bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomics of primary chemoresistance and remission induction failure in pediatric and adult acute myeloid leukemia
Authors: Brown Fiona C. , Cifani Paolo , Drill Esther , He Jie , Still Eric , Zhong Shan , Balasubramanian Sohail , Pavlick Dean , Yilmazel Bahar , Knapp Kristina M. , Alonzo Todd A. , Meshinchi Soheil , Stone Richard M. , Kornblau Steven M. , Marcucci Guido , Gamis Alan S. , Byrd John C. , Gonen Mithat , Levine Ross L. , Kentsis Alex 
Published: May 2016

AbstractDespite intense efforts, the cure rates of children and adults with AML remain unsatisfactory in large part due to resistance to chemotherapy. Whilst cytogenetic risk stratification proved valuable in identifying causes of therapy failure and disease relapse, cytogenetically normal AML remains the most prevalent disease type, with significant heterogeneity of clinical outcomes, including primary chemoresistance. Using targeted sequencing of 670 genes recurrently mutated in hematologic malignancies, we investigated the genetic basis of primary chemotherapy resistance and remission induction failure of 107 primary cases obtained at diagnosis from children and adults with cytogenetically normal AML. Comparative analysis revealed mutations ofSETBP1, ASXL1andRELNto be significantly enriched at diagnosis in primary induction failure as compared to remission cases. In addition, this analysis revealed novel genomic alterations not previously described in AML, as well as distinct genes that are significantly overexpressed in therapy resistant AML. However, identified gene mutations were sufficient to explain only a minority of cases of primary induction failure. Thus, additional genetic or molecular mechanisms must cause primary chemoresistance in pediatric and adult acute myeloid leukemias.Key PointsTargeted gene sequencing of 670 genes in adult and pediatric AMLProfiling of 107 primary AML samples identifies new genomic alterations for primary chemoresistance
Large-scale analysis of post-translational modifications in E. coli under glucose-limiting conditions
Authors: Brown Colin W , Sridhara Viswanadham , Boutz Daniel R , Person Maria D , Marcotte Edward M , Barrick Jeffrey E , Wilke Claus O 
Published: May 2016

AbstractBackgroundPost-translational modification (PTM) of proteins is central to many cellular processes across all domains of life, but despite decades of study and a wealth of genomic and proteomic data the biological function of many PTMs remains unknown. This is especially true for prokaryotic PTM systems, many of which have only recently been recognized and studied in depth. It is increasingly apparent that a deep sampling of abundance across a wide range of environmental stresses, growth conditions, and PTM types, rather than simply cataloging targets for a handful of modifications, is critical to understanding the complex pathways that govern PTM deposition and downstream effects.ResultsWe utilized a deeply-sampled dataset of MS/MS proteomic analysis covering 9 timepoints spanning theEscherichia coligrowth cycle and an unbiased PTM search strategy to construct a temporal map of abundance for all PTMs within a 400 Da window of mass shifts. Using this map, we are able to identify novel targets and temporal patterns for N-terminal Nα acetylation, C-terminal glutamylation, and asparagine deamidation. Furthermore, we identify a possible relationship between N-terminal Na acetylation and regulation of protein degradation in stationary phase, pointing to a previously unrecognized biological function for this poorly-understood PTM.ConclusionsUnbiased detection of PTM in MS/MS proteomics data facilitates the discovery of novel modification types and previously unobserved dynamic changes in modification across growth timepoints.
Genetic prediction of the effectiveness of biologics for psoriasis treatment
Authors: Nishikawa Rika , Nagai Hiroshi , Bito Toshinori , Ikeda Tetsuya , Horikawa Tatsuya , Adachi Atsuko , Matsubara Tsukasa , Nishigori Chikako 
Published: May 2016

