bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient biomarkers for the characterization of bone tissue
Authors: Gil J. E. , Aranda J. P. , Mérida‐Casermeiro E. , Ujaldón M.
Published: August 2012

This work describes an expert system aimed to an accurate classification of cell tissue on microscopic images coming from studies of bone tissue regeneration from stem cells. We analyze a wide number of phenotype and color issues to build effective vectors of features for the subsequent characterization of tissue into five different classes: bone, cartilage, muscle, fiber and spine. The features selection includes texture, shape and color descriptors, among which we consider color histograms, Zernike moments and circular parameters. Once a preliminary set of vectors candidates are selected, several trained and non‐parametric classifiers based on neural networks, decision trees, Bayesian classifiers and association rules are analyzed, and later compared with unsupervised methods to determine those that fit more closely to our needs for distinguishing bone tissue. Because of the high resolution of our biomedical images, we effectively decompose them into smaller windows for a faster execution, with the impact of the window size being discussed in terms of speed and robustness. Our final study compares accuracy and computational time together with different stainings for revealing tissue properties: Picrosirius red, alcian blue and safranin blue. Overall, safranin blue reveals as the best staining and multilayer perceptron as the most effective classifier. Copyright © 2012 John Wiley & Sons, Ltd.
Evaluation of carotid stent scaffolding through patient‐specific finite element analysis
Authors: Auricchio F. , Conti M. , Ferraro M. , Reali A.
Published: August 2012

After carotid artery stenting, the plaque remains contained between the stent and the vessel wall, moving consequently physicians’ concerns toward the stent capability of limiting the plaque protrusion, that is, toward vessel scaffolding, to avoid that some debris is dislodged after the procedure. Vessel scaffolding is usually measured as the cell area of the stent in free‐expanded configuration, neglecting thus the actual stent configuration within the vascular anatomy. In the present study, we measure the cell area of four different stent designs deployed in a realistic carotid artery model through patient‐specific finite element analysis. The results suggest that after deployment, the cell area change along the stent length and the related reduction with respect to the free‐expanded configuration are functions of the vessel tapering. Hence, the conclusions withdrawn from the free‐expanded configuration appear to be qualitatively acceptable for comparative purposes, but they should be carefully handled because they neglect the post‐implant variability, which seems to be more pronounced in open‐cell designs, especially at the bifurcation segment. Even though the investigation is limited to few stent designs and one vascular anatomy, our study confirms the capability of dedicated computer‐based simulations to provide useful information about complex stent features as vessel scaffolding. Copyright © 2012 John Wiley & Sons, Ltd.
Incentives and the needham paradox: An agent‐based perspective
Authors: Leong Chee Kian
Published: August 2012

This article discusses how restructured incentives could have inhibited innovation in ancient China and explain the Needham paradox. Agents in a genetic algorithmic game maximize their payoffs by choosing between innovating and studying the Classics. By restructuring incentives toward studying the Classics, initial spurts of innovation are smothered, resulting in a population with all agents studying the Classics. The incentive structure has a statistically and quantitatively significant impact on the expected average payoffs and the strategy profile of the population: the average payoffs for a regime which rewards innovation fluctuate more but are always higher and the strategy profile is varied. © 2012 Wiley Periodicals, Inc. Complexity, 2012
Involvement of the MLL gene in adult T‐lymphoblastic leukemia
Authors: Türkmen Seval , Timmermann Bernd , Bartels Gesine , Gröger Daniela , Meyer Claus , Schwartz Stefan , Haferlach Claudia , Rieder Harald , Gökbuget Nicola , Hoelzer Dieter , Marschalek Rolf , Burmeister Thomas
Published: August 2012

While the MLL “recombinome” is relatively well characterized in B‐cell precursor acute lymphoblastic leukemia (BCP ALL), available data for adult acute T‐lymphoblastic leukemia (T‐ALL) are scarce. We performed fluorescence in situ hybridization (FISH) for an MLL split signal on 223 adult T‐ALL samples obtained within the framework of the German Multicenter ALL 07/2003 therapy trial. Three biphenotypic leukemias (T‐ALL/AML) were also included in the analysis. Samples showing any alteration by FISH were further investigated to characterize the MLL aberration. In addition, they were investigated for common genetic lesions known in T‐ALL. Twenty‐two cases (9.5%) showed an abnormal MLL signal by FISH analysis. Most of these appeared to be deletions or gains but in five cases (2.1%) a chromosomal translocation involving the MLL gene was identified. The translocation partners and chromosomal breakpoints were molecularly characterized. Three T‐ALLs had an MLL‐AF6/t(6;11) and two biphenotypic leukemias had an MLL‐ELL/t(11;19). The chromosomal breakpoints in two of the MLL‐AF6‐positive cases were located outside the classical MLL major breakpoint cluster known from BCP ALL. In conclusion, the spectrum of MLL translocation partners in adult T‐ALL much more resembles that of AML than that of BCP ALL and thus the mechanisms by which MLL contributes to leukemogenesis in adult T‐ALL appear to differ from those in BCP ALL. Proposals are made for the diagnostic assessment of MLL fusion genes in adult T‐ALL. © 2012 Wiley Periodicals, Inc.
Aberrant promoter methylation of beta‐1,4 galactosyltransferase 1 as potential cancer‐specific biomarker of colorectal tumors
Authors: Poeta Maria Luana , Massi Emanuela , Parrella Paola , Pellegrini Pasquale , De Robertis Mariangela , Copetti Massimiliano , Rabitti Carla , Perrone Giuseppe , Muda Andrea Onetti , Molinari Francesca , Zanellato Elena , Crippa Stefano , Caputo Damiano , Caricato Marco , Frattini Milo , Coppola Roberto , Fazio Vito Michele
Published: August 2012

