bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome network medicine: innovation to overcome huge challenges in cancer therapy
Authors: Roukos Dimitrios H. 
Published: December 2013

The post‐ENCODE era shapes now a new biomedical research direction for understanding transcriptional and signaling networks driving gene expression and core cellular processes such as cell fate, survival, and apoptosis. Over the past half century, the Francis Crick ‘central dogma’ of single n gene/protein‐phenotype (trait/disease) has defined biology, human physiology, disease, diagnostics, and drugs discovery. However, the ENCODE project and several other genomic studies using high‐throughput sequencing technologies, computational strategies, and imaging techniques to visualize regulatory networks, provide evidence that transcriptional process and gene expression are regulated by highly complex dynamic molecular and signaling networks. This Focus article describes the linear experimentation‐based limitations of diagnostics and therapeutics to cure advanced cancer and the need to move on from reductionist to network‐based approaches. With evident a wide genomic heterogeneity, the power and challenges of next‐generation sequencing (NGS) technologies to identify a patient's personal mutational landscape for tailoring the best target drugs in the individual patient are discussed. However, the available drugs are not capable of targeting aberrant signaling networks and research on functional transcriptional heterogeneity and functional genome organization is poorly understood. Therefore, the future clinical genome network medicine aiming at overcoming multiple problems in the new fields of regulatory DNA mapping, noncoding RNA, enhancer RNAs, and dynamic complexity of transcriptional circuitry are also discussed expecting in new innovation technology and strong appreciation of clinical data and evidence‐based medicine. The problematic and potential solutions in the discovery of next‐generation, molecular, and signaling circuitry‐based biomarkers and drugs are explored. WIREs Syst Biol Med 2014, 6:201–208. doi: 10.1002/wsbm.1254This article is categorized under:

Laboratory Methods and Technologies > Genetic/Genomic Methods
Biological Mechanisms > Regulatory Biology
Translational, Genomic, and Systems Medicine > Therapeutic Methods
Using systems approaches to address challenges for clinical implementation of pharmacogenomics
Authors: Karnes Jason H. , Van Driest Sara , Bowton Erica A. , Weeke Peter E. , Mosley Jonathan D. , Peterson Josh F. , Denny Joshua C. , Roden Dan M. 
Published: December 2013

Many genetic variants have been shown to affect drug response through changes in drug efficacy and likelihood of adverse effects. Much of pharmacogenomic science has focused on discovering and clinically implementing single gene variants with large effect sizes. Given the increasing complexities of drug responses and their variability, a systems approach may be enabling for discovery of new biology in this area. Further, systems approaches may be useful in addressing challenges in moving these data to clinical implementation, including creation of predictive models of drug response phenotypes, improved clinical decision‐making through complex biological models, improving strategies for integrating genomics into clinical practice, and evaluating the impact of implementation programs on public health. WIREs Syst Biol Med 2014, 6:125–135. doi: 10.1002/wsbm.1255This article is categorized under:

Translational, Genomic, and Systems Medicine > Translational Medicine
Histological Damage of Colonic Epithelium is Associated with Clinical Severity and Outcome in Colectomized Critically Ill Patients
Authors: Sipola S. , Ala‐Kokko T. I. , Laurila J. J. , Vakkala M. , Ohtonen P. , Saarnio J. , Karttunen T. J. , Syrjälä H. 
Published: December 2013

AbstractBackgroundSevere intestinal mucosal damage and organ failure has been associated in experimental models. Our purpose was to determine whether there is any association between histopathological findings and postoperative mortality among ICU patients undergoing emergency colectomies for various illnesses.MethodsIn a retrospective case control study, total colectomy specimens from 50 patients in a mixed ICU were analysed: 18 had sepsis, 11 vascular operations, and 21 Clostridium difficile colitis. Overall thickness, the width of epithelial defects, and presence of cryptal damage were assessed. Extent of necrosis and amount of neutrophils were separately evaluated in the layers of the colonic wall. Clinical features, including sequential organ failure assessment (SOFA) scores and survival, were registered.ResultsThe histopathological findings for the three clinical entities were similar, except for the abundance of characteristic pseudomembranes in the Clostridium group. Mucosal height (maximum) showed a negative correlation with SOFA score on admission (ρ = −0.296, P = 0.037), and with preoperative blood lactate level (ρ = −0.316; P = 0.027). The nonsurvivors had wider enterocyte defects (60 vs. 40.8, P = 0.002) and more severe crypt damage (61 vs. 27 %; P = 0.024) than the survivors.ConclusionsThe histopathological damage involves all layers of the colon wall among ICU patients being largely similar in sepsis, C. difficile infection, and ischemia after vascular operations. Mucosal epithelial damage is associated with clinical severity of the illness and mortality.
Laparoscopic Roux‐En‐Y Gastric Bypass is Effective and Safe in Over 55‐year‐old Patients: A Comparative Analysis
Authors: Giordano Salvatore , Victorzon Mikael 
Published: December 2013

