bluuebunny/crossref_metadata_2025_split huggingface dataset:
An under-represented and underserved population in trials: methodological, structural, and systemic barriers to the inclusion of adults lacking capacity to consent
Authors: Shepherd Victoria 
Published: May 2020

Abstract
Background
There is increasing international recognition that populations included in trials should adequately represent the population treated in clinical practice; however, adults who lack the capacity to provide informed consent are frequently excluded from trials. Addressing the under-representation of groups such as those with impaired capacity to consent is essential to develop effective interventions and provide these groups with the opportunity to benefit from evidence-based care. While the spotlight has been on ensuring only appropriate and justifiable exclusion criteria are used in trials, barriers to the inclusion of adults lacking capacity are multifactorial and complex, and addressing their under-representation will require more than merely widening eligibility criteria. This commentary draws on the literature exploring the inclusion of adults lacking the capacity to consent in research and a number of recent studies to describe the methodological, structural, and systemic factors that have been identified.

Main text
A number of potentially modifiable factors contributing to the under-representation of adults lacking the capacity to consent in trials have been identified. In addition to restrictive eligibility criteria, methodological issues include developing appropriate interventions and outcome measures for populations with impaired capacity. Structurally determined factors include the resource-intensive nature of these trials, the requirement for more appropriate research infrastructure, and a lack of interventions to inform and support proxy decision-makers. Systemic factors include the complexities of the legal frameworks, the challenges of ethical review processes, and paternalistic attitudes towards protecting adults with incapacity from the perceived harms of research.

Conclusions
Measures needed to address under-representation include greater scrutiny of exclusion criteria by those reviewing study proposals, providing education and training for personnel who design, conduct, and review research, ensuring greater consistency in the reviews undertaken by research ethics committees, and extending processes for advance planning to include prospectively appointing a proxy for research and documenting preferences about research participation. Negative societal and professional attitudes towards the inclusion of adults with impaired capacity in research should also be addressed, and the development of trials that are more person-centred should be encouraged. Further work to conceptualise under-representation in trials for such populations may also be helpful.
Configuration of active site segments in lytic polysaccharide monooxygenases steers oxidative xyloglucan degradation
Authors: Sun Peicheng , Laurent Christophe V. F. P. , Scheiblbrandner Stefan , Frommhagen Matthias , Kouzounis Dimitrios , Sanders Mark G. , van Berkel Willem J. H. , Ludwig Roland , Kabel Mirjam A. 
Published: May 2020

Abstract
Background
Lytic polysaccharide monooxygenases (LPMOs) are powerful enzymes that oxidatively cleave plant cell wall polysaccharides. LPMOs classified as fungal Auxiliary Activities family 9 (AA9) have been mainly studied for their activity towards cellulose; however, various members of this AA9 family have been also shown to oxidatively cleave hemicelluloses, in particularly xyloglucan (XG). So far, it has not been studied in detail how various AA9 LPMOs act in XG degradation, and in particular, how the mode-of-action relates to the structural configuration of these LPMOs.

Results
Two Neurospora crassa (Nc) LPMOs were found to represent different mode-of-action towards XG. Interestingly, the configuration of active site segments of these LPMOs differed as well, with a shorter Segment 1 (−Seg1) and a longer Segment 2 (+Seg2) present in NcLPMO9C and the opposite for NcLPMO9M (+Seg1−Seg2). We confirmed that NcLPMO9C cleaved the non-reducing end of unbranched glucosyl residues within XG via the oxidation of the C4-carbon. In contrast, we found that the oxidative cleavage of the XG backbone by NcLPMO9M occurred next to both unbranched and substituted glucosyl residues. The latter are decorated with xylosyl, xylosyl–galactosyl and xylosyl–galactosyl–fucosyl units. The relationship between active site segments and the mode-of-action of these NcLPMOs was rationalized by a structure-based phylogenetic analysis of fungal AA9 LPMOs. LPMOs with a −Seg1+Seg2 configuration clustered together and appear to have a similar XG substitution-intolerant cleavage pattern. LPMOs with the +Seg1−Seg2 configuration also clustered together and are reported to display a XG substitution-tolerant cleavage pattern. A third cluster contained LPMOs with a −Seg1−Seg2 configuration and no oxidative XG activity.

