bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive multicenter comparison of whole genome sequencing pipelines using a uniform tumor-normal sample pair
Authors: Buchhalter Ivo , Hutter Barbara , Alioto Tyler S. , Beck Timothy A. , Boutros Paul C. , Brors Benedikt , Butler Adam P. , Chotewutmontri Sasithorn , Denroche Robert E. , Derdak Sophia , Diessl Nicolle , Feuerbach Lars , Fujimoto Akihiro , Gröbner Susanne , Gut Marta , Harding Nicholas J. , Heinold Michael , Heisler Lawrence E. , Hinton Jonathan , Jäger Natalie , Jones David , Kabbe Rolf , Korshunov Andrey , McPherson John D. , Menzies Andrew , Nakagawa Hidewaki , Previti Christopher , Raine Keiran , Ribeca Paolo , Schmidt Sabine , Shepherd Rebecca , Stebbings Lucy , Tarpey Patrick S. , Teague Jon W. , Tonon Laurie , Wheeler David A. , Xi Liu , Yamaguchi Takafumi N. , Sertier Anne-Sophie , Pfister Stefan M. , Campbell Peter J. , Schlesner Matthias , Lichter Peter , Eils Roland , Gut Ivo G. , Jones David T. W. ,   on behalf of the ICGC Verification and Validation Working Group
Published: December 2014

AbstractAs next-generation sequencing becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Through the International Cancer Genome Consortium (ICGC), we compared sequencing pipelines at five independent centers (CNAG, DKFZ, OICR, RIKEN and WTSI) using a single tumor-blood DNA pair. Analyses by each center and with one standardized algorithm revealed significant discrepancies. Although most pipelines performed well for coding mutations, library preparation methods and sequencing coverage metrics clearly influenced downstream results. PCR-free methods showed reduced GC-bias and more even coverage. Increasing sequencing depth to ∼100x (two- to three-fold higher than current standards) showed a benefit, as long as the tumor:control coverage ratio remained balanced. To become part of routine clinical care, high-throughput sequencing must be globally compatible and comparable. This benchmarking exercise has highlighted several fundamental parameters to consider in this regard, which will allow for better optimization and planning of both basic and translational studies.
RAX2: genome-wide detection of condition-associated transcription variation
Authors: Tan Yuan-De , Deng Jixin , Neilson Joel R. 
Published: December 2014

AbstractAlmost all of mammalian genes have mRNA variants due to alternative promoters, alternative splice sites, and alternative cleavage and polyadenylation sites. In most cases, change in transcript due to choosing alternative cleavage and polyadenylation sites does not lead to change in protein sequence, while selection of alternative promoters and alternative splice sites would alter protein sequence. Nevertheless, all these alternations would give rise to different RNA isoforms. Selection of alternative RNA isoforms has been found to be associated with change in condition. For example, many studies have revealed that alternative cleavage and polyadenylation (poly(A)) are correlated to proliferation, differentiation, and cellular transformation. Thus, unlike gene expression in microarray, change in usage of splice sites or poly(A) sites associated with conditions does not involve differential expression and hence cannot be detected by differential analysis methods but can be done by association methods. Traditional association methods such as Pearson chi-square test and Fisher Exact test are single test methods and do not work on the RNA count data derived from replicate libraries. For this reason, we here developed a large-scale association method, called ranking analysis of chi-squares (RAX2). Simulations demonstrated that RAX2 worked well for finding association of changes in usage of poly(A) sites with condition change. We applied our RAX2 to our primary T-cell transcriptomic data of over 9899 tags scattered in 3812 genes and found that 1610 (16.3%) tags were associated in transcription with immune stimulation at FDR < 0.05 and most of these tags associated with stimulation also had differential expression. Analysis of two and three tags within genes revealed that under immune stimulation, short RNA isoforms were significantly preferably used. Like cell proliferation and division, short RNA isoforms are highly prioritized to be used for cell growth.
FLAVODIIRON2 and FLAVODIIRON4 Proteins Mediate an Oxygen-Dependent Alternative Electron Flow in Synechocystis sp. PCC 6803 under CO2-Limited Conditions
Authors: Shimakawa Ginga , Shaku Keiichiro , Nishi Akiko , Hayashi Ryosuke , Yamamoto Hiroshi , Sakamoto Katsuhiko , Makino Amane , Miyake Chikahiro 
Published: December 2014