Epigenetic alterations, such as CpG islands methylation and histone modifications, are recognized key characteristics of cancer. Glycogenes are a group of genes which epigenetic status was found to be changed in several tumors. In this study, we determined promoter methylation status of the glycogene beta‐1,4‐galactosyltransferase 1 (B4GALT1) in colorectal cancer patients. Methylation status of B4GALT1 was assessed in 130 colorectal adenocarcinomas, 13 adenomas, and in paired normal tissue using quantitative methylation specific PCR (QMSP). B4GALT1 mRNA expression was evaluated in methylated/unmethylated tumor and normal specimens. We also investigated microsatellite stability and microsatellite instability status and KRAS/BRAF mutations. Discriminatory power of QMSP was assessed by receiving operating curve (ROC) analysis on a training set of 24 colorectal cancers and paired mucosa. The area under the ROC curve (AUC) was 0.737 (95% confidence interval [CI]:0.591–0.881, P = 0.005) with an optimal cutoff value of 2.07 yielding a 54% sensitivity (95% CI: 35.1%–72.1%) and a specificity of 91.7% (95% CI: 74.1%–97.7%). These results were confirmed in an independent validation set where B4GALT1 methylation was detected in 52/106 patients. An inverse correlation was observed between methylation and B4GALT1 mRNA expression levels (r = −0.482, P = 0.037). Significant differences in methylation levels and frequencies was demonstrated in invasive lesions as compared with normal mucosa (P = 0.0001) and in carcinoma samples as compared with adenoma (P = 0.009). B4GALT1 methylation is a frequent and specific event in colorectal cancer and correlates with downregulation of mRNA expression. These results suggest that the glycogene B4GALT1 represent a valuable candidate biomarker of invasive phenotype of colorectal cancer. © 2012 Wiley Periodicals, Inc.
Poly‐gene fusion transcripts and chromothripsis in prostate cancer
Authors: Wu Chunxiao , Wyatt Alexander W. , McPherson Andrew , Lin Dong , McConeghy Brian J. , Mo Fan , Shukin Robert , Lapuk Anna V. , M. Jones Steven J. , Zhao Yongjun , Marra Marco A. , Gleave Martin E. , Volik Stanislav V. , Wang Yuzhuo , Sahinalp S. Cenk , Collins Colin C.
Published: August 2012

Complex genome rearrangements are frequently observed in cancer but their impact on tumor molecular biology is largely unknown. Recent studies have identified a new phenomenon involving the simultaneous generation of tens to hundreds of genomic rearrangements, called chromothripsis. To understand the molecular consequences of these events, we sequenced the genomes and transcriptomes of two prostate tumors exhibiting evidence of chromothripsis. We identified several complex fusion transcripts, each containing sequence from three different genes, originating from different parts of the genome. One such poly‐gene fusion transcript appeared to be expressed from a chain of small genomic fragments. Furthermore, we detected poly‐gene fusion transcripts in the prostate cancer cell line LNCaP, suggesting they may represent a common phenomenon. Finally in one tumor with chromothripsis, we identified multiple mutations in the p53 signaling pathway, expanding on recent work associating aberrant DNA damage response mechanisms with chromothripsis. Overall, our data show that chromothripsis can manifest as massively rearranged transcriptomes. The implication that multigenic changes can give rise to poly‐gene fusion transcripts is potentially of great significance to cancer genetics. © 2012 Wiley Periodicals, Inc.
Dietary trans‐Fatty Acid Induced NASH is Normalized Following Loss of trans‐Fatty Acids from Hepatic Lipid Pools
Authors: Neuschwander‐Tetri Brent A. , Ford David A. , Acharya Sahaja , Gilkey George , Basaranoglu Metin , Tetri Laura H. , Brunt Elizabeth M.
Published: August 2012

Previous experiments in mice showed that dietary trans‐fats could play a role in non‐alcoholic steatohepatitis (NASH) yet little is known about the accumulation trans‐fats in hepatic lipid pools in relationship to liver injury. NASH is also associated with obesity yet improves with only modest weight loss. To distinguish the role of obesity versus sustained consumption of a trans‐fat containing diet in causing NASH, mice with obesity and NASH induced by consuming a high trans‐fat diet for 16 weeks were subsequently fed standard chow or maintained on trans‐fat chow for another 8 weeks. The accumulation, partitioning and loss of trans‐fats in the major hepatic lipid pools during and after trans‐fat consumption were determined. Obese mice switched to standard chow remained obese but steatohepatitis improved. trans‐fats were differentially incorporated into the major hepatic lipid pools and the loss of trans‐fats after crossover to control chow was greatest in the cholesteryl ester pool. In summary, dietary changes can improve the biochemical and histopathological changes of NASH despite persistent obesity in mice. Analysis of hepatic lipids confirmed that dietary trans‐fats accumulate in the major lipid pools and are released differentially with diet normalization. The substantial loss of trans‐fats from the cholesteryl ester pool in parallel with improvement in NASH suggests that this pool of trans‐fats could play a role in the pathogenesis of NASH.
A Novel Method for Simultaneous Monitoring of 2‐MCPD, 3‐MCPD and Glycidyl Esters in Oils and Fats
Authors: Ermacora A. , Hrncirik K.
Published: August 2012

