Items 1-20 of 679

    • Journal Article

      Improving bimanual interaction with a prosthesis using semi-autonomous control 

      Volkmar, Robin; Dosen, Strahinja; Gonzalez-Vargas, Jose; Baum, Marcus; Markovic, Marko
      Journal of NeuroEngineering and Rehabilitation. 2019 Nov 14;16(1):140
      Abstract Background The loss of a hand is a traumatic experience that substantially compromises an individual’s capability to interact with his environment. The myoelectric prostheses are state-of-the-art (SoA) functional replacements for the lost limbs. Their overall mechanical design and dexterity have improved over the last few decades, but the users have not been able to fully exploit these advances because of the lack of effective and intuitive control. Bimanual tasks are particularly challenging for an amputee since prosthesis control needs to be coordinated with the movement of the sound limb. So far, the bimanual activities have been often neglected by the prosthetic research community. Methods We present a novel method to prosthesis control, which uses a semi-autonomous approach in order to simplify bimanual interactions. The approach supplements the commercial SoA two-channel myoelectric control with two additional sensors. Two inertial measurement units were attached to the prosthesis and the sound hand to detect the movement of both limbs. Once a bimanual interaction is detected, the system mimics the coordination strategies of able-bodied subjects to automatically adjust the prosthesis wrist rotation (pronation, supination) and grip type (lateral, palmar) to assist the sound hand during a bimanual task. The system has been evaluated in eight able-bodied subjects performing functional uni- and bi-manual tasks using the novel method and SoA two-channel myocontrol. The outcome measures were time to accomplish the task, semi-autonomous system misclassification rate, subjective rating of intuitiveness, and perceived workload (NASA TLX). Results The results demonstrated that the novel control interface substantially outperformed the SoA myoelectric control. While using the semi-autonomous control the time to accomplish the task and the perceived workload decreased for 25 and 27%, respectively, while the subjects rated the system as more intuitive then SoA myocontrol. Conclusions The novel system uses minimal additional hardware (two inertial sensors) and simple processing and it is therefore convenient for practical implementation. By using the proposed control scheme, the prosthesis assists the user’s sound hand in performing bimanual interactions while decreasing cognitive burden.
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    • Journal Article

      Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants 

      Álvarez-Escribano, Isidro; Sasse, Christoph; Bok, Jin W; Na, Hyunsoo; Amirebrahimi, Mojgan; Lipzen, Anna; Schackwitz, Wendy; Martin, Joel; Barry, Kerrie; Gutiérrez, Gabriel; et al.
      Cea-Sánchez, SaraMarcos, Ana TGrigoriev, Igor VKeller, Nancy PBraus, Gerhard HCánovas, David
      BMC Biology. 2019 Nov 11;17(1):88
      Abstract Background Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. Results We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11 (A. flavus), 1.1 × 10−11 (A. fumigatus) and 4.1 × 10−11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11 (A. flavus), 2.2 × 10−11 (A. fumigatus) and 4.5 × 10−11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. Conclusions We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified.
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    • Journal Article

      Natalizumab promotes activation and pro-inflammatory differentiation of peripheral B cells in multiple sclerosis patients 

      Traub, Jan W; Pellkofer, Hannah L; Grondey, Katja; Seeger, Ira; Rowold, Christoph; Brück, Wolfgang; Husseini, Leila; Häusser-Kinzel, Silke; Weber, Martin S
      Journal of Neuroinflammation. 2019 Nov 16;16(1):228
      Abstract Background In the past, multiple sclerosis (MS) medications have been primarily designed to modulate T cell properties. Based on the emerging concept that B cells are equally important for the propagation of MS, we compared the effect of four commonly used, primarily T cell-targeting MS medications on B cells. Methods Using flow cytometry, we analyzed peripheral blood mononuclear cells (PBMC) of untreated (n = 19) and dimethyl fumarate (DMF; n = 21)-, fingolimod (FTY; n = 17)-, glatiramer acetate (GA; n = 18)-, and natalizumab (NAT; n = 20)-treated MS patients, focusing on B cell maturation, differentiation, and cytokine production. Results While GA exerted minor effects on the investigated B cell properties, DMF and FTY robustly inhibited pro-inflammatory B cell function. In contrast, NAT treatment enhanced B cell differentiation, activation, and pro-inflammatory cytokine production when compared to both intraindividual samples collected before NAT treatment initiation as well as untreated MS controls. Our mechanistic in vitro studies confirm this observation. Conclusion Our data indicate that common MS medications have differential, in part opposing effects on B cells. The observed activation of peripheral B cells upon NAT treatment may be instructive to interpret its unfavorable effect in certain B cell-mediated inflammatory conditions and to elucidate the immunological basis of MS relapses after NAT withdrawal. Trial registration Protocols were approved by the ethical review committee of the University Medical Center Göttingen (#3/4/14).
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    • Journal Article