AbstractBackgroundControversy exists regarding the effectiveness and safety of laparoscopic Roux‐en‐Y gastric bypass (LRYGB) in elderly patients. We evaluated our outcomes of LRYGB in patients aged ≥55 years.MethodsA total of 549 consecutive patients underwent LRYGB as primary operation and 132 were ≥55 years old. Patients were divided in two groups: group <55 years comprised 417 patients, with mean age (±SD) of 41.15 ± 8.47 years; group ≥55 years comprised 132 patients, with mean age of 59.43 ± 3.81 years. Mean preoperative body mass index was 47.01 ± 7.47 and 46.21 ± 7.47 respectively, whereas mean excess weightloss percent (EW%) was 88.06 ± 30.28 and 84.86 ± 29.87 %. Early morbidity (30 days) and outcomes at 6, 12, and 24 months follow‐up were evaluated.ResultsSignificant difference was found in operative time (84.19 ± 29.05 vs. 90.89 ± 30.95 min, p = 0.03). One conversion to open procedure occurred in group <55 years, whereas three occurred in group ≥55 years (p = 0.04). Intraoperative complications occurred in 22 patients (5.27 %) in group <55 years versus 19 in group ≥55 years (14.39 %), which was statistically significant (p = 0.001). One case of death occurred in the younger group. Overall postoperative morbidity rate was 18.7 % in group <55 years and 25.76 % in group ≥55 years, with no significant difference (p = 0.08). Mean EWL% at 12 months in group <55 years was 65.95.05 ± 26.96 versus 62.61 ± 41.78 in group ≥55 years, whereas at 24 months it was 65.08 ± 29.68 versus 64.48 ± 18.44 with no significant difference between the groups (p = 0.51; p = 0.92).ConclusionsLRYGB for patients ≥55 years achieves outcomes and complications rates comparable to the younger population. Patients should not be denied bariatric surgery for the age alone.
Separation of Acylglycerides Obtained by Enzymatic Esterification Using Solvent Extraction
Authors: Sánchez Daniel Alberto , Tonetto Gabriela Marta , Ferreira María Luján 
Published: December 2013

AbstractNew avenues to add value to glycerol are currently being explored. One of them is the synthesis of structured lipids through glycerol esterification. In this work we have analyzed the recovery and purification of dicaprin obtained by esterification of glycerol with capric acid (C) in heptane, mediated by Lipozyme RM IM. This is an intermediate step to obtain lipids MLM. In the first stage, the diglyceride synthesis MGM (being G a central HC–OH) was carried out. When M = C, the diglyceride is CGC. Recovery of the diglyceride CGC is required to carry out the esterification of the sn‐2 position with palmitic acid (P), thus obtaining the triglyceride CPC. Different solvents were evaluated using Ecofac 1.0 (a molecular design software solvent) through a theoretical approach to explore the best solvents for the acylglycerides separation. Then, the performance of the selected solvents to separate dicaprin from mono and tricaprin was experimentally studied in a liquid–liquid extraction process. Previously, the remaining fatty acid had been neutralized. With liquid–liquid extraction in three simple steps, using ethanol/water, 94 % of the dicaprin obtained by enzymatic esterification was recovered with a purity of 89 % (wt%). It was also possible to obtain dicaprin with a purity of 97 % but with a yield of 56 %.
Chemical Composition and Ability of Essential Oils from Six Aromatic Plants to Counteract Lipid Oxidation in Emulsions
Authors: Tchobo Fidèle Paul , Alitonou Guy Alain , Soumanou Mohamed Mansourou , Barea Bruno , Bayrasy Christelle , Laguerre Mickaël , Lecomte Jérôme , Villeneuve Pierre , Souhounhloue K. C. Dominique 
Published: December 2013

