Items 21-40 of 579

    • Journal Article

      Tax4Fun2: prediction of habitat-specific functional profiles and functional redundancy based on 16S rRNA gene sequences 

      Wemheuer, Franziska; Taylor, Jessica A; Daniel, Rolf; Johnston, Emma; Meinicke, Peter; Thomas, Torsten; Wemheuer, Bernd
      Environmental Microbiome. 2020 May 18;15(1):11
      Abstract Background Sequencing of 16S rRNA genes has become a powerful technique to study microbial communities and their responses towards changing environmental conditions in various ecosystems. Several tools have been developed for the prediction of functional profiles from 16S rRNA gene sequencing data, because numerous questions in ecosystem ecology require knowledge of community functions in addition to taxonomic composition. However, the accuracy of these tools relies on functional information derived from genomes available in public databases, which are often not representative of the microorganisms present in the studied ecosystem. In addition, there is also a lack of tools to predict functional gene redundancy in microbial communities. Results To address these challenges, we developed Tax4Fun2, an R package for the prediction of functional profiles and functional gene redundancies of prokaryotic communities from 16S rRNA gene sequences. We demonstrate that functional profiles predicted by Tax4Fun2 are highly correlated to functional profiles derived from metagenomes of the same samples. We further show that Tax4Fun2 has higher accuracies than PICRUSt and Tax4Fun. By incorporating user-defined, habitat-specific genomic information, the accuracy and robustness of predicted functional profiles is substantially enhanced. In addition, functional gene redundancies predicted with Tax4Fun2 are highly correlated to functional gene redundancies determined for simulated microbial communities. Conclusions Tax4Fun2 provides researchers with a unique tool to predict and investigate functional profiles of prokaryotic communities based on 16S rRNA gene sequencing data. It is easy-to-use, platform-independent and highly memory-efficient, thus enabling researchers without extensive bioinformatics knowledge or access to high-performance clusters to predict functional profiles. Another unique feature of Tax4Fun2 is that it allows researchers to calculate the redundancy of specific functions, which is a potentially important measure of how resilient a community will be to environmental perturbation. Tax4Fun2 is implemented in R and freely available at https://github.com/bwemheu/Tax4Fun2.
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    • Journal Article

      Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine 

      Reintam Blaser, Annika; Preiser, Jean-Charles; Fruhwald, Sonja; Wilmer, Alexander; Wernerman, Jan; Benstoem, Carina; Casaer, Michael P; Starkopf, Joel; van Zanten, Arthur; Rooyackers, Olav; et al.
      Jakob, Stephan MLoudet, Cecilia IBear, Danielle EElke, GunnarKott, MatthiasLautenschläger, IngmarSchäper, JörnGunst, JanStoppe, ChristianNobile, LedaFuhrmann, ValentinBerger, Mette MOudemans-van Straaten, Heleen MArabi, Yaseen MDeane, Adam M
      Critical Care. 2020 May 15;24(1):224
      Abstract Background Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. Methods This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. Results Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. Conclusions Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.
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    • Journal Article

      Evaluation of a communication skills training to facilitate addressing palliative care related topics in advanced cancer patients: study protocol of a multicenter randomized controlled trial (PALLI-KOM) 

      Harnischfeger, Nele; Rath, Hilke M; Ullrich, Anneke; Alt-Epping, Bernd; Letsch, Anne; Thuss-Patience, Peter; Bokemeyer, Carsten; Oechsle, Karin; Bergelt, Corinna
      BMC Palliative Care. 2020 May 12;19(1):67
      Abstract Background Early integration of palliative care concurrently to standard cancer care is associated with several benefits for patients and their caregivers. However, communication barriers on part of the caring physicians often impede a timely referral to palliative care. This study describes the protocol of the evaluation of a communication skills training aiming to strengthen the ability of physicians to address palliative care related topics adequately and early during disease trajectory. Methods We will implement a communication skills training and evaluate it within a prospective, multi-centered, two-armed randomized controlled trial (RCT), which will be conducted at four sites in Germany. Eligible subjects are all physicians treating patients with advanced cancer in their daily routine. An intervention group (IG) receiving a group training will be compared to a wait-list control group (CG) receiving the training after completion of data collection. At pre- and post-measurement points, participants will conduct videotaped conversations with standardized simulated patients (SP). Primary outcome will be the external rating of communication skills and consulting competencies addressing palliative care related topics. Secondary outcomes on core concepts of palliative care, basic knowledge, attitudes, confidence and self-efficacy will be assessed by standardized questionnaires and self-developed items. A further external assessment of the quality of physician-patient-interaction will be conducted by the SP. Longitudinal quantitative data will be analyzed using covariate-adjusted linear mixed-models. Discussion If the communication skills training proves to be effective, it will provide a feasible intervention to promote an earlier communication of palliative care related topics in the care of advanced cancer patients. This would help to further establish early integration of palliative care as it is recommended by national and international guidelines. Trial registration German Clinical Trials Register DRKS00017025 (date of registration: 4 June 2019).
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    • Journal Article

