specifically, we first construct a gold-standard positive dataset from drugs’ ATC-code annotation databases. Then we characterize ATC-code and drug by their similarity profiles and define kernel function to correlate them. Finally, we use a kernel method, support vector machine, to automatically predict drug’s ATC-codes. Our method was validated on four drug datasets with various target proteins, including enzymes, ion channels, G-protein couple receptors and nuclear receptors. We found that both drug’s chemical structure and target protein are predictive, and target protein information has better accuracy. Further integrating these two data sources revealed more experimentally validated ATC-codes for drugs. We extensively compared our NetPredATC with SuperPred, which is a chemical similarity-only based method. Experimental results showed that our NetPredATC outperforms SuperPred not only in predictive coverage but also in accuracy. In addition, database search and functional annotation analysis support that our novel predictions are worthy of future experimental validation.

Conclusion: In conclusion, our new method, NetPredATC, can predict drug’s ATC-codes more accurately by incorporating drug-target network and integrating data, which will promote drug mechanism understanding and drug repositioning and discovery.

Availability: NetPredATC is available at http://doc.aporc.org/wiki/NetPredATC.

Contact:  ycwang@nwipb.cas.cn or ywang@amss.ac.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
Active learning-based information structure analysis of full scientific articles and two applications for biomedical literature review
Authors: Guo Yufan , Silins Ilona , Stenius Ulla , Korhonen Anna
Published: April 2013

Motivation: Techniques that are capable of automatically analyzing the information structure of scientific articles could be highly useful for improving information access to biomedical literature. However, most existing approaches rely on supervised machine learning (ML) and substantial labeled data that are expensive to develop and apply to different sub-fields of biomedicine. Recent research shows that minimal supervision is sufficient for fairly accurate information structure analysis of biomedical abstracts. However, is it realistic for full articles given their high linguistic and informational complexity? We introduce and release a novel corpus of 50 biomedical articles annotated according to the Argumentative Zoning (AZ) scheme, and investigate active learning with one of the most widely used ML models—Support Vector Machines (SVM)—on this corpus. Additionally, we introduce two novel applications that use AZ to support real-life literature review in biomedicine via question answering and summarization.

Results: We show that active learning with SVM trained on 500 labeled sentences (6% of the corpus) performs surprisingly well with the accuracy of 82%, just 2% lower than fully supervised learning. In our question answering task, biomedical researchers find relevant information significantly faster from AZ-annotated than unannotated articles. In the summarization task, sentences extracted from particular zones are significantly more similar to gold standard summaries than those extracted from particular sections of full articles. These results demonstrate that active learning of full articles’ information structure is indeed realistic and the accuracy is high enough to support real-life literature review in biomedicine.

Availability: The annotated corpus, our AZ classifier and the two novel applications are available at http://www.cl.cam.ac.uk/∼yg244/12bioinfo.html.

Contact:  yg244@cam.ac.uk
MonaLisa—visualization and analysis of functional modules in biochemical networks
Authors: Einloft Jens , Ackermann Jörg , Nöthen Joachim , Koch Ina
Published: April 2013

Summary: Structural modeling of biochemical networks enables qualitative as well as quantitative analysis of those networks. Automated network decomposition into functional modules is a crucial point in network analysis. Although there exist approaches for the analysis of networks, there is no open source tool available that combines editing, visualization and the computation of steady-state functional modules. We introduce a new tool called MonaLisa, which combines computation and visualization of functional modules as well as an editor for biochemical Petri nets. The analysis techniques allow for network decomposition into functional modules, for example t-invariants (elementary modes), maximal common transition sets, minimal cut sets and t-clusters. The graphical user interface provides various functionalities to construct and modify networks as well as to visualize the results of the analysis.

Availability and implementation: MonaLisa is licensed under the Artistic License 2.0. It is freely available at http://www.bioinformatik.uni-frankfurt.de/software.html. MonaLisa requires at least Java 6 and runs under Linux, Microsoft Windows and Mac OS.