AbstractEssential oils with antioxidant properties are of increasing interest in West Africa where there are many antioxidant rich plants. The objective of this study was to determine the essential oil extracted from six native plants (Lippia multiflora, Lippia rugosa, Monodora tenuifolia, Ocimum gratissimum, Pimenta racemosa, Cymbopogon citratus) extracted by hydrodistillation from local plants in Benin. These samples were also evaluated for their antioxidant capacity using the conjugated autoxidizable triene (CAT) assay performed in stripped tung oil‐in‐water emulsion. The essential oil of P. racemosa, containing high amounts of chavicol (10.3 %) and eugenol (54.5 %), showed the strongest antioxidant activity, followed by that from O. gratissimum containing large amounts of thymol (50.2 %). The essential oil extracted from M. tenuifolia exhibited a moderate antioxidant activity. This essential oil is primarily composed of sesquiterpene alcohols such as α‐cadinol (20.5 %), its isomer, α‐muurolol (14.7 %), and germacrene D‐4‐ol (16.8 %). Essential oils from L. multiflora, L. rugosa and C. citratus oils showed poor ability to protect tung oil from oxidation. Finally, essential oils containing phenolic compounds and, in a lesser extent, sesquiterpene alcohols, exhibited the highest CAT values indicating that these compounds are the key determinants of the antioxidant activity of these essential oils in oil‐in‐water emulsions.
Identification of Immunity-Related Genes in Arabidopsis and Cassava Using Genomic Data
Authors: Leal Luis Guillermo , Perez Álvaro , Quintero Andrés , Bayona Ángela , Ortiz Juan Felipe , Gangadharan Anju , Mackey David , López Camilo , López-Kleine Liliana 
Published: December 2013

Abstract
Recent advances in genomic and post-genomic technologies have provided the opportunity to generate a previously unimaginable amount of information. However, biological knowledge is still needed to improve the understanding of complex mechanisms such as plant immune responses. Better knowledge of this process could improve crop production and management. Here, we used holistic analysis to combine our own microarray and RNA-seq data with public genomic data from Arabidopsis and cassava in order to acquire biological knowledge about the relationships between proteins encoded by immunity-related genes (IRGs) and other genes. This approach was based on a kernel method adapted for the construction of gene networks. The obtained results allowed us to propose a list of new IRGs. A putative function in the immunity pathway was predicted for the new IRGs. The analysis of networks revealed that our predicted IRGs are either well documented or recognized in previous co-expression studies. In addition to robust relationships between IRGs, there is evidence suggesting that other cellular processes may be also strongly related to immunity.
Liver function tests may be useful tools for advanced cancer patient care: A preliminary single‐center result
Authors: Tsai Hui‐Ju , Hsieh Ming‐Yen , Tsai Yi‐Chun , Liu Zi‐Yun , Hsieh Hui‐Ya , Lee Chiou‐Mei , Chien Ching‐Hsin , Chiu Yu‐Wen , Chuang Hung‐Yi , Huang Chia‐Tsuan 
Published: December 2013

AbstractAccurate prognostication in advanced cancer may facilitate better palliative care. An objective marker may be more applicable and appropriate than a subjective evaluation by physicians. The aim of this study was to evaluate liver function tests as useful prognostic factors for survival in patients with advanced cancer. We recruited advanced cancer patients from January 2007 to December 2009. Data on age, sex, cancer diagnosis, site of metastases, clinical symptoms, and performance status were collected at the time of admission to the palliative care unit. Analyzed laboratory data were obtained on the Day 1 of admission to the palliative care unit. A total of 522 patients were enrolled; 322 (61.7%) of them were males. The mean age was 60.6 ± 13.2 years. Multiple logistic regression analysis adjusting for age and sex demonstrated aspartate transaminase (AST) > 80 IU/L [odds ratio (OR) = 2.01, p = 0.010] and alanine transaminase > 80 IU/L (OR = 1.89, p = 0.047) were independently significant prognostic factors of death within 14 days. AST > 80 IU/L (OR = 3.67, p = 0.017) and albumin < 3.0 g/dL (OR = 1.98, p = 0.048) were independently significant prognostic factors of death within 6 months. Liver function tests may be useful prognostic factors for patients in the palliative care unit, in addition to being useful for patients with hepatobiliary cancer or liver metastasis. These biochemical tests of liver function with cutoff values can easily be used in palliative care.
2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host
Authors: Rubin Lorry G. , Levin Myron J. , Ljungman Per , Davies E. Graham , Avery Robin , Tomblyn Marcie , Bousvaros Athos , Dhanireddy Shireesha , Sung Lillian , Keyserling Harry , Kang Insoo 
Published: December 2013