      Surgical approaches for treatment of ureteropelvic junction obstruction – a systematic review and network meta-analysis 

      Uhlig, Annemarie; Uhlig, Johannes; Trojan, Lutz; Hinterthaner, Marc; von Hammerstein-Equord, Alexander; Strauss, Arne
      BMC Urology. 2019 Nov 11;19(1):112
      Abstract Background Multiple surgical treatment options are available for the treatment of ureteropelvic junction obstruction (UPJO). The aim of this study is to compare the most frequently used technics in a comprehensive network approach. Methods A systematic literature search of the EMBASE, MEDLINE and COCHRANE libraries was conducted in January 2018. Publications were included that evaluated at least two of the following surgical techniques: open pyeloplasty (OP), endopyelotomy (EP), laparoscopic (LP) and robot assisted pyeloplasty (RP). Main outcomes were operative success, complications, urinary leakage, re-operation, transfusion rate, operating time, and length of stay. Network meta-analyses with random effects models simultaneously assessed effectiveness of all surgical techniques. Results A total of 26 studies including 3143 patients were analyzed. Compared with RP, EP and LP showed lower operative success rates (EP: OR = 0.09, 95%CI:0.05–0.19; p < 0.001; LP: OR = 0.51, 95%CI:0.31–0.84; p = 0.008). Compared with OP, LP and RP had lower risk for complications (LP: OR = 0.62; 95%CI:0.41–0.95; p = 0.027; RP: OR = 0.41; 95%CI:0.22–0.79; p = 0.007). Compared with RP, no significant differences were detected for urinary leakage or re-operation, transfusion rates. Compared with EP, RP yielded longer operating time (mean = 102.87 min, 95%CI:41.79 min–163.95 min, p = < 0.001). Further significant differences in operating times were detected when comparing LP to EP (mean = 115.13 min, 95%CI:65.63 min–164.63 min, p = < 0.001) and OP to EP (mean = 91.96 min, 95%CI:32.33 min–151.58 min, p = 0.003). Conclusions Multiple surgical techniques are available for treatment of UPJO. RP has the highest rates of operative success and as well as LP lower complication rates than OP. Although surgical outcomes are worse for EP, its operating time is shorter than OP, RP, and LP. Surgeons should consider these findings when selecting the optimal treatment method for individual patients.
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    • Journal Article

      Comparative transcriptomics in Syllidae (Annelida) indicates that posterior regeneration and regular growth are comparable, while anterior regeneration is a distinct process 

      Ribeiro, Rannyele P; Ponz-Segrelles, Guillermo; Bleidorn, Christoph; Aguado, Maria T
      BMC Genomics. 2019 Nov 14;20(1):855
      Abstract Background Annelids exhibit remarkable postembryonic developmental abilities. Most annelids grow during their whole life by adding segments through the action of a segment addition zone (SAZ) located in front of the pygidium. In addition, they show an outstanding ability to regenerate their bodies. Experimental evidence and field observations show that many annelids are able to regenerate their posterior bodies, while anterior regeneration is often limited or absent. Syllidae, for instance, usually show high abilities of posterior regeneration, although anterior regeneration varies across species. Some syllids are able to partially restore the anterior end, while others regenerate all lost anterior body after bisection. Here, we used comparative transcriptomics to detect changes in the gene expression profiles during anterior regeneration, posterior regeneration and regular growth of two syllid species: Sphaerosyllis hystrix and Syllis gracilis; which exhibit limited and complete anterior regeneration, respectively. Results We detected a high number of genes with differential expression: 4771 genes in S. hystrix (limited anterior regeneration) and 1997 genes in S. gracilis (complete anterior regeneration). For both species, the comparative transcriptomic analysis showed that gene expression during posterior regeneration and regular growth was very similar, whereas anterior regeneration was characterized by up-regulation of several genes. Among the up-regulated genes, we identified putative homologs of regeneration-related genes associated to cellular proliferation, nervous system development, establishment of body axis, and stem-cellness; such as rup and JNK (in S. hystrix); and glutamine synthetase, elav, slit, Hox genes, β-catenin and PL10 (in S. gracilis). Conclusions Posterior regeneration and regular growth show no significant differences in gene expression in the herein investigated syllids. However, anterior regeneration is associated with a clear change in terms of gene expression in both species. Our comparative transcriptomic analysis was able to detect differential expression of some regeneration-related genes, suggesting that syllids share some features of the regenerative mechanisms already known for other annelids and invertebrates.
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    • Journal Article

