bluuebunny/crossref_metadata_2025 huggingface dataset:
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

To 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.
Correction to: Intra-cluster correlation coefficients in primary care patients with type 2 diabetes and hypertension
Authors: Lee Yi Lin , Lim Yvonne Mei Fong , Law Kian Boon , Sivasampu Sheamini
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
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

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

Background

Arboviruses 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.

Methods

Our 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.

Results

The 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.

Conclusions

The 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

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

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

Background

To examine the relation between inflammatory potential of diet and incident knee osteoarthritis (OA) and the role of BMI in the association of interest.

Methods

In 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.

Results

Over 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.

Conclusions

A 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.
Tocilizumab may slow radiographic progression in patients with systemic or polyarticular-course juvenile idiopathic arthritis: post hoc radiographic analysis from two randomized controlled trials
Authors: Malattia Clara , Ruperto Nicolino , Pederzoli Silvia , Palmisani Elena , Pistorio Angela , Wouters Carine , Dolezalova Pavla , Flato Berit , Garay Stella , Giancane Gabriella , Wells Chris , Douglass Wendy , Brunner Hermine I. , De Benedetti Fabrizio , Ravelli Angelo ,   for the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)
Published: September 2020

Background

Few clinical trials have investigated the prevention of radiographic progression in children with juvenile idiopathic arthritis treated with antirheumatic drugs. This study aimed to investigate radiographic progression in patients with systemic juvenile idiopathic arthritis (sJIA) and patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with the anti–interleukin-6 receptor antibody tocilizumab for 2 years in the TENDER and CHERISH randomized controlled trials, respectively.

Methods

Standard radiographs of both wrists and both hands in the posteroanterior view were obtained within 4 weeks of baseline and were repeated at weeks 52 ± 4 and 104 ± 4 in both trials. All films were scored by two independent readers using the adapted Sharp–van der Heijde (aSH) and Poznanski scoring methods. Although the Poznanski score indicates bone growth limitation or cartilage growth decrease, which are not the same as joint space narrowing in rheumatoid arthritis, its change reflects damage to cartilage. Therefore, impairment in the Poznanski score as well as the aSH score was considered as a measure of structural joint damage. Radiographic progression was defined as worsening of radiographic scores beyond the smallest detectable difference.

Results

Poznanski and aSH scores were available at baseline and at one or more postbaseline time points for 33 and 47 of 112 sJIA patients and 61 and 87 of 188 pcJIA patients, respectively, providing a representative subset of the study populations. The inter-reader and intra-reader agreement intra-class correlation coefficient was > 0.8. Median baseline Poznanski and aSH scores, respectively, were − 2.4 and 24.6 for sJIA patients and − 1.5 and 8.0 for pcJIA patients. Compared with baseline, aSH scores remained stable for all sJIA patients at week 52, whereas 9.4% of sJIA patients had radiographic progression according to Poznanski scores at week 52; at 104 weeks, radiographic progression according to aSH and Poznanski scores was observed in 5.4% and 11.5%, respectively. In pcJIA patients, radiographic progression from baseline at 52 weeks and at 104 weeks was 12.5% and 2.9%, respectively, using aSH scoring and 6.5% and 4%, respectively, using Poznanski scoring.

Conclusion

Tocilizumab may delay radiographic progression in children with sJIA and children with pcJIA.

Trial registration

Trial registration numbers and dates: TENDER, NCT00642460 (March 19, 2008); CHERISH, NCT00988221 (October 1, 2009)
Genetic relatedness of the Enterococcus faecalis isolates in stool and urine samples of patients with community-acquired urinary tract infection
Authors: Ghalavand Zohreh , Alebouyeh Masoud , Ghanati Kiandokht , Azimi Leila , Rashidan Marjan
Published: September 2020

Background

Community-acquired urinary tract infection (CA-UTI) could be caused by endogenous or exogenous routes. To show this relationship, we investigated molecular fingerprints and genotypes of paired Enterococcus faecalis isolated from the urine of symptomatic patients and their fecal samples.

Results

Out of the studied patients, 63 pairs of E. faecalis isolates were obtained simultaneously from their urine and feces samples. All the strains were sensitive to vancomycin, linezolid, nitrofurantoin, and daptomycin (MIC value: ≤ 4 µg/ml), while resistance to tetracycline (urine: 88.9%; stool: 76.2%) and minocycline (urine: 87.3%, stool: 71.4%) was detected in most of them. The most common detected virulence genes were included efbA, ace, and gelE. RAPD-PCR and PFGE analyses showed the same patterns of molecular fingerprints between paired of the isolates in 26.9% and 15.8% of the patients, respectively.