The availability of a reliable methodology for the quantification of fatty acid esters of monochloropropropanediol (MCPD) and glycidol is essential for understanding the mechanism of formation of these process contaminants and for developing effective mitigation strategies. While several analytical methods for the determination of MCPD esters have already been developed and evaluated, only very few procedures are currently available for the analysis of glycidyl esters. This work presents a new indirect method for the simultaneous quantification of fatty acid esters of 2‐MCPD, 3‐MCPD and glycidol. The method is based on the acid‐catalyzed conversion of glycidyl esters into 3‐monobromopropanediol (3‐MBPD) monoesters which, owing to the structural similarity to MCPD esters, are quantified by using the procedure we previously optimized for the analysis of MCPD esters. The critical step of the method, which is the conversion of glycidyl esters, was optimized by testing different reagent concentrations and varying other condition settings. The novel method showed good repeatability (RSD <2.5 %) and between‐day reproducibility (RSD ≤5 %). The limit of detection was 0.04 mg/kg for bound 2‐MCPD and 3‐MCPD and 0.06 mg/kg for bound glycidol. The trueness of the method was evaluated by the analysis of spiked samples and by interlaboratory comparison.
New Environmentally Friendly Oxidative Scission of Oleic Acid into Azelaic Acid and Pelargonic Acid
Authors: Godard Anaïs , De Caro Pascale , Thiebaud‐Roux Sophie , Vedrenne Emeline , Mouloungui Zéphirin
Published: August 2012

Oleic acid (OA) is a renewable monounsaturated fatty acid obtained from high oleic sunflower oil. This work was focused on the oxidative scission of OA, which yields a mono‐acid (pelargonic acid, PA) and a di‐acid (azelaic acid, AA) through an emulsifying system. The conventional method for producing AA and PA consists of the ozonolysis of oleic acid, a process which presents numerous drawbacks. Therefore, we proposed to study a new alternative process using a green oxidant and a solvent‐free system. OA was oxidized in a batch reactor with a biphasic organic‐aqueous system consisting of hydrogen peroxide (H2O2, 30 %) as an oxidant and a peroxo–tungsten complex Q3{PO4[WO(O2)2]4} as a phase‐transfer catalyst/co‐oxidant. Several phase‐transfer catalysts were prepared in situ from tungstophosphoric acid, H2O2 and different quaternary ammonium salts (Q+, Cl–). The catalyst [C5H5N(n‐C16H33)]3{PO4[WO(O2)2]4} was found to give the best results and was chosen for the optimization of the other parameters of the process. This optimization led to a complete conversion of OA into AA and PA with high yields (>80 %) using the system OA/H2O2/[C5H5N(n‐C16H33)]3{PO4[WO(O2)2]4} (1/5/0.02 molar ratio) at 85 °C for 5 h. In addition, a new treatment was developed in order to recover the catalyst.
ICRP PUBLICATION 118: ICRP Statement on Tissue Reactions and Early and Late Effects of Radiation in Normal Tissues and Organs — Threshold Doses for Tissue Reactions in a Radiation Protection Context
Authors: Stewart F.A. , Akleyev A.V. , Hauer-Jensen M. , Hendry J.H. , Kleiman N.J. , MacVittie T.J. , Aleman B.M. , Edgar A.B. , Mabuchi K. , Muirhead C.R. , Shore R.E. , Wallace W.H.
Published: August 2012

This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of ‘practical’ threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye.

Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40–50 years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower.

A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1–1.2, and in a few cases 1.5–2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors.

Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5 Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.
Prevalence of and risk factors for pelvic organ prolapse and lower urinary tract symptoms among women in rural Nepal
Authors: Lien Ying‐Shuang , Chen Gin‐Den , Ng Soo‐Cheen
Published: August 2012

Objective

To evaluate the prevalence and associated risk factors of pelvic organ prolapse (POP) and lower urinary tract symptoms (LUTS) among women seeking healthcare services in 3 discrete rural areas in Nepal.

Methods

A cross‐sectional study was conducted using a Nepalese‐specific questionnaire to obtain demographic and personal information. Urinary symptoms were examined using the Urogenital Distress Inventory Short form questionnaire, while POP severity was staged according to the POP‐Q system. The χ2 test and multivariate logistic regression analysis were used to determine POP risk factors.

Results

Of the 174 women included in the analysis, 106 (60.9%) had stage II POP or greater. In all, 93 women (53.4%) had cystocele, 63 (36.2%) had rectocele, and 37 (21.3%) had uterine prolapse. Univariate analysis identified high parity; young age at first delivery; menopause; squatting or standing position during delivery; and early return to work after delivery as risk factors for POP. Multivariate logistic regression revealed that delivery in a lying position presented a lower risk for cystocele than squatting or standing (odds ratio 0.34; P < 0.01).

