bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling the monthly abundance of Culicoides biting midges in nine European countries using Random Forests machine learning
Authors: Cuéllar Ana Carolina , Kjær Lene Jung , Baum Andreas , Stockmarr Anders , Skovgard Henrik , Nielsen Søren Achim , Andersson Mats Gunnar , Lindström Anders , Chirico Jan , Lühken Renke , Steinke Sonja , Kiel Ellen , Gethmann Jörn , Conraths Franz J. , Larska Magdalena , Smreczak Marcin , Orłowska Anna , Hamnes Inger , Sviland Ståle , Hopp Petter , Brugger Katharina , Rubel Franz , Balenghien Thomas , Garros Claire , Rakotoarivony Ignace , Allène Xavier , Lhoir Jonathan , Chavernac David , Delécolle Jean-Claude , Mathieu Bruno , Delécolle Delphine , Setier-Rio Marie-Laure , Scheid Bethsabée , Chueca Miguel Ángel Miranda , Barceló Carlos , Lucientes Javier , Estrada Rosa , Mathis Alexander , Venail Roger , Tack Wesley , Bødker Rene
Published: April 2020

Background

Culicoides biting midges transmit viruses resulting in disease in ruminants and equids such as bluetongue, Schmallenberg disease and African horse sickness. In the past decades, these diseases have led to important economic losses for farmers in Europe. Vector abundance is a key factor in determining the risk of vector-borne disease spread and it is, therefore, important to predict the abundance of Culicoides species involved in the transmission of these pathogens. The objectives of this study were to model and map the monthly abundances of Culicoides in Europe.

Methods

We obtained entomological data from 904 farms in nine European countries (Spain, France, Germany, Switzerland, Austria, Poland, Denmark, Sweden and Norway) from 2007 to 2013. Using environmental and climatic predictors from satellite imagery and the machine learning technique Random Forests, we predicted the monthly average abundance at a 1 km2 resolution. We used independent test sets for validation and to assess model performance.

Results

The predictive power of the resulting models varied according to month and the Culicoides species/ensembles predicted. Model performance was lower for winter months. Performance was higher for the Obsoletus ensemble, followed by the Pulicaris ensemble, while the model for Culicoides imicola showed a poor performance. Distribution and abundance patterns corresponded well with the known distributions in Europe. The Random Forests model approach was able to distinguish differences in abundance between countries but was not able to predict vector abundance at individual farm level.

Conclusions

The models and maps presented here represent an initial attempt to capture large scale geographical and temporal variations in Culicoides abundance. The models are a first step towards producing abundance inputs for R0 modelling of Culicoides-borne infections at a continental scale.
Leishmania infantum and Dirofilaria immitis infections in Italy, 2009–2019: changing distribution patterns
Authors: Mendoza-Roldan Jairo , Benelli Giovanni , Panarese Rossella , Iatta Roberta , Furlanello Tommaso , Beugnet Frederic , Zatelli Andrea , Otranto Domenico
Published: April 2020

Background

For long time, canine leishmaniosis (CanL) was considered endemic in the southern, central, and insular regions of Italy, whereas heartworm disease (HW) caused by Dirofilaria immitis was considered endemic in the northern region and in the swampy Po Valley. Following the reports of new foci of both diseases, in this study we update the distribution patterns and occurrence of new foci of CanL and HW discussing the main drivers for the changes in the epidemiology of these two important zoonotic canine vector-borne diseases.

Methods

Based on the statistical analyses of serological assays (n = 90,633) on L. infantum exposure and D. immitis infection performed by two reference diagnostic centres in Italy over a ten-year period (2009–2019) irrespective of the anamnesis of dogs. The distribution patterns of both parasites are herein presented along with the occurrence of new foci.

Results

Results highlighted the changing distribution patterns of L. infantum vs D. immitis infection in Italy. CanL is endemic in some areas of northern regions and HW has endemic foci in central and southern regions and islands. Significant differences in L. infantum exposure and HW infection prevalence among the study macroareas were detected. The overall results of the positive tested samples were 28.2% in southern Italy and islands, 29.6% in central Italy and 21.6% in northern Italy for L. infantum and 2.83% in northern Italy, 7.75% in central Italy and 4.97% in southern Italy and islands for HW. HW positivity significantly varied over years (χ2 = 108.401, df = 10, P < 0.0001), gradually increasing from 0.77% in 2009 to 8.47% in 2016–2017.