Conclusions

Similarity of E. faecalis strains between the urine and feces samples confirmed the occurrence of endogenous infection via contamination with colonized bacteria in the intestinal tract. Carriage of a complete virulence genotype in the responsible strains was statistically in correlation with endogenous UTI, which shows their possible involvement in pathogenicity of uropathogenic E. faecalis strains.
Annotated genome sequences of the carnivorous plant Roridula gorgonias and a non-carnivorous relative, Clethra arborea
Authors: Hartmann Stefanie , Preick Michaela , Abelt Silke , Scheffel André , Hofreiter Michael
Published: September 2020

Objective

Plant carnivory is distributed across the tree of life and has evolved at least six times independently, but sequenced and annotated nuclear genomes of carnivorous plants are currently lacking. We have sequenced and structurally annotated the nuclear genome of the carnivorous Roridula gorgonias and that of a non-carnivorous relative, Madeira’s lily-of-the-valley-tree, Clethra arborea, both within the Ericales. This data adds an important resource to study the evolutionary genetics of plant carnivory across angiosperm lineages and also for functional and systematic aspects of plants within the Ericales.

Results

Our assemblies have total lengths of 284 Mbp (R. gorgonias) and 511 Mbp (C. arborea) and show high BUSCO scores of 84.2% and 89.5%, respectively. We used their predicted genes together with publicly available data from other Ericales’ genomes and transcriptomes to assemble a phylogenomic data set for the inference of a species tree. However, groups of orthologs showed a marked absence of species represented by a transcriptome. We discuss possible reasons and caution against combining predicted genes from genome- and transriptome-based assemblies.
Altered vaginal microbiome and relative co-abundance network in pregnant women with penicillin allergy
Authors: Li Xiaohua , Luo Jun , Nie Chuan , Li Qingxia , Sun Xiaofeng , Li Hongping , Zhang Yong
Published: September 2020

Background

Penicillin allergy is frequently reported in adults and children. Recent studies suggest that microbiota plays a key role in the development and progression of allergy. In this study, the relationship between vaginal microbiome and pregnant women with penicillin allergy was investigated.

Methods

Vaginal samples before labor from 12 pregnant women with penicillin allergy and 15 non-allergic pregnant women were collected. Bacterial community structure of all study subjects and the discrepancies between the two groups were analyzed using 16S rRNA sequencing based on Illumina Hiseq 2500 platform.

Results

The abundant phyla among all participants were Firmicutes, Actinobacteria and Bacteroidetes. The predominant genus was Lactobacillus. Compared to non-allergic pregnant women, Actinobacteria, Coriobacteriaceae, Lachnospiraceae, Paraprevotella and Anoxybacillus significantly decreased, whereas Deltaproteobacteria, Peptostreptococcaceae, Enterococcus and Megamonas were more abundant in penicillin allergic women. Additionally, obvious discrepancies were observed in the co-abundance network at the genus level between the two groups.

Conclusions

There were differences in the microbial community structure and composition of reproduction tract between penicillin allergic and non-allergic pregnant women. These shifts may be related to maternal and neonatal health.
Pericardial effusion and cardiac tamponade requiring pericardial window in an otherwise healthy 30-year-old patient with COVID-19: a case report
Authors: Walker Christina , Peyko Vincent , Farrell Charles , Awad-Spirtos Jeanine , Adamo Matthew , Scrocco John
Published: September 2020

Background

This case report demonstrates pericardial effusion, acute pericarditis, and cardiac tamponade in an otherwise healthy woman who had a positive test result for coronavirus disease 2019. Few case reports have been documented on patients with this presentation, and it is important to share novel presentations of the disease as they are discovered.

Case presentation

A Caucasian patient with coronavirus disease 2019 returned to the emergency department of our hospital 2 days after her initial visit with worsening chest pain and shortness of breath. Imaging revealed new pericardial effusion since the previous visit. The patient became hypotensive, was taken for pericardial window for cardiac tamponade with a drain placed, and was treated for acute pericarditis.