Conclusion

Both LUTS and POP are common among women in rural Nepal. Cystocele is the most frequent, advanced, and symptomatic form of POP observed in this population.
The effect of post‐cesarean rectal misoprostol on intestinal motility
Authors: Adanikin Abiodun I. , Orji Ernest O. , Fasubaa Olusola B. , Onwudiegwu Uche , Ijarotimi Omotade A. , Olaniyan Oluwaseyi
Published: August 2012

Objective

To determine whether rectally administered misoprostol can induce intestinal motility compared with oxytocin infusion when used to prevent primary postpartum hemorrhage after cesarean delivery.

Methods

In a prospective randomized double‐blind study in Nigeria, 218 parturients undergoing cesarean delivery who had risk factors for primary postpartum hemorrhage were enrolled between July 1, 2010, and March 31, 2011. Participants received 600 μg of rectal misoprostol or 20 intravenous units of oxytocin for 4 hours after surgery. The primary outcome was time until passage of flatus. Adverse effects, need for additional analgesic, and length of hospital stay were also assessed.

Results

The misoprostol group had a significantly shorter mean postoperative interval to passage of flatus (20.27 ± 7.77 hours versus 38.34 ± 10.98 hours; P < 0.001) and commencement of regular diet (21.08 ± 7.69 hours versus 39.13 ± 10.94 hours; P < 0.001). Gastrointestinal adverse effects were more frequent, albeit not significantly, in the misoprostol group: nausea, 6.4% versus 1.8%; vomiting, 7.3% versus 2.8%; and abdominal distension, 3.7% versus 2.8%. The need for additional analgesic was the same in the 2 groups.

Conclusion

After cesarean delivery, rectal misoprostol had the added benefit of inducing intestinal motility. Misoprostol might be considered in a clinical setting where postoperative ileus is anticipated.
Use of early transverse annular compression sutures for complete placenta previa during cesarean delivery
Authors: Huang Yi‐Ying , Zhuang Jing‐Yi , Bao Yi‐Rong , Ying Hao , Wang De‐Fen
Published: August 2012

Objective

To compare the difference in maternal outcomes between early and late use of transverse annular compression sutures (TACS) during cesarean delivery among women with complete placenta previa (CPP).

Methods

A retrospective study of 36 women with CPP was conducted. Percentiles of blood loss before TACS were calculated. The transfusion rate, sensitivity, specificity, Youden index, positive predictive value, and negative predictive value were also estimated. Patients were assigned to either the early TACS group or the late TACS group based on the highest Youden index. Maternal outcomes of the 2 groups were compared.

Results

The Youden index for transfusion rate was highest when blood loss before TACS reached 500 mL. Blood loss before intervention in the late TACS group was significantly higher than in the early TACS group (735.0 ± 123.7 mL versus 396.9 ± 76.3 mL; P < 0.001). More women in the late TACS group than in the early TACS group required blood transfusion (60.0% versus 12.5%; P = 0.004) and the volume of blood transfused was significantly lower in the early TACS group than in the late TACS group (137.5 ± 377.5 mL versus 806.7 ± 619.3 mL; P = 0.001).

Conclusion

Early implementation of TACS could lead to improved maternal outcomes.
Provenance and climate change inferred from Sr–Nd–Pb isotopes of late Quaternary sediments in the Huanghe (Yellow River) Delta, China
Authors: Hu Bangqi , Li Guogang , Li Jun , Bi Jianqiang , Zhao Jingtao , Bu Ruyuan
Published: August 2012

We present a provenance study of core ZK2 from the Huanghe (Yellow River) Delta in order to assess the impacts of climate change on the sediment supplies during the last glacial–interglacial cycle. Facies analysis and sequence stratigraphy methods are used to construct the age model. Sr isotopic compositions of ZK2 range from 0.716389 to 0.723884, with 87Sr/86Sr increased with decreasing grain size. Nd and Pb isotopic compositions display two large major excursions during Marine Oxygen Isotope stages (MIS) 2 and 4, with less radiogenic εNd and lower 208Pb/204Pb, 207Pb/204Pb, and 206Pb/204Pb values during these periods. These excursions have been explained in terms of changes in the mixing proportion of sediments from the Loess Plateau and Ordos Plateau, resulting from East Asian monsoon intensity variations. The weak summer monsoon precipitation resulted in decreased erosion of Loess Plateau during MIS 2, 4 and the middle of MIS 3. Meanwhile, both the intensified East Asian winter monsoon and the southward expansions of Mu Us desert significantly enhanced the eolian sand entering the Huanghe. Therefore, our results highlight the impact of monsoon variability on erosion patterns in the Huanghe basin.
Evaluating Pulmonary Vein Isolation
Authors: Shah Dipen
Published: August 2012

Pulmonary vein isolation is the electrophysiological endpoint of complete conduction block at the level of the veno‐atrial junction and must be explicitly distinguished from encircling PV ablation which frequently does not result in isolation.