AbstractAnti‐tumor necrosis factor (TNF)‐α therapy is used for the treatment of psoriasis, with varying outcomes. However, the specific cause of inadequate response or treatment failure remains unknown. The aim of the present study was to identify useful clinical biomarkers for predicting therapeutic responses or to serve as new drug targets for refractory psoriasis cases. We performed a genome‐wide association study (GWAS) of 65 psoriasis patients who were prospectively followed after beginning anti‐TNF‐α therapy using Human Omni Express‐8 v1.2 Beadchips. Patients were enrolled at the dermatology departments of Kobe University Hospital and six collaborative hospitals. Associations between single nucleotide polymorphisms (SNP) and changes in the Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment were evaluated. After genome data collection and quality control, a total of 731 442 SNPs were identified in 65 Asian psoriasis patients who were treated with adalimumab or infliximab. Here, we present 10 SNPs, such as those in JAG2 and ADRA2A, that were associated with treatment responses to anti‐TNF‐α agents (strongest effect, P < 7.11E‐06). This is the first GWAS to examine SNP associated with treatment responses in psoriasis patients. In addition, we identified other SNP that exhibited potential associations with anti‐TNF‐α treatment response, which merit further study. Of these, rs11096957 on TLR10, which is associated with increased TNF‐α production, was previously reported to be associated with treatment responses to TNF‐α inhibitors.
Three hundred and eight nanometer excimer light therapy for alopecia universalis that is resistant to other treatments: A clinical study of 11 patients
Authors: Arakawa Yukiyasu , Nomiyama Tomoko , Katoh Norito 
Published: May 2016

AbstractThree hundred and eight nanometer excimer light therapy has recently been reported to be effective against patchy alopecia areata (AA) in several clinical studies. However, these studies only included a few patients with severe forms of AA, and all of them exhibited poor outcomes. We further investigated the use of excimer light as a therapeutic option for cases of alopecia universalis (AU) that are resistant to other treatments. Eleven treatment‐resistant AU patients were treated with a 308‐nm excimer light at 2‐week intervals for more than 16 sessions. Four patients achieved good responses and two patients exhibited poor responses. Three patients had Japanese skin type 1 and all of them achieved good responses. The radiation dose was increased until the patients exhibited marked erythema. The patients with Japanese skin type 3 who achieved good responses exhibited strong pigmentation at the irradiated sites. In conclusion, 308‐nm excimer light therapy has significant effects on some AU patients who are resistant to other treatments and may be an alternative therapeutic option for AU. During the treatment of AU, high doses of radiation should be administrated until a strong inflammatory skin reaction is seen.
Dissection of the contributions of cyclophilin genes to development and virulence in a fungal insect pathogen
Authors: Zhou Yonghong , Keyhani Nemat O. , Zhang Yongjun , Luo Zhibing , Fan Yanhua , Li Yujie , Zhou Qiaosheng , Chen Jianjun , Pei Yan 
Published: May 2016

SummaryCyclophilins are ubiquitous proteins found in all domains of life, catalyzing peptidyl‐prolylcis‐transisomerization (PPIase activity) and functioning in diverse cellular processes. The filamentous insect pathogenic fungus,Beauveria bassiana, contains 11 cyclophilin genes whose roles were probed via individual gene knockouts, construction of over‐expression strains, and a simultaneous gene knockdown strategy using tandem SiRNA. Mutants were examined for effects on conidiation, hyphal growth, cyclosporine and stress resistance, and insect virulence.BbCypAwas found to be the most highly expressed cyclophilin during growth and purified recombinant BbCypA displayed cyclosporine sensitive PPIase activity. Except for ΔBbCypA, targeted gene knockouts or overexpression of any cyclophilin resulted in temperature sensitivity (TS). Specific cyclophilin mutants showed impaired hyphal growth and differential effects on conidiation and cyclosporine resistance. Insect bioassays revealed decreased virulence for two cyclophilins (ΔBbCypEand ΔBbCyp6) and the simultaneous gene knockdown mutant constructs (SiRNA30). TheBbSiRNA30strains were unaffected in growth, conidiation, or under osmotic or cell wall perturbing stress, but did show increased resistance to cyclosporine and a TS phenotype. These results revealed common and unique roles for cyclophilins inB. bassianaand validate a method for examining the effects of multi‐gene families via simultaneous gene knockdown.
Rice false smut fungus hijacks the rice nutrients supply by blocking and mimicking the fertilization of rice ovary
Authors: Song Jie‐Hui , Wei Wei , Lv Bo , Lin Yang , Yin Wei‐Xiao , Peng You‐Liang , Schnabel Guido , Huang Jun‐Bin , Jiang Dao‐Hong , Luo Chao‐Xi 
Published: May 2016

