bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cloning, expression and enzyme activity delineation of two novel CANT1 mutations: the disappearance of dimerization may indicate the change of protein conformation and even function
Authors: Wang Hong-Dan , Guo Liang-Jie , Feng Zhan-Qi , Zhang Da-Wei , Zhang Meng-Ting , Gao Yue , Chen Chuan-Liang , Zhu Bo-Feng 
Published: September 2020

Abstract
Background
Desbuquois dysplasia (DBQD) was a rare autosomal recessive skeletal dysplasia. Calcium activated nucleotidase 1 (CANT1) mutation was identified as a common pathogenic change for DBQD type 1 and Kim variant but not for DBQD type 2. To our knowledge, all patients with DBQD type 1 currently found could be explained by mutations in the CANT1 gene, but mutations in the CANT1 gene might not be directly diagnosed as DBQD type 1.

Results
We have identified two novel CANT1 mutations (mut1: c.594G > A [p.Trp198*], mut2: c.734C > T [p.Pro245Leu]) in three children from a family of Chinese origin for the first time. Two of the three children could be diagnosed as typical DBQD type 1 and one child could not be diagnosed as DBQD type 1 based on the clinical data we had. To further clarify the effect of the two mutations of the CANT1 gene, we studied the CANT1 gene expression and detected the protein secretion and nucleotide enzyme activity through cDNA cloning and expression vectors construction for wild and mutant types. The mut1 was a nonsense mutation which could lead to premature termination and produced the truncated bodies; The CANT1 dimer of mut2 was significantly reduced and even undetectable. The extracellular secretion of mut1 was extremely high while mut2 was significantly reduced compared with the wild type. And mut1 and mut2 also could result in a significant reduction in the activity of CANT1 nucleotidease. From the results we could deduce that the two mutations of the CANT1 gene were the causes of the two cases in this study.

Conclusions
Regarding the particularity of the cases reported in this study, the pathogenesis of CANT1 might be more complicated. The genetic and phenotype of three children with the same genetic background need to be further studied. Larger cohort of patients was needed to establish genotype–phenotype correlations in DBQD.
The first RT-qPCR confirmed case of tick-borne encephalitis in a dog in Scandinavia
Authors: Andersson Elina , Kendall Anna , Url Angelika , Auer Angelika , Leschnik Michael 
Published: September 2020

Abstract
Background
Tick-borne encephalitis (TBE) is a zoonotic neurological disease caused by tick-borne encephalitis virus (TBEV), a flavivirus endemic in parts of Europe and Asia. Seroconversion without signs of clinical disease is common in dogs and most of the cases previously described have been tentatively diagnosed by combining neurologic signs with serum antibody titres. Here, the first Scandinavian RT-qPCR-confirmed clinical case of TBE in a dog is reported.

Case presentation
A 4-year old castrated male Pointer Labrador cross was presented with acute-onset ataxia. During hospitalisation, the dog developed seizures. Despite aggressive treatment with steroids, antimicrobials and sedation/anaesthesia, there was continued deterioration during the following 24 h after admission and the dog was euthanised and submitted for necropsy. Histopathological changes in the brain were consistent with lymphoplasmacytic and histiocytic meningoencephalomyelitis. RT-qPCR examination of the brain was positive for TBEV, confirming infection.

Conclusions
Meningoencephalomyelitis caused by TBEV should be a diagnostic consideration in dogs presenting with clinical signs of central nervous system disease such as acute-onset ataxia and seizures in areas where TBEV-positive ticks are endemic. Clinical TBE may be underdiagnosed in dogs due to lack of specific testing.
Ocular ultrasonography of sea turtles
Authors: Muramoto Caterina , Cardoso-Brito Vinícius , Raposo Ana Cláudia , Pires Thais Torres , Oriá Arianne Pontes 
Published: September 2020

Abstract
Background
Environmental changes contribute to the development of ophthalmic diseases in sea turtles, but information on their eye biometrics is scarce. The aim of this study was to describe ophthalmic ultrasonographic features of four different sea turtle species; Caretta caretta (Loggerhead turtle; n = 10), Chelonia mydas (Green turtle; n = 8), Eretmochelys imbricata (Hawksbill turtle; n = 8) and Lepidochelys olivacea (Olive ridley; n = 6) under human care. Corneal thickness, scleral ossicle width and thickness, anterior chamber depth, axial length of the lens, vitreous chamber depth and axial globe length were measured by B-mode sonography with a linear transducer. Carapace size and animal weight were recorded. A sonographic description of the eye structures was established.