Conclusions
The detailed characterization of XG degradation products released by LPMOs reveal a correlation between the configuration of active site segments and mode-of-action of LPMOs. In particular, oxidative XG-active LPMOs, which are tolerant and intolerant to XG substitutions are structurally and phylogenetically distinguished from XG-inactive LPMOs. This study contributes to a better understanding of the structure–function relationship of AA9 LPMOs.
Inter-annual variability of the effects of intrinsic and extrinsic drivers affecting West Nile virus vector Culex pipiens population dynamics in northeastern Italy
Authors: Fornasiero Diletta , Mazzucato Matteo , Barbujani Marco , Montarsi Fabrizio , Capelli Gioia , Mulatti Paolo 
Published: May 2020

AbstractBackgroundVector-borne infectious diseases (VBDs) represent a major public health concern worldwide. Among VBDs, West Nile virus (WNV) showed an increasingly wider spread in temperate regions of Europe, including Italy. During the last decade, WNV outbreaks have been recurrently reported in mosquitoes, horses, wild birds, and humans, showing great variability in the temporal and spatial distribution pattern. Due to the complexity of the environment–host–vector–pathogen interaction and the incomplete understanding of the epidemiological pattern of the disease, WNV occurrences can be difficult to predict. The analyses of ecological drivers responsible for the earlier WNV reactivation and transmission are pivotal; in particular, variations in the vector population dynamics may represent a key point of the recent success of WNV and, more in general, of the VBDs.MethodsWe investigated the variations ofCulex pipienspopulation abundance using environmental, climatic and trapping data obtained over nine years (2010 to 2018) through the WNV entomological surveillance programme implemented in northeastern Italy. An information theoretic approach (IT-AICc) and model-averaging algorithms were implemented to examine the relationship between the seasonal mosquito population growth rates and both intrinsic (e.g. intraspecific competition) and extrinsic (e.g. environmental and climatic variables) predictors, to identify the most significant combinations of variables outlining theCx. pipienspopulation dynamics.ResultsPopulation abundance (proxy for intraspecific competition) and length of daylight were the predominant factors regulating the mosquito population dynamics; however, other drivers encompassing environmental and climatic variables also had a significant impact, although sometimes counterintuitive and not univocal. The analyses of the single-year datasets, and the comparison with the results obtained from the overall model (all data available from 2010 to 2018), highlighted remarkable differences in coefficients magnitude, sign and significance. These outcomes indicate that different combinations of factors might have distinctive, and sometimes divergent, effects on mosquito population dynamics.ConclusionsA more realistic acquaintance of the intrinsic and extrinsic mechanisms of mosquito population fluctuations in relation to continuous changes in environmental and climatic conditions is paramount to properly reinforce VBDs risk-based surveillance activities, to plan targeted density control measures and to implement effective early detection programmes.
Neutrophil FcγRIIA availability is associated with disease activity in systemic lupus erythematosus
Authors: Bengtsson Anders A. , Tyden Helena , Lood Christian 
Published: May 2020

Abstract
Background
Immune complexes (ICs) are detectable in a variety of inflammatory diseases, including systemic lupus erythematosus (SLE), reflecting autoantibody binding to antigens. Though ICs are the main contributors to disease pathogenesis through FcγR-mediated inflammation and organ damage, IC levels are not part of the clinical assessment of SLE. The aim of this study was to explore the clinical utility of analyzing levels of ICs in SLE patients using a novel technology, IC-FLOW.

Methods
Paired serum samples, at the time point of high and low disease activity (n = 92), were analyzed using two assays: an IC ELISA from a commercial company and a novel in-house flow cytometry-based method, IC-FLOW. IC-FLOW measures FcγRIIA availability on the neutrophil cell surface by flow cytometry, whereas the commercial ELISA measures IC binding to C1q.

Results
Using IC-FLOW, 90% of SLE patients with active disease had elevated levels of circulating ICs (p < 0.0001). Using the commercial assay, only 17% of SLE patients had elevated levels of circulating ICs. For both assays, levels of ICs reflected active disease as determined by SLEDAI (r = 0.45, p < 0.0001) and were associated with type I IFN activity (r = 0.37, p = 0.001), and complement consumption (p = 0.0002). Levels of ICs measured with IC-FLOW, but not with the commercial ELISA, were associated with active lupus nephritis (p = 0.004).