      Genetic variants in FBLIM1 gene do not contribute to SAPHO syndrome and chronic recurrent multifocal osteomyelitis in typical patient groups 

      Assmann, Gunter; Köhm, Michaela; Schuster, Volker; Behrens, Frank; Mössner, Rotraut; Magnolo, Nina; Oji, Vinzenz; Burkhardt, Harald; Hüffmeier, Ulrike
      BMC Medical Genetics. 2020 May 12;21(1):102
      Abstract Background Syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) and chronic recurrent multifocal osteomyelitis (CRMO) present two diseases of a dermatologic and rheumatologic spectrum that are variable in manifestation und therapeutic response. Genetic risk factors have long been assumed in both diseases, but no single reliable factor has been identified yet. Therefore, we aimed to clinically characterize a patient group with syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) (n = 47) and chronic recurrent multifocal osteomyelitis (CRMO)/ chronic non-bacterial osteomyelitis (CNO) (n = 9) and analyze a CRMO candidate gene. Methods Clinical data of all patients were collected and assessed for different combinations of clinical symptoms. SAPHO patients were grouped into categories according to the acronym; disease-contribution by pathogens was evaluated. We sequenced coding exons of FBLIM1. Results Palmoplantar pustular psoriasis (PPP) was the most common skin manifestation in CRMO/CNO and SAPHO patients; most SAPHO patients had sterno-costo-clavicular hyperostosis. The most common clinical category of the acronym was S_PHO (n = 26). Lack of pathogen detection from bone biopsies was more common than microbial isolation. We did not identify autosomal-recessive FBLIM1 variants. Conclusions S_PHO is the most common combination of symptoms of its acronym. Genetic analyses of FBLIM1 did not provide evidence that this gene is relevant in our patient group. Our study indicates the need to elucidate SAPHO’s and CRMO/CNO’s pathogenesis.
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    • Journal Article

      Correction to: SMART coils for intracranial aneurysm repair - a single center experience 

      Behme, Daniel; Sack, Henrik; Tsogkas, Ioannis; Rohde, Veit; Psychogios, Marios-Nikos
      BMC Neurology. 2020 May 14;20(1):188
      An amendment to this paper has been published and can be accessed via the original article.
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    • Journal Article

      Genomic variation among closely related Vibrio alginolyticus strains is located on mobile genetic elements 

      Chibani, Cynthia M; Roth, Olivia; Liesegang, Heiko; Wendling, Carolin C
      BMC Genomics. 2020 May 11;21(1):354
      Abstract Background Species of the genus Vibrio, one of the most diverse bacteria genera, have undergone niche adaptation followed by clonal expansion. Niche adaptation and ultimately the formation of ecotypes and speciation in this genus has been suggested to be mainly driven by horizontal gene transfer (HGT) through mobile genetic elements (MGEs). Our knowledge about the diversity and distribution of Vibrio MGEs is heavily biased towards human pathogens and our understanding of the distribution of core genomic signatures and accessory genes encoded on MGEs within specific Vibrio clades is still incomplete. We used nine different strains of the marine bacterium Vibrio alginolyticus isolated from pipefish in the Kiel-Fjord to perform a multiscale-comparative genomic approach that allowed us to investigate [1] those genomic signatures that characterize a habitat-specific ecotype and [2] the source of genomic variation within this ecotype. Results We found that the nine isolates from the Kiel-Fjord have a closed-pangenome and did not differ based on core-genomic signatures. Unique genomic regions and a unique repertoire of MGEs within the Kiel-Fjord isolates suggest that the acquisition of gene-blocks by HGT played an important role in the evolution of this ecotype. Additionally, we found that ~ 90% of the genomic variation among the nine isolates is encoded on MGEs, which supports ongoing theory that accessory genes are predominately located on MGEs and shared by HGT. Lastly, we could show that these nine isolates share a unique virulence and resistance profile which clearly separates them from all other investigated V. alginolyticus strains and suggests that these are habitat-specific genes, required for a successful colonization of the pipefish, the niche of this ecotype. Conclusion We conclude that all nine V. alginolyticus strains from the Kiel-Fjord belong to a unique ecotype, which we named the Kiel-alginolyticus ecotype. The low sequence variation of the core-genome in combination with the presence of MGE encoded relevant traits, as well as the presence of a suitable niche (here the pipefish), suggest, that this ecotype might have evolved from a clonal expansion following HGT driven niche-adaptation.
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    • Journal Article