Conclusions

New potential epidemiological scenarios are discussed according to a range of factors (e.g. environmental modifications, occurrence of competent insect vectors, transportation of infected animals to non-endemic areas, chemoprophylaxis or vector preventative measures), which may affect the current distribution. Overall, the results advocate for epidemiological surveillance programmes, more focussed preventative and control measures even in areas where few or no cases of both diseases have been diagnosed.
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

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

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

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

Background

Longitudinal 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.

Methods

We 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.

Results

During 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).

Conclusions

We 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

Background

This 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 presentation

A 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.

Conclusions

Milk 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

Root-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

Ammonia 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

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

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

Background

The 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.

Results

In 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).

Conclusion

Dietary 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

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

Although 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.
Foetal onset of EIF2B related disorder in two siblings: cerebellar hypoplasia with absent Bergmann glia and severe hypomyelination
Authors: Trimouille Aurélien , Marguet Florent , Sauvestre Fanny , Lasseaux Eulalie , Pelluard Fanny , Martin-Négrier Marie-Laure , Plaisant Claudio , Rooryck Caroline , Lacombe Didier , Arveiler Benoît , Boespflug-Tanguy Odile , Naudion Sophie , Laquerrière Annie
Published: April 2020

Bi-allelic pathogenic variants in genes of the EIF2B family are responsible for Childhood Ataxia with Central nervous system Hypomyelination/Vanishing White Matter disease, a progressive neurodegenerative disorder of the central white matter. Only seven molecularly proven cases with antenatal onset have been reported so far. We report for the first time the neuropathological findings obtained from two foetuses harbouring deleterious variants in the EIF2B5 gene who presented in utero growth retardation and microcephaly with simplified gyral pattern that led to a medical termination of the pregnancy at 27 and 32 weeks of gestation. Neuropathological examination confirmed microcephaly with delayed gyration, periventricular pseudo-cysts and severe cerebellar hypoplasia. Histologically, the cerebellar cortex was immature, the dentate nuclei were fragmented and myelin stains revealed almost no myelination of the infratentorial structures. Bergmann glia was virtually absent associated to a drastic decreased number of mature astrocytes in the cerebellar white matter, multiple nestin-positive immature astrocytes as well as increased numbers of PDGRFα-positive oligodendrocyte precursors. Whole exome sequencing performed in the two foetuses and their parents allowed the identification of two EIF2B5 compound heterozygous variants in the two foetuses: c.468C > G p.Ile156Met and c.1165G > A p.Val389Met, the parents being heterozygous carriers. These variants are absent in the genome Aggregation Database (gnomAD r2.0.2). Contrary to the variant Ile156Met already described in a patient with CACH syndrome, the variant p.Val389Met is novel and predicted to be deleterious using several softwares. Neuropathological findings further expand the phenotypic spectrum of the disease that very likely occurs during early gestation and may manifest from the second half of pregnancy by a severe impairment of cerebral and cerebellar development.
Using an artificial life simulation to enhance reflective critical thinking among student teachers
Authors: Bunt Byron , Gouws Grantt
Published: April 2020

This paper presents a methodology for developing critical reflection among student teachers by using a novel artificial life simulation called Creatures. The paper is a report of an initial investigation that connects some theory to the affordances of a particular video game, and is a conceptual paper. In this paper, the various theories and concepts central to the methodology is outlined, and ultimately be combined and explored in depth. The game Creatures is also explored for its potential use as a reflective teaching tool. The actual methodology is then outlined for future research using this approach, ultimately concluding with tentative hypotheses regarding the significance of using artificial life for teacher education. Based on our combined experience in a higher education context lecturing education modules, student teachers do not critically reflect on their practice sufficiently and especially on the impact that their teaching will have on learners in the future. The Creatures simulation offers a viable solution to this problem, in which artificial creatures called Norns can be interacted with and taught important language and behavioral skills. In so doing, the student teachers who play the simulation may have a non-invasive manner in which to experience firsthand how their decisions may impact on future learning, and to reflect upon it using critical reflection.
Coincidence energy spectra due to the intrinsic radioactivity of LYSO scintillation crystals
Authors: Enríquez-Mier-y-Terán Francisco Eduardo , Ortega-Galindo Ana Saret , Murrieta-Rodríguez Tirso , Rodríguez-Villafuerte Mercedes , Martínez-Dávalos Arnulfo , Alva-Sánchez Héctor
Published: April 2020