Conclusion

Much is still unknown about the implications of coronavirus disease 2019. With the novel coronavirus disease 2019 pandemic, research is still in process, and we are slowly learning about new signs and symptoms of the disease. This case report documents a lesser-known presentation of a patient with coronavirus disease 2019 and will help to further understanding of a rare presentation.
Global cerebral infarction after aortic arch replacement surgery in a patient with postoperatively revealed factor XII deficiency: a case report
Authors: Yoshida Keisuke , Tanaka Shiori , Sato Yuki , Watanabe Kazuhiro , Muramatsu Kenichi , Murakawa Masahiro
Published: September 2020

Background

This case report presents a case of a patient with global cerebral infarction of uncertain etiology following an emergency surgery for acute type A aortic dissection. As a result, factor XII deficiency was revealed postoperatively. To date, there have been several reports of cardiovascular surgery in patients with factor XII deficiency. However, all previous reports were of patients whose factor XII deficiency had been detected preoperatively; therefore, before this, there had been no reports of complications associated with factor XII deficiency following cardiovascular surgery.

Case presentation

We report a case of emergency aortic arch replacement surgery for acute type A aortic dissection in a 57-year-old Japanese man. A blood test prior to the surgery showed coagulopathy, a platelet count of 117 × 109/L, a prothrombin time–international normalized ratio of 1.78, an activated partial thromboplastin time of 69.7 seconds, and fibrinogen < 50 mg/dl. A smaller-than-usual dose of heparin (8000 IU) was administered because the patient’s activated clotting time was extremely prolonged (> 999 seconds). After the heparin administration, the activated clotting time, measured every 30–60 minutes, remained unchanged (> 999 seconds); therefore, additional heparin was not administered during the surgery, and there was no clinical problem during cardiopulmonary bypass. However, a diagnosis of global cerebral infarction was made on the first postoperative day. An additional blood coagulation test performed on postoperative day 9 revealed factor XII deficiency (8.0%). Regarding the reason that global cerebral infarction occurred in the present case, two reasons were considered: One was factor XII deficiency itself, and the other was low-dose heparin administration during the cardiopulmonary bypass due to excessively prolonged activated clotting time caused by factor XII deficiency.

Conclusions

Factor XII deficiency should be considered in patients with prolonged activated clotting time and spontaneous thrombosis in vascular surgeries. Moreover, the present case emphasizes that management of heparin during cardiopulmonary bypass should not be performed on the basis of activated clotting time monitoring alone, especially in a case with prolonged activated clotting time.
Association between fetal sex and maternal plasma microRNA responses to prenatal alcohol exposure: evidence from a birth outcome-stratified cohort
Authors: Salem Nihal A. , Mahnke Amanda H. , Wells Alan B. , Tseng Alexander M. , Yevtushok Lyubov , Zymak-Zakutnya Natalya , Wertlecki Wladimir , Chambers Christina D. , Miranda Rajesh C. ,   Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD)
Published: September 2020

Most persons with fetal alcohol spectrum disorders (FASDs) remain undiagnosed or are diagnosed in later life. To address the need for earlier diagnosis, we previously assessed miRNAs in the blood plasma of pregnant women who were classified as unexposed to alcohol (UE), heavily exposed with affected infants (HEa), or heavily exposed with apparently unaffected infants (HEua). We reported that maternal miRNAs predicted FASD-related growth and psychomotor deficits in infants. Here, we assessed whether fetal sex influenced alterations in maternal circulating miRNAs following prenatal alcohol exposure (PAE). To overcome the loss of statistical power due to disaggregating maternal samples by fetal sex, we adapted a strategy of iterative bootstrap resampling with replacement to assess the stability of statistical parameter estimates. Bootstrap estimates of parametric and effect size tests identified male and female fetal sex-associated maternal miRNA responses to PAE that were not observed in the aggregated sample. Additionally, we observed, in HEa mothers of female, but not male fetuses, a network of co-secreted miRNAs whose expression was linked to miRNAs encoded on the X-chromosome. Interestingly, the number of significant miRNA correlations for the HEua group mothers with female fetuses was intermediate between HEa and UE mothers at mid-pregnancy, but more similar to UE mothers by the end of pregnancy. Collectively, these data show that fetal sex predicts maternal circulating miRNA adaptations, a critical consideration when adopting maternal miRNAs as diagnostic biomarkers. Moreover, a maternal co-secretion network, predominantly in pregnancies with female fetuses, emerged as an index of risk for adverse birth outcomes due to PAE.
Pathobiology of the highly pathogenic avian influenza viruses H7N1 and H5N8 in different chicken breeds and role of Mx 2032 G/A polymorphism in infection outcome
Authors: Sánchez-González Raúl , Ramis Antonio , Nofrarías Miquel , Wali Nabil , Valle Rosa , Pérez Mónica , Perlas Albert , Majó Natàlia
Published: September 2020

