Items 1-20 of 690

    • Journal Article

      A Case Report: Building communities with training and resources for Open Science trainers 

      Brinken, Helene; Kuchma, Iryna; Kalaitzi, Vasso; Davidson, Joy; Pontika, Nancy; Cancellieri, Matteo; Correia, Antónia; Carvalho, José; Melero, Remedios; Kastelic, Damjana; et al.
      Borba, FilomenaLenaki, KaterinaToelch, UlfZourou, KaterinaKnoth, PetrSchmidt, BirgitRodrigues, Eloy
      LIBER Quarterly 2018; 29(1)
      To foster responsible research and innovation, research communities, institutions, and funders are shifting their practices and requirements towards Open Science. Open Science skills are becoming increasingly essential for researchers. Indeed general awareness of Open Science has grown among EU researchers, but the practical adoption can be further improved. Recognizing a gap between the needed and the provided training offer, the FOSTER project offers practical guidance and training to help researchers learn how to open up their research within a particular domain or research environment. Aiming for a sustainable approach, FOSTER focused on strengthening the Open Science training capacity by establishing and supporting a community of trainers. The creation of an Open Science training handbook was a first step towards bringing together trainers to share their experiences and to create an open and living knowledge resource. A subsequent series of train-the-trainer bootcamps helped trainers to find inspiration, improve their skills and to intensify exchange within a peer group. Four trainers, who attended one of the bootcamps, contributed a case study on their experiences and how they rolled out Open Science training within their own institutions. On its platform the project provides a range of online courses and resources to learn about key Open Science topics. FOSTER awards users gamification badges when completing courses in order to provide incentives and rewards, and to spur them on to even greater achievements in learning. The paper at hand describes FOSTER Plus’ training strategies, shares the lessons learnt and provides guidance on how to reuse the project’s materials and training approaches.
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    • Journal Article

      Mothers’ experiences of quality of care and potential benefits of implementing the WHO safe childbirth checklist: a case study of Aceh Indonesia 

      Doria, Siobhan; Diba, Farah; Susanti, Suryane S; Vollmer, Sebastian; Monfared, Ida G
      BMC Pregnancy and Childbirth. 2019 Dec 03;19(1):461
      Abstract Background In an effort to mitigate missed opportunities to provide high-quality care, the World Health Organization (WHO) has developed the Safe Childbirth Checklist (SCC) to support health providers perform essential tasks. Our qualitative study is a baseline assessment of quality of care (QoC) perceived by mothers who gave birth at health facilities aiming to highlight areas where implementing the SCC can potentially improve the QoC as well as areas that are not part of the SCC yet require improvement. Methods Assessing the overall experience of care, our qualitative study focuses on 8 out of 29 items in the checklist that are related to the personal interactions between healthcare provider and mothers. Using a set of semi-structured questions, we interviewed 26 new mothers who gave institutional births in Aceh province in Indonesia. Results Our findings revealed some gaps where implementing the SCC can potentially improve safety and QoC. They include communicating danger signs at critical points during birth and after discharge, encouraging breastfeeding, and providing mothers with information on family planning. Moreover, taking a qualitative approach allowed us to identify additional aspects such as need for clarity at the point of admission, maintaining dignity, and protecting mothers’ rights in the decision-making process to be also essential for better QoC. Conclusions Our study highlights the need to actively listen to and engage with the experiences of women in the adaptation and implementation of the checklist. While our findings indicate that implementing the SCC has the potential to improve the quality of maternal care and overall birth experience, a more holistic understanding of the lived experiences of women and the dynamics of their interactions with health facilities, care providers, and their birth companions can complement the implementation of the checklist.
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    • Journal Article

      Health-related quality of life in early-onset-scoliosis patients treated with growth-friendly implants is influenced by etiology, complication rate and ambulatory ability 