      FoxB, a new and highly conserved key factor in arthropod dorsal–ventral (DV) limb patterning 

      Heingård, Miriam; Turetzek, Natascha; Prpic, Nikola-Michael; Janssen, Ralf
      EvoDevo. 2019 Nov 08;10(1):28
      Abstract Forkhead box (Fox) transcription factors evolved early in animal evolution and represent important components of conserved gene regulatory networks (GRNs) during animal development. Most of the researches concerning Fox genes, however, are on vertebrates and only a relatively low number of studies investigate Fox gene function in invertebrates. In addition to this shortcoming, the focus of attention is often restricted to a few well-characterized Fox genes such as FoxA (forkhead), FoxC (crocodile) and FoxQ2. Although arthropods represent the largest and most diverse animal group, most other Fox genes have not been investigated in detail, not even in the arthropod model species Drosophila melanogaster. In a general gene expression pattern screen for panarthropod Fox genes including the red flour beetle Tribolium castaneum, the pill millipede Glomeris marginata, the common house spider Parasteatoda tepidariorum, and the velvet worm Euperipatoides kanangrensis, we identified a Fox gene with a highly conserved expression pattern along the ventral ectoderm of arthropod and onychophoran limbs. Functional investigation of FoxB in Parasteatoda reveals a hitherto unrecognized important function of FoxB upstream of wingless (wg) and decapentaplegic (dpp) in the GRN orchestrating dorsal–ventral limb patterning.
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    • Journal Article

      Development and validation of a Bayesian survival model for inclusion body myositis 

      Capkun, Gorana; Schmidt, Jens; Ghosh, Shubhro; Sharma, Harsh; Obadia, Thomas; de Vera, Ana; Risson, Valery; Amzal, Billy
      Theoretical Biology and Medical Modelling. 2019 Nov 07;16(1):17
      Abstract Background Associations between disease characteristics and payer-relevant outcomes can be difficult to establish for rare and progressive chronic diseases with sparse available data. We developed an exploratory bridging model to predict premature mortality from disease characteristics, and using inclusion body myositis (IBM) as a representative case study. Methods Candidate variables that may be potentially associated with premature mortality were identified by disease experts and from the IBM literature. Interdependency between candidate variables in IBM patients were assessed using existing patient-level data. A Bayesian survival model for the IBM population was developed with identified variables as predictors for premature mortality in the model. For model selection and external validation, model predictions were compared to published mortality data in IBM patient cohorts. After validation, the final model was used to simulate the increased risk of premature death in IBM patients. Baseline survival was based on age- and gender-specific survival curves for the general population in Western countries as reported by the World Health Organisation. Results Presence of dysphagia, aspiration pneumonia, falls, being wheelchair-bound and 6-min walking distance (6MWD in meters) were identified as candidate variables to be used as predictors for premature mortality based on inputs received from disease experts and literature. There was limited correlation between these functional performance measures, which were therefore treated as independent variables in the model. Based on the Bayesian survival model, among all candidate variables, presence of dysphagia and decrease in 6MWD [m] were associated with poorer survival with contributing hazard ratios (HR) 1.61 (95% credible interval [CrI]: 0.84–3.50) and 2.48 (95% CrI: 1.27–5.00) respectively. Excess mortality simulated in an IBM cohort vs. an age- and gender matched general-population cohort was 4.03 (95% prediction interval 1.37–10.61). Conclusions For IBM patients, results suggest an increased risk of premature death compared with the general population of the same age and gender. In the absence of hard data, bridging modelling generated survival predictions by combining relevant information. The methodological principle would be applicable to the analysis of associations between disease characteristics and payer-relevant outcomes in progressive chronic and rare diseases. Studies with lifetime follow-up would be needed to confirm the modelling results.
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    • Journal Article

      Imported cutaneous leishmaniasis: molecular investigation unveils Leishmania major in Bangladesh 