AbstractAn international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investigation are highlighted.
Effect of Wheat Grain Steaming and Washing on Lipase Activity in Whole Grain Flour
Authors: De Almeida Juliano Luiz , Pareyt Bram , Gerits Lien R. , Delcour Jan A. 
Published: December 2013

ABSTRACTDuring whole grain flour (WGF) storage, lipase activity causes partial loss of its functionality and the sensory acceptability of products produced from it. The objective of this research was to evaluate the effect of steaming and washing on lipase activity in (fractions of) wheat. Steam treatment conditions were optimized for wheat grains and their bran, shorts, and flour fractions. Lipase activities were determined colorimetrically, as were peroxidase, endoxylanase, and α‐amylase activities. Steaming grains for 180 s effectively inactivated lipase, peroxidase, endoxylanase, and part of the α‐amylase without gelatinizing starch. The work further demonstrated that lipase is mainly, if not only, located in the bran fraction. Separate bran treatment holds promise for obtaining WGF with reduced lipase activity but without altered functional properties. Washing grains did not reduce WGF lipase activity.
First Report of Blossom Blight Caused by Sclerotinia sclerotiorum on Japanese Plum, Nectarine, and Sweet Cherry Orchards in Chile
Authors: Ferrada E. E. , Díaz G. A. , Zoffoli J. P. , Latorre B. A. 
Published: December 2013

Blossom blight of Japanese plum (Prunus salicina), nectarine (P. persica var. nectarina), and sweet cherry (P. avium) was observed in commercial orchards in central Chile in 2012. Disease prevalence of 8% and 1% were estimated in 2012 and 2013, respectively. Early symptoms appeared as small pale-brown necrotic lesions on the petals that eventually affected the entire flowers. White and cottony fungal colonies were consistently isolated on potato dextrose agar acidified with 0.5 ml/liter of 92% lactic acid (APDA), incubated for 5 days at 20°C. Black spherical to elongated sclerotia of 2.5 to 4.2 × 2.8 to 5.3 mm (n = 60) were formed on APDA. This fungus was tentatively identified as Sclerotinia sclerotiorum (Lib.) de Bary. The identity of the fungus was confirmed by BLAST analysis of the internal transcribed spacer (ITS) region (GenBank Accession Nos. KF148604 to KF148609) of rDNA, amplified with PCR primers ITS1/ITS4 (3), demonstrating a 99 to 100% similarity with the reference S. sclerotiorum strains (EU082466 and JX307092). The pathogenicity was studied in detached flowers of ‘Larry Ann’ Japanese plum, ‘Summer Bright’ nectarine, and ‘Bing’ sweet cherry that were inoculated with a mycelial suspension (106 fragments/ml) of six isolates of S. sclerotiorum and incubated for 5 days at 20°C in humid chambers (>80% relative humidity). Inoculated flowers developed a light brown petal necrosis that eventually comprised the entire flower. The same S. sclerotiorum isolates were inoculated in mature fruits of ‘Larry Ann’ Japanese plum, ‘Summer Bright’ nectarine, and ‘Staccato’ sweet cherry. Surface disinfected (1% NaOCl for 1 min) fruits were inoculated by placing a mycelium plug (4 mm in diameter) into a wound made with a sterile scalpel and incubated for 3 days at 20°C in humid chambers. Symptoms consisted on light brown soft lesions that varied from 8.7 to 46.5 mm in diameter. A superficial white and cottony septated mycelium was also obtained. An equal number of non-inoculated flowers and wounded but non-inoculated fruits remained healthy. S. sclerotiorum was re-isolated from 100% of the artificially inoculated flowers and fruits, completing Koch's postulates. S. sclerotiorum was reported causing shoot blight on apricot (P. armeniaca), lemon tree (Citrus limon), and table grapes (Vitis vinifera) in Chile (1,2), and to our knowledge, this is the first report of S. sclerotiorum associated with blossom blight in Japanese plum, nectarine, and sweet cherry in Chile. References: (1) R. Acuña. Compendio de Bacterias y Hongos de Frutales y Vides en Chile. Servicio Agrícola y Ganadero, Santiago, Chile, 2010. (2) B. A. Latorre and M. J. Guerrero. Plant Dis. 85:1122, 2001. (3) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, CA, 1990.
Species Delimitation using Genome-Wide SNP Data
Authors: Leaché Adam D. , Fujita Matthew K. , Minin Vladimir N. , Bouckaert Remco R. 
Published: December 2013

