bluuebunny/crossref_metadata_2025_split huggingface dataset:
An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes
Authors: Khan Md Anik Ashfaq , Ami Jenifar Quaiyum , Faisal Khaledul , Chowdhury Rajashree , Ghosh Prakash , Hossain Faria , Abd El Wahed Ahmed , Mondal Dinesh 
Published: April 2020

Abstract
Background
Visceral leishmaniasis (VL) caused by dimorphic Leishmania species is a parasitic disease with high socioeconomic burden in endemic areas worldwide. Sustaining control of VL in terms of proper and prevailing immunity development is a global necessity amid unavailability of a prophylactic vaccine. Screening of experimental proteome of the human disease propagating form of Leishmania donovani (amastigote) can be more pragmatic for in silico mining of novel vaccine candidates.

Methods
By using an immunoinformatic approach, CD4+ and CD8+ T cell-specific epitopes from experimentally reported L. donovani proteins having secretory potential and increased abundance in amastigotes were screened. A chimera linked with a Toll-like receptor 4 (TLR4) peptide adjuvant was constructed and evaluated for physicochemical characteristics, binding interaction with TLR4 in simulated physiological condition and the trend of immune response following hypothetical immunization.

Results
Selected epitopes from physiologically important L. donovani proteins were found mostly conserved in L. infantum, covering theoretically more than 98% of the global population. The multi-epitope chimeric vaccine was predicted as stable, antigenic and non-allergenic. Structural analysis of vaccine-TLR4 receptor docked complex and its molecular dynamics simulation suggest sufficiently stable binding interface along with prospect of non-canonical receptor activation. Simulation dynamics of immune response following hypothetical immunization indicate active and memory B as well as CD4+ T cell generation potential, and likely chance of a more Th1 polarized response.

Conclusions
The methodological approach and results from this study could facilitate more informed screening and selection of candidate antigenic proteins for entry into vaccine production pipeline in future to control human VL.
A standardised method of marking male mosquitoes with fluorescent dust
Authors: Culbert Nicole J. , Kaiser Maria , Venter Nelius , Vreysen Marc J. B. , Gilles Jeremie R. L. , Bouyer Jérémy 
Published: April 2020

Abstract
Background
Prior to a major release campaign of sterile insects, including the sterile insect technique, male mosquitoes must be marked and released (small scale) to determine key parameters including wild population abundance, dispersal and survival. Marking insects has been routinely carried out for over 100 years; however, there is no gold standard regarding the marking of specific disease-transmitting mosquitoes including Anopheles arabiensis, Aedes aegypti and Aedes albopictus. The research presented offers a novel dusting technique and optimal dust colour and quantities, suitable for small-scale releases, such as mark-release-recapture studies.

Methods
We sought to establish a suitable dust colour and quantity for batches of 100 male An. arabiensis, that was visible both by eye and under UV light, long-lasting and did not negatively impact longevity. A set of lower dust weights were selected to conduct longevity experiments with both Ae. aegypti and Ae. albopictus to underpin the optimal dust weight. A further study assessed the potential of marked male An. arabiensis to transfer their mark to undusted males and females.

Results
The longevity of male An. arabiensis marked with various dust colours was not significantly reduced when compared to unmarked controls. Furthermore, the chosen dust quantity (5 mg) did not negatively impact longevity (P = 0.717) and provided a long-lasting mark. Dust transfer was found to occur from marked An. arabiensis males to unmarked males and females when left in close proximity. However, this was only noticeable when examining individuals under a stereomicroscope and thus deemed negligible. Overall, male Ae. aegypti and Ae. albopictus displayed a greater sensitivity to dusting. Only the lowest dust weight (0.5 mg) did not significantly reduce longevity (P = 0.888) in Ae. aegypti, whilst the lowest two dust weights (0.5 and 0.75 mg) had no significant impact on longevity (P = 0.951 and 0.166, respectively) in Ae. albopictus.

Conclusion
We have devised a fast, inexpensive and simple marking method and provided recommended dust quantities for several major species of disease-causing mosquitoes. The novel technique provides an evenly distributed, long-lasting mark which is non-detrimental. Our results will be useful for future MRR studies, prior to a major release campaign.
Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany
Authors: Heiligenhaus Arnd , Klotsche Jens , Niewerth Martina , Horneff Gerd , Ganser Gerd , Haas Johannes-Peter , Minden Kirsten 
Published: April 2020

Abstract
Background
To analyze whether ANA-positive idiopathic anterior uveitis differs from JIA-associated uveitis concerning clinical course, response to treatment, and disease outcome.