Results
The four species presented an ovate eyeball, a relatively thin cornea, and a small-sized lens positioned rostrally in the eye bulb, near the cornea, resulting in a shallow anterior chamber. The scleral ossicles did not prevent the evaluation of intraocular structures, even with a rotated eye or closed eyelids; image formation beyond the ossicles and measurements of all proposed structures were possible. B-mode sonography was easily performed in all animals studied. The sonographic characteristics of the eye were similar among the four species. Since there was a correlation between the size of the eye structures and the size of the individual, especially its carapace size, the differences found between E. imbricata and Caretta caretta are believed to be due to their overall difference in size.

Conclusions
Sonography is a valuable tool in ophthalmic evaluation of these species. Only minor differences were found between the species in this study, reinforcing their phylogenetic proximity and their similar functions and habitats.
Addressing COVID-19 in humanitarian settings: a call to action
Authors: Alawa Jude , Alawa Nawara , Coutts Adam , Sullivan Richard , Khoshnood Kaveh , Fouad Fouad M. 
Published: September 2020

AbstractRefugees and internally displaced persons in humanitarian settings are particularly susceptible to the spread of infectious illnesses such as COVID-19 due to overcrowding and inadequate access to clean water, sanitation, and hygiene facilities. Countries facing conflict or humanitarian emergencies often have damaged or fragmented health systems and little to no capacity to test, isolate, and treat COVID-19 cases. Without a plan to address COVID-19 in humanitarian settings, host governments, aid agencies, and international organizations risk prolonging the spread of the virus across borders, threatening global health security, and devastating vulnerable populations. Stakeholders must coordinate a multifaceted response to address COVID-19 in humanitarian settings that incorporates appropriate communication of risks, sets forth resource-stratified guidelines for the use of limited testing, provides resources to treat affected patients, and engages displaced populations.
Evolution and current state of global research on paediatric resuscitation: a systematic scientometric analysis
Authors: Scholz Sean S. , Borgstedt Rainer , Menzel Leoni C. , Rehberg Sebastian , Jansen Gerrit 
Published: September 2020

Abstract
Background
Paediatric resuscitation is rare but potentially associated with maximal lifetime reduction. Notably, several nations experience high infant mortality rates even today. To improve clinical outcomes and promote research, detailed analyses on evolution and current state of research on paediatric resuscitation are necessary.

Methods
Research on paediatric resuscitation published in-between 1900 and 2019 were searched using Web of Science. Metadata were extracted and analyzed based on the science performance evaluation (SciPE) protocol. Research performance was evaluated regarding quality and quantity over time, including comparisons to adult resuscitation. National research performance was related to population, financial capacities, infant mortality rate, collaborations, and authors’ gender.

Results
Similar to adult resuscitation, research performance on paediatric resuscitation grew exponentially with most original articles being published during the last decade (1106/1896). The absolute number, however, is only 14% compared to adults. The United States dominate global research by contributing the highest number of articles (777), Hirsch-Index (70), and citations (18,863). The most productive collaboration was between the United States and Canada (52). When considering nation’s population and gross domestic product (GDP) rate, Norway is leading regarding population per article (62,467), per Hirsch-Index (223,841), per citation (2226), and per GDP (2.3E-04). Regarding publications per infant mortality rate, efforts of India and Brazil are remarkable. Out of the 100 most frequently publishing researchers, 25% were female.

Conclusion
Research efforts on paediatric resuscitation have increased but remain underrepresented. Specifically, nations with high infant mortality rates should be integrated by collaborations. Additional efforts are required to overcome gender disparities.
Primo: integration of multiple GWAS and omics QTL summary statistics for elucidation of molecular mechanisms of trait-associated SNPs and detection of pleiotropy in complex traits
Authors: Gleason Kevin J. , Yang Fan , Pierce Brandon L. , He Xin , Chen Lin S. 
Published: September 2020

AbstractTo provide a comprehensive mechanistic interpretation of how known trait-associated SNPs affect complex traits, we propose a method, Primo, for integrative analysis of GWAS summary statistics with multiple sets of omics QTL summary statistics from different cellular conditions or studies. Primo examines association patterns of SNPs to complex and omics traits. In gene regions harboring known susceptibility loci, Primo performs conditional association analysis to account for linkage disequilibrium. Primo allows for unknown study heterogeneity and sample correlations. We show two applications using Primo to examine the molecular mechanisms of known susceptibility loci and to detect and interpret pleiotropic effects.
High levels of third-stage larvae (L3) overwinter survival for multiple cattle gastrointestinal nematode species on western Canadian pastures as revealed by ITS2 rDNA metabarcoding
Authors: Wang Tong , Avramenko Russell W. , Redman Elizabeth M. , Wit Janneke , Gilleard John S. , Colwell Douglas D. 
Published: September 2020

Abstract
Background
The ability of infective larvae of cattle gastrointestinal nematode (GIN) species to overwinter on pastures in northerly climatic zones with very cold dry winters is poorly understood. This is an important knowledge gap with critical implications for parasite risk assessment and control.