The prerequisites for successful PV isolation include a knowledge of the individual anatomy of the PVs and the left atrium, appropriate positioning of circular mapping catheters, and a knowledge of the electrophysiology of PV activation, in addition to effective ablation tools. Excessive ablation, and possibly complications, can be avoided by the recognition of non‐PV myocardial contributions to electrograms recorded from within the PVs. The posterior wall of the left atrial appendage contributes far‐field electrograms to recordings from all or nearly all left superior PVs, the low anterior left atrium to 80% of left inferior PV recordings and the superior vena cava to 23% of right superior PV recordings. Recognition of these far‐field components is feasible and accurate in sinus rhythm as well as during ongoing atrial fibrillation. Finally, the creation of temporally stable PV isolation remains a currently unsolved problem although prolonged post isolation surveillance, may be helpful.
Genetic Background of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Time to Start Asian Registry!
Authors: Horie Minoru , Ishida Katsuya , Nishio Yukiko , Nagaoka Iori , Matsui Keiji
Published: August 2012

Arrhythmogenic right venticular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy with a very low penetrance affecting the right ventricle (RV) and presenting palpitation and syncope due to ventricular tachycardia (VT) originating from RV. The VT can degenerate into ventricular fibrillation and sudden cardiac death. The genetic background of ARVD/C has recently been found to be heterogeneous, mainly resulting from cell adhesion abnormalities due to mutations in five different genes encoding members of the desmosome complex. In Asian countries, however, the genetic aspect of the disease has not been fully studied, although the clinical features of Asian ARVD/C patients are different from those in Western countries in the penetrance of phenotypes, relation to Brugada syndrome and link to RV outflow tract ventricular tachycardia. It is of urgent need to have a registry of Asian ARVD/C patients and to conduct a more detailed genetic survey on the candidate genes, including desomosomal ones.
Identification and Radiofrequency Catheter Ablation of a Nonsustained Atrial Tachycardia at the Septal Mitral Annulus with the Use of a Noncontact Mapping System: A Case Report
Authors: Narita Sumito , Tsuchiya Takeshi , Ushinohama Hiroya , Ando Shin‐ichi
Published: August 2012

Here we report a case of a 16‐year old female with symptomatic nonsustained atrial tachycardia (NSAT) originating from the septal mitral annulus. NSAT was induced by atrial burst pacing after an intravenous isoproterenol (ISP) injection. The array mode of the noncontact mapping system (NCM) allowed us to quickly identify the tachycardia focus at the septal mitral annulus, where the contact bipolar voltage map revealed no low voltage area (<0.5 mV). The NSAT was eliminated by a radiofrequency energy application to the identified tachycardia focus during sinus rhythm, and the patient has been free from any symptoms during 10 months of follow‐up.
ST‐T Abnormalities on ECG in Relation to Cardiovascular Risk Factors
Authors: Chinushi Yuko , Watanabe Hiroshi , Chinushi Masaomi , Aizawa Yoshifusa
Published: August 2012

Background: Significance of an ST‐T abnormality in subjects with no apparent heart diseases is to be determined.

Subjects and methods: The study involved 44,990 adults (16,368 males and 28,622 females) aged 40‐85 years who under went an annual health examination. Cardiovascular risks (CVRs) were considered positive if 1) body mass index was ≥ 25Kg/m2, 2) systolic blood pressure (BP) ≥ 130 mmHg and/or diastolic BP ≥ 85mmHg, 3) triglyceride ≥ 150 mg/ dl, 4) HDL‐C level ≤ 40mg/dl for men and ≤ 50mg/dl for women, or 5) fasting blood glucose ≤ 110 mg/dl. The relation between CVRs and ST‐T abnormalities were evaluated.

Results: ST‐T abnormalities were found in 6.49% in males, and more frequently in females: 8.45%. Each CVR and the number of combined CVRs were risk factors for ST‐T abnormalities on ECG (P < 0.0001 for a trend). On the other hand, ECG‐based LVH was found in 5.7% but showed no relation with CVRs or their com binations. ST‐T abnormalities may represent preclinical cardiac involvement of CVRs more sensitively than LVH on ECG and ECG findings may be used in mass examinations.

Conclusions: ST‐T abnormalities without apparent heart diseas may be considered to be nonspecific but this cross‐sectional study showed that they are related to CVRs and may be used as an early marker of preclinical cardiac damage by CVRs.
The Relationship between Optimization for Cardiac Resynchronization Therapy by Measurement of dp/dt and the Middle‐to‐long‐term Prognosis of Heart Failure Patients
Authors: Kabutoya Tomoyuki , Mitsuhashi Takeshi , Watanabe Tomonori , Nakagami Rieko , Hata Yoshihito , Shimada Kazuyuki , Kario Kazuomi
Published: August 2012

Background: The relationship between optimization according to left ventricular (LV) dp/dt, changes in LV performance, and prognosis of heart failure patients who undergo cardiac resynchronization therapy (CRT) remains unclear.

Methods: We studied 27 consecutive patients who underwent CRT implantation (18 males, 9 females; age, 67.3 ± 8.3 years). We measured LV dp/dt to determine the timing of LV‐right ventricular (RV) sequential pacing. Echocardiographic examination was performed before and after the CRT procedure to assess LV ejection fraction (LVEF) and LV end‐diastolic diameter (LVEDD). Primary endpoints were all‐cause death and cardiac hospitalization.