Methods
Prospective study of the National Paediatric Rheumatological Database (NPRD) including its uveitis add-on module from the years 2002 to 2016. Cross-sectional data from the years 2002 to 2016 were analyzed. Patients with JIA-associated uveitis and with ANA-positive idiopathic anterior uveitis were included and the disease manifestation investigated in terms of uveitis characteristics and disease course.

Results
Of the total cohort of 34,458 patients enrolled in the NPRD, including 3551 patients with uveitis, those with detailed uveitis documentation were taken into account: 62 ANA-positive patients with idiopathic anterior uveitis (group 1), 688 patients with initial uveitis diagnosis after JIA onset (group 2), and 61 JIA patients with initial uveitis diagnosis before arthritis onset (group 3). Anterior uveitis was documented in 100%, 94%, and 80% of patients and with insidious onset of uveitis flare in 50%, 70.9%, and 56.1% each in groups 1, 2, and 3, respectively. Use of topical or systemic corticosteroids and conventional synthetic or biological DMARDs did not significantly differ between the patient groups, either at the initial or the 2-year follow-up (2-FU) visits (mean 2 years, each p > 0.05). At 2-FU, uveitis inactivity was achieved in 64.7%, 55.8%, and 61.5% of patients in groups 1, 2, and 3 (p > 0.05). Uveitis-related complications were more frequent at the initial visit and at 2-FU in groups 1 and 3, as compared to group 2.

Conclusions
ANA-positive idiopathic uveitis and JIA-associated uveitis do not significantly differ concerning clinical course of uveitis, treatment, and response to corticosteroids and DMARDs.
Repeated measurements of serum urate and mortality: a prospective cohort study of 152,358 individuals over 8 years of follow-up
Authors: Li Shanshan , Cui Liufu , Cheng Jin , Shu Rong , Chen Shuohua , Nguyen Uyen-Sa , Misra Devyani , Wu Shouling , Gao Xiang 
Published: April 2020

AbstractBackgroundLongitudinal evidence on change of serum urate level with mortality risk is limited as prior studies have a measurement of serum urate at a single time point. Further, the combined effect of serum urate and systemic inflammation on mortality is unknown.MethodsWe conducted a prospective cohort study of 152,358 participants (122,045 men and 30,313 women) with repeated measurements of serum urate in 2006, 2008, 2010, and 2012 (107,751 participants had all four measurements of serum urate). We used the Cox proportional hazard model to examine the association between cumulative average and changes in serum urate with mortality. The combined effect of serum urate and systemic inflammation was determined by testing the interaction of serum urate and high-sensitive C-reactive protein (hs-CRP) in relation to mortality risk.ResultsDuring a median follow-up of 8.7 (interquartile range 6.3–9.2) years, we identified 7564 all-cause deaths, 1763 CVD deaths, 1706 cancer deaths, and 1572 other deaths. We observed U-shaped relationships of cumulative average serum urate with all-cause mortality, cardiovascular mortality, and other mortalities. Compared with participants with stable serum urate, those with greater increases in serum urate had a 1.7-fold elevated mortality (hazard ratio (HR) = 1.66, 95% confidence interval (CI) = 1.49–1.84), and those with decreased serum urate had a 2-fold elevated mortality risk (HR = 2.14, 95% CI 1.93–2.37). Participants with both hyperuricemia and hs-CRP had 1.6 times higher mortality, compared with those with low serum urate and hs-CRP levels (HR = 1.56, 95% CI 1.37–1.76).ConclusionsWe observed a U-shaped relationship of long-term cumulative average serum urate with all-cause mortality, cardiovascular mortality, and other mortalities. Compared with participants with relatively stable serum urate levels, a greater increase or decrease in serum urate was associated with elevated mortality. Participants with both hyperuricemia and high systemic inflammation had the greatest mortality risk compared with those with low serum urate and low hs-CRP levels.
A case of allergy to Silybum marianum (milk thistle) and Eragrostis tef (teff)
Authors: Wojas O. , Krzych-Fałta E. , Samel-Kowalik P. , Żalikowska-Gardocka M. , Majsiak E. , Mari A. , Samoliński B. 
Published: April 2020