Contact:  ina.koch@bioinformatik.uni-frankfurt.de
The Economic Impact of Social Ties: Evidence from German Reunification*
Authors: Burchardi Konrad B. , Hassan Tarek A.
Published: April 2013

We use the fall of the Berlin Wall in 1989 to show that personal relationships which individuals maintain for noneconomic reasons can be an important determinant of regional economic growth. We show that West German households who had social ties to East Germany in 1989 experienced a persistent rise in their personal incomes after the fall of the Berlin Wall. Moreover, the presence of these households significantly affects economic performance at the regional level: it increases the returns to entrepreneurial activity, the share of households who become entrepreneurs, and the likelihood that firms based within a given West German region invest in East Germany. As a result, West German regions that (for idiosyncratic reasons) have a high concentration of households with social ties to the East exhibit substantially higher growth in income per capita in the early 1990s. A one standard deviation rise in the share of households with social ties to East Germany in 1989 is associated with a 4.7 percentage point rise in income per capita over six years. We interpret our findings as evidence of a causal link between social ties and regional economic development.
Texcoconibacillus texcoconensis gen. nov., sp. nov., alkalophilic and halotolerant bacteria isolated from soil of the former lake Texcoco (Mexico)
Authors: Ruiz-Romero Erick , Coutiño-Coutiño María de los Angeles , Valenzuela-Encinas César , López-Ramírez María Patricia , Marsch Rodolfo , Dendooven Luc
Published: April 2013

A novel Gram-positive, rod-shaped, spore-forming bacterium, designated 13CCT was isolated from soil of the former lake Texcoco. The strain was aerobic, catalase-positive and oxidase-negative. It grew at salinities of 0–26 % (w/v) NaCl with an optimum at 9–16 % (w/v) NaCl. The cells contain peptidoglycan type A1γ, A1γ′ with glycine instead of l-alanine and three variations of peptidoglycan type A4γ. The only quinone detected was MK-7. The major fatty acid was anteiso-C15 : 0. The polar lipids fraction consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and three different phospholipids. The DNA G+C content was 37.5 mol%. Maximum-likelihood phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 13CCT was closely related to members of the genus

Bacillus

and shared 92.35 % similarity with

Bacillus agaradhaerens

, 92.28 % with

Bacillus neizhouensis

and 92.21 % with

Bacillus locisalis

. It is proposed based on the phenotypic, genotypic and phylogenetic analyses that the novel isolate should be classified as a representative of a new genus and novel species, for which the name Texcoconibacillus texcoconensis gen. nov., sp. nov. is proposed. The type strain of Texcoconibacillus texcoconensis is 13CCT ( = JCM 17654T = DSM 24696T).
Flavobacterium

marinum sp. nov., isolated from seawater
Authors: Song Lei , Liu Hongcan , Huang Ying , Dai Xin , Zhou Yuguang
Published: April 2013

A Gram-staining-negative, strictly aerobic, non-gliding, rod-shaped bacterial strain, designated SW105T, was isolated from a seawater sample collected from the Indian Ocean. The strain produced flexirubin-type pigments and grew at 15–45 °C (optimum, 35 °C), at pH 5.5–8.5 (optimum, pH 7.0–7.5) and in the presence of 0–5.0 % (w/v) NaCl (optimum, 1.0–1.5 %). The predominant cellular fatty acids were iso-C15 : 0, summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), iso-C17 : 1ω9c and iso-C17 : 0 3-OH. The major menaquinone was menaquinone 6 (MK-6) and the major polar lipids were phosphatidylethanolamine and two unidentified aminophospholipids. The genomic DNA G+C content of strain SW105T was 36.2 mol%. Phylogenetic analyses based on 16S rRNA gene sequences revealed that the novel isolate was related to members of the genus

Flavobacterium

, showing the highest similarity to

Flavobacterium ummariense

DS-12T and

Flavobacterium ceti

CCUG 52969T (94.3 and 93.0 % sequence similarity, respectively). On the basis of phylogenetic inference and phenotypic characteristics, it is proposed that strain SW105T represents a novel species of the genus

Flavobacterium

, for which the name

Flavobacterium

marinum sp. nov. is proposed. The type strain is SW105T ( = CGMCC 1.10825T = JCM 18132T).
Parabacteroides

chinchillae sp. nov., isolated from chinchilla (Chincilla lanigera) faeces
Authors: Kitahara Maki , Sakamoto Mitsuo , Tsuchida Sayaka , Kawasumi Koh , Amao Hiromi , Benno Yoshimi , Ohkuma Moriya
Published: April 2013