      Hell, Anna K; Braunschweig, Lena; Behrend, Jennifer; Lorenz, Heiko M; Tsaknakis, Konstantinos; von Deimling, Urs; Mladenov, Kiril
      BMC Musculoskeletal Disorders. 2019 Dec 07;20(1):588
      Abstract Background Progressive Early-Onset Scoliosis (EOS) in children may lead to surgical interventions with growth-friendly implants, which require repeated lengthening procedures in order to allow adequate growth. Quality of life was studied using the validated German version of the EOS-Questionnaire (EOSQ-24-G) in surgically treated EOS children with different lengthening modalities. Methods EOSQ-24-G and the KINDLR questionnaire were given to families with EOS children who had been treated by either vertical expandable prosthetic titanium rib implants and repetitive lengthening surgeries every 6 months or children who had received a magnetically expansion controlled implant, which was externally lengthened every 3 months. Results were compared according to differences between the two tests, and with possible influencing factors such as surgical method, severity of scoliosis, relative improvement of curvature, etiology, weight, age, travelling distance, complications, ambulatory ability and others. Results 56 children with an average curve angle of 69° corrected to 33° (52%; average age 5.6 yrs) answered the EOSQ-24-G and the KINDLR after an average follow-up of 3.9 years. Health-related quality of life (HRQoL) was not affected by the initial scoliosis correction, the number of surgeries or the implant type. However, there was a negative correlation with non-ambulatory status, complications during treatment and for children with a neuromuscular scoliosis. Conclusion Using the validated EOSQ-24-G, no statistically significant differences were found between the group of children receiving repetitive surgeries and children with external lengthening procedures without surgery. However, results were influenced by the etiology, complication rate or ambulatory ability. Level of Evidence/Clinical relevance Therapeutic Level IV
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    • Journal Article

      Improvement and use of CRISPR/Cas9 to engineer a sperm-marking strain for the invasive fruit pest Drosophila suzukii 

      Ahmed, Hassan M M; Hildebrand, Luisa; Wimmer, Ernst A
      BMC Biotechnology. 2019 Dec 05;19(1):85
      Abstract Background The invasive fruit pest Drosophila suzukii was reported for the first time in Europe and the USA in 2008 and has spread since then. The adoption of type II clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) as a tool for genome manipulation provides new ways to develop novel biotechnologically-based pest control approaches. Stage or tissue-specifically expressed genes are of particular importance in the field of insect biotechnology. The enhancer/promoter of the spermatogenesis-specific beta-2-tubulin (β2t) gene was used to drive the expression of fluorescent proteins or effector molecules in testes of agricultural pests and disease vectors for sexing, monitoring, and reproductive biology studies. Here, we demonstrate an improvement to CRISPR/Cas-based genome editing in D. suzukii and establish a sperm-marking system. Results To improve genome editing, we isolated and tested the D. suzukii endogenous promoters of the small nuclear RNA gene U6 to drive the expression of a guide RNA and the Ds heat shock protein 70 promoter to express Cas9. For comparison, we used recombinant Cas9 protein and in vitro transcribed gRNA as a preformed ribonucleoprotein. We demonstrate the homology-dependent repair (HDR)-based genome editing efficiency by applying a previously established transgenic line that expresses DsRed ubiquitously as a target platform. In addition, we isolated the Ds_β2t gene and used its promoter to drive the expression of a red fluorescence protein in the sperm. A transgenic sperm-marking strain was then established by the improved HDR-based genome editing. Conclusion The deployment of the endogenous promoters of the D. suzukii U6 and hsp70 genes to drive the expression of gRNA and Cas9, respectively, enabled the effective application of helper plasmid co-injections instead of preformed ribonucleoproteins used in previous reports for HDR-based genome editing. The sperm-marking system should help to monitor the success of pest control campaigns in the context of the Sterile Insect Technique and provides a tool for basic research in reproductive biology of this invasive pest. Furthermore, the promoter of the β2t gene can be used in developing novel transgenic pest control approaches and the CRISPR/Cas9 system as an additional tool for the modification of previously established transgenes.
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    • Journal Article

      Comparative knowledge, attitudes, and practices regarding anthrax, brucellosis, and rabies in three districts of northern Tanzania 