Results: An increase in LV dp/dt during CRT was significantly associated with an increase in LVEF (r = 0.47, p = 0.018), but was not associated with a decrease in LVEDD. The mean follow‐up period was 14 ± 13 months, and six endpoints were observed. In the control group, no subjects encountered any of the endpoints, and they had higher LVEDD reductions (5.7 ± 8.4 vs. ± 2.5 ± 4.6 mm; p = 0.034) than those in the event group. Cox regression analysis revealed that a reduction in LVEDD was a significant predictor of event‐free survival.

Conclusions: The measurement of LV dp/dt might be useful for the optimization of CRT. Reductions in LVEDD are necessary to achieve improvements in the long‐term prognosis of CRT patients.
Development of Lower Loop Reentrant Atrial Tachycardia in a Patient Late after Surgical Operation of Multiple Right‐sided Accessory Pathways
Authors: Oginosawa Yasushi , Abe Haruhiko , Kohno Ritsuko , Minamiguchi Hitoshi , Tamura Masahito , Takeuchi Masaaki , Otsuji Yutaka
Published: August 2012

A 50‐year‐old man developed a symptomatic tachyarrhythmia 22 years after surgical division of multiple right‐sided accessory pathways. Electro‐anatomical mapping during sinus rhythm revealed an electrically isolated ectopic focus on the right atrial free wall near the tricuspid annulus (TA). Activation map during tachycardia indicated the presence of lower loop reentry (LLR) with collision of the wavefronts in the high right atrium. The isthmus of slow conduction was located between the surgical incision near the posterior TA and the inferior vena cava. LLR was eliminated by radiofrequency linear ablation at the cavotricuspid isthmus.
Transgenerational epigenetic effects of theApobec1cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability
Authors: Nelson Vicki R. , Heaney Jason D. , Tesar Paul J. , Davidson Nicholas O. , Nadeau Joseph H.
Published: August 2012

Environmental agents and genetic variants can induce heritable epigenetic changes that affect phenotypic variation and disease risk in many species. These transgenerational effects challenge conventional understanding about the modes and mechanisms of inheritance, but their molecular basis is poorly understood. The Deadend1 (Dnd1) gene enhances susceptibility to testicular germ cell tumors (TGCTs) in mice, in part by interacting epigenetically with other TGCT modifier genes in previous generations. Sequence homology toA1cf, the RNA-binding subunit of the ApoB editing complex, raises the possibility that the function ofDnd1is related toApobec1activity as a cytidine deaminase. We conducted a series of experiments with a genetically engineered deficiency ofApobec1on the TGCT-susceptible 129/Sv inbred background to determine whether dosage ofApobec1modifies susceptibility, either alone or in combination withDnd1,and either in a conventional or a transgenerational manner. In the paternal germ-lineage,Apobec1deficiency significantly increased susceptibility among heterozygous but not wild-type male offspring, without subsequent transgenerational effects, showing that increased TGCT risk resulting from partial loss ofApobec1function is inherited in a conventional manner. By contrast, partial deficiency in the maternal germ-lineage led to suppression of TGCTs in both partially and fully deficient males and significantly reduced TGCT risk in a transgenerational manner among wild-type offspring. These heritable epigenetic changes persisted for multiple generations and were fully reversed after consecutive crosses through the alternative germ-lineage. These results suggest thatApobec1plays a central role in controlling TGCT susceptibility in both a conventional and a transgenerational manner.
TRFolder-W: a web server for telomerase RNA structure prediction in yeast genomes
Authors: Zhang Dong , Xue Xingran , Malmberg Russell L. , Cai Liming
Published: August 2012

Summary: TRFolder-W is a web server capable of predicting core structures of telomerase RNA (TR) in yeast genomes. TRFolder is a command-line Python toolkit for TR-specific structure prediction. We developed a web-version built on the django web framework, leveraging the work done previously, to include enhancements to increase flexibility of usage. To date, there are five core sub-structures commonly found in TR of fungal species, which are the template region, downstream pseudoknot, boundary element, core-closing stem and triple helix. The aim of TRFolder-W is to use the five core structures as fundamental units to predict potential TR genes for yeast, and to provide a user-friendly interface. Moreover, the application of TRFolder-W can be extended to predict the characteristic structure on species other than fungal species.

Availability: The web server TRFolder-W is available at http://rna-informatics.uga.edu/?f=software&p=TRFolder-w.

Contact: cai@cs.uga.edu

Supplementary information:  http://rna-informatics.uga.edu/?f=software&p=TRFolder-w-supplement.
Qualitative translation of relations from BioPAX to SBML qual
Authors: Büchel Finja , Wrzodek Clemens , Mittag Florian , Dräger Andreas , Eichner Johannes , Rodriguez Nicolas , Le Novère Nicolas , Zell Andreas
Published: August 2012

Motivation: The biological pathway exchange language (BioPAX) and the systems biology markup language (SBML) belong to the most popular modeling and data exchange languages in systems biology. The focus of SBML is quantitative modeling and dynamic simulation of models, whereas the BioPAX specification concentrates mainly on visualization and qualitative analysis of pathway maps. BioPAX describes reactions and relations. In contrast, SBML core exclusively describes quantitative processes such as reactions. With the SBML qualitative models extension (qual), it has recently also become possible to describe relations in SBML. Before the development of SBML qual, relations could not be properly translated into SBML. Until now, there exists no BioPAX to SBML converter that is fully capable of translating both reactions and relations.