Chickens are highly susceptible to highly pathogenic avian influenza viruses (HPAIVs). However, the severity of infection varies depending of the viral strain and the genetic background of the host. In this study, we evaluated the pathogenesis of two HPAIVs (H7N1 and H5N8) and assessed the susceptibility to the infection of local and commercial chicken breeds from Spain. Eight chicken breeds were intranasally inoculated with 105 ELD50 of A/Chicken/Italy/5093/1999 (H7N1) or A/Goose/Spain/IA17CR02699/2017 (H5N8 clade 2.3.4.4. B) and monitored during 10 days. Chickens were highly susceptible to both HPAIVs, but H7N1 was considerably more virulent than H5N8 as demonstrated by the highest mortality rates and shortest mean death times (MDT). Both HPAIVs produced severe necrosis and intense viral replication in the central nervous system, heart and pancreas; however, the lesions and replication in other tissues were virus-dependent. High levels of viral RNA were detected by the oral route with both viruses. In contrast, a low number of H5N8-inoculated chickens shed by the cloacal route, demonstrating a different pattern of viral shedding dependent of the HPAIV. We found a high variation in the susceptibility to HPAIVs between the different chicken breeds. The birds carrying the genotype AA and AG at position 2032 in chicken Mx gene presented a slightly higher, but not significant, percentage of survival and a statistically significant longer MDT than GG individuals. Our study demonstrated that the severity of HPAI infection is largely dependent of the viral isolate and host factors, underlining the complexity of HPAI infections.
Construction of polycistronic baculovirus surface display vectors to express the PCV2 Cap(d41) protein and analysis of its immunogenicity in mice and swine
Authors: Chen Ya-Yi , Yang Wei-Chen , Chang Yu-Kang , Wang Chi-Young , Huang Wei-Ru , Li Jyun-Yi , Chuang Kuo-Pin , Wu Hung-Yi , Chang Ching-Dong , Nielsen Brent L. , Liu Hung-Jen
Published: September 2020

To increase expression levels of the PCV2 Cap(d41) protein, novel baculovirus surface display vectors with multiple expression cassettes were constructed to create recombinant baculoviruses BacSC-Cap(d41), BacDD-2Cap(d41), BacDD-3Cap(d41), and BacDD-4Cap(d41). Our results reveal that the recombinant baculovirus BacDD-4Cap(d41) was able to express the highest levels of Cap(d41) protein. Optimum conditions for expressing the PCV2 Cap(d41) protein were determined, and our results show that 107 of Sf-9 infected with the recombinant baculovirus BacDD-4Cap(d41) at an MOI of 5 for 3 days showed the highest level of protein expression. Mice immunized with the 4Cap(d41) vaccine which was prepared from the recombinant baculovirus-infected cells (107) elicited higher ELISA titers compared to the Cap (d41) vaccine. The 4Cap(d41) vaccine could elicit anti-PCV2 neutralizing antibodies and IFN-γ in mice, as confirmed by virus neutralization test and IFN-γ ELISA. Moreover, the swine lymphocyte proliferative responses indicated that the 4Cap(d41) vaccine was able to induce a clear cellular immune response. Flow cytometry analysis showed that the percentage of CD4+ T cells and CD4+/CD8+ ratio was increased significantly in SPF pigs immunized with the 4Cap(d41) vaccine. Importantly, the 4Cap(d41) vaccine induced an IFN-γ response, further confirming that its effect is through cellular immunity in SPF pigs. An in vivo challenge study revealed that the 4Cap(d41) and the commercial vaccine groups significantly reduce the viral load of vaccinated pigs as compared with the CE negative control group. Taken together, we have successfully developed a 4Cap(d41) vaccine that may be a potential subunit vaccine for preventing the disease associated with PCV2 infections.
Undervirilized male infant with in utero exposure to maternal use of high dose antifungal therapy
Authors: Gujral Jasmine , Costin Gertrude , Khurana Divya , Yau Mabel , Wallach Elizabeth , Romero Christopher J. , Wilkes Meredith , Sethuram Swathi , Rapaport Robert
Published: September 2020

Background

Antifungals act on fungal sterols structurally similar to human cholesterol. Ketoconazole reversibly suppresses steroidogenesis by inhibiting cytochrome P450 enzymes and interferes with dihydrotestosterone (DHT) activity by binding to the androgen receptor. Hypospadias was reported in infants exposed to nystatin in utero.