Methods
Infective third-stage larvae (L3) were quantified in samples of fecal pats, together with adjacent grass and soil, before and after winter on three farms in southern, central and northern Alberta. Nemabiome ITS2 metabarcoding was then performed on the harvested L3 populations to determine the species composition. Finally, parasite-free tracer calves were used to investigate if the L3 surviving the winter could infect calves and develop to adult worms in spring.

Results
Farm level monitoring, using solar powered weather stations, revealed that ground temperatures were consistently higher, and less variable, than the air temperatures; minimum winter air and ground temperatures were − 32.5 °C and − 24.7 °C respectively. In spite of the extremely low minimum temperatures reached, L3 were recovered from fecal pats and grass before and after winter with only a 38% and 61% overall reduction over the winter, respectively. Nemabiome ITS2 metabarcoding assay revealed that the proportion of L3 surviving the winter was high for both Cooperia oncophora and Ostertagia ostertagi although survival of the former species was statistically significantly higher than the latter. Nematodirus helvetinaus and Trichostrongylus axei could be detected after winter whereas Haemonchus placei L3 could not overwinter at all. Adult C. oncophora, O. ostertagi and N. helvetianus could be recovered from tracer calves grazing after the winter.

Conclusions
The largest proportion of L3 were recovered from fecal pats suggesting this is important refuge for L3 survival. Results also show that L3 of several GIN parasite species can survive relatively efficiently on pastures even in the extreme winter conditions in western Canada. Tracer calf experiments confirmed that overwintered L3 of both C. oncophora and O. ostertagi were capable of establishing a patent infection in the following spring. These results have important implications for the epidemiology, risk of production impact and the design of effective control strategies. The work also illustrates the value of applying ITS2 nemabiome metabarcoding to environmental samples.
Spatial risk analysis for the introduction and circulation of six arboviruses in the Netherlands
Authors: Esser Helen Joan , Liefting Yorick , Ibáñez-Justicia Adolfo , van der Jeugd Henk , van Turnhout Chris A. M. , Stroo Arjan , Reusken Chantal B. E. M. , Koopmans Marion P. G. , de Boer Willem Fred 
Published: September 2020

AbstractBackgroundArboviruses are a growing public health concern in Europe, with both endemic and exotic arboviruses expected to spread further into novel areas in the next decades. Predicting where future outbreaks will occur is a major challenge, particularly for regions where these arboviruses are not endemic. Spatial modelling of ecological risk factors for arbovirus circulation can help identify areas of potential emergence. Moreover, combining hazard maps of different arboviruses may facilitate a cost-efficient, targeted multiplex-surveillance strategy in areas where virus transmission is most likely. Here, we developed predictive hazard maps for the introduction and/or establishment of six arboviruses that were previously prioritized for the Netherlands: West Nile virus, Japanese encephalitis virus, Rift Valley fever virus, tick-borne encephalitis virus, louping-ill virus and Crimean-Congo haemorrhagic fever virus.MethodsOur spatial model included ecological risk factors that were identified as relevant for these arboviruses by an earlier systematic review, including abiotic conditions, vector abundance, and host availability. We used geographic information system (GIS)-based tools and geostatistical analyses to model spatially continuous datasets on these risk factors to identify regions in the Netherlands with suitable ecological conditions for arbovirus introduction and establishment.ResultsThe resulting hazard maps show that there is spatial clustering of areas with either a relatively low or relatively high environmental suitability for arbovirus circulation. Moreover, there was some overlap in high-hazard areas for virus introduction and/or establishment, particularly in the southern part of the country.ConclusionsThe similarities in environmental suitability for some of the arboviruses provide opportunities for targeted sampling of vectors and/or sentinel hosts in these potential hotspots of emergence, thereby increasing the efficient use of limited resources for surveillance.
Secukinumab leads to shifts from stage-based towards response-based disease clusters—comparative data from very early and established psoriatic arthritis
Authors: Kampylafka Eleni , Tascilar Koray , Lerchen Veronika , Linz Christina , Sokolova Maria , Zekovic Ana , Kleyer Arnd , Simon David , Rech Jürgen , Sticherling Michael , Schett Georg , Hueber Axel J. 
Published: September 2020

Abstract
Background
Limited information exists about the very early forms of psoriatic arthritis. In particular, differences and responsiveness of patient-reported outcomes (PROs) in very early as compared to established PsA have not been investigated to date.

Methods
Cross-sectional and prospective longitudinal evaluation of PROs related to pain (VAS), physical function (HAQ-DI, SF-36 physical), mental function (SF-36 mental), impact of psoriatic skin (DLQI), joint (PsAID), and global disease (VAS) in two small prospective observational studies on secukinumab 300 mg over 6 months in very early disease patients (IVEPSA study, N = 20) and established PsA (PSARTROS study, N = 20). Cluster analysis was performed at baseline and 24-weeks of follow-up.