Results: The entire nature pathway interaction database has been converted from BioPAX (Level 2 and Level 3) into SBML (Level 3 Version 1) including both reactions and relations by using the new qual extension package. Additionally, we present the new webtool BioPAX2SBML for further BioPAX to SBML conversions. Compared with previous conversion tools, BioPAX2SBML is more comprehensive, more robust and more exact.

Availability: BioPAX2SBML is freely available at http://webservices.cs.uni-tuebingen.de/ and the complete collection of the PID models is available at http://www.cogsys.cs.uni-tuebingen.de/downloads/Qualitative-Models/.

Contact:  finja.buechel@uni-tuebingen.de

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Information-theoretic analysis and prediction of protein atomic burials: on the search for an informational intermediate between sequence and structure
Authors: Rocha Juliana R. , van der Linden Marx G. , Ferreira Diogo C. , Azevêdo Paulo H. , Pereira de Araújo Antônio F.
Published: August 2012

Motivation: It has been recently suggested that atomic burials, as expressed by molecular central distances, contain sufficient information to determine the tertiary structure of small globular proteins. A possible approach to structural determination from sequence could therefore involve a sequence-to-burial intermediate prediction step whose accuracy, however, is theoretically limited by the mutual information between these two variables. We use a non-redundant set of globular protein structures to estimate the mutual information between local amino acid sequence and atomic burials. Discretizing central distances of or atoms in equiprobable burial levels, we estimate relevant mutual information measures that are compared with actual predictions obtained from a Naive Bayesian Classifier (NBC) and a Hidden Markov Model (HMM).

Results: Mutual information density for 20 amino acids and two or three burial levels were estimated to be roughly 15% of the unconditional burial entropy density. Lower estimates for the mutual information between local amino acid sequence and burial of a single residue indicated an increase in mutual information with the number of burial levels up to at least five or six levels. Prediction schemes were found to efficiently extract the available burial information from local sequence. Lower estimates for the mutual information involving single burials are consistently approached by predictions from the NBC and actually surpassed by predictions from the HMM. Near-optimal prediction for the HMM is indicated by the agreement between its density of prediction information and the corresponding density of mutual information between input and output representations.

Availability: The dataset of protein structures and the prediction implementations are available at http://www.btc.unb.br/ (in ‘Software’).

Contact:  aaraujo@unb.br

Supplementary information:  Supplementary data are available at Bioinformatics online.
Static network structure can be used to model the phenotypic effects of perturbations in regulatory networks
Authors: Feiglin Ariel , Hacohen Adar , Sarusi Avital , Fisher Jasmin , Unger Ron , Ofran Yanay
Published: August 2012

Motivation: Biological processes are dynamic, whereas the networks that depict them are typically static. Quantitative modeling using differential equations or logic-based functions can offer quantitative predictions of the behavior of biological systems, but they require detailed experimental characterization of interaction kinetics, which is typically unavailable. To determine to what extent complex biological processes can be modeled and analyzed using only the static structure of the network (i.e. the direction and sign of the edges), we attempt to predict the phenotypic effect of perturbations in biological networks from the static network structure.

Results: We analyzed three networks from different sources: The EGFR/MAPK and PI3K/AKT network from a detailed experimental study, the TNF regulatory network from the STRING database and a large network of all NCI-curated pathways from the Protein Interaction Database. Altogether, we predicted the effect of 39 perturbations (e.g. by one or two drugs) on 433 target proteins/genes. In up to 82% of the cases, an algorithm that used only the static structure of the network correctly predicted whether any given protein/gene is upregulated or downregulated as a result of perturbations of other proteins/genes.

Conclusion: While quantitative modeling requires detailed experimental data and heavy computations, which limit its scalability for large networks, a wiring-based approach can use available data from pathway and interaction databases and may be scalable. These results lay the foundations for a large-scale approach of predicting phenotypes based on the schematic structure of networks.

Contact:  yanay@ofranlab.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
RIsearch: fast RNA–RNA interaction search using a simplified nearest-neighbor energy model
Authors: Wenzel Anne , Akbaşli Erdinç , Gorodkin Jan
Published: August 2012

Motivation: Regulatory, non-coding RNAs often function by forming a duplex with other RNAs. It is therefore of interest to predict putative RNA–RNA duplexes in silico on a genome-wide scale. Current computational methods for predicting these interactions range from fast complementary-based searches to those that take intramolecular binding into account. Together these methods constitute a trade-off between speed and accuracy, while leaving room for improvement within the context of genome-wide screens. A fast pre-filtering of putative duplexes would therefore be desirable.

Results: We present RIsearch, an implementation of a simplified Turner energy model for fast computation of hybridization, which significantly reduces runtime while maintaining accuracy. Its time complexity for sequences of lengths m and n is with a much smaller pre-factor than other tools. We show that this energy model is an accurate approximation of the full energy model for near-complementary RNA–RNA duplexes. RIsearch uses a Smith–Waterman-like algorithm using a dinucleotide scoring matrix which approximates the Turner nearest-neighbor energies. We show in benchmarks that we achieve a speed improvement of at least 2.4× compared with RNAplex, the currently fastest method for searching near-complementary regions. RIsearch shows a prediction accuracy similar to RNAplex on two datasets of known bacterial short RNA (sRNA)–messenger RNA (mRNA) and eukaryotic microRNA (miRNA)–mRNA interactions. Using RIsearch as a pre-filter in genome-wide screens reduces the number of binding site candidates reported by miRNA target prediction programs, such as TargetScanS and miRanda, by up to 70%. Likewise, substantial filtering was performed on bacterial RNA–RNA interaction data.