      Soil-plant co-stimulation during forest vegetation restoration in a subtropical area of southern China 

      Chen, Chan; Fang, Xi; Xiang, Wenhua; Lei, Pifeng; Ouyang, Shuai; Kuzyakov, Yakov
      Forest Ecosystems. 2020 May 08;7(1):32
      Abstract Background Soil and vegetation have a direct impact on the process and direction of plant community succession, and determine the structure, function, and productivity of ecosystems. However, little is known about the synergistic influence of soil physicochemical properties and vegetation features on vegetation restoration. The aim of this study was to investigate the co-evolution of soil physicochemical properties and vegetation features in the process of vegetation restoration, and to distinguish the primary and secondary relationships between soil and vegetation in their collaborative effects on promoting vegetation restoration in a subtropical area of China. Methods Soil samples were collected to 40 cm in four distinct plant communities along a restoration gradient from herb (4–5 years), to shrub (11–12 years), to Pinus massoniana coniferous and broadleaved mixed forest (45–46 years), and to evergreen broadleaved forest (old growth forest). Measurements were taken of the soil physicochemical properties and Shannon–Wiener index (SD), diameter at breast height (DBH), height (H), and biomass. Principal component analysis, linear function analysis, and variation partitioning analysis were then performed to prioritize the relative importance of the leading factors affecting vegetation restoration. Results Soil physicochemical properties and vegetation features showed a significant trend of improvement across the vegetation restoration gradient, reflected mainly in the high response rates of soil organic carbon (SOC) (140.76%), total nitrogen (TN) (222.48%), total phosphorus (TP) (59.54%), alkaline hydrolysis nitrogen (AN) (544.65%), available phosphorus (AP) (53.28%), species diversity (86.3%), biomass (2906.52%), DBH (128.11%), and H (596.97%). The soil properties (pH, SOC, TN, AN, and TP) and vegetation features (biomass, DBH, and H) had a clear co-evolutionary relationship over the course of restoration. The synergistic interaction between soil properties and vegetation features had the greatest effect on biomass (55.55%–72.37%), and the soil properties contributed secondarily (3.30%–31.44%). The main impact factors of biomass varied with the restoration periods. Conclusions In the process of vegetation restoration, soil and vegetation promoted each other. Vegetation restoration was the cumulative result of changes in soil fertility and vegetation features.
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    • Journal Article

      H2 influenza A virus is not pathogenic in Tmprss2 knock-out mice 

      Lambertz, Ruth L O; Gerhauser, Ingo; Nehlmeier, Inga; Gärtner, Sabine; Winkler, Michael; Leist, Sarah R; Kollmus, Heike; Pöhlmann, Stefan; Schughart, Klaus
      Virology Journal. 2020 Apr 22;17(1):56
      Abstract The host cell protease TMPRSS2 cleaves the influenza A virus (IAV) hemagglutinin (HA). Several reports have described resistance of Tmprss2−/− knock-out (KO) mice to IAV infection but IAV of the H2 subtype have not been examined yet. Here, we demonstrate that TMPRSS2 is able to cleave H2-HA in cell culture and that Tmprss2−/− mice are resistant to infection with a re-assorted PR8_HA(H2) virus. Infection of KO mice did not cause major body weight loss or death. Furthermore, no significant increase in lung weights and no virus replication were observed in Tmprss2−/− mice. Finally, only minor tissue damage and infiltration of immune cells were detected and no virus-positive cells were found in histological sections of Tmprss2−/− mice. In summary, our studies indicate that TMPRSS2 is required for H2 IAV spread and pathogenesis in mice. These findings extend previous results pointing towards a central role of TMPRSS2 in IAV infection and validate host proteases as a potential target for antiviral therapy.
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    • Journal Article

      Hey surgeons! It is time to lead and be a champion in preventing and managing surgical infections! 