Background

Lutetium oxyorthosilicate or lutetium yttrium oxyorthosilicate (LYSO) scintillation crystals used in most current PET scanner detectors contain 176Lu, which decays by beta emission to excited states of 176Hf accompanied by the emission of prompt gamma rays or internal conversion electrons. This intrinsic radioactivity can be self-detected in singles mode as a constant background signal that has an energy spectrum whose structure has been explained previously. In this work, we studied the energy spectrum due to the intrinsic radioactivity of LYSO scintillation crystals of two opposing detectors working in coincidence mode. The investigation included experimental data, Monte Carlo simulations and an analytical model.

Results

The structure of the energy spectrum was completely understood and is the result of the self-detection of beta particles from 176Lu in one crystal and the detection of one or more prompt gamma rays detected in coincidence by the opposing crystal. The most probable coincidence detection involves the gamma rays of 202 and 307 keV, which result in two narrow photopeaks, superimposed on a continuous energy distribution due to the beta particle energy deposition. The relative intensities of the gamma ray peaks depend on crystal size and detector separation distance, as is explained by the analytical model and verified through the Monte Carlo simulations and experiments.

Conclusions

The analytical model used in this work accurately explains the general features of the coincidence energy spectrum due to the presence of 176Lu in the scintillation crystals, as observed experimentally and with Monte Carlo simulations. This work will be useful to those research studies aimed at using the intrinsic radioactivity of LYSO crystals for transmission scans and detector calibration in coincidence mode.
Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor
Authors: García Patricia , Bizama Carolina , Rosa Lorena , Espinoza Jaime A. , Weber Helga , Cerda-Infante Javier , Sánchez Marianela , Montecinos Viviana P. , Lorenzo-Bermejo Justo , Boekstegers Felix , Dávila-López Marcela , Alfaro Francisca , Leiva-Acevedo Claudia , Parra Zasha , Romero Diego , Kato Sumie , Leal Pamela , Lagos Marcela , Roa Juan Carlos
Published: April 2020

Background

Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry.

Results

After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes. RNA sequencing confirmed the increased expression of cytokeratin and mucin genes, and also of TP53 and ERBB2 with some differences among the three cells lines, and revealed a novel exonic mutation in NF1. The PUC-GBC3 clone was the most aggressive according to histopathological features and the tumorigenic capacity in NSG mice.

Conclusions

The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.
The prevalence of anxiety symptoms in infertile women: a systematic review and meta-analysis
Authors: Kiani Zahra , Simbar Masoumeh , Hajian Sepideh , Zayeri Farid , Shahidi Maryam , Saei Ghare Naz Marzieh , Ghasemi Vida
Published: April 2020

Background

Infertile women are exposed more frequently to anxiety risk than are infertile men, thereby adversely affecting the procedures with which they are treated and the quality of their lives. Yet, this problem is often disregarded. This study accordingly determined the prevalence of anxiety symptoms among infertile women.

Methods

All Persian and English studies published from the early 2000s to May 2019 were searched in international (i.e., PubMed, the Cochrane Library, Web of Science, Scopus, Embase, and PsycINFO) and national (i.e., SID, Magiran) databases as well as through Google Scholar. After the titles and abstracts of the articles were reviewed, their quality was evaluated, and relevant works for examination were selected in consideration of established inclusion and exclusion criteria. The risk of biases of individual studies according to Newcastle - Ottawa Scale was assessed. The heterogeneity of the studies was assessed using the I2 statistic, and indicators of publication bias were ascertained using Egger’s test. Stata (version 14) was employed in analyzing the findings.