      Kiffner, Christian; Latzer, Michelle; Vise, Ruby; Benson, Hayley; Hammon, Elizabeth; Kioko, John
      BMC Public Health. 2019 Dec 03;19(1):1625
      Abstract Background Knowledge, attitudes, and practices (KAP) surveys regarding zoonotic diseases are crucial to understanding the extent of knowledge among citizens and for guiding health-related education programs. Method Employing a structured questionnaire, we interviewed residents (n = 388) in three districts of northern Tanzania (Karatu n = 128, Monduli n = 114, Babati n = 146) to assess knowledge, attitudes and reported practices regarding three zoonotic diseases that occur in the region (anthrax, brucellosis, and rabies). We used generalized linear mixed effects models and multi-model inference to identify demographic correlates of knowledge. Results Proportional average district- and disease- specific knowledge scores ranged from 0.14–0.61. We found positive correlations between age and knowledge of symptoms, causes and treatments of anthrax (three districts), brucellosis (three districts), and rabies (one district). Gender, ethnic identity, formal education and ownership of livestock or dogs had variable effects on knowledge among the interviewed population. Risk perceptions regarding different diseases varied across districts and were positively correlated with knowledge of the specific diseases. Direct interactions with livestock and domestic dogs were reported to occur across all demographic groups, suggesting that most people living in rural settings of our study area are potentially exposed to zoonotic diseases. Behaviors which may favor transmission of specific pathogens (such as consumption of raw milk or meat) were occasionally reported and varied by district. Wildlife was generally regarded as negative or neutral with regard to overall veterinary and human health. Conclusion The combination of variable knowledge about zoonotic diseases in the three districts, reported occurrence of practices that are conducive to pathogen transmission, and previously documented circulation of pathogens causing anthrax, brucellosis and rabies in our study system, call for health education programs embedded in a holistic One Health approach.
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    • Journal Article

      Unlocking the Digital Potential of Scholarly Monographs in 21st Century Research 

      Bargheer, Margo; Dogan, Zeki Mustafa; Horstmann, Wolfram; Mertens, Mike; Rapp, Andrea
      LIBER QUARTERLY 2017; 27(1) p.194-211
      In the light of new digital production and dissemination practices, the scholarly publishing system has seen significant and also disruptive changes, especially in STM (science, technology and medicine) and with regard to the predominant format “journal article.” The digital transformation also holds true for those disciplines that continue to rely on the scholarly monograph as a publication format and means for reputation building, namely the Humanities and the Social Sciences with a qualitative approach (HSS). In our paper we analyse the reasons why the monograph has not yet reached its full potential in the digital paradigm, especially in the uptake of Open Access and innovative publishing options. We highlight some of the principal underlying factors for this, and suggest how especially practices, now more widespread in HSS but arising from the Digital Humanities, could play a role in moving forward the rich digitality of the scholarly monograph.
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    • Journal Article

      Mechanical power at a glance: a simple surrogate for volume-controlled ventilation 

      Giosa, Lorenzo; Busana, Mattia; Pasticci, Iacopo; Bonifazi, Matteo; Macrì, Matteo M; Romitti, Federica; Vassalli, Francesco; Chiumello, Davide; Quintel, Michael; Marini, J. J; et al.
      Gattinoni, Luciano
      Intensive Care Medicine Experimental. 2019 Nov 27;7(1):61
      Abstract Background Mechanical power is a summary variable including all the components which can possibly cause VILI (pressures, volume, flow, respiratory rate). Since the complexity of its mathematical computation is one of the major factors that delay its clinical use, we propose here a simple and easy to remember equation to estimate mechanical power under volume-controlled ventilation: Mechanical Power=VE×Peak Pressure+PEEP+F/620$$ \mathrm{Mechanical}\ \mathrm{Power}=\frac{\mathrm{VE}\times \left(\mathrm{Peak}\ \mathrm{Pressure}+\mathrm{PEEP}+F/6\right)}{20} $$ where the mechanical power is expressed in Joules/minute, the minute ventilation (VE) in liters/minute, the inspiratory flow (F) in liters/minute, and peak pressure and positive end-expiratory pressure (PEEP) in centimeter of water. All the components of this equation are continuously displayed by any ventilator under volume-controlled ventilation without the need for clinician intervention. To test the accuracy of this new equation, we compared it with the reference formula of mechanical power that we proposed for volume-controlled ventilation in the past. The comparisons were made in a cohort of mechanically ventilated pigs (485 observations) and in a cohort of ICU patients (265 observations). Results Both in pigs and in ICU patients, the correlation between our equation and the reference one was close to the identity. Indeed, the R2 ranged from 0.97 to 0.99 and the Bland-Altman showed small biases (ranging from + 0.35 to − 0.53 J/min) and proportional errors (ranging from + 0.02 to − 0.05). Conclusions Our new equation of mechanical power for volume-controlled ventilation represents a simple and accurate alternative to the more complex ones available to date. This equation does not need any clinical intervention on the ventilator (such as an inspiratory hold) and could be easily implemented in the software of any ventilator in volume-controlled mode. This would allow the clinician to have an estimation of mechanical power at a simple glance and thus increase the clinical consciousness of this variable which is still far from being used at the bedside. Our equation carries the same limitations of all other formulas of mechanical power, the most important of which, as far as it concerns VILI prevention, are the lack of normalization and its application to the whole respiratory system (including the chest wall) and not only to the lung parenchyma.
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    • Journal Article