      Khan, Md A A; Chowdhury, Rajashree; Nath, Rupen; Hansen, Sören; Nath, Progga; Maruf, Shomik; Abd El Wahed, Ahmed; Mondal, Dinesh
      Parasites & Vectors. 2019 Nov 07;12(1):527
      Abstract Background The main clinical forms of leishmaniasis in Bangladesh are visceral leishmaniasis and post-kala-azar dermal leishmaniasis, which are caused by Leishmania donovani. Imported cutaneous leishmaniasis (CL) is emerging globally due mainly to increased human mobility. In recent years, several imported CL cases have also been reported in Bangladesh. Sporadic atypical cases of CL can be challenging for diagnosis and clinical management, while occurrence of infection on a frequent basis can be alarming. We report of a case of a Bangladeshi temporary-migrant worker who, upon return, presented development of skin lesions that are characteristic of CL. Methods A serum sample was collected and tested with an rK39 immunochromatographic test. Nucleic acid from skin biopsy derived culture sample was extracted and screened with a real-time PCR assay which targets the conserved REPL repeat region of L. donovani complex. The internal transcribed spacer 2 region of the ribosomal RNA gene cluster was amplified and sequenced. Results The suspect had a history of travel in both CL and VL endemic areas and had a positive rK39 test result. Based on clinical presentation, travel history and demonstration of the parasite in the skin biopsy, CL was diagnosed and the patient underwent a combination therapy with Miltefosine and liposomal amphotericin B. While typical endemic species were not detected, we identified Leishmania major, a species that, to our knowledge, has never been reported in Bangladesh. Conclusions Proper monitoring and reporting of imported cases should be given careful consideration for both clinical and epidemiological reasons. Molecular tests should be performed in diagnosis to avoid dilemma, and identification of causative species should be prioritized.
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    • Journal Article

      Correction to: Mitochondrial phylogeography of baboons (Papio spp.) – Indication for introgressive hybridization? 

      Zinner, Dietmar; Groeneveld, Linn F; Keller, Christina; Roos, Christian
      BMC Evolutionary Biology. 2019 Nov 04;19(1):198
      Following publication of the original article [1], we have been notified that some of the NCB accession numbers were incorrectly associated to their corresponding taxon in the Additional file 1.
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    • Journal Article

      Consensus in determining the resectability of locally progressed pancreatic ductal adenocarcinoma – results of the Conko-007 multicenter trial 

      Wittel, U. A; Lubgan, D.; Ghadimi, M.; Belyaev, O.; Uhl, W.; Bechstein, W. O; Grützmann, R.; Hohenberger, W. M; Schmid, A.; Jacobasch, L.; et al.
      Croner, R. SReinacher-Schick, A.Hopt, U. TPirkl, A.Oettle, H.Fietkau, R.Golcher, H.
      BMC Cancer. 2019 Oct 22;19(1):979
      Abstract Background One critical step in the therapy of patients with localized pancreatic cancer is the determination of local resectability. The decision between primary surgery versus upfront local or systemic cancer therapy seems especially to differ between pancreatic cancer centers. In our cohort study, we analyzed the independent judgement of resectability of five experienced high volume pancreatic surgeons in 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer. Methods Pretherapeutic CT or MRI scans of 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer were evaluated by 5 independent pancreatic surgeons. Resectability and the degree of abutment of the tumor to the venous and arterial structures adjacent to the pancreas were reported. Interrater reliability and dispersion indices were compared. Results One hundred ninety-four CT scans and 6 MRI scans were evaluated and all parameters were evaluated by all surgeons in 133 (66.5%) cases. Low agreement was observed for tumor infiltration of venous structures (κ = 0.265 and κ = 0.285) while good agreement was achieved for the abutment of the tumor to arterial structures (interrater reliability celiac trunk κ = 0.708 P < 0.001). In patients with vascular tumor contact indicating locally advanced disease, surgeons highly agreed on unresectability, but in patients with vascular tumor abutment consistent with borderline resectable disease, the judgement of resectability was less uniform (dispersion index locally advanced vs. borderline resectable p < 0.05). Conclusion Excellent agreement between surgeons exists in determining the presence of arterial abutment and locally advanced pancreatic cancer. The determination of resectability in borderline resectable patients is influenced by additional subjective factors. Trial registration EudraCT:2009-014476-21 (2013-02-22) and NCT01827553 (2013-04-09).
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    • Journal Article

      Identification of genomic regions regulating sex determination in Atlantic salmon using high density SNP data 