Results

Thirteen studies having a collective sample size of 5055 infertile women were subjected to meta-analysis, with study heterogeneity incorporated into a random effects model. The findings indicated that 36% of the infertile women involved in the evaluated studies self-reported their experience with anxiety. The pooled prevalence of the condition among the subjects was 36.17% [95% confidence interval (CI): 22.47–49.87]. The pooled prevalence levels in low- and middle-income countries and high-income countries were 54.24% (95% CI: 31.86–78.62) and 25.05% (95% CI: 15.76–34.34), respectively. The results revealed no evidence of publication bias (P Egger’s test = 0.406).

Conclusion

Considering the prevalence of anxiety in infertile women and its effects on health processes and quality of life, this problem requires serious consideration and planning for effective intervention, especially in low- and middle-income nations.
Orthotopic heart transplantation with reconstruction of persistent left superior vena cava
Authors: Handa Kazuma , Hata Hiroki , Toda Koichi , Miyagawa Shigeru , Yoshikawa Yasushi , Yoshioka Daisuke , Sawa Yoshiki
Published: April 2020

Background

Persistent left superior vena cava is a not uncommon congenital vascular abnormality. We report a case of heart transplantation with reconstruction of persistent left superior vena cava using a prosthetic vascular graft.

Case presentation

A 20-year-old man with idiopathic dilated cardiomyopathy and persistent left superior vena cava underwent orthotopic heart transplantation 2 years and 3 months after left ventricular assist device implantation. Because the persistent left superior vena cava had a larger diameter than the right superior vena cava, the transected persistent left superior vena cava was reconstructed with a prosthetic vascular graft anastomosed to the free wall of the right atrium. Postoperative enhanced computed tomography revealed good patency of the graft. The patient’s postoperative course has been uneventful during 2 years of follow-up, despite the risk of complications.

Conclusions

Reconstruction of a persistent left superior vena cava with a prosthetic vascular graft may be one option at the time of heart transplantation.
Undernutrition among Ethiopian adults living with HIV: a meta-analysis
Authors: Alebel Animut , Kibret Getiye Dejenu , Petrucka Pammla , Tesema Cheru , Moges Nurilign Abebe , Wagnew Fasil , Asmare Getnet , Kumera Gemechu , Bitew Zebenay Workneh , Ketema Daniel Bekele , Tiruneh Tesfahun , Melkamu Mamaru Wubale , Hibstie Yitbarek Tenaw , Temesgen Belisty , Eshetie Setegn
Published: April 2020

Background

Malnutrition and human immunodeficiency virus (HIV) are interlaced in a vicious cycle and worsened in low and middle-income countries. In Ethiopia, even though individuals are dually affected by both malnutrition and HIV, there is no a nationwide study showing the proportion of malnutrition among HIV-positive adults. Consequently, this review addressed the pooled burden of undernutrition among HIV-positive adults in Ethiopia.

Methods

We searched for potentially relevant studies through manual and electronic searches. An electronic search was carried out using the database of PubMed, Google Scholar, and Google for gray literature and reference lists of previous studies. A standardized data extraction checklist was used to extract the data from each original study. STATA Version 13 statistical software was used for our analysis. Descriptive summaries were presented in tables, and the quantitative result was presented in a forest plot. Heterogeneity within the included studies was examined using the Cochrane Q test statistics andI2test. Finally, a random-effects meta-analysis model was computed to estimate the pooled proportion of undernutrition among HIV-positive adults.

Results

After reviewing 418 studies, 15 studies met the inclusion criteria and were included in the meta-analysis. Findings from 15 studies revealed that the pooled percentage of undernutrition among HIV-positive adults in Ethiopia was 26% (95% CI: 22, 30%). The highest percentage of undernutrition (46.8%) was reported from Jimma University specialized hospital, whereas the lowest proportion of undernutrition (12.3%) was reported from Dilla Hospital. The subgroup analyses of this study also indicated that the percentage of undernourishment among HIV-positive adults is slightly higher in the Northern and Central parts of Ethiopia (27.5%) as compared to the Southern parts of Ethiopia (25%).