Strains of Gram-stain-negative, anaerobic, rod-shaped bacteria were isolated from chinchilla (Chinchilla lanigera) faeces, and strain ST166T was investigated taxonomically. Phylogenetic analyses of 16S rRNA gene sequences revealed that strain ST166T belonged to the genus

Parabacteroides

. Strain ST166T formed a distinct line of descent, and the highest sequence similarity to ST166T was found with

Parabacteroides merdae

JCM 9497T (95.6 %) and

Parabacteroides johnsonii

JCM 13406T (95.0 %). Analysis of hsp60 gene sequences also supported these relationships. Based on the phenotypic and phylogenetic characteristics, the novel species

Parabacteroides

chinchillae sp. nov. is proposed. The type strain of P. chinchillae sp. nov. is ST166T ( = JCM 17104T = CCUG 62154T).
Halopiger

salifodinae sp. nov., an extremely halophilic archaeon isolated from a salt mine
Authors: Zhang Wei-Yan , Meng Yuan , Zhu Xu-Fen , Wu Min
Published: April 2013

A novel extremely halophilic archaeon KCY07-B2T was isolated from a salt mine in Kuche county, Xinjiang province, China. Colonies were cream-pigmented and cells were pleomorphic rod-shaped. Strain KCY07-B2T was able to grow at 25–50 °C (optimum 37–45 °C) and pH 6.0–8.0 (optimum 7.0). The strain required at least 1.9 M NaCl for growth. MgCl2 was not required. Cells lysed in distilled water. Polar lipid analysis revealed the presence of phosphatidylglycerol and phosphatidylglycerol phosphate methyl ester, derived from both C20C20 and C20C25 glycerol diethers, together with five glyolipids. The bis-sulfated glycolipid S2-DGD-1 was present. The DNA G+C content was 62.5 mol%. Analysis of the 16S rRNA gene sequence revealed that strain KCY07-B2T was closely related to

Halopiger xanaduensis

SH-6T and

Halopiger aswanensis

56T (95.8 % and 95.5 % similarity, respectively). On the basis of its phenotypic, chemotaxonomic and genotypic characteristics, strain KCY07-B2T is considered to represent a novel species of the genus

Halopiger

, for which the name

Halopiger

salifodinae sp. nov. is proposed. The type strain is KCY07-B2T ( = JCM 18547T = CGMCC 1.12284T).
Genome of the pathogen Porphyromonas gingivalis recovered from a biofilm in a hospital sink using a high-throughput single-cell genomics platform
Authors: McLean Jeffrey S. , Lombardo Mary-Jane , Ziegler Michael G. , Novotny Mark , Yee-Greenbaum Joyclyn , Badger Jonathan H. , Tesler Glenn , Nurk Sergey , Lesin Valery , Brami Daniel , Hall Adam P. , Edlund Anna , Allen Lisa Z. , Durkin Scott , Reed Sharon , Torriani Francesca , Nealson Kenneth H. , Pevzner Pavel A. , Friedman Robert , Venter J. Craig , Lasken Roger S.
Published: April 2013

Although biofilms have been shown to be reservoirs of pathogens, our knowledge of the microbial diversity in biofilms within critical areas, such as health care facilities, is limited. Available methods for pathogen identification and strain typing have some inherent restrictions. In particular, culturing will yield only a fraction of the species present, PCR of virulence or marker genes is mainly focused on a handful of known species, and shotgun metagenomics is limited in the ability to detect strain variations. In this study, we present a single-cell genome sequencing approach to address these limitations and demonstrate it by specifically targeting bacterial cells within a complex biofilm from a hospital bathroom sink drain. A newly developed, automated platform was used to generate genomic DNA by the multiple displacement amplification (MDA) technique from hundreds of single cells in parallel. MDA reactions were screened and classified by 16S rRNA gene PCR sequence, which revealed a broad range of bacteria covering 25 different genera representing environmental species, human commensals, and opportunistic human pathogens. Here we focus on the recovery of a nearly complete genome representing a novel strain of the periodontal pathogen Porphyromonas gingivalis (P. gingivalis JCVI SC001) using the single-cell assembly tool SPAdes. Single-cell genomics is becoming an accepted method to capture novel genomes, primarily in the marine and soil environments. Here we show for the first time that it also enables comparative genomic analysis of strain variation in a pathogen captured from complex biofilm samples in a healthcare facility.