Conclusions
This novel FcγRIIA-IC assay can detect levels of circulating ICs in patients with SLE. Analyzing IC levels may facilitate monitoring of disease activity, as well as identify patients at risk of lupus nephritis, allowing for early preventive interventions.
A novel 5-Plex qPCR-HRM assay detecting human diarrheal parasites
Authors: Lamien-Meda Aline , Schneider Renate , Walochnik Julia , Auer Herbert , Wiedermann Ursula , Leitsch David 
Published: May 2020

Abstract
Background
Intestinal parasitic diseases occur worldwide, and their diagnosis poses considerable challenges. Cryptosporidium spp., Entamoeba histolytica, Giardia intestinalis, (and, arguably, Dientamoeba fragilis and Blastocystis spp.) are among the most important and common parasitic protozoans causing diarrhea. Several multiplex real-time PCR assays have been developed for the synchronous detection of these parasites. However, most assays include the use of hydrolysis probes, increasing the cost of stool examination. In this study, we designed and evaluated a real-time PCR protocol, based on high-resolution melting (HRM) curve analysis, to simultaneously detect and differentiate five gastrointestinal parasites.

Results
Using a blinded panel of 143 clinical samples with laboratory diagnostic data to evaluate the method, we obtained a 95.8% concordance with conventional methods. Moreover, 4.2% of the samples were positive for D. fragilis and 2.8% additional Cryptosporidium infections were found with our multiplex assay. Our method is sensitive and specific for the selected parasites with the additional possibility of being run in single-plex as a backup control for mixed infections.

Conclusions
The assay is a convenient and cost-effective method that could contribute to a quicker and accurate diagnosis as well as to more targeted therapies of parasite-derived diarrhea. Finally, this new multiplex PCR assay could also be instrumental in epidemiology studies on these parasites.
QSAR-derived affinity fingerprints (part 1): fingerprint construction and modeling performance for similarity searching, bioactivity classification and scaffold hopping
Authors: Škuta C. , Cortés-Ciriano I. , Dehaen W. , Kříž P. , van Westen G. J. P. , Tetko I. V. , Bender A. , Svozil D. 
Published: May 2020

AbstractAn affinity fingerprint is the vector consisting of compound’s affinity or potency against the reference panel of protein targets. Here, we present the QAFFP fingerprint, 440 elements long in silico QSAR-based affinity fingerprint, components of which are predicted by Random Forest regression models trained on bioactivity data from the ChEMBL database. Both real-valued (rv-QAFFP) and binary (b-QAFFP) versions of the QAFFP fingerprint were implemented and their performance in similarity searching, biological activity classification and scaffold hopping was assessed and compared to that of the 1024 bits long Morgan2 fingerprint (the RDKit implementation of the ECFP4 fingerprint). In both similarity searching and biological activity classification, the QAFFP fingerprint yields retrieval rates, measured by AUC (~ 0.65 and ~ 0.70 for similarity searching depending on data sets, and ~ 0.85 for classification) and EF5 (~ 4.67 and ~ 5.82 for similarity searching depending on data sets, and ~ 2.10 for classification), comparable to that of the Morgan2 fingerprint (similarity searching AUC of ~ 0.57 and ~ 0.66, and EF5 of ~ 4.09 and ~ 6.41, depending on data sets, classification AUC of ~ 0.87, and EF5 of ~ 2.16). However, the QAFFP fingerprint outperforms the Morgan2 fingerprint in scaffold hopping as it is able to retrieve 1146 out of existing 1749 scaffolds, while the Morgan2 fingerprint reveals only 864 scaffolds.
Experimental Coxiella burnetii infection in non-pregnant goats and the effect of breeding
Authors: Roest Hendrik I. J. , Dinkla Annemieke , Koets Ad P. , Post Jacob , van Keulen Lucien 
Published: May 2020