SummaryRice false smut disease is an increasing threat to rice production in the world. Despite of best efforts, research for the infection of the fungus has yielded equivocal and conflicting results about where and how the infection is initiated and developed. Here we show a stepwise infection pattern and sophisticated regulation during this process. Initial infection occurred on the filaments, which prevented the production of mature pollen thus blocked the pollination. In the following days, the pathogen invaded the stigmas and styles, occasionally the ovaries. Expression analysis indicated that the fungus mimicked a successful fertilization process and enabled the continuous supply of nutrients for fungus to produce false smut balls. The stepwise infection of flower organs and mimicry of ovary fertilization unveiled in this study guided the rice plant into supplying nutrients for false smut ball development and represents a new and unique biological process of host pathogen interactions.
Environmental filtering decreases with fish development for the assembly of gut microbiota
Authors: Yan Qingyun , Li Jinjin , Yu Yuhe , Wang Jianjun , He Zhili , Van Nostrand Joy D. , Kempher Megan L. , Wu Liyou , Wang Yaping , Liao Lanjie , Li Xinghao , Wu Shu , Ni Jiajia , Wang Chun , Zhou Jizhong 
Published: May 2016

SummaryGut microbiota typically occupy habitats with definable limits/borders that are comparable to oceanic islands. The gut therefore can be regarded as an ‘island’ for the assembly of microbial communities within the ‘sea’ of surrounding environments. This study aims to reveal the ecological mechanisms that govern microbiota in the fish gut ‘island’ ecosystem. Taxonomic compositions, phylogenetic diversity, and community turnover across host development were analyzed via the high‐throughput sequencing of 16S rRNA gene amplicons. The results indicate that the Shannon diversity of gut microbiota in the three examined freshwater fish species all significantly decreased with host development, and the dominant bacterial taxa also changed significantly during host development. Null model and phylogenetic‐based mean nearest taxon distance (MNTD) analyses suggest that host gut environmental filtering led to the assembly of microbial communities in the fish gut ‘island’. However, the phylogenetic clustering of local communities and deterministic processes that governed community turnover became less distinct as the fish developed. The observed mechanisms that shaped fish gut microbiota seemed to be mainly shaped by the gut environment and by some other selective changes accompanying the host development process. These findings greatly enhance our understanding of stage‐specific community assembly patterns in the fish gut ecosystem.
Rhizoxin analogs, orfamide A and chitinase production contribute to the toxicity of Pseudomonas protegens strain Pf‐5 to Drosophila melanogaster
Authors: Loper Joyce E. , Henkels Marcella D. , Rangel Lorena I. , Olcott Marika H. , Walker Francesca L. , Bond Kise L. , Kidarsa Teresa A. , Hesse Cedar N. , Sneh Baruch , Stockwell Virginia O. , Taylor Barbara J. 
Published: May 2016

SummaryPseudomonas protegens strain Pf‐5 is a soil bacterium that was first described for its capacity to suppress plant diseases and has since been shown to be lethal to certain insects. Among these is the common fruit fly Drosophila melanogaster, a well‐established model organism for studies evaluating the molecular and cellular basis of the immune response to bacterial challenge. Pf‐5 produces the insect toxin FitD, but a ΔfitD mutant of Pf‐5 retained full toxicity against D. melanogaster in a noninvasive feeding assay, indicating that FitD is not a major determinant of Pf‐5's oral toxicity against this insect. Pf‐5 also produces a broad spectrum of exoenzymes and natural products with antibiotic activity, whereas a mutant with a deletion in the global regulatory gene gacA produces none of these exoproducts and also lacks toxicity to D. melanogaster. In this study, we made use of a panel of Pf‐5 mutants having single or multiple mutations in the biosynthetic gene clusters for seven natural products and two exoenzymes that are produced by the bacterium under the control of gacA. Our results demonstrate that the production of rhizoxin analogs, orfamide A, and chitinase are required for full oral toxicity of Pf‐5 against D. melanogaster, with rhizoxins being the primary determinant.
Patients’ knowledge and fear of colorectal cancer risk in inflammatory bowel disease
Authors: Lopez Anthony , Collet‐Fenetrier Benjamin , Belle Arthur , Peyrin‐Biroulet Laurent 
Published: May 2016