      Sartelli, Massimo; Coccolini, Federico; Abu-Zidan, Fikri M; Ansaloni, Luca; Bartoli, Stefano; Biffl, Walter; Borghi, Felice; Chouillard, Elie; Cui, Yunfeng; Nascimento, Rafael D O; et al.
      De Simone, BelindaDi Saverio, SalomoneDuane, ThereseEckmann, ChristianEid, Hani OGomes, Carlos AGomes, Felipe CHecker, AndreasHecker, BirgitIsik, ArdaItani, Kamal M FLeppaniemi, AriLitvin, AndreyLuppi, DavideMaier, RonaldManzano-Nunez, RamiroMarwah, SanjayMazuski, JohnMoore, ErnestPerrone, GennaroRasa, KemalRubio, InesSawyer, RobertLabricciosa, Francesco MCatena, Fausto
      World Journal of Emergency Surgery. 2020 Apr 19;15(1):28
      Abstract Appropriate measures of infection prevention and management are integral to optimal clinical practice and standards of care. Among surgeons, these measures are often over-looked. However, surgeons are at the forefront in preventing and managing infections. Surgeons are responsible for many of the processes of healthcare that impact the risk for surgical site infections and play a key role in their prevention. Surgeons are also at the forefront in managing patients with infections, who often need prompt source control and appropriate antibiotic therapy, and are directly responsible for their outcome. In this context, the direct leadership of surgeons in infection prevention and management is of utmost importance. In order to disseminate worldwide this message, the editorial has been translated into 9 different languages (Arabic, Chinese, French, German, Italian, Portuguese, Spanish, Russian, and Turkish).
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    • Journal Article

      COVID-19 pneumonia: ARDS or not? 

      Gattinoni, Luciano; Chiumello, Davide; Rossi, Sandra
      Critical Care. 2020 Apr 16;24(1):154
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    • Journal Article

      Bayesian spatial modelling of childhood cancer incidence in Switzerland using exact point data: a nationwide study during 1985–2015 

      Konstantinoudis, Garyfallos; Schuhmacher, Dominic; Ammann, Roland A; Diesch, Tamara; Kuehni, Claudia E; Spycher, Ben D
      International Journal of Health Geographics. 2020 Apr 17;19(1):15
      Abstract Background The aetiology of most childhood cancers is largely unknown. Spatially varying environmental factors such as traffic-related air pollution, background radiation and agricultural pesticides might contribute to the development of childhood cancer. This study is the first investigation of the spatial disease mapping of childhood cancers using exact geocodes of place of residence. Methods We included 5947 children diagnosed with cancer in Switzerland during 1985–2015 at 0–15 years of age from the Swiss Childhood Cancer Registry. We modelled cancer risk using log-Gaussian Cox processes and indirect standardisation to adjust for age and year of diagnosis. We examined whether the spatial variation of risk can be explained by modelled ambient air concentration of NO2, modelled exposure to background ionising radiation, area-based socio-economic position (SEP), linguistic region, duration in years of general cancer registration in the canton or degree of urbanisation. Results For all childhood cancers combined, the posterior median relative risk (RR), compared to the national level, varied by location from 0.83 to 1.13 (min to max). Corresponding ranges were 0.96 to 1.09 for leukaemia, 0.90 to 1.13 for lymphoma, and 0.82 to 1.23 for central nervous system (CNS) tumours. The covariates considered explained 72% of the observed spatial variation for all cancers, 81% for leukaemia, 82% for lymphoma and 64% for CNS tumours. There was weak evidence of an association of CNS tumour incidence with modelled exposure to background ionising radiation (RR per SD difference 1.17; 0.98–1.40) and with SEP (1.6; 1.00–1.13). Conclusion Of the investigated diagnostic groups, childhood CNS tumours showed the largest spatial variation. The selected covariates only partially explained the observed variation of CNS tumours suggesting that other environmental factors also play a role.
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    • Journal Article