Abstract
This study aims to elucidate the molecular mechanism of an alternative electron flow (AEF) functioning under suppressed (CO2-limited) photosynthesis in the cyanobacterium Synechocystis sp. PCC 6803. Photosynthetic linear electron flow, evaluated as the quantum yield of photosystem II [Y(II)], reaches a maximum shortly after the onset of actinic illumination. Thereafter, Y(II) transiently decreases concomitantly with a decrease in the photosynthetic oxygen evolution rate and then recovers to a rate that is close to the initial maximum. These results show that CO2 limitation suppresses photosynthesis and induces AEF. In contrast to the wild type, Synechocystis sp. PCC 6803 mutants deficient in the genes encoding FLAVODIIRON2 (FLV2) and FLV4 proteins show no recovery of Y(II) after prolonged illumination. However, Synechocystis sp. PCC 6803 mutants deficient in genes encoding proteins functioning in photorespiration show AEF activity similar to the wild type. In contrast to Synechocystis sp. PCC 6803, the cyanobacterium Synechococcus elongatus PCC 7942 has no FLV proteins with high homology to FLV2 and FLV4 in Synechocystis sp. PCC 6803. This lack of FLV2/4 may explain why AEF is not induced under CO2-limited photosynthesis in S. elongatus PCC 7942. As the glutathione S-transferase fusion protein overexpressed in Escherichia coli exhibits NADH-dependent oxygen reduction to water, we suggest that FLV2 and FLV4 mediate oxygen-dependent AEF in Synechocystis sp. PCC 6803 when electron acceptors such as CO2 are not available.
DEVELOPMENTALLY REGULATED PLASMA MEMBRANE PROTEIN of Nicotiana benthamiana Contributes to Potyvirus Movement and Transports to Plasmodesmata via the Early Secretory Pathway and the Actomyosin System
Authors: Geng Chao , Cong Qian-Qian , Li Xiang-Dong , Mou An-Li , Gao Rui , Liu Jin-Liang , Tian Yan-Ping 
Published: December 2014

Abstract
The intercellular movement of plant viruses requires both viral and host proteins. Previous studies have demonstrated that the frame-shift protein P3N-PIPO (for the protein encoded by the open reading frame [ORF] containing 5′-terminus of P3 and a +2 frame-shift ORF called Pretty Interesting Potyviridae ORF and embedded in the P3) and CYLINDRICAL INCLUSION (CI) proteins were required for potyvirus cell-to-cell movement. Here, we provide genetic evidence showing that a Tobacco vein banding mosaic virus (TVBMV; genus Potyvirus) mutant carrying a truncated PIPO domain of 58 amino acid residues could move between cells and induce systemic infection in Nicotiana benthamiana plants; mutants carrying a PIPO domain of seven, 20, or 43 amino acid residues failed to move between cells and cause systemic infection in this host plant. Interestingly, the movement-defective mutants produced progeny that eliminated the previously introduced stop codons and thus restored their systemic movement ability. We also present evidence showing that a developmentally regulated plasma membrane protein of N. benthamiana (referred to as NbDREPP) interacted with both P3N-PIPO and CI of the movement-competent TVBMV. The knockdown of NbDREPP gene expression in N. benthamiana impeded the cell-to-cell movement of TVBMV. NbDREPP was shown to colocalize with TVBMV P3N-PIPO and CI at plasmodesmata (PD) and traffic to PD via the early secretory pathway and the actomyosin motility system. We also show that myosin XI-2 is specially required for transporting NbDREPP to PD. In conclusion, NbDREPP is a key host protein within the early secretory pathway and the actomyosin motility system that interacts with two movement proteins and influences virus movement.
Thresholds in Caribbean coral reefs: implications for ecosystem‐based fishery management
Authors: Karr Kendra A. , Fujita Rod , Halpern Benjamin S. , Kappel Carrie V. , Crowder Larry , Selkoe Kimberly A. , Alcolado Pedro M. , Rader Doug 
Published: December 2014

Summary

Ecosystem‐based management of coral reef fisheries aims to sustainably deliver a diverse portfolio of ecosystem services. This goal can be undermined if the ecosystem shifts into a different state, with altered ecosystem functions and benefits to people. If levels of drivers that cause transitions between states are identified, management measures could be aimed at maintaining drivers below these levels to avoid ecosystem shifts.

Analysing data from a large number of Caribbean coral reefs (N = 2001), suites of nonlinear thresholds were identified between metrics of coral reef processes and structure along a gradient of total fish biomass (a proxy for fishing pressure). Several metrics (macroalgal cover, invertivorous fishes and fish species richness) associated with coral‐dominated reefs exhibited thresholds at relatively high fish biomass levels (50–88% of unfished biomass). Other metrics (urchin biomass, ratio of macroalgal to coral cover, herbivorous fishes and coral cover) showed thresholds at lower fish biomass levels (28–37% of unfished biomass).