AbstractObjectiveTo investigate knowledge and fear of colorectal cancer (CRC) risk in inflammatory bowel disease (IBD) patients.MethodsA 12‐item self‐administered questionnaire, developed after a careful literature review, was administered to all consecutive IBD patients treated with infliximab who were followed up at Nancy University Hospital (Vandoeuvre‐lès‐Nancy, France) between February and May 2012.ResultsAltogether 100 patients including 72 with Crohn's disease (CD) were included. Only 7.0% of patients spontaneously mentioned CRC risk as a main feature of IBD and 37.0% as a potential IBD complication. CRC was the most feared complication by 26 patients [ulcerative colitis (UC) 46.4% vs CD 18.1%, P < 0.01]. Two‐thirds of patients knew that IBD increases CRC risk (UC 81.9% vs CD 57.1%, P = 0.02). Their main source of information was their gastroenterologist (52.0%). On the best screening method for CRC, 86.0% of the respondents mentioned colonoscopy. Only 32.0% of patients knew that it has to be performed 10 years after diagnosis. In case of dysplasia, 51.0% of the patients would not undergo colectomy (CD 59.7% vs UC 28.6%, P < 0.01), mainly due to the fear of having ostomy bags. Only one‐quarter of UC patients were aware of the chemopreventive effect of 5‐aminosalicylates on CRC risk.ConclusionsTwo‐thirds of IBD patients are aware of the risk of CRC. UC patients have a better knowledge of this risk and are more afraid of this complication. Our results underscore the need for therapeutic education about CRC in IBD patients.
Characterizing Drought in Irrigated Agricultural Systems: The Surface Water Delivery Index (SWDI)
Authors: Hoekema David J. , Ryu Jae Hyeon 
Published: May 2016

AbstractQuantifying surface water shortages in arid and semiarid agricultural regions is challenging because limited water supplies are distributed over long distances based on complex water management systems constrained by legal, economic, and social frameworks that evolve with time. In such regions, the water supply is often derived in a climate dramatically different from where the water is diverted to meet agricultural demand. The existing drought indices which rely on local climate do not portray the complexities of the economic and legal constraints on water delivery. Nor do these indices quantify the shortages that occur in drought. Therefore, this research proposes a methodological approach to define surface water shortages in irrigated agricultural systems using a newly developed index termed the Surface Water Delivery Index (SWDI). The SWDI can be used to uniformly quantify surface water deficits/shortages at the end of the irrigation season. Results from the SWDI clearly illustrate how water shortages in droughts identified by the existing indices (e.g., SPI and PDSI) vary strongly both within and between basins. Some surface water entities are much more prone to water shortages than other entities based both on their source of water supply and water right portfolios.
Prediction of excessive weight gain in insulin treated patients with type 2 diabetes
Authors: Cichosz Simon Lebech , Lundby‐Christensen Louise , Johansen Mette D. , Tarnow Lise , Almdal Thomas Peter , Hejlesen Ole K. , Group The C.I.M.T. Trial 
Published: May 2016

AbstractBackgroundWeight gain is an ongoing challenge when initiating insulin therapy in patients with type 2 diabetes mellitus (T2DM). However, if prediction of insulin‐associated weight gain was possible on an individual level, targeted initiatives could be implemented to reduce weight gain. The aim of the present study was to identify predictors of weight gain in insulin‐treated patients with T2DM.MethodsIn all, 412 individuals with T2DM were, in addition to metformin or placebo, randomized into 18‐month treatment groups with three different insulin analog treatment regimens (biphasic, aspart, detemir). Participants with excessive weight gain were defined as the group with weight gain in the 4th quartile (>6.2 kg).We developed a pattern classification method to predict individuals prone to excessive weight gain.ResultsOver the 18‐month treatment period, median weight gain among all 412 patients was 2.4 kg (95% prediction interval [PI] –5.6, 12.4 kg), whereas median weight gain for those in the upper 4th quartile (n = 103) was 8.9 kg (95% PI 6.3, 15.2 kg). No clinical baseline data were strong predictors of excessive weight gain. However, the weight gain during the first 3 months of the trial and the subsequent dose of insulin yielded a useful predictor for weight gain at the 18‐month follow‐up. Combining these two predictors into a prediction model with other clinical available information produced a receiver operating characteristic area under the curve of 0.80.ConclusionsWe have developed a prediction model that could help identify a substantial proportion of individuals with T2DM prone to large weight gain during insulin therapy.
Characterization of the Pharmacokinetics of Phosphatidylethanol 16:0/18:1 and 16:0/18:2 in Human Whole Blood After Alcohol Consumption in a Clinical Laboratory Study
Authors: Javors Martin A. , Hill‐Kapturczak Nathalie , Roache John D. , Karns‐Wright Tara E. , Dougherty Donald M. 
Published: May 2016