Case presentation

A male infant exposed to antepartum nystatin presented with severe under-undervirilization and transient adrenal corticosteroid abnormalities. He was born in USA at 31 weeks gestation to a mother treated with vaginal Polygynax capsules (nystatin-100,000 international units, neomycin sulphate-35,000 international units and polymyxin B-35,000 international units) for vaginal discharge in the Ivory Coast. She used approximately 60 capsules between the first trimester until delivery. The infant was born with micropenis, chordee, perineo-scrotal hypospadias and bifid scrotum with bilaterally palpable gonads. The karyotype was 46,XY. No Mullerian structures were seen on ultrasound. Serum 17-hydroxyprogesterone (17 OHP) on newborn screening was high (304 ng/ml, normal < 35). Cortisol response to cosyntropin on the 3rd day of life (DOL) was 10 mcg/ml; the subnormal cortisol response may have resulted from prematurity and the predelivery treatment with betamethasone. The elevation of several adrenal corticosteroids was not consistent with any specific enzymatic defect. Hydrocortisone and fludrocortisone were initiated at another hospital for suspected mild glucocorticoid and mineralocorticoid deficiencies. Genetic screening for adrenal and gonadal developmental defects performed when transferred to our care were normal. All medications were gradually discontinued over 5–8 months. Adrenal and testicular responses to cosyntropin and human chorionic gonadotropin (hCG) were normal at 8 months.

Conclusions

We report severe undervirilization in a 46,XY infant born to a mother treated with prolonged and high dose nystatin during pregnancy. This presentation suggests that prolonged antepartum use of high dose nystatin could lead to severe but transient defects in androgen synthesis and/or action possibly by acting as an endocrine disruptor. Further studies are warranted to confirm this finding. Thus, endocrine disruptors should be considered in male newborns with atypical genitalia not explained by common pathologies.
Solutions for impulsive fractional pantograph differential equation via generalized anti-periodic boundary condition
Authors: Ahmed Idris , Kumam Poom , Abubakar Jamilu , Borisut Piyachat , Sitthithakerngkiet Kanokwan
Published: September 2020

This study investigates the solutions of an impulsive fractional differential equation incorporated with a pantograph. This work extends and improves some results of the impulsive fractional differential equation. A differential equation of an impulsive fractional pantograph with a more general anti-periodic boundary condition is proposed. By employing the well-known fixed point theorems of Banach and Krasnoselskii, the existence and uniqueness of the solution of the proposed problem are established. Furthermore, two examples are presented to support our theoretical analysis.
New finite-time synchronization analysis of a delayed memristive neurodynamic model
Authors: Ren Dandan , Yao Aidi
Published: September 2020

This paper presents theoretical results on the finite-time synchronization of delayed memristive neural networks (MNNs). Compared with existing ones on finite-time synchronization of discontinuous NNs, we directly regard the MNNs as a switching system, by introducing a novel analysis method, new synchronization criteria are established without employing differential inclusion theory and non-smooth finite time convergence theorem. Finally, we give a numerical example to support the effectiveness of the theoretical results.
Uniqueness of meromorphic functions concerning their difference operators and derivatives
Authors: Wei Dong-Mei , Huang Zhi-Gang
Published: September 2020

Let f and g be two nonconstant meromorphic functions. Shared value problems related to f and g are investigated in this paper. We give sufficient conditions in terms of weighted value sharing which imply that f is a linear transformation or inversion transformation of g. We also investigate the uniqueness problem of meromorphic functions with their difference operators and derivatives sharing some values.
Effects of short-term training on pastoral community employment creation and livelihood improvement: a study on selected Ethiopian pastoral areas
Authors: Shiferaw Robson Mekonnin
Published: September 2020