Ratios of total fish biomass in fishing areas to closed areas (unfished biomass) in the Caribbean indicate that reefs may generally be at risk for change at ratios between 0·5 (coral dominated) and 0·3 (macroalgal dominated). Similar relationships were found for coral reefs in the Indian Ocean. While these results illustrate thresholds at the scale of the entire Caribbean, assessing local reefs is advisable because biomass levels vary within the region, and reef trajectories depend on past, present and future local conditions.

Synthesis and applications. If the thresholds in this study are generalizable to scales relevant to management, it may be possible to produce sustainable yield while simultaneously maintaining coral‐dominated reefs by restricting fishing mortality to levels that result in biomass ratios near 0·5. Fishing down to biomass ratios near 0·3 may increase the risk of overfishing (resulting in lower long‐term yields) and transition to macroalgal‐dominated reefs. Thresholds offer a simple and powerful way for managers to operationalize precautionary ecosystem‐based fishery management by adaptively limiting fishing pressure in order to (i) maintain desirable coral reef conditions, (ii) establish a system‐specific target for generating pretty good yield and (iii) maintain sustainable multi‐species fishery yields.
Elevated cannabinoid receptor 1 and G protein‐coupled receptor 55 expression in proximal tubule cells and whole kidney exposed to diabetic conditions
Authors: Jenkin Kayte A , McAinch Andrew J , Zhang Yuan , Kelly Darren J , Hryciw Deanne H 
Published: December 2014

SummaryHyperglycaemia increases the risk of developing diabetic nephropathy, with primary targets in the glomerulus and proximal tubule. Importantly, glomerular damage in the kidney leads to elevated albumin levels in the filtrate, which contributes to tubular structural modifications that lead to dysfunction. Diabetes alters the endocannabinoid system in a number of target organs, with previous research characterizing tissue‐specific changes in the expression of the cannabinoid receptor 1 (CB1) and G protein‐coupled receptor 55 (GPR55), a putative cannabinoid receptor, in diabetes. Although these receptors have a functional role in the cannabinoid system in the kidney, there has been little investigation into changes in the expression of CB1 and GPR55 in the proximal tubule under diabetic conditions. In this study, CB1 and GPR55 messenger RNA and protein levels were quantified in cultured human kidney cells and then treated with either elevated glucose, elevated albumin, or a combination of glucose and albumin for 4, 6, 18, or 24 h. In addition, CB1 and GPR55 protein expression was characterized in whole‐kidney lysate from streptozotocin‐induced diabetic Sprague‐Dawley rats. In vitro exposure to elevated glucose and albumin increased CB1 and GPR55 messenger RNA and protein expression in proximal tubule cells in a time‐dependant manner. In whole kidney of streptozotocin‐induced diabetic rats, CB1 protein was upregulated, whereas GPR55 protein concentration was not altered. Thus, expression of CB1 and GPR55 in proximal tubules is altered in response to elevated levels of glucose and albumin. Further investigations should determine if these receptors are effective physiological targets for the treatment and prevention of diabetic nephropathy.
On Trojan Horses and revolving doors: Assessing the autonomy of national officials in the European Commission
Authors: Trondal Jarle , Murdoch Zuzana , Geys Benny 
Published: December 2014

AbstractNational officials working in international bureaucracies regularly invoke the fear that member states strategically use such officials for influencing decision making and agenda‐setting to their advantage. This article theoretically analyses conditions under which the autonomy of national civil servants in international bureaucracies might become compromised. The ensuing predictions are then tested using a unique survey among seconded national experts (SNEs) in the European Commission (N ≈ 400). Finally, evaluating the characteristics linked to reduced autonomy among SNEs in the Commission, the article illustrates that these officials are, in practice, likely to be relatively independent from member state influence.
Skin Autofluorescence Is a Predictor of Cardiovascular Disease in Chronic Kidney Disease Patients
Authors: Furuya Fumihiko , Shimura Hiroki , Takahashi Kazuya , Akiyama Daiichiro , Motosugi Ai , Ikegishi Yukinobu , Haraguchi Kazutaka , Kobayashi Tetsuro 
Published: December 2014