BackgroundThe purpose of this study was to characterize the pharmacokinetics of 2 homologues of phosphatidylethanol (PEth) and their combined total in uncoagulated, whole blood samples taken from participants in a human clinical laboratory study after consumption of low doses of ethanol (EtOH).MethodsAs part of a larger study, 14 male and 13 female participants received either 0.25 or 0.50 g/kg oral doses of EtOH during a 15‐minute period. Blood samples were collected before and throughout 6 hours after each EtOH dose on the day of consumption and then every 3 days during the next 14 days. PEth 16:0/18:1 and PEth 16:0/18:2 levels were quantified in blood samples by HPLC/MS/MS and reported separately or as their combined total (combined PEth). Breath alcohol concentrations (BrACs) were measured concurrently with each blood collection. Transdermal alcohol concentrations were measured every 30 minutes during the entire 22‐day study to confirm the absence of drinking during a 7‐day period before and the 14‐day period after EtOH consumption.Results(i) Single doses of 0.25 and 0.50 g EtOH/kg produced proportional increases in BrAC and combined PEth levels of all participants; (ii) the areas under the curve (AUCs) for each participant's BrAC levels during the 6‐hour period after EtOH administration were correlated with AUCs of cPEth (calculated as the AUC of the increase above baseline for combined PEth); (iii) the mean half‐life of combined PEth, determined during the 14‐day period after EtOH consumption, was 4.6 ± 3.5 (SD) days (range: 1.0 to 13.1 days).ConclusionsCombined PEth is a sensitive biomarker for the identification of relatively low levels of EtOH consumption. The measurement of these 2 homologues may provide additional sensitivity to identify low levels of drinking.
A Mechanistic Review of Cell Death in Alcohol‐Induced Liver Injury
Authors: Wang Shaogui , Pacher Pal , De Lisle Robert C. , Huang Heqing , Ding Wen‐Xing 
Published: May 2016

Alcoholic liver disease (ALD) is a major health problem in the United States and worldwide without successful treatments. Chronic alcohol consumption can lead to ALD, which is characterized by steatosis, inflammation, fibrosis, cirrhosis, and even liver cancer. Recent studies suggest that alcohol induces both cell death and adaptive cell survival pathways in the liver, and the balance of cell death and cell survival ultimately decides the pathogenesis of ALD. This review summarizes the recent progress on the role and mechanisms of apoptosis, necroptosis, and autophagy in the pathogenesis of ALD. Understanding the complex regulation of apoptosis, necrosis, and autophagy may help to develop novel therapeutic strategies by targeting all 3 pathways simultaneously.
Alcohol Increases Delay and Probability Discounting of Condom‐Protected Sex: A Novel Vector for Alcohol‐Related HIV Transmission
Authors: Johnson Patrick S. , Sweeney Mary M. , Herrmann Evan S. , Johnson Matthew W. 
Published: May 2016

BackgroundAlcohol use, especially at binge levels, is associated with sexual HIV risk behavior, but the mechanisms through which alcohol increases sexual risk taking are not well‐examined. Delay discounting, that is, devaluation of future consequences as a function of delay to their occurrence, has been implicated in a variety of problem behaviors, including risky sexual behavior. Probability discounting is studied with a similar framework as delay discounting, but is a distinct process in which a consequence is devalued because it is uncertain or probabilistic.MethodsTwenty‐three, nondependent alcohol users (13 male, 10 female; mean age = 25.3 years old) orally consumed alcohol (1 g/kg) or placebo in 2 separate experimental sessions. During sessions, participants completed tasks examining delay and probability discounting of hypothetical condom‐protected sex (Sexual Delay Discounting Task, Sexual Probability Discounting Task) and of hypothetical and real money.ResultsAlcohol decreased the likelihood that participants would wait to have condom‐protected sex versus having immediate, unprotected sex. Alcohol also decreased the likelihood that participants would use an immediately available condom given a specified level of sexually transmitted infection (STI) risk. Alcohol did not affect delay discounting of money, but it did increase participants' preferences for larger, probabilistic monetary rewards over smaller, certain rewards.ConclusionsAcute, binge‐level alcohol intoxication may increase sexual HIV risk by decreasing willingness to delay sex in order to acquire a condom in situations where one is not immediately available, and by decreasing sensitivity to perceived risk of STI contraction. These findings suggest that delay and probability discounting are critical, but heretofore unrecognized, processes that may mediate the relations between alcohol use and HIV risk.