Availability: The source code for RIsearch is available at: http://rth.dk/resources/risearch.

Contact:  gorodkin@rth.dk

Supplementary information:  Supplementary data are available at Bioinformatics online.
HSPIR: a manually annotated heat shock protein information resource
Authors: R. Ratheesh Kumar , N. S. Nagarajan , S. P. Arunraj , Sinha Devanjan , Veedin Rajan Vinoth Babu , Esthaki Vinoth Kumar , D’Silva Patrick
Published: August 2012

Summary: Heat shock protein information resource (HSPIR) is a concerted database of six major heat shock proteins (HSPs), namely, Hsp70, Hsp40, Hsp60, Hsp90, Hsp100 and small HSP. The HSPs are essential for the survival of all living organisms, as they protect the conformations of proteins on exposure to various stress conditions. They are a highly conserved group of proteins involved in diverse physiological functions, including de novo folding, disaggregation and protein trafficking. Moreover, their critical role in the control of disease progression made them a prime target of research. Presently, limited information is available on HSPs in reference to their identification and structural classification across genera. To that extent, HSPIR provides manually curated information on sequence, structure, classification, ontology, domain organization, localization and possible biological functions extracted from UniProt, GenBank, Protein Data Bank and the literature. The database offers interactive search with incorporated tools, which enhances the analysis. HSPIR is a reliable resource for researchers exploring structure, function and evolution of HSPs.

Availability:  http://pdslab.biochem.iisc.ernet.in/hspir/

Contact:  patrick@biochem.iisc.ernet.in

Supplementary information:  Supplementary data are available at Bioinformatics online.
Quality of life monitoring in ambulatory heart failure patients: temporal changes and prognostic value
Authors: Lupón Josep , Gastelurrutia Paloma , de Antonio Marta , González Beatriz , Cano Lucía , Cabanes Roser , Urrutia Agustín , Díez Crisanto , Coll Ramón , Altimir Salvador , Bayes‐Genis Antoni
Published: August 2012

Aims

Heart failure (HF) is a chronic condition that typically affects a patient's quality of life (QoL). Little is known about long‐term QoL monitoring in HF. This study aimed to evaluate the temporal changes and prognostic value of QoL assessment in a real‐life cohort of HF patients.

Methods and results

The Minnesota Living with Heart Failure Questionnaire was used to monitor QoL at baseline and at 1, 3, and 5 years for 1151 consecutive patients {71.7% men, median age 69 years [25th–75th percentiles (P25–P75) 59–76]} in an HF unit. Follow‐up for prognosis assessment was extended to 6 years. The number of answered questionnaires was 1151 at baseline, 746 at 1 year, 268 at 3 years, and 240 at 5 years. QoL scores showed a steep decrease (indicating QoL improvement) during the first year [29 (P25–P75 16–43) at baseline vs. 15 (P25–P75 8–27) at 1 year, P < 0.001], which was tempered, yet significant up to 5 years [12 (P25–P75 7–23) at 3 years vs. 10 (P25–P75 5–21) at 5 years, P = 0.012]. We recorded 457 deaths during follow‐up. In a comprehensive multivariable Cox regression analysis, baseline QoL remained a significant prognosticator during follow‐up [hazard ratio (HR)Cox for death 1.012, 95% confidence interval 1.006–1.018, P < 0.001]. QoL monitoring showed that a score increase ≥10% between consecutive assessments stratified high‐risk patients within the next 12 months (P = 0.008).

Conclusion

Both baseline and follow‐up QoL monitoring were useful for patient risk stratification in a real‐life HF cohort. Worse QoL may warn of a worse prognosis. Widespread QoL monitoring in routine clinical practice is recommended.
CHOROIDAL INFARCTION AFTER PHOTODYNAMIC THERAPY COMBINED WITH BEVACIZUMAB AND TRIAMCINOLONE REVERSED BY TISSUE PLASMINOGEN ACTIVATOR
Authors: Chen San-Ni , Lin Chun-Ju , Li Kun-Hsien , Hwang Jiunn-Feng
Published: August 2012

Purpose:

To present a case of choroidal infarction after combined therapy of photodynamic therapy, intravitreal bevacizumab, and sub-Tenon triamcinolone injection salvaged by tissue plasminogen activator administration.

Methods:

Interventional case report.

Results:

Combined therapy of full-fluence photodynamic therapy, intravitreal bevacizumab, and sub-Tenon triamcinolone injection was given on the same day to treat neovascular age-related macular degeneration in an 82-year-old patient. Subsequent acute visual loss and marked macular edema as a result of choroidal infarction were noted. Intravitreal and sub-Tenon administration of tissue plasminogen activator were performed 9 days later to salvage the choroidal infarction, and visual improvement was noted. Fundoscopy and optical coherent tomography showed almost complete resolution of macular edema. Indocyanine green angiography revealed reperfusion of the choroidal vessels.

Conclusion:

Choroidal infarction may happen after combined therapy. Tissue plasminogen activator administration may reverse the infarction and help visual recovery.