AbstractAccelerated formation and tissue accumulation of advanced glycation end products (AGEs), reflecting cumulative glycemic and oxidative stress, occurs in age‐related and chronic diseases like diabetes mellitus (DM) and renal failure, and contributes to vascular damage. Skin autofluorescence (AFR), a noninvasive measurement method, reflects tissue accumulation of AGEs. AFR has been reported to be an independent predictor of mortality in Caucasian hemodialysis patients. We assessed the relationship between levels of AFR and the prevalence of cardiovascular disease (CVD), and clarified the prognostic usefulness of skin AFR levels in Asian (non‐Caucasian) hemodialysis (HD) patients. AFR was measured with an autofluorescence reader in 64 HD patients. Overall and cardiovascular mortality was monitored prospectively during the 3‐year follow‐up. During follow‐up, CVD events occurred in 21 patients. The deaths of 10 HD patients were associated with CVD. Multivariate logistic regression analyses showed that initial AFR was an independent risk factor for de novo CVD in HD patients with or without diabetes. When patients were classified on the basis of AFR tertiles, Cochran‐Armitage analysis demonstrated that the highest tertile of AFR level showed an increased odds ratio for the prevalence of CVD. These findings suggest that AFR levels can be used to detect the prevalence of CVD in HD patients with or without diabetes.
Descriptions and comparison of two species closely resembling Simulium (Simulium) including a new species with an updated key to Korean Simuliidae (Diptera)
Authors: Kim Sam‐Kyu 
Published: December 2014

AbstractImmature stages of Simulium (Simulium) coreanum sp. nov. and morphologically similar Simulium (Simulium) nikkoense are described from Korea. Detailed descriptions are supplemented with photographs and habitat information. The new species can be distinguished from the latter by rectal papillae with 3 simple lobes and labral fan with 51–58 primary rays. Keys to larvae and pupae of all known Korean simuliid species are also provided.
A two‐year follow‐up of oral antioxidant supplementation in primary open‐angle glaucoma: an open‐label, randomized, controlled trial
Authors: Garcia‐Medina Jose Javier , Garcia‐Medina Manuel , Garrido‐Fernandez Pablo , Galvan‐Espinosa Jose , Garcia‐Maturana Carlos , Zanon‐Moreno Vicente , Pinazo‐Duran Maria Dolores 
Published: December 2014

AbstractPurposeTo evaluate the effect of oral antioxidant supplementation (OAS) on primary open‐angle glaucoma (POAG) over a 2‐year follow‐up period.Patients and methodsIn this open‐label, randomized controlled trial, 117 eyes of 117 patients with mild or moderate POAG and intraocular pressure under control with topical antiglaucoma medications were recruited and randomly divided into three groups according to supplementation: (1) OAS with (ICAPS R® – Alcon Laboratories, n = 26); (2) OAS without ω‐3 fatty acids (OFTAN MACULA® – Laboratorios Esteve, n = 28); and (3) a control group without OAS (n = 63). They all underwent visual field (VF) tests (Humphrey 24‐2) and scans using a Fourier‐domain optical coherence tomography (FD‐OCT) device (RTVue‐100) at the beginning of the study and 2 years later. Mean deviation (MD), standard pattern deviation (PSD), peripapillary retinal nerve fibre layer (RNFL) and macular ganglion cell complex (GCC) parameters were considered for the analysis. Patients were also classified according to MD deterioration (fast deterioration vs. slow deterioration).ResultsVisual field global indices, peripapillary RNFL thickness and macular GCC thickness showed no differences among the groups at the beginning and end of the follow‐up. Besides all the comparisons among groups for differences before and after the follow‐up of the MD, PSD, RNFL and GCC parameters were also non‐significant. The proportions of patients according to MD deterioration were similar among the groups and subgroups (p > 0.05 for all the comparisons).ConclusionOral antioxidant supplementation with or without ω‐3 fatty acids does not appear useful as an adjuvant treatment of mild/moderate POAG in the short term.
Adiponectin ‐11377C/G and +276G/T Polymorphisms affect Adiponectin Levels but do not Modify Responsiveness to Therapy in Resistant Hypertension
Authors: de Faria Ana Paula C. , Modolo Rodrigo , Sabbatini Andréa R. , Barbaro Natália R. , Corrêa Nathália B. , Brunelli Veridiana , Tanus‐Santos José E. , Fontana Vanessa , Moreno Heitor 
Published: December 2014