AbstractBackgroundThis paper presents a peculiar first case of an allergy to Silybum marianum (milk thistle) and Eragrostis tef (teff). Both teff and milk thistle have been presented in the literature (both domestic and foreign) in a positive light, the former as a new part of gluten-free diet, and the latter as a treatment for a number of conditions, particularly those of the liver.Case presentationA 29-year-old male presented at our clinic due to an episode of itching and burning in his mouth, swollen tongue, and difficulty swallowing following ingestion of teff flakes. He also reported sneezing, runny nose, watering and burning eyes, and wheezing following inhalation exposure to ground milk thistle. The patient’s occupation is associated with exposure to these allergens. The patient underwent comprehensive allergy diagnostic assessments (including skin-prick testing, serum specific IgE levels, Faber test, spirometry, and acoustic rhinometry) and gastroenterological assessments. The diagnosis was established on skin tests with native allergens (milk thistle 16/35, teff flour 22/60, negative control 0/0, histamine 3/5) provided by the patient. There are no commercially available (standardized) tests for milk thistle or teff either in Poland or anywhere else in the world.ConclusionsMilk thistle is available in the form of dry, finely-ground preparations (which are used as additives to bread, soups, and yoghurts) and extracts (which are used as ingredients in over-the-counter herbal remedies). Teff is a gluten-free cereal whose grains are rich in methionine, calcium, iron, folic acid, and antioxidants. This case report presents milk thistle and teff as potentially new allergens. A literature review revealed no similar allergy cases in Poland or elsewhere in the world.
Exploring the key microbial changes in the rhizosphere that affect the occurrence of tobacco root-knot nematodes
Authors: Huang Kuo , Jiang Qipeng , Liu Liehua , Zhang Shuting , Liu Chaoli , Chen Haitao , Ding Wei , Zhang Yongqiang 
Published: April 2020

AbstractRoot-knot nematode (RKN) disease is a soil-borne disease. However, most studies on RKN have focused on the screening of agents and the cultivation of resistant varieties, and reports on the interaction of RKNs with soil microorganisms are few. In this study, we performed Illumina high-throughput sequencing to analyze diseased and healthy soil and the microbial-community changes in rhizosphere soil after microbial treatment (Pseudomonas flurescens, Bacillus subtilis, Paecolomyces lilacinus). Results showed significant differences in the bacterial community richness and diversity between diseased and healthy soil and the presence of different microbial species. After treatment, the richness and diversity of microbial communities in soil, as well as the number and incidence of second-stage juvenile of RKNs, decreased. Through linear discriminant analysis effect size, Pearson correlation, and Venn diagram analysis, we screened five genera that were closely related to disease occurrence, among which Pseudomonas was most related to disease inhibition. Our results suggested that the occurrence of tobacco RKN was related to changes in soil microbial communities, and that the interactions among Pseudomonas, Bryobacter, Variibacter, Coniochaeta, and Metarhizium affected the health of rhizosphere soil.
Construction of engineered yeast producing ammonia from glutamine and soybean residues (okara)
Authors: Watanabe Yukio , Kuroda Kouichi , Tatemichi Yuki , Nakahara Takeharu , Aoki Wataru , Ueda Mitsuyoshi 
Published: April 2020

AbstractAmmonia is an essential substance for agriculture and the chemical industry. The intracellular production of ammonia in yeast (Saccharomyces cerevisiae) by metabolic engineering is difficult because yeast strongly assimilates ammonia, and the knockout of genes enabling this assimilation is lethal. Therefore, we attempted to produce ammonia outside the yeast cells by displaying a glutaminase (YbaS) from Escherichia coli on the yeast cell surface. YbaS-displaying yeast successfully produced 3.34 g/L ammonia from 32.6 g/L glutamine (83.2% conversion rate), providing it at a higher yield than in previous studies. Next, using YbaS-displaying yeast, we also succeeded in producing ammonia from glutamine in soybean residues (okara) produced as food waste from tofu production. Therefore, ammonia production outside cells by displaying ammonia-lyase on the cell surface is a promising strategy for producing ammonia from food waste as a novel energy resource, thereby preventing food loss.
BMP2K dysregulation promotes abnormal megakaryopoiesis in acute megakaryoblastic leukemia
Authors: Wang Manman , Zhang Tan , Zhang Xuechun , Jiang Zhou , Peng Min , Huang Zan 
Published: April 2020

Abstract
Background
Forced polyploidization is an effective strategy for acute megakaryoblastic leukemia (AMKL) therapy and factors controlling polyploidization are potential targets for drug development. Although bone morphology protein 2-inducible kinase (BMP2K) has been implied to be a potential target for fasudil, a potent polyploidy-inducing compound, the function of BMP2K in megakaryopoiesis and AMKL remains unknown. This study aimed to investigate the role of BMP2K as a novel regulator in megakaryocyte polyploidization and differentiation and its implication in AMKL therapy.