This study investigated the effects of a short-term training on pastoral community employment creation and livelihood improvement. The study investigated the perception of beneficiaries pertinent to the benefits of a short-term training scholarship, experiences of graduate trainees, estimation of employability rate after training, and types of employment TVET graduates are engaged during the year 2014 to 2017 in Pastoral Resilience Improvement through Market Extension project operating clusters. Self-administered survey questionnaires were used and distributed to 128 project beneficiaries in Afar, Eastern, and Southern clusters of Ethiopia. Since the instrument was close-ended questionnaires in the form of a dichotomous, and quantitative research approach was deployed. The quantitative part of the assessment was analyzed using descriptive and inferential statistics with the support of SPSS version 20. The finding of the study indicated that the reasons for unemployment of the beneficiaries were mainly lack of financial support and poor industry linkage with employers in the areas. On the other hand, such activities should be assessed once again for financial and material support since the majority of the trainees were unemployed and seeking support besides the training received from the program in all clusters from all concerned development partners. The finding of the study depicted, gender-related issues in all clusters implies that women involvements or participation shows a variation in some clusters. However, the project more benefited male beneficiaries than women in all clusters. Therefore, if the project will continue this type of program, balancing gender and equal benefit should be maintained in all clusters. Redesigning the program is required because due to providing training alone cannot bring livelihood changes as the finding of the study revealed. This is because the beneficiaries of the program were selected from an economically poor family background. Therefore, the program should evaluate once again for financial and equipment support since the majority of the trainees were unemployed and seeking support from different development stakeholders in the three clusters.
Soil microbiota manipulation and its role in suppressing soil-borne plant pathogens in organic farming systems under the light of microbiome-assisted strategies
Authors: De Corato Ugo
Published: September 2020

Soil microbiota plays a key role in suppressing soil-borne plant pathogens improving the natural soil suppressiveness. Microbiome disturbance triggers specific perturbation to change and shape the soil microbial communities’ network for increasing suppression against phytopathogens and related diseases. Very important goals have been reached in manipulation of soil microbiota through agronomical practices based on soil pre-fumigation, organic amendment, crop rotation and intercropping. Nevertheless, to limit inconsistencies, drawbacks and failures related to soil microbiota disturbance, a detailed understanding of the microbiome shifts during its manipulation is needed under the light of the microbiome-assisted strategies. Next-generation sequencing often offers a better overview of the soil microbial communities during microbiomes manipulation, but sometime it does not provide information related to the highest taxonomic resolution of the soil microbial communities. This review work reports and discusses the most reliable findings in relation to a comprehensive understanding of soil microbiota and how its manipulation can improve suppression against soil-borne diseases in organic farming systems. Role and functionality of the soil microbiota in suppressing soil-borne pathogens affecting crops have been basically described in the first section of the paper. Characterization of the soil microbiomes network by high-throughput sequencing has been introduced in the second section. Some relevant findings by which soil microbiota manipulation can address the design of novel sustainable cropping systems to sustain crops’ health without use (or reduced use) of synthetic fungicides and fumigants have been extensively presented and discussed in the third and fourth sections, respectively, under the light of the new microbiome-assisted strategies. Critical comparisons on the next-generation sequencing have been provided in the fifth section. Concluding remarks have been drawn in the last section.
Thermodynamic and detailed kinetic study of the formation of orthophthalaldehyde-agmatine complex by fluorescence intensities
Authors: Kital Khémesse , Traoré Moumouny , Sarr Diégane , Mbaye Moussa , Seye Mame Diabou Gaye , Coly Atanasse , Delattre François , Tine Alphonse
Published: September 2020

The aim of this work is to determine the thermodynamic parameters and the kinetics of complex formation between orthophthalaldehyde (OPA) and agmatine (AGM) in an alkaline medium (pH 13). Firstly, the association constant (Ka) between orthophthalaldehyde and agmatine was determined at different temperatures (between 298 K and 338 K) with a step size of 10 K. Secondly, the thermodynamic parameters such as standard enthalpy (ΔH°), standard entropy (ΔS°),and Gibbs energy (∆G) were calculated, where a positive value ofΔH° (+45.50 kJ/mol) was found, which shows that the reaction is endothermic. In addition, the low value of ΔS°(+0.24 kJ/mol) indicates a slight increase in the disorder in the reaction medium. Furthermore, the negative values ofΔGbetween −35.62 kJ/mol and −26.02 kJ/mol show that the complex formation process is spontaneous. Finally, the parameters of the kinetics of the reaction between OPA and AGM were determined as follows: when the initial concentration ofAGM(5 × 10−6 M) is equal to that of the OPA, the results show that the reaction follows an overall 1.5 order kinetics with an initial rate of 5.1 × 10−7Mmin−1and a half-life of 8.12 min. The partial order found in relation to the AGM is 0.8. This work shows that the excess of OPA accelerates the formation reaction of the complex.
Correction to: Intravenous patient-controlled analgesia: in vitro stability profiles of mixtures containing fentanyl, hydromorphone, oxycodone, nefopam, ondansetron, and ramosetron
Authors: Lee Chung Hun , Kim Ah Rahn , Lee Mi Kyoung , Oh Jung Suk , Lee Dong Kyu , Choi Sang Sik
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
Genome-wide association analysis of idiopathic epilepsy in the Belgian shepherd
Authors: Belanger J. M. , Famula T. R. , Gershony L. C. , Palij M. K. , Oberbauer A. M.
Published: September 2020