AbstractResistant hypertension (RHTN) is a multifactorial and polygenic disease, frequently associated with obesity. Low plasma adiponectin levels, a hormone produced by the adipose tissue, were associated withRHTN. Single nucleotide polymorphisms (SNPs) ‐11377C/G (rs266729) and +276G/T (rs1501299) inADIPOQ(adiponectin gene) were associated with hypertension. This study evaluated the association between twoSNPs (‐11377C/G and +276G/T) and adiponectin levels inRHTN. This study comprised 109 patients withRHTNgenotyped for both polymorphisms. A cross‐sectional study was designed to compare features ofCChomozygousversusG allele carriers for ‐11377C/G andGGhomozygousversusT allele carriers for +276G/T. Office and ambulatoryBPmeasurements were similar among genotypes subgroups in bothSNPs as well as the markers of target organ damage (arterial stiffness, left ventricular mass index and microalbuminuria). Adiponectin concentrations were significantly higher inCCcompared to G carrier for ‐11377C/G (CC:7.0 (4.0–10.2) versusG allele:5.5 (2.5–7.9),p = 0.04) and lower inGGcompared to T carrier for +276G/T (GG:5.3 (2.3–7.7) versusT allele:7.1 (3.6–10.5),p = 0.04). Adjusting for systolic ambulatoryBP, body mass index, age, gender, race and presence of type 2 diabetes, multiple linear regression analyses revealed that the minor alleles G (β‐coefficient= ‐0.14,SE=0.07,p = 0.03) and T (β‐coefficient=0.12,SE=0.06,p = 0.04) were independent predictors of adiponectin. The ‐11377C/G and +276G/TSNPs inADIPOQwere associated with adiponectin levels inRHTNindividuals.
Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B‐cell lymphoma: mature results of a phase II multicentre study
Authors: Kirschey Sebastian , Flohr Thomas , Wolf Hans H. , Frickhofen Norbert , Gramatzki Martin , Link Hartmut , Basara Nadezda , Peter Norma , Meyer Ralf G. , Schmitz Norbert , Weidmann Eckhart , Banat Andre , Schulz Andrea , Kolbe Karin , Derigs Guenter , Theobald Matthias , Hess Georg 
Published: December 2014

SummarySalvage therapy followed by high‐dose therapy (HDT) remains a mainstay for patients with relapsed lymphoma, however no optimal regimen has been defined. Here we report on the results of R‐DexaBEAM (rituximab, dexamethasone, carmustine, etoposide, cytarabine, melphalan) followed by HDT. Patients aged 18–65 years, Eastern Cooperative Oncology Group performance score 0–2, with relapsed/refractory B‐cell non‐Hodgkin lymphoma (NHL) were eligible. R‐Dexa‐BEAM was given for two cycles followed by stem cell mobilization and HDT. Primary endpoint of the trial was progression‐free‐survival (PFS). One hundred and three patients were included: aggressive NHL (aNHL): diffuse large B‐cell lymphoma 55, mantle cell lymphoma 7, follicular lymphoma (FL) grade 3: 5, indolent Lymphoma (iNHL): FL grade 1–2: 29, marginal zone lymphoma 6, Immunocytoma 1. The overall response rate after salvage therapy was 62% for aNHL and 78% for iNHL patients. 66% of patients with aNHL and 86% with iNHL underwent HDT. Treatment‐related mortality for HDT was 1·3%. For aNHL patients, the median PFS was 0·83 years with 44% alive at the median follow‐up of 7·3 years. Corresponding figures for iNHL were: median PFS 3·7 years and 72% alive after 8 years. The combination of rituximab with DexaBEAM followed by HDT resulted in high response rates and sustained remissions in responders. R‐DexaBEAM followed by HDT can be considered a valid salvage option for NHL.
Occupational contact allergy in nurses: results from the Information Network of Departments of Dermatology 2003–2012
Authors: Molin Sonja , Bauer Andrea , Schnuch Axel , Geier Johannes 
Published: December 2014

SummaryBackgroundHealthcare workers are occupationally exposed to various allergens in protective gloves, surface or instrument disinfectants, drugs, and skin care products. An increased prevalence of sensitization to thiurams, glutaraldehyde, formaldehyde and glyoxal in nurses with occupational contact dermatitis (OCD) has been known since the 1990s.ObjectivesTo update the range of occupational allergens in healthcare professionals.MethodsWe retrospectively analysed patch test data from the Information Network of Departments of Dermatology (IVDK), 2003–2012. Patch test results from 2248 nurses with OCD were compared with those of 2138 nurses without OCD.ResultsSignificantly increased sensitization rates were found for thiuram mix (6.7%), potassium dichromate (5.7%), methylchloroisothiazolinone/methylisothiazolinone (4.4%), colophonium (3.4%), 2‐bromo‐2‐nitropropane‐1,3‐diol (1.7%), and zinc diethyldithiocarbamate (1.7%). Patch testing with products from the patients' workplaces gave additional clues to further allergens, for example tetrazepam.ConclusionsThe known range of contact sensitization in nurses with OCD has been confirmed. Formaldehyde allergy seems to be less important today. Drugs such as tetrazepam are occupational sensitizers in nurses. The increase in chromium sensitization remains unexplained.