      Growing a circular economy with fungal biotechnology: a white paper 

      Meyer, Vera; Basenko, Evelina Y; Benz, J. P; Braus, Gerhard H; Caddick, Mark X; Csukai, Michael; de Vries, Ronald P; Endy, Drew; Frisvad, Jens C; Gunde-Cimerman, Nina; et al.
      Haarmann, ThomasHadar, YitzhakHansen, KimJohnson, Robert IKeller, Nancy PKraševec, NadaMortensen, Uffe HPerez, RolandoRam, Arthur F JRecord, EricRoss, PhilShapaval, VolhaSteiniger, Charlottevan den Brink, Hansvan Munster, JolandaYarden, OdedWösten, Han A B
      Fungal Biology and Biotechnology. 2020 Apr 02;7(1):5
      Abstract Fungi have the ability to transform organic materials into a rich and diverse set of useful products and provide distinct opportunities for tackling the urgent challenges before all humans. Fungal biotechnology can advance the transition from our petroleum-based economy into a bio-based circular economy and has the ability to sustainably produce resilient sources of food, feed, chemicals, fuels, textiles, and materials for construction, automotive and transportation industries, for furniture and beyond. Fungal biotechnology offers solutions for securing, stabilizing and enhancing the food supply for a growing human population, while simultaneously lowering greenhouse gas emissions. Fungal biotechnology has, thus, the potential to make a significant contribution to climate change mitigation and meeting the United Nation’s sustainable development goals through the rational improvement of new and established fungal cell factories. The White Paper presented here is the result of the 2nd Think Tank meeting held by the EUROFUNG consortium in Berlin in October 2019. This paper highlights discussions on current opportunities and research challenges in fungal biotechnology and aims to inform scientists, educators, the general public, industrial stakeholders and policymakers about the current fungal biotech revolution.
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    • Journal Article

      Comparison of estimators of variance for forest inventories with systematic sampling - results from artificial populations 

      Magnussen, Steen; McRoberts, Ronald E; Breidenbach, Johannes; Nord-Larsen, Thomas; Ståhl, Göran; Fehrmann, Lutz; Schnell, Sebastian
      Forest Ecosystems. 2020 Mar 23;7(1):17
      Abstract Background Large area forest inventories often use regular grids (with a single random start) of sample locations to ensure a uniform sampling intensity across the space of the surveyed populations. A design-unbiased estimator of variance does not exist for this design. Oftentimes, a quasi-default estimator applicable to simple random sampling (SRS) is used, even if it carries with it the likely risk of overestimating the variance by a practically important margin. To better exploit the precision of systematic sampling we assess the performance of five estimators of variance, including the quasi default. In this study, simulated systematic sampling was applied to artificial populations with contrasting covariance structures and with or without linear trends. We compared the results obtained with the SRS, Matérn’s, successive difference replication, Ripley’s, and D’Orazio’s variance estimators. Results The variances obtained with the four alternatives to the SRS estimator of variance were strongly correlated, and in all study settings consistently closer to the target design variance than the estimator for SRS. The latter always produced the greatest overestimation. In populations with a near zero spatial autocorrelation, all estimators, performed equally, and delivered estimates close to the actual design variance. Conclusion Without a linear trend, the SDR and DOR estimators were best with variance estimates more narrowly distributed around the benchmark; yet in terms of the least average absolute deviation, Matérn’s estimator held a narrow lead. With a strong or moderate linear trend, Matérn’s estimator is choice. In large populations, and a low sampling intensity, the performance of the investigated estimators becomes more similar.
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    • Journal Article

      Changes in shunt, ventilation/perfusion mismatch, and lung aeration with PEEP in patients with ARDS: a prospective single-arm interventional study 

      Karbing, Dan S; Panigada, Mauro; Bottino, Nicola; Spinelli, Elena; Protti, Alessandro; Rees, Stephen E; Gattinoni, Luciano
      Critical Care. 2020 Mar 23;24(1):111
      Abstract Background Several studies have found only a weak to moderate correlation between oxygenation and lung aeration in response to changes in PEEP. This study aimed to investigate the association between changes in shunt, low and high ventilation/perfusion (V/Q) mismatch, and computed tomography-measured lung aeration following an increase in PEEP in patients with ARDS. Methods In this preliminary study, 12 ARDS patients were subjected to recruitment maneuvers followed by setting PEEP at 5 and then either 15 or 20 cmH2O. Lung aeration was measured by computed tomography. Values of pulmonary shunt and low and high V/Q mismatch were calculated by a model-based method from measurements of oxygenation, ventilation, and metabolism taken at different inspired oxygen levels and an arterial blood gas sample. Results Increasing PEEP resulted in reduced values of pulmonary shunt and the percentage of non-aerated tissue, and an increased percentage of normally aerated tissue (p < 0.05). Changes in shunt and normally aerated tissue were significantly correlated (r = − 0.665, p = 0.018). Three distinct responses to increase in PEEP were observed in values of shunt and V/Q mismatch: a beneficial response in seven patients, where shunt decreased without increasing high V/Q; a detrimental response in four patients where both shunt and high V/Q increased; and a detrimental response in a patient with reduced shunt but increased high V/Q mismatch. Non-aerated tissue decreased with increased PEEP in all patients, and hyperinflated tissue increased only in patients with a detrimental response in shunt and V/Q mismatch. Conclusions The results show that improved lung aeration following an increase in PEEP is not always consistent with reduced shunt and V/Q mismatch. Poorly matched redistribution of ventilation and perfusion, between dependent and non-dependent regions of the lung, may explain why patients showed detrimental changes in shunt and V/Q mismatch on increase in PEEP, despite improved aeration. Trial registration ClinicalTrails.gov, NCT04067154. Retrospectively registered on August 26, 2019.
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      The complete mitochondrial genome of a parasite at the animal-fungal boundary 