AbstractQ fever is a zoonosis caused by the intracellular bacterium Coxiella burnetii. In Europe, small ruminants are the main source of human Q fever. Small ruminant herds can be infectious during several lambing seasons. However, it is not clear how infection is maintained in a herd and what role non-pregnant animals play in the transmission of C. burnetii. We therefore inoculated nulliparous goats with C. burnetii, isolated from the outbreak of Q fever in the Netherlands, to gain a better understanding of the role of non-pregnant goats. Seroconversion and excretion of C. burnetii were monitored after inoculation. To study the effect of breeding on the excretion of C. burnetii, the goats were naturally bred and monitored during gestation and after lambing. Our results indicate that C. burnetii infection prior to breeding did not result in infection of the placenta nor did it affect the gestation length or the number of kids born. However, one of the ten does did excrete C. burnetii in the colostrum post-partum and the bacterium was detected in the mammary gland and associated lymph nodes at necropsy. This result indicates that non-pregnant goats might play a role in maintaining Q fever in a goat herd as persistent carriers of infection.
Prevalence, the antibiogram and the frequency of virulence genes of the most predominant bacterial pathogens incriminated in calf pneumonia
Authors: Algammal Abdelazeem M. , El-Sayed Mahmoud E. , Youssef Fatma M. , Saad Shefaa A. , Elhaig Mahmoud M. , Batiha Gaber E. , Hozzein Wael N. , Ghobashy Madeha O. I. 
Published: May 2020

AbstractThe purpose of this study was to investigate the prevalence, antibiotic resistance and certain virulence genes of the most predominant bacterial pathogens causing BRD. A total of 225 calves; 55 apparently healthy and 170 diseased; were sampled. Bacteriological examination, antimicrobial susceptibility testing and PCR based detection of some virulence genes were performed. In addition, the serotyping of E. coli was performed using the slide agglutination test. The most predominant bacterial pathogens retrieved from apparently healthy calves were E. coli (16.4%) and S. aureus (10.9%), and in pneumonic calves were E. coli (23.5%), P. vulgaris (12.4%) and S. aureus (11.8%). The most prevalent virulence gene in E. coli was the fimH gene (100%), followed by eaeA gene (24.5%) and hly gene (20.4%). All the examined S. aureus strains harbored spa and coa genes; likewise, all P. multocida strains harbored toxA gene. The majority of the isolated strains displayed remarkable sensitivity to norfloxacin and enrofloxacin; furthermore, the retrieved E. coli strains exhibited multidrug-resistance to gentamicin, erythromycin, streptomycin and trimethoprim-sulphamethoxazole, in addition, the isolated S. aureus and P. aeruginosa strains showed multidrug-resistance to amoxicillin, ampicillin and tetracycline. E. coli serogroups including O18, O143, O1, and O6 were retrieved from pneumonic calves as the first report in Egypt. In conclusion, the synergism between the conventional and genotypic analysis is an effective gadget for the characterization of bacterial pathogens causing BRD. Continuous surveillance of antimicrobial susceptibility is essential to select the drug of choice due to the development of multidrug-resistant strains.
An improved urban cellular automata model by using the trend-adjusted neighborhood
Authors: Li Xuecao , Zhou Yuyu , Chen Wei 
Published: May 2020

Abstract
Background
Cellular automata (CA)-based models have been extensively used in urban sprawl modeling. Presently, most studies focused on the improvement of spatial representation in the modeling, with limited efforts for considering the temporal context of urban sprawl. In this paper, we developed a Logistic-Trend-CA model by proposing a trend-adjusted neighborhood as a weighting factor using the information of historical urban sprawl and integrating this factor in the commonly used Logistic-CA model. We applied the developed model in the Beijing-Tianjin-Hebei region of China and analyzed the model performance to the start year, the suitability surface, and the neighborhood size.

Results
Our results indicate the proposed Logistic-Trend-CA model outperforms the traditional Logistic-CA model significantly, resulting in about 18% and 14% improvements in modeling urban sprawl at medium (1 km) and fine (30 m) resolutions, respectively. The proposed Logistic-Trend-CA model is more suitable for urban sprawl modeling over a long temporal interval than the traditional Logistic-CA model. In addition, this new model is not sensitive to the suitability surface calibrated from different periods and spaces, and its performance decreases with the increase of the neighborhood size.

Conclusion
The proposed model shows potential for modeling future urban sprawl spanning a long period at regional and global scales.
Psychological status and behavior changes of the public during the COVID-19 epidemic in China
Authors: Liu Xi , Luo Wen-Tao , Li Ying , Li Chun-Na , Hong Zhong-Si , Chen Hui-Li , Xiao Fei , Xia Jin-Yu 
Published: May 2020

Abstract
Background
A cluster of pneumonia cases were reported by Wuhan Municipal Health Commission, China in December 2019. A novel coronavirus was eventually identified, and became the COVID-19 epidemic that affected public health and life. We investigated the psychological status and behavior changes of the general public in China from January 30 to February 3, 2020.