Background

Idiopathic epilepsy (IE) is a common neurological disorder in the domestic dog, and is defined as repeated seizure activity having no identifiable underlying cause. Some breeds, such as the Belgian shepherd dog, have a greater prevalence of the disorder. Previous studies in this and other breeds have identified ADAM23 as a gene that confers risk of IE, although additional loci are known to exist. The present study sought to identify additional loci that influence IE in the Belgian shepherd dog.

Results

Genome-wide association studies (GWAS) revealed a significant association between IE and CFA 14 (p < 1.03 E− 08) and a suggestive association on CFA 37 (p < 2.91 E− 06) in a region in linkage disequilibrium with ADAM23. Logistic regression identified a 2-loci model that demonstrated interaction between the two chromosomal regions that when combined predicted IE risk with high sensitivity.

Conclusions

Two interacting loci, one each on CFAs 14 and 37, predictive of IE in the Belgian shepherd were identified. The loci are adjacent to potential candidate genes associated with neurological function. Further exploration of the region is warranted to identify causal variants underlying the association. Additionally, although the two loci were very good at predicting IE, they failed to capture all the risk, indicating additional loci or incomplete penetrance are also likely contributing to IE expression in the Belgian shepherd dog.
Reasons for and Consequences of Low Energy Availability in Female and Male Athletes: Social Environment, Adaptations, and Prevention
Authors: Wasserfurth Paulina , Palmowski Jana , Hahn Andreas , Krüger Karsten
Published: September 2020

Low energy availability (LEA) represents a state in which the body does not have enough energy left to support all physiological functions needed to maintain optimal health. When compared to the normal population, athletes are particularly at risk to experience LEA and the reasons for this are manifold. LEA may result from altered dietary behaviours that are caused by body dissatisfaction, the belief that a lower body weight will result in greater performance, or social pressure to look a certain way. Pressure can also be experienced from the coach, teammates, and in this day and age through social media platforms. While LEA has been extensively described in females and female athletes have started fighting against the pressure to be thin using their social media platforms, evidence shows that male athletes are at risk as well. Besides those obvious reasons for LEA, athletes engaging in sports with high energy expenditure (e.g. rowing or cycling) can unintentionally experience LEA; particularly, when the athletes’ caloric intake is not matched with exercise intensity. Whether unintentional or not, LEA may have detrimental consequences on health and performance, because both short-term and long-term LEA induces a variety of maladaptations such as endocrine alterations, suppression of the reproductive axis, mental disorders, thyroid suppression, and altered metabolic responses. Therefore, the aim of this review is to increase the understanding of LEA, including the role of an athlete’s social environment and the performance effects related to LEA.
Partnerships with local organisations are vital for conducting health research in Syria—personal reflections
Authors: Ekzayez Abdulkarim
Published: September 2020

Throughout the 9 years of the Syrian conflict, humanitarian actors have accumulated enormous experience of dealing with this complex environment and collected substantial data—only a tiny fraction, however, is being used in informing practice and research. Partnering with academic institutions could enable these actors to foster their efforts in data collection, analysis and research production. These partnerships should go beyond the traditional understanding of partnerships to include elements of a two-way capacity strengthening paradigm, and equal benefits and opportunities. Drawing on my personal experience of providing clinical medicine in field hospitals in conflict-affected areas in Syria, as well as my experience in the humanitarian response there working with Save the Children and a number of local organisations, and then moving to policy and research working with London School of Hygiene and Tropical Medicine, Chatham House and King’s College London, I conclude equal partnerships and effective collaborations between academic institutions and humanitarian actors could provide a concrete and sustainable approach of conducting health research in conflict settings.