Results
BMP2K upregulation was observed in human megakaryopoiesis and leukemia cells whereas BMP2K was downregulated in AMKL cells forced to undergo terminal differentiation. Functionally, BMP2K suppressed MLN8237-induced megakaryocytic differentiation in AMKL cells and dampened megakaryocyte differentiation in primary mouse fetal liver cells. Furthermore, BMP2K overexpression conferred resistance to multiple chemotherapy compounds in AMKL cells. Mechanistically, cyclin-dependent kinase 2 (CDK2) interacted with BMP2K and partially mediated its function. In transient MLN8237 and nocodazole challenge cell model, BMP2K reduced cell percentage of G2/M phase but increased G1 phase, suggesting a role of BMP2K antagonizing polyploidization and promoting mitosis by regulating cell cycle in megakaryopoiesis.

Conclusions
BMP2K negatively regulates polyploidization and megakaryocyte differentiation by interacting CDK2 and promoting mitosis in megakaryopoiesis. BMP2K may serve as a potential target for improvement of AMKL therapy.
Effect of age and sex on strength and spatial electromyography during knee extension
Authors: Pradhan Ashirbad , Malagon Gemma , Lagacy Rebecca , Chester Victoria , Kuruganti Usha 
Published: April 2020

Abstract
Background
Multichannel surface electromyography (EMG) is a method to examine properties of motor unit (MU) activity using multiple electrodes arranged on a two-dimensional grid. This technique can be used to examine alterations in EMG activity distribution due to contraction intensity as well as due to physiological differences such as age or sex. Therefore, the purpose of this study was to compare strength and high-density surface EMG (HDsEMG) features during isometric and isokinetic knee extensions between older and younger men and women.

Methods
Twenty younger (ages 19–25 years) and twenty older (ages 64–78) men and women performed submaximal and maximal isometric (at a joint angle of 90°) and isokinetic knee extensions, while HDsEMG was recorded from the vastus lateralis. Spatial distribution was estimated using the root mean square (RMS), and 2-dimensional (2D) maps were developed to examine spatial features. Coefficient of variation (CV) and modified entropy were used to examine alterations in muscle heterogeneity and pattern. Peak torque and HDsEMG parameters were compared across age and gender.

Results
Younger males and females produced significantly higher mean torque than the older group (p < 0.001) for all contractions. Both age- and sex-related significant differences (p < 0.05) were found for EMG spatial features suggesting neuromuscular differences. Modified entropy was significantly higher and CV was lower for young females compared to young males (p < 0.05) across both isometric and isokinetic contractions.

Conclusions
We found that isometric and isokinetic knee extension strength, spatial distribution, and intensity differ as a function of age and sex during knee extensions. While there were no differences detected in entropy between age groups, there were sex-related differences in the younger age category. The lack of age-related differences in entropy was surprising given the known effects of aging on muscle fiber composition. However, it is often reported that muscle coactivation increases with age and this work was limited to the study of one muscle of the knee extensors (vastus lateralis) which should be addressed in future work. The findings suggest while both age and sex affect muscle activation, sex had a greater effect on heterogeneity. The results obtained will help to develop improved rehabilitation programs for aging men and women.
Effect of dietary fiber and threonine content on intestinal barrier function in pigs challenged with either systemic E. coli lipopolysaccharide or enteric Salmonella Typhimurium
Authors: Wellington Michael O. , Hamonic Kimberley , Krone Jack E. C. , Htoo John K. , Van Kessel Andrew G. , Columbus Daniel A. 
Published: April 2020