Methods
Respondents were recruited via social media (WeChat) and completed an online questionnaire. We used the State-Trait Anxiety Inventory, Self-rating Depression Scale, and Symptom Checklist-90 to evaluate psychological status. We also investigated respondents’ behavior changes. Quantitative data were analyzed by t-tests or analysis of variance, and classified data were analyzed with chi-square tests.

Results
In total, 608 valid questionnaires were obtained. More respondents had state anxiety than trait anxiety (15.8% vs 4.0%). Depression was found among 27.1% of respondents and 7.7% had psychological abnormalities. About 10.1% of respondents suffered from phobia. Our analysis of the relationship between subgroup characteristics and psychological status showed that age, gender, knowledge about COVID-19, degree of worry about epidemiological infection, and confidence about overcoming the outbreak significantly influenced psychological status. Around 93.3% of respondents avoided going to public places and almost all respondents reduced Spring Festival-related activities. At least 70.9% of respondents chose to take three or more preventive measures to avoid infection. The three most commonly used prevention measures were making fewer trips outside and avoiding contact (98.0%), wearing a mask (83.7%), and hand hygiene (82.4%).

Conclusions
We need to pay more attention to public psychological stress, especially among young people, as they are likely to experience anxiety, depression, and psychological abnormalities. Different psychological interventions could be formulated according to the psychological characteristics of different gender and age groups. The majority of respondents followed specific behaviors required by the authorities, but it will take time to observe the effects of these behaviors on the epidemic.
Humanized tau antibodies promote tau uptake by human microglia without any increase of inflammation
Authors: Zilkova Monika , Nolle Anna , Kovacech Branislav , Kontsekova Eva , Weisova Petronela , Filipcik Peter , Skrabana Rostislav , Prcina Michal , Hromadka Tomas , Cehlar Ondrej , Rolkova Gabriela Paulikova , Maderova Denisa , Novak Michal , Zilka Norbert , Hoozemans Jeroen J. M. 
Published: May 2020

AbstractImmunotherapies targeting pathological tau have recently emerged as a promising approach for treatment of neurodegenerative disorders. We have previously showed that the mouse antibody DC8E8 discriminates between healthy and pathological tau, reduces tau pathology in murine tauopathy models and inhibits neuronal internalization of AD tau species in vitro.Here we show, that DC8E8 and antibodies elicited against the first-in-man tau vaccine, AADvac1, which is based on the DC8E8 epitope peptide, both promote uptake of pathological tau by mouse primary microglia. IgG1 and IgG4 isotypes of AX004, the humanized versions of DC8E8, accelerate tau uptake by human primary microglia isolated from post-mortem aged and diseased brains. This promoting activity requires the presence of the Fc-domain of the antibodies.The IgG1 isotype of AX004 showed greater ability to promote tau uptake compared to the IgG4 isotype, while none of the antibody-tau complexes provoked increased pro-inflammatory activity of microglia. Our data suggest that IgG1 has better suitability for therapeutic development.
Fungal pretreatment of lignocellulosic biomass for the production of plant hormone by Pichia fermentans under submerged conditions
Authors: Giri Rajat , Sharma Rakesh Kumar 
Published: May 2020

AbstractThe study was designed to evaluate the production of auxin by eukaryotic unicellular organism Pichia fermentans. Different media formulations were used for the production of indole-3-acetic acid (IAA) under broth and submerged conditions. Wheat straw-based production medium was formulated and optimized using statistical approach. The IAA production was significantly enhanced by nine folds, when the wheat straw was pretreated with Phanerochaete chrysosporium (150 µg/ml) as compared to untreated wheat straw (16.44 µg/ml). Partial purification of IAA was carried out by silica gel column chromatography and further confirmed by high-performance liquid chromatography. Exogenous application of crude and partially purified IAA positively influenced the Vigna radiata seedling growth. The number of lateral roots in the growing seedlings was significantly higher as compared to the control seeds. Thus, the present findings point towards an efficient production of plant hormone by yeast and white rot fungus using abundantly available wheat straw, which may lead to the development of cost-effective production of such metabolites and their further use in agricultural field to reduce the negative impact of chemical fertilizers.