      Sana, Salma; Hardouin, Emilie A; Paley, Richard; Zhang, Tiantian; Andreou, Demetra
      Parasites & Vectors. 2020 Feb 17;13(1):81
      Abstract Background Sphaerothecum destruens is an obligate intracellular fish parasite which has been identified as a serious threat to freshwater fishes. Taxonomically, S. destruens belongs to the order Dermocystida within the class Ichthyosporea (formerly referred to as Mesomycetozoea), which sits at the animal-fungal boundary. Mitochondrial DNA (mtDNA) sequences can be valuable genetic markers for species detection and are increasingly used in environmental DNA (eDNA) based species detection. Furthermore, mtDNA sequences can be used in epidemiological studies by informing detection, strain identification and geographical spread. Methods We amplified the entire mitochondrial (mt) genome of S. destruens in two overlapping long fragments using primers designed based on the cox1, cob and nad5 partial sequences. The mt-genome architecture of S. destruens was then compared to close relatives to gain insights into its evolution. Results The complete mt-genome of Sphaerothecum destruens is 23,939 bp in length and consists of 47 genes including 21 protein-coding genes, 2 rRNA, 22 tRNA and two unidentified open reading frames. The mitochondrial genome of S. destruens is intronless and compact with a few intergenic regions and includes genes that are often missing from animal and fungal mt-genomes, such as, the four ribosomal proteins (small subunit rps13 and 14; large subunit rpl2 and 16), tatC (twin-arginine translocase component C), and ccmC and ccmF (cytochrome c maturation protein ccmC and heme lyase). Conclusions We present the first mt-genome of S. destruens which also represents the first mt-genome for the order Dermocystida. The availability of the mt-genome can assist the detection of S. destruens and closely related parasites in eukaryotic diversity surveys using eDNA and assist epidemiological studies by improving molecular detection and tracking the parasite’s spread. Furthermore, as the only representative of the order Dermocystida, its mt-genome can be used in the study of mitochondrial evolution of the unicellular relatives of animals.
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      Are scurs in heterozygous polled (Pp) cattle a complex quantitative trait? 

      Gehrke, Lilian J; Capitan, Aurélien; Scheper, Carsten; König, Sven; Upadhyay, Maulik; Heidrich, Kristin; Russ, Ingolf; Seichter, Doris; Tetens, Jens; Medugorac, Ivica; et al.
      Thaller, Georg
      Genetics Selection Evolution. 2020 Feb 07;52(1):6
      Abstract Background Breeding genetically hornless, i.e. polled, cattle provides an animal welfare-friendly and non-invasive alternative to the dehorning of calves. However, the molecular regulation of the development of horns in cattle is still poorly understood. Studying genetic characters such as polledness and scurs, can provide valuable insights into this process. Scurs are hornlike formations that occur occasionally in a wide variety of sizes and forms as an unexpected phenotype when breeding polled cattle. Methods We present a unique dataset of 885 Holstein–Friesian cattle with polled parentage. The horn phenotype was carefully examined, and the phenotypic heterogeneity of the trait is described. Using a direct gene test for polledness, the polled genotype of the animals was determined. Subsequently, the existence of a putative scurs locus was investigated using high-density genotype data of a selected subset of 232 animals and two mapping approaches: mixed linear model-based association analyses and combined linkage disequilibrium and linkage analysis. Results The results of an exploratory data analysis indicated that the expression of scurs depends on age at phenotyping, sex and polled genotype. Scurs were more prevalent in males than in females. Moreover, homozygous polled animals did not express any pronounced scurs and we found that the Friesian polled allele suppresses the development of scurs more efficiently than the Celtic polled allele. Combined linkage and linkage disequilibrium mapping revealed four genome-wide significant loci that affect the development of scurs, one on BTA5 and three on BTA12. Moreover, suggestive associations were detected on BTA16, 18 and 23. The mixed linear model-based association analysis supports the results of the combined linkage and linkage disequilibrium analysis. None of the mapping approaches provided convincing evidence for a monogenic inheritance of scurs. Conclusions Our results contradict the initial and still broadly accepted model for the inheritance of horns and scurs. We hypothesise an oligogenetic model to explain the development of scurs and polledness.
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      Motor, cognitive and mobility deficits in 1000 geriatric patients: protocol of a quantitative observational study before and after routine clinical geriatric treatment – the ComOn-study 