      Short-term discontinuation of vagal nerve stimulation alters 18F-FDG blood pool activity: an exploratory interventional study in epilepsy patients 

      Boswijk, Ellen; Franssen, Renee; Vijgen, Guy H E J; Wierts, Roel; van der Pol, Jochem A J; Mingels, Alma M A; Cornips, Erwin M J; Majoie, Marian H J M; van Marken Lichtenbelt, Wouter D; Mottaghy, Felix M; et al.
      Wildberger, Joachim EBucerius, Jan
      EJNMMI Research. 2019 Nov 27;9(1):101
      Abstract Background Vagus nerve activation impacts inflammation. Therefore, we hypothesized that vagal nerve stimulation (VNS) influenced arterial wall inflammation as measured by 18F-FDG uptake. Results Ten patients with left-sided VNS for refractory epilepsy were studied during stimulation (VNS-on) and in the hours after stimulation was switched off (VNS-off). In nine patients, 18F-FDG uptake was measured in the right carotid artery, aorta, bone marrow, spleen, and adipose tissue. Target-to-background ratios (TBRs) were calculated to normalize the respective standardized uptake values (SUVs) for venous blood pool activity. Median values are shown with interquartile range and compared using the Wilcoxon signed-rank test. Arterial SUVs tended to be higher during VNS-off than VNS-on [SUVmax all vessels 1.8 (1.5–2.2) vs. 1.7 (1.2–2.0), p = 0.051]. However, a larger difference was found for the venous blood pool at this time point, reaching statistical significance in the vena cava superior [meanSUVmean 1.3 (1.1–1.4) vs. 1.0 (0.8–1.1); p = 0.011], resulting in non-significant lower arterial TBRs during VNS-off than VNS-on. Differences in the remaining tissues were not significant. Insulin levels increased after VNS was switched off [55.0 pmol/L (45.9–96.8) vs. 48.1 pmol/L (36.9–61.8); p = 0.047]. The concurrent increase in glucose levels was not statistically significant [4.8 mmol/L (4.7–5.3) vs. 4.6 mmol/L (4.5–5.2); p = 0.075]. Conclusions Short-term discontinuation of VNS did not show a consistent change in arterial wall 18F-FDG-uptake. However, VNS did alter insulin and 18F-FDG blood levels, possibly as a result of sympathetic activation.
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    • Journal Article

      Patients’ and researchers’ experiences with a patient board for a clinical trial on urinary tract infections 

      Schilling, Imke; Behrens, Heike; Bleidorn, Jutta; Gágyor, Ildikó; Hugenschmidt, Claudia; Jilani, Hannah; Schmiemann, Guido; Gerhardus, Ansgar
      Research Involvement and Engagement. 2019 Nov 28;5(1):38
      Abstract Background Patient and public involvement (PPI) has become an essential part of the design, conduct, and dissemination of research. While researchers who employed PPI mainly report on the positive aspects, in practice PPI is still an exception in clinical trials in Germany. There are specific challenges in the process of involvement that can jeopardize the conduct of involvement. The aim of our study was to analyze the experience of patients and researchers with PPI in a clinical trial in Germany, so we could learn more about potential challenges and how they could be addressed. Methods We established a patient board for a randomized controlled trial on urinary tract infections, where patients and researchers regularly met to discuss relevant aspects of the trial. Minutes were taken for each meeting and the moderator also noted her observations in a postscript. After four meetings, we conducted two focus groups, one each with the patients and researchers. We analyzed and categorized the minutes, postscripts, and focus group transcripts using thematic qualitative text analysis. Results Patients and researchers felt comfortable with the composition of the patient board and its’ atmosphere. In terms of challenges, patients and researchers needed time to get familiar with PPI. Both parties saw a need for training in PPI but differed in their views on the relevant topics. Patients wished to learn more about their role and tasks within the board at the onset of the PPI. They also preferred to meet more frequently and get more intensely involved in the trial. In contrast, researchers perceived that they were already highly involved. They further felt that the involvement was of benefit to them, the trial and future research. Patients described benefits for themselves, but also wondered if their involvement had had an impact on the trial. Conclusions To facilitate effective PPI, resources, adequate structures, and training are needed. Patients and researchers need to agree on their respective roles, training needs, and the mode of cooperation right at the beginning. The parties involved should continuously reflect on the actual benefits of PPI, describe them explicitly and make them transparent for all.
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    • Journal Article