AbstractThe multi-species coalescent has provided important progress for evolutionary inferences, including increasing the statistical rigor and objectivity of comparisons among competing species delimitation models. However, Bayesian species delimitation methods typically require brute force integration over gene trees via Markov chain Monte Carlo (MCMC), which introduces a large computation burden and precludes their application to genomic-scale data. Here we combine a recently introduced dynamic programming algorithm for estimating species trees that bypasses MCMC integration over gene trees with sophisticated methods for estimating marginal likelihoods, needed for Bayesian model selection, to provide a rigorous and computationally tractable technique for genome-wide species delimitation. We provide a critical yet simple correction that brings the likelihoods of different species trees, and more importantly their corresponding marginal likelihoods, to the same common denominator, which enables direct and accurate comparisons of competing species delimitation models using Bayes factors. We test this approach, which we call Bayes factor delimitation (*with genomic data;BFD*), using common species delimitation scenarios with computer simulations. Varying the numbers of loci and the number of samples suggest that the approach can distinguish the true model even with few loci and limited samples per species. Misspecification of the prior for population sizeθhas little impact on support for the true model. We apply the approach to West African forest geckos (Hemidactylus fasciatuscomplex) using genome-wide SNP data data. This new Bayesian method for species delimitation builds on a growing trend for objective species delimitation methods with explicit model assumptions that are easily tested.
Inducible offences affect predator–prey interactions and life‐history plasticity in both predators and prey
Authors: Kishida Osamu , Costa Zacharia , Tezuka Ayumi , Michimae Hirofumi 
Published: December 2013

Summary

Phenotypic plasticity can have strong impacts on predator–prey interactions. Although much work has examined the effects of inducible defences, less understood is how inducible offences in predators affect predator–prey interactions and predator and prey phenotypes.

Here, we examine the impacts of an inducible offence on the interactions and life histories of a cohort of predatory Hynobius retardatus salamander larvae and their prey, Rana pirica tadpoles. We examined larval (duration, survival) and post‐metamorphic (size) traits of both species after manipulating the presence/absence of tadpoles and salamanders with offensive (broadened gape width) or non‐offensive phenotypes in pond enclosures.

Offensive phenotype salamanders reduced tadpole survival and metamorph emergence by 58% compared to tadpole‐only treatments, and by over 30% compared to non‐offensive phenotypes. Average time to metamorphosis of frogs was delayed by 30% in the presence of salamanders, although this was independent of salamander phenotype. Thus, offensive phenotype salamanders reduced the number of tadpoles remaining in the pond over time by reducing tadpole survival, not by altering patterns of metamorph emergence. Offensive phenotypes also caused tadpoles to metamorphose 19% larger than no salamander treatments and 6% larger than non‐offensive phenotype treatments. Pooled across salamander treatments, tadpoles caused salamanders to reach metamorphosis faster and larger. Moreover, in the presence of tadpoles, offensive phenotype salamanders metamorphosed 25% faster and 5% larger than non‐offensive phenotype salamanders, but in their absence, neither their size nor larval period differed from non‐offensive phenotype individuals.

To our knowledge, this study is the first to demonstrate that inducible offences in predators can have strong impacts on predator and prey phenotypes across multiple life stages. Since early metamorphosis at a larger size has potential fitness advantages, the impacts of offensive phenotypes on frog and salamander life histories likely have significant consequences for individuals and populations. Furthermore, increased predation on tadpoles likely causes offensive phenotype individuals to have strong impacts on pond communities. Future studies should examine the fitness consequences of morphological and life‐history plasticity across multiple life stages and should address the population and community level consequences of offensive phenotypes.