AbstractBackgroundThe independent and interactive effects of dietary fiber (DF) and threonine (Thr) were investigated in growing pigs challenged with either systemicE. colilipopolysaccharide (LPS) or entericSalmonellaTyphimurium (ST) to characterise their effect on intestinal barrier function.ResultsIn experiment 1, intestinal barrier function was assessed via oral lactulose and mannitol (L:M) gavage and fecal mucin analysis in pigs challenged withE. coliLPS and fed low fiber (LF) or high fiber (HF) diets with graded dietary Thr. Urinary lactulose recovery and L:M ratio increased (P < 0.05) during the LPS inoculation period in LF fed pigs but not in HF fed pigs. Fecal mucin output was increased (P < 0.05) in pigs fed HF compared to LF fed pigs. In experiment 2, RT-qPCR, ileal morphology, digesta volatile fatty acid (VFA) content, and fecal mucin output were measured inSalmonellaTyphimurium challenged pigs, fed LF or HF diets with standard or supplemented dietary Thr.Salmonellainoculation increased (P < 0.05) fecal mucin output compared to the unchallenged period. Supplemental Thr increased fecal mucin output in the HF-fed pigs (Fib × Thr;P < 0.05). Feeding HF increased (P < 0.05) VFA concentration in cecum and colon. No effect of either Thr or fiber on expression of gene markers was observed except a tendency (P = 0.06) for increased MUC2 expression with the HF diet. Feeding HF increased goblet cell numbers (P < 0.05).ConclusionDietary fiber appears to improve barrier function through increased mucin production capacity (i.e., goblet cell numbers, MUC2 gene expression) and secretion (i.e., fecal mucin output). The lack of effect of dietary Thr inSalmonella-challenged pigs provides further evidence that mucin secretion in the gut is conserved and, therefore, Thr may be limiting for growth under conditions of increased mucin production.
Efficacy and safety of rituximab in autoimmune and microangiopathic hemolytic anemia: a systematic review and meta-analysis
Authors: Chao Shih-Hsuan , Chang Yuh-Lih , Yen Jiin-Cherng , Liao Hsien-Tzung , Wu Tsai-Hung , Yu Chia-Li , Tsai Chang-Youh , Chou Yueh-Ching 
Published: April 2020

Abstract
Background
The efficacy and safety of rituximab (RTX) on hemolytic anemia (HA) is unknown. Therefore we retrospectively analyze the efficacy and safety of RTX in autoimmune hemolytic anemia (AIHA) and microangiopathic hemolytic anemia (MAHA) from the previous literature.

Methods
Data in clinical trials and observational studies were collected from PubMed, Cochrane, Embase, and Google Scholar until Oct 15, 2018. The efficacy and safety of RTX in patients with AIHA or MAHA were assessed and overall response rates (ORRs), complete response rates (CRRs), adverse events (AEs) and relapse rates (RRs) were extracted if available. A meta-analysis was performed with a random-effects model, estimating mean proportions in all studies, and relative rates in comparative studies.

Results
After quality assessment, a total of 37 investigations encompassing 1057 patients eligible for meta-analysis were included. Pooled mean proportion of ORR was 0.84 (95% confidence interval [CI] 0.80–0.88), and that of CRR was 0.61 (95% CI 0.49–0.73). Mean AE rate was 0.14 (95% CI 0.10–0.17), and mean RR was 0.21 (95% CI 0.15–0.26). Relative ORR was 1.18 (95% CI 1.02–1.36), and relative CRR was 1.17 (95% CI 0.98–1.39) fold more than the respective non-RTX counter parts. Relative AE rate was 0.77 (95% CI 0.36–1.63), and relative RR was 0.93 (95% CI 0.56–1.55) fold less than the respective non-RTX counter parts.

Conclusion
RTX is more effective than the treatments without RTX for AIHA and MAHA and is well-tolerated.
Abnormal mitosis in reactive astrocytes
Authors: Sosunov Alexander , Wu Xiaoping , McGovern Robert , Mikell Charles , McKhann Guy M. , Goldman James E. 
Published: April 2020

AbstractAlthough abnormal mitosis with disarranged metaphase chromosomes or many micronuclei in astrocytes (named “Alzheimer I type astrocytes” and later “Creutzfeldt-Peters cells”) have been known for nearly 100 years, the origin and mechanisms of this pathology remain elusive. In experimental brain insults in rats, we show that abnormal mitoses that are not followed by cytokinesis are typical for reactive astrocytes. The pathology originates due to the inability of the cells to form normal mitotic spindles with subsequent metaphase chromosome congression, which, in turn may be due to shape constraints aggravated by cellular enlargement and to the accumulation of large amounts of cytosolic proteins. Many astrocytes escape from arrested mitosis by producing micronuclei. These polyploid astrocytes can survive for long periods of time and enter into new cell cycles.