      Psychological burden in family caregivers of patients with advanced cancer at initiation of specialist inpatient palliative care 

      Oechsle, Karin; Ullrich, Anneke; Marx, Gabriella; Benze, Gesine; Heine, Julia; Dickel, Lisa-Marie; Zhang, Youyou; Wowretzko, Feline; Wendt, Kim N; Nauck, Friedemann; et al.
      Bokemeyer, CarstenBergelt, Corinna
      BMC Palliative Care. 2019 Nov 18;18(1):102
      Abstract Background This study prospectively evaluated distress, depressive and anxiety symptoms as well as associated factors in family caregivers (FC) of advanced cancer patients at initiation of specialist inpatient palliative care. Methods Within 72 h after the patient’s first admission, FCs were asked to complete German versions of the Distress Thermometer, Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire depression module 9-item scale (PHQ-9) for outcome measure. Multivariate logistic regression analyses were used to identify associated factors. Results In 232 FCs (62% spouses/partners), mean level of distress was 7.9 (SD 1.8; range, 2–10) with 95% presenting clinically relevant distress levels. Most frequent problems were sadness (91%), sorrows (90%), anxiety (78%), exhaustion (77%) and sleep disturbances (73%). Prevalence rates of moderate to severe anxiety and depressive symptoms were 47 and 39%, respectively. Only 25% of FCs had used at least one source of support previously. In multivariate regression analysis, being female (OR 2.525), spouse/partner (OR 2.714), exhaustion (OR 10.267), and worse palliative care outcome ratings (OR 1.084) increased the likelihood for moderate to severe anxiety symptom levels. Being female (OR 3.302), low socio-economic status (OR 6.772), prior patient care other than home-based care (OR 0.399), exhaustion (OR 3.068), sleep disturbances (OR 4.183), and worse palliative care outcome ratings (OR 1.100) were associated with moderate to severe depressive symptom levels. Conclusions FCs of patients presenting with indication for specialist palliative care suffer from high distress and relevant depressive and anxiety symptoms, indicating the high need of psychological support not only for patients, but also their FCs. Several socio-demographic and care-related risk-factors influence mental burden of FCs and should be in professional caregivers’ focus in daily clinical practice.
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    • Journal Article

      Various forms of double burden of malnutrition problems exist in rural Kenya 

      Fongar, Andrea; Gödecke, Theda; Qaim, Matin
      BMC Public Health. 2019 Nov 21;19(1):1543
      Abstract Background The coexistence of overweight/obesity and undernutrition is often referred to as the double burden of malnutrition (DB). DB was shown to exist in many developing countries, especially in urban areas. Much less is known about DB in rural areas of developing countries. Also, the exact definition of DB varies between studies, making comparison difficult. The objective of this study is to analyse DB problems in rural Kenya, using and comparing different DB definitions and measurement approaches. Methods Food intake and anthropometric data were collected from 874 male and female adults and 184 children (< 5 years) through a cross-section survey in rural areas of Western Kenya. DB at the individual level is defined as a person suffering simultaneously from overweight/obesity and micronutrient deficiency or stunting. DB at the household level is defined as an overweight/obese adult and an undernourished child living in the same household, using underweight, stunting, wasting, and micronutrient deficiency as indicators of child undernutrition. Results DB at the individual level is found in 19% of the adults, but only in 1% of the children. DB at the household level is relatively low (1–3%) when using wasting or underweight as indicators of child undernutrition, but much higher (13–17%) when using stunting or micronutrient deficiency as indicators. Conclusion Various forms of DB problems exist in rural Kenya at household and individual levels. Prevalence rates depend on how exactly DB is defined and measured. The rise of overweight and obesity, even in rural areas, and their coexistence with different forms of undernutrition are challenges for food and nutrition policies.
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    • 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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      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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      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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      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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