      Gabián, María; Morán, Paloma; Fernández, Ana I; Villanueva, Beatriz; Chtioui, Amel; Kent, Matthew P; Covelo-Soto, Lara; Fernández, Almudena; Saura, María
      BMC Genomics. 2019 Oct 22;20(1):764
      Abstract Background A complete understanding of the genetic basis for sexual determination and differentiation is necessary in order to implement efficient breeding schemes at early stages of development. Atlantic salmon belongs to the family Salmonidae of fishes and represents a species of great commercial value. Although the species is assumed to be male heterogametic with XY sex determination, the precise genetic basis of sexual development remains unclear. The complexity is likely associated to the relatively recent salmonid specific whole genome duplication that may be responsible for certain genome instability. This instability together with the capacity of the sex-determining gene to move across the genome as reported by previous studies, may explain that sexual development genes are not circumscribed to the same chromosomes in all members of the species. In this study, we have used a 220 K SNP panel developed for Atlantic salmon to identify the chromosomes explaining the highest proportion of the genetic variance for sex as well as candidate regions and genes associated to sexual development in this species. Results Results from regional heritability analysis showed that the chromosomes explaining the highest proportion of variance in these populations were Ssa02 (heritability = 0.42, SE = 0.12) and Ssa21 (heritability = 0.26, SE = 0.11). After pruning by linkage disequilibrium, genome-wide association analyses revealed 114 SNPs that were significantly associated with sex, being Ssa02 the chromosome containing a greatest number of regions. Close examination of the candidate regions evidenced important genes related to sex in other species of Class Actinopterygii, including SDY, genes from family SOX, RSPO1, ESR1, U2AF2A, LMO7, GNRH-R, DND and FIGLA. Conclusions The combined results from regional heritability analysis and genome-wide association have provided new advances in the knowledge of the genetic regulation of sex determination in Atlantic salmon, supporting that Ssa02 is the candidate chromosome for sex in this species and suggesting an alternative population lineage in Spanish wild populations according to the results from Ssa21.
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    • Journal Article

      First report of hare treponematosis seroprevalence of European brown hares (Lepus europaeus) in the Czech Republic: seroprevalence negatively correlates with altitude of sampling areas 

      Nováková, Markéta; Najt, David; Mikalová, Lenka; Kostková, Marcela; Vrbová, Eliška; Strouhal, Michal; Posautz, Annika; Knauf, Sascha; Šmajs, David
      BMC Veterinary Research. 2019 Oct 18;15(1):350
      Abstract Background The aim of this study was to quantify the seroprevalence of hare treponematosis in European brown hare (Lepus europaeus) populations in the Czech Republic and to test for an association between treponematosis prevalence and the altitude of the areas in which hares were sampled. We tested 289 serum samples of brown hares collected between 2015 and 2017. The sampling areas included 12 districts (73 villages) distributed throughout the Czech Republic. Serum samples were tested for the presence of antibodies against the causative agent of hare treponematosis (Treponema paraluisleporidarum ecovar Lepus, TPeL) using two serological tests for human syphilis that cross-react with TPeL: the Treponema pallidum hemagglutination assay (TPHA) and the fluorescent treponemal antibody absorption (FTA-ABS) test. To account for the imperfect diagnostic sensitivity and specificity of each test, apparent prevalence estimates of TPeL were converted to true prevalence estimates using the Rogan Gladen estimator. The correlation between TPeL true seroprevalence and altitude of sampling areas was analyzed using Pearson’s correlation coefficient at three levels of spatial resolution: (1) four groups, each composed of two merged districts, with ≥20 samples collected, differing in their altitude median (206, 348, 495, and 522 m above sea level); (2) separately tested eight districts, where ≥20 samples were collected per district; and (3) 27 groups composed of villages of the same altitude level distributed across the whole dataset. Results One hundred and seven of the 289 samples were seropositive to both tests, the FTA-ABS test was positive for an additional 47 samples. Seropositive samples were found in all 12 districts. True seroprevalence of TPeL in the sampled hares was 52% (95% confidence interval 46 to 58%). A statistically significant negative correlation between TPeL seroprevalence and altitude was identified at the district level (Pearson’s r = − 0.722, p = 0.043). Conclusions Between 2015 and 2017 hare treponematosis was present at a relatively high prevalence in brown hares in all 12 districts in the Czech Republic where sampling was carried out. The seroprevalence of TPeL in brown hares was negatively correlated with the altitude of the areas in which hares were sampled.
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    • Journal Article