      Geritz, Johanna; Maetzold, Sara; Steffen, Maren; Pilotto, Andrea; Corrà, Marta F; Moscovich, Mariana; Rizzetti, Maria C; Borroni, Barbara; Padovani, Alessandro; Alpes, Annekathrin; et al.
      Bang, CorinnaBarcellos, IgorBaron, RalfBartsch, ThorstenBecktepe, Jos SBerg, DanielaBergeest, Lu MBergmann, PhilippBouça-Machado, RaquelDrey, MichaelElshehabi, MoradFarahmandi, SusanFerreira, Joaquim JFranke, AndreFriederich, AnjaGeisler, CorinnaHüllemann, PhilippGierthmühlen, JanneGranert, OliverHeinzel, SebastianHeller, Maren KHobert, Markus AHofmann, MarcJemlich, BjörnKerkmann, LauraKnüpfer, StephanieKrause, KatharinaKress, MaximilianKrupp, SonjaKudelka, JenniferKuhlenbäumer, GregorKurth, RolandLeypoldt, FrankMaetzler, CorinaMaia, Luis FMoewius, AndreasNeumann, PatriciaNiemann, KatharinaOrtlieb, Christian TPaschen, SteffenPham, Minh HPuehler, ThomasRadloff, FranziskaRiedel, ChristianRogalski, MartenSablowsky, SimoneSchanz, Elena MSchebesta, LindaSchicketmüller, AndreasStudt, SimoneThieves, MartinaTönges, LarsUllrich, SebastianUrban, Peter PVila-Chã, NunoWiegard, AnnaWarmerdam, ElkeWarnecke, TobiasWeiss, MichaelWelzel, JuliusHansen, ClintMaetzler, Walter
      BMC Geriatrics. 2020 Feb 06;20(1):45
      Abstract Background Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). Methods This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week’s inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. Discussion This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.
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      Gene content evolution in the arthropods 

      Thomas, Gregg W C; Dohmen, Elias; Hughes, Daniel S T; Murali, Shwetha C; Poelchau, Monica; Glastad, Karl; Anstead, Clare A; Ayoub, Nadia A; Batterham, Phillip; Bellair, Michelle; et al.
      Binford, Greta JChao, HsuChen, Yolanda HChilders, ChristopherDinh, HuyenDoddapaneni, Harsha VDuan, Jian JDugan, ShannonEsposito, Lauren AFriedrich, MarkusGarb, JessicaGasser, Robin BGoodisman, Michael A DGundersen-Rindal, Dawn EHan, YiHandler, Alfred MHatakeyama, MasatsuguHering, LarsHunter, Wayne BIoannidis, PanagiotisJayaseelan, Joy CKalra, DivyaKhila, AbderrahmanKorhonen, Pasi KLee, Carol ELee, Sandra LLi, YiyuanLindsey, Amelia R IMayer, GeorgMcGregor, Alistair PMcKenna, Duane DMisof, BernhardMunidasa, MalaMunoz-Torres, MonicaMuzny, Donna MNiehuis, OliverOsuji-Lacy, NkechinyerePalli, Subba RPanfilio, Kristen APechmann, MatthiasPerry, TrentPeters, Ralph SPoynton, Helen CPrpic, Nikola-MichaelQu, JiaxinRotenberg, DorithSchal, CobySchoville, Sean DScully, Erin DSkinner, EvetteSloan, Daniel BStouthamer, RichardStrand, Michael RSzucsich, Nikolaus UWijeratne, AselaYoung, Neil DZattara, Eduardo EBenoit, Joshua BZdobnov, Evgeny MPfrender, Michael EHackett, Kevin JWerren, John HWorley, Kim CGibbs, Richard AChipman, Ariel DWaterhouse, Robert MBornberg-Bauer, ErichHahn, Matthew WRichards, Stephen
      Genome Biology. 2020 Jan 23;21(1):15
      Abstract Background Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Results Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. Conclusions These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.
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    • Journal Article