Results
While responses in pain and physical activity-related PROs to secukinumab were more pronounced in established PsA than a very early disease, effects on PROs related to general health perception, as well as those related to emotional and mental well-being, were modified in a similar way in very early disease and established PsA. Cluster analysis based on global disease activity and PROs showed that baseline clusters reflected very early disease and established PsA, while after secukinumab treatment these clusters were abolished and new clusters based on differential responses to physically and mentally oriented PROs formed.

Conclusions
Inhibition of IL-17A by secukinumab leads to comprehensive improvement of general health perception and mental well-being in very early and established PsA, while overall responses in pain and physical activity are more pronounced in established disease. Most importantly, treatment restructures the original patients’ clusters based on disease stage and leads to the formation of new clusters that reflect their response in physical and mental-orientated PROs.

Trial registration
NCT02483234, registered 26 June 2015, retrospectively registered.
The prevalence and impact of comorbidities on patients with axial spondyloarthritis: results from a nationwide population-based study
Authors: Redeker Imke , Callhoff Johanna , Hoffmann Falk , Marschall Ursula , Haibel Hildrun , Sieper Joachim , Zink Angela , Poddubnyy Denis 
Published: September 2020

Abstract
Background
In contrast to other chronic rheumatic musculoskeletal diseases such as rheumatoid arthritis, comorbidities in axial spondyloarthritis (axSpA) and their impact on disease outcomes are less well studied. The aim of this study was to investigate the prevalence of comorbidities and their association with disease activity and functional impairment in a large population-based cohort of patients with axSpA.

Methods
A random sample of patients with axSpA, stratified by age and sex, was drawn from health insurance data. Patients in the sample received a survey on demographic, socioeconomic, and disease-related parameters. Comorbidities were defined using the Elixhauser coding algorithms excluding rheumatoid arthritis/collagen vascular diseases and including osteoporosis and fibromyalgia, resulting in a set of 32 comorbidities. The prevalence of comorbidities in the axSpA patients and their pharmacological treatment were examined. Multivariable linear regression models were calculated to determine the association of comorbidities with disease activity and functional status.

Results
A total of 1776 axSpA patients were included in the analyses (response, 47%; mean age, 56 years; 46% female). The most prevalent comorbidities were hypertension, depression, and chronic pulmonary disorders. The number of comorbidities was significantly associated with both the BASDAI and BASFI: β (95% CI) = 0.17 (0.09–0.24) and 0.24 (0.15–0.32), respectively. When analysed separately, hypertension, depression, and chronic pulmonary disease were comorbidities with a significant and independent association with BASFI, while for BASDAI, such an association was found for depression and chronic pulmonary disease only.

Conclusions
Comorbidities are common in axSpA patients and are associated with higher disease activity and higher levels of functional impairment. Higher disease activity and higher levels of functional impairment might be indicators of severe disease resulting in the development of comorbidities.
Inflammatory potential of diet and risk of incident knee osteoarthritis: a prospective cohort study
Authors: Liu Qiang , Hebert James R. , Shivappa Nitin , Guo Jianjun , Tao Ke , Zeng Chao , Lei Guanghua , Lin Jianhao , Zhang Yuqing 
Published: September 2020

AbstractBackgroundTo examine the relation between inflammatory potential of diet and incident knee osteoarthritis (OA) and the role of BMI in the association of interest.MethodsIn the Osteoarthritis Initiative, the energy-adjusted dietary inflammatory index (E-DII™) scores were calculated based on the Block Brief 2000 Food Frequency Questionnaire and categorized into sex-specific quartiles. Outcomes were incident (1) radiographic knee OA (ROA) (i.e., a KL grade ≥ 2) and (2) symptomatic knee OA (SxOA) (i.e., a combination of frequent knee pain and ROA). We fitted generalized estimating equation models to examine the association between E-DII scores and incident knee OA. We performed mediation analyses to assess the potential mediation by BMI in the DII-OA relation.ResultsOver a 48-month follow-up period, 232 and 978 knees developed ROA and SxOA, respectively. Compared with the lowest (most anti-inflammatory) E-DII quartile, the odds ratio (OR) of incident ROA for the highest (most pro-inflammatory) E-DII quartile was 1.73 (95% confidence interval (CI) 1.15 to 2.62,Ptrend = 0.007). The corresponding OR for SxOA was 1.43 (95% CI 1.16 to 1.76,Ptrend = 0.001). The DII-OA association was significantly mediated via BMI with an indirect effect of 1.08 (95% CI 1.04, 1.13) for ROA and 1.13 (95% CI 1.09, 1.16) for SxOA, accounting for 20.4% and 44.5% of the total effect, respectively.ConclusionsA higher inflammatory potential of diet increased the risk of knee OA. The association was significantly mediated via BMI. Targeting the inflammatory potential of diet may be beneficial to reduce the risk of knee OA.