      Single-plant GWAS coupled with bulk segregant analysis allows rapid identification and corroboration of plant-height candidate SNPs 

      Gyawali, Abiskar; Shrestha, Vivek; Guill, Katherine E; Flint-Garcia, Sherry; Beissinger, Timothy M
      BMC Plant Biology. 2019 Oct 08;19(1):412
      Abstract Background Genome wide association studies (GWAS) are a powerful tool for identifying quantitative trait loci (QTL) and causal single nucleotide polymorphisms (SNPs)/genes associated with various important traits in crop species. Typically, GWAS in crops are performed using a panel of inbred lines, where multiple replicates of the same inbred are measured and the average phenotype is taken as the response variable. Here we describe and evaluate single plant GWAS (sp-GWAS) for performing a GWAS on individual plants, which does not require an association panel of inbreds. Instead sp-GWAS relies on the phenotypes and genotypes from individual plants sampled from a randomly mating population. Importantly, we demonstrate how sp-GWAS can be efficiently combined with a bulk segregant analysis (BSA) experiment to rapidly corroborate evidence for significant SNPs. Results In this study we used the Shoepeg maize landrace, collected as an open pollinating variety from a farm in Southern Missouri in the 1960’s, to evaluate whether sp-GWAS coupled with BSA can efficiently and powerfully used to detect significant association of SNPs for plant height (PH). Plant were grown in 8 locations across two years and in total 768 individuals were genotyped and phenotyped for sp-GWAS. A total of 306 k polymorphic markers in 768 individuals evaluated via association analysis detected 25 significant SNPs (P ≤ 0.00001) for PH. The results from our single-plant GWAS were further validated by bulk segregant analysis (BSA) for PH. BSA sequencing was performed on the same population by selecting tall and short plants as separate bulks. This approach identified 37 genomic regions for plant height. Of the 25 significant SNPs from GWAS, the three most significant SNPs co-localize with regions identified by BSA. Conclusion Overall, this study demonstrates that sp-GWAS coupled with BSA can be a useful tool for detecting significant SNPs and identifying candidate genes. This result is particularly useful for species/populations where association panels are not readily available.
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      Bayesian localization of CNV candidates in WGS data within minutes 

      Wiedenhoeft, John; Cagan, Alex; Kozhemyakina, Rimma; Gulevich, Rimma; Schliep, Alexander
      Algorithms for Molecular Biology. 2019 Sep 23;14(1):20
      Abstract Background Full Bayesian inference for detecting copy number variants (CNV) from whole-genome sequencing (WGS) data is still largely infeasible due to computational demands. A recently introduced approach to perform Forward–Backward Gibbs sampling using dynamic Haar wavelet compression has alleviated issues of convergence and, to some extent, speed. Yet, the problem remains challenging in practice. Results In this paper, we propose an improved algorithmic framework for this approach. We provide new space-efficient data structures to query sufficient statistics in logarithmic time, based on a linear-time, in-place transform of the data, which also improves on the compression ratio. We also propose a new approach to efficiently store and update marginal state counts obtained from the Gibbs sampler. Conclusions Using this approach, we discover several CNV candidates in two rat populations divergently selected for tame and aggressive behavior, consistent with earlier results concerning the domestication syndrome as well as experimental observations. Computationally, we observe a 29.5-fold decrease in memory, an average 5.8-fold speedup, as well as a 191-fold decrease in minor page faults. We also observe that metrics varied greatly in the old implementation, but not the new one. We conjecture that this is due to the better compression scheme. The fully Bayesian segmentation of the entire WGS data set required 3.5 min and 1.24 GB of memory, and can hence be performed on a commodity laptop.
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      The first fungal laccase with an alkaline pH optimum obtained by directed evolution and its application in indigo dye decolorization 