Conclusion

This study noted that undernutrition among HIV-positive adults in Ethiopia was quite common. This study also revealed that undernutrition is more common among HIV-positive adults with advanced disease stage, anemia, diarrhea, CD4 count less than 200 cells/mm3, and living in rural areas. Based on our findings, we suggested that all HIV-positive adults should be assessed for nutritional status at the time of ART commencement.
Hemorrhagic complications associated with suprachoroidal buckling
Authors: Antaki Fares , Dirani Ali , Ciongoli Marina Ravagnani , Steel David H. W. , Rezende Flavio
Published: April 2020

Background

Multiple surgical techniques exist for the repair of rhegmatogenous retinal detachments (RRD). Suprachoroidal buckling (SCB), consisting of injecting viscoelastic material in the suprachoroidal space to allow chorioretinal apposition, has been recently described in the repair of RRD. The aim of this study is to report the complications of SCB and to propose measures to decrease their incidence during the learning curve.

Methods

A total of 26 eyes of 26 patients who underwent a SCB procedure for the management of RRD secondary to a single or multiple retinal breaks were enrolled. Patients were operated between January 2014 and March 2017 at two academic institutions. Patient and retinal detachment characteristics were obtained from the charts. Surgical videos were reviewed for every case and intraoperative complications were recorded. Complications observed postoperatively were obtained from the charts.

Results

Sixteen eyes (62%) underwent SCB alone, 5 eyes (19%) underwent additional gas tamponade and 5 eyes (19%) had combined pars plana vitrectomy. The most common complication was hemorrhage (6 cases, 23%). There were no cases of ischemic choroidal changes or hyperpigmentation at the edge of the dome. All six complications occurred in phakic patients who had inferior RRD with retinal breaks in the inferior quadrants. Isolated subretinal hemorrhage occurred in 4 patients and isolated suprachoroidal hemorrhage in 1 patient, and those did not affect final visual outcome. Extensive combined subretinal and suprachoroidal hemorrhage occurred in one case, and was complicated by phthisis bulbi. Re-detachment occurred in 4/6 (67%) of patients, and 5/6 (83%) of patients required a secondary procedure. Three out of 6 patients (50%) had at least 2 lines of visual acuity improvement.

Conclusion

SCB performed for RRD can be associated with hemorrhagic complications. The hemorrhages are usually self-limited but may occasionally result in severe visual compromise when involving the suprachoroidal space. Specific surgical measures need to be undertaken in order to decrease the likelihood of complications and further studies are needed to assess the safety and efficacy of this technique.
Raising and stabilization phase of the sit-to-stand movement better discriminate healthy elderly adults from young subjects: a pilot cross-sectional study
Authors: Piano Leonardo , Geri Tommaso , Testa Marco
Published: April 2020

Background

The sit-to-stand (STS) test is usually included in the clinical assessment of balance and its instrumented analysis may support clinicians in objectively assessing the risk of falling. The aim of the present study was to assess if kinetic parameters of STS collected using a force platform, with particular focus on the raising and stabilization phase, could discriminate between young and older adults.

Methods

Twenty-four adults (age ranging from 18 to 65 years old) and 28 elderly adults (older than 65 years old) performed STS on a force platform. Data on ground reaction forces, sway, displacement and velocity of the center of pressure were gathered during the raising and the stabilization phases.

Results

elderly subjects showed significant greater global sway (146.97 vs 119.85; p < 0.05) and a higher velocity (vs 40.03 vs 34.35 mm/s; p < 0.05) of execution of STS. Between-group comparisons highlighted a greater postural sway in the raising phase (21.63 vs 13.58; p < 0.001) and a doubled sway during the stabilization phase (12.38 vs 4.98; p < 0.001).

Conclusions

The analysis of STS performed on a force platform provides further information about the age-specific pattern of STS execution. The stabilization phase of STS seems to be the more challenging for functional independent older adults and should be considered during balance assessment.

Further studies are needed to confirm findings and improve generalizability of this study.