      Profiling of the muscle-specific dystroglycan interactome reveals the role of Hippo signaling in muscular dystrophy and age-dependent muscle atrophy 

      Yatsenko, Andriy S; Kucherenko, Mariya M; Xie, Yuanbin; Aweida, Dina; Urlaub, Henning; Scheibe, Renate J; Cohen, Shenhav; Shcherbata, Halyna R
      BMC Medicine. 2020 Jan 21;18(1):8
      Abstract Background Dystroglycanopathies are a group of inherited disorders characterized by vast clinical and genetic heterogeneity and caused by abnormal functioning of the ECM receptor dystroglycan (Dg). Remarkably, among many cases of diagnosed dystroglycanopathies, only a small fraction can be linked directly to mutations in Dg or its regulatory enzymes, implying the involvement of other, not-yet-characterized, Dg-regulating factors. To advance disease diagnostics and develop new treatment strategies, new approaches to find dystroglycanopathy-related factors should be considered. The Dg complex is highly evolutionarily conserved; therefore, model genetic organisms provide excellent systems to address this challenge. In particular, Drosophila is amenable to experiments not feasible in any other system, allowing original insights about the functional interactors of the Dg complex. Methods To identify new players contributing to dystroglycanopathies, we used Drosophila as a genetic muscular dystrophy model. Using mass spectrometry, we searched for muscle-specific Dg interactors. Next, in silico analyses allowed us to determine their association with diseases and pathological conditions in humans. Using immunohistochemical, biochemical, and genetic interaction approaches followed by the detailed analysis of the muscle tissue architecture, we verified Dg interaction with some of the discovered factors. Analyses of mouse muscles and myocytes were used to test if interactions are conserved in vertebrates. Results The muscle-specific Dg complexome revealed novel components that influence the efficiency of Dg function in the muscles. We identified the closest human homologs for Dg-interacting partners, determined their significant enrichment in disease-associations, and verified some of the newly identified Dg interactions. We found that Dg associates with two components of the mechanosignaling Hippo pathway: the WW domain-containing proteins Kibra and Yorkie. Importantly, this conserved interaction manages adult muscle size and integrity. Conclusions The results presented in this study provide a new list of muscle-specific Dg interactors, further analysis of which could aid not only in the diagnosis of muscular dystrophies, but also in the development of new therapeutics. To regulate muscle fitness during aging and disease, Dg associates with Kibra and Yorkie and acts as a transmembrane Hippo signaling receptor that transmits extracellular information to intracellular signaling cascades, regulating muscle gene expression.
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    • Journal Article

      Transcriptome of pleuropodia from locust embryos supports that these organs produce enzymes enabling the larva to hatch 

      Konopová, Barbora; Buchberger, Elisa; Crisp, Alastair
      Frontiers in Zoology. 2020 Jan 16;17(1):4
      Abstract Background Pleuropodia are limb-derived glandular organs that transiently appear on the first abdominal segment in embryos of insects from majority of “orders”. They are missing in the genetic model Drosophila and little is known about them. Experiments carried out on orthopteran insects 80 years ago indicated that the pleuropodia secrete a “hatching enzyme” that digests the serosal cuticle to enable the larva to hatch, but evidence by state-of-the-art molecular methods is missing. Results We used high-throughput RNA-sequencing to identify the genes expressed in the pleuropodia of the locust Schistocerca gregaria (Orthoptera). First, using transmission electron microscopy we studied the development of the pleuropodia during 11 stages of the locust embryogenesis. We show that the glandular cells differentiate and start secreting just before the definitive dorsal closure of the embryo and the secretion granules outside the cells become more abundant prior to hatching. Next, we generated a comprehensive embryonic reference transcriptome for the locust and used it to study genome wide gene expression across ten morphologicaly defined stages of the pleuropodia. We show that when the pleuropodia have morphological markers of functional organs and produce secretion, they are primarily enriched in transcripts associated with transport functions. They express genes encoding enzymes capable of digesting cuticular protein and chitin. These include the potent cuticulo-lytic Chitinase 5, whose transcript rises just before hatching. Unexpected finding was the enrichment in transcripts for immunity-related enzymes. This indicates that the pleuropodia are equipped with epithelial immunity similarly as barrier epithelia in postembryonic stages. Conclusions These data provide transcriptomic support for the historic hypothesis that pleuropodia produce cuticle-degrading enzymes and function in hatching. They may also have other functions, such as facilitation of embryonic immune defense. By the genes that they express the pleuropodia are specialized embryonic organs and apparently an important though neglected part of insect physiology.
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