      Yin, Qiang; Zhou, Gang; Peng, Can; Zhang, Yinliang; Kües, Ursula; Liu, Juanjuan; Xiao, Yazhong; Fang, Zemin
      AMB Express. 2019 Sep 18;9(1):151
      Abstract Engineering of fungal laccases with optimum catalytic activity at alkaline pH has been a long-lasting challenge. In this study, a mutant library containing 3000 clones was obtained by error-prone PCR to adapt the optimum pH of a fungal laccase Lcc9 from the basidiomycete Coprinopsis cinerea. After three rounds of functional screening, a mutant with three amino acid changes (E116K, N229D, I393T) named PIE5 was selected. PIE5 showed an optimum pH of 8.5 and 8.0 against guaiacol and 2,6-DMP when expressed in Pichia pastoris, representing the first fungal laccase that possesses an optimum pH at an alkaline condition. Site directed mutagenesis disclosed that N229D contributed the most to the optimum pH increment. A single N229D mutation caused an increase in optimum pH by 1.5 units. When used in indigo dye decolorization, PIE5 efficiently decolorized 87.1 ± 1.1% and 90.9 ± 0.3% indigo dye at the optimum conditions of pH 7.0–7.5 and 60 °C, and with either methyl 3,5-dimethoxy-4-hydroxybenzoate or 2,2′-azino-bis(3-ethylbenzothazoline-6-sulfonate) as the mediator. In comparison, the commercially available fungal laccase TvLac from Trametes villosa decolorized 84.3 ± 1.8% of indigo dye under its optimum conditions (opt. pH 5.0 and 60 °C). The properties of an alkaline-dependent activity and the high indigo dye decolorization ability (1.3-fold better than the parental Lcc9) make the new fungal laccase PIE5 an alternative for specific industrial applications.
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      How I wean patients from veno-venous extra-corporeal membrane oxygenation 

      Vasques, Francesco; Romitti, Federica; Gattinoni, Luciano; Camporota, Luigi
      Critical Care. 2019 Sep 18;23(1):316
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      An ethical comparison of living kidney donation and surrogacy: understanding the relational dimension 

      Beier, Katharina; Wöhlke, Sabine
      Philosophy, Ethics, and Humanities in Medicine. 2019 Sep 18;14(1):13
      Abstract Background The bioethical debates concerning living donation and surrogacy revolve around similar ethical questions and moral concepts. Nevertheless, the ethical discourses in both fields grew largely isolated from each other. Methods Based on a review of ethical, sociological and anthropological research this paper aims to link the ethical discourses on living kidney donation and surrogacy by providing a comparative analysis of the two practices’ relational dimension with regard to three aspects, i.e. the normative role of relational dynamics, social norms and gender roles, and reciprocity. Based on this analysis, we derive conclusions for the framing of living organ donation and surrogacy in ethical theory and practice. Results First, our analysis emphasizes the relevance of acknowledging the complex relational implications of living kidney donation and surrogacy. Underestimating this relational dimension may not only lead to individual crises but endanger existing as well as newly emerging familial relationships. Second, we point out differences in the normative assessment of social norms and gender roles in the ethical debates about living kidney donation and surrogacy. In particular, we show how different evaluations of altruism affect the understanding of autonomy in both contexts. In addition, we sensitize for biased perceptions of gender roles. Finally, we argue that challenges resulting from unresolved reciprocity are an issue in living kidney donation and surrogacy independent of whether the exchange of body parts or bodily services is framed as a gift or commercial exchange. By pointing out the limits of financial compensation, we stress the relevance of non-material, relational rewards as potential remedy.
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      Model-based myocardial T1 mapping with sparsity constraints using single-shot inversion-recovery radial FLASH cardiovascular magnetic resonance 

      Wang, Xiaoqing; Kohler, Florian; Unterberg-Buchwald, Christina; Lotz, Joachim; Frahm, Jens; Uecker, Martin
      Journal of Cardiovascular Magnetic Resonance. 2019 Sep 19;21(1):60
      Abstract Background This study develops a model-based myocardial T1 mapping technique with sparsity constraints which employs a single-shot inversion-recovery (IR) radial fast low angle shot (FLASH) cardiovascular magnetic resonance (CMR) acquisition. The method should offer high resolution, accuracy, precision and reproducibility. Methods The proposed reconstruction estimates myocardial parameter maps directly from undersampled k-space which is continuously measured by IR radial FLASH with a 4 s breathhold and retrospectively sorted based on a cardiac trigger signal. Joint sparsity constraints are imposed on the parameter maps to further improve T1 precision. Validations involved studies of an experimental phantom and 8 healthy adult subjects. Results In comparison to an IR spin-echo reference method, phantom experiments with T1 values ranging from 300 to 1500 ms revealed good accuracy and precision at simulated heart rates between 40 and 100 bpm. In vivo T1 maps achieved better precision and qualitatively better preservation of image features for the proposed method than a real-time CMR approach followed by pixelwise fitting. Apart from good inter-observer reproducibility (0.6% of the mean), in vivo results confirmed good intra-subject reproducibility (1.05% of the mean for intra-scan and 1.17, 1.51% of the means for the two inter-scans, respectively) of the proposed method. Conclusion Model-based reconstructions with sparsity constraints allow for single-shot myocardial T1 maps with high spatial resolution, accuracy, precision and reproducibility within a 4 s breathhold. Clinical trials are warranted.
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    • Monograph

      DINI-Zertifikat für Open-Access-Publikationsdienste 2019 

      Müller, Uwe; Scholze, Frank; Vierkant, Paul; Arning, Ursula; Beucke, Daniel; Blumtritt, Ute; Bove, Karolin; Braun, Kim; Deppe, Arvid Sönke; Deinzer, Gernot; et al.
      Fenner, MartinKlotz-Berendes, BrunoMeinecke, IsabellaPampel, HeinzSchirrwagen, JochenSeveriens, ThomasSummann, FriedrichSteinke, TobiasTullney, MarcoVoigt, MichaelaWalger, WalgerWeimar, AlexanderWolf, Stefan
      DINI Schriften 3-de; Version 6.0
      Deutsche initiative für netzwerkinformation e. V., 2019
      Das Publikationswesen ist ein wesentlicher Stützpfeiler des wissenschaftlichen Erkenntnisfortschritts und der Wissenschaft insgesamt. Zu seinen Kennzeichen gehören a. die Organisation einer effektiven Kommunikation zwischen Forschenden (zwischen Autor*innen und allen potenziellen Rezipient*innen, d. h. die Sicherstellung einer adäquaten Verbreitung), b. ein hohes Maß an Vertrauenswürdigkeit, das den Nutzenden des Publikationswesens (d.h. den Forschenden) vermittelt wird (z.B. in Bezug auf das Prioritätsrecht, die Wahrung des Urheberrechts sowie die Authentizität und die inhaltliche Qualität wissenschaftlicher Arbeiten), sowie c. Nachhaltigkeit und Nachprüfbarkeit (dauerhafte Zitierbarkeit und langfristige Verfügbarkeit, Nachvollziehbarkeit von einzelnen Schritten auf dem Weg zur Veröffentlichung). Mit dem vorliegenden Kriterienkatalog werden diese allgemeinen Erwartungen an das wissenschaftliche Publizieren in konkrete Mindestanforderungen übersetzt, die an Open-Access-Publikationsdienste zu stellen sind.
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    • Journal Article

      Using peer education to improve diabetes management and outcomes in a low-income setting: a randomized controlled trial 

      Seuring, Till; Marthoenis; Rhode, Sabrina; Rogge, Lisa; Rau, Holger; Besançon, Stéphane; Zufry, Hendra; Sofyan, Hizir; Vollmer, Sebastian
      Trials. 2019 Sep 02;20(1):548
      Abstract Background Diabetes is an important health burden in Indonesia. However, diabetes management and treatment remain poor, with most people with diabetes in Indonesia not achieving the recommended blood glucose levels. Peer education may have particular potential in low-income settings in complementing diabetes care without being a large additional strain on the health system. Methods/design This cluster randomized controlled trial aims to identify the effect of the implementation of peer education for patients with type 2 diabetes on diabetes-related outcomes in Aceh, Indonesia, which will complement the diabetes treatment provided at primary-care health posts (puskesmas). Altogether, 29 puskesmas were recruited in Banda Aceh and Aceh Besar, each of which was randomly assigned to either the control or the intervention group. Then, 534 people with diabetes were identified and recruited through their respective puskesmas. The intervention consists of up to two peer education groups per puskesmas, which are led by previously trained people with diabetes. Peer education sessions are held every month for 18 months, with follow-up data being collected 9 and 18 months after the first peer education session. The main objective is to improve diabetes management and the health behavior of participants receiving peer education to reduce their average blood glucose levels as measured by glycated hemoglobin (HbA1c) levels. Secondary outcomes are the effects of peer education on lipid levels, waist circumference, blood pressure, quality of life, treatment adherence, diabetes knowledge, physical activity, and dietary diversity. Data sources for the measurement of outcomes include patient and health facility surveys and biomarker measurements. An economic evaluation will be conducted to assess the cost-effectiveness of the intervention. Discussion This trial will contribute to the evidence on the effectiveness and cost-effectiveness of peer education in improving diabetes management in a low-income setting in Indonesia and in other comparable contexts. Trial registration ISRCTN registry, ISRCTN68253014 . Registered on 18 February 2019.
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