bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactate dehydrogenase-elevating virus enhances natural killer cell-mediated immunosurveillance of mouse mesothelioma development
Authors: Mandour Mohamed F. , Soe Pyone Pyone , Uyttenhove Catherine , Van Snick Jacques , Marbaix Etienne , Coutelier Jean-Paul
Published: May 2020

Background

Viral infections can reduce early cancer development through enhancement of cancer immunosurveillance. This study was performed to analyse this effect of viral infection in a mouse model of solid tumor.

Methods

The experimental model used was the effect of BALB/c mouse infection by lactate dehydrogenase-elevating virus on AB1 mesothelioma cancer development.

Results

Acute infection with lactate dehydrogenase-elevating virus strongly reduced in vivo early AB1 mesothelioma growth and death resulting from cancer development. This effect was not due to a direct cytolytic effect of the virus on AB1 cells, but to an in vivo activation of natural killer cells. Gamma-interferon production rather than cytotoxic activity against AB1 cells mediated this protective effect. This gamma-interferon production by natural killer cells was dependent on interleukin-12 production.

Conclusions

Together with other reported effects of infectious agents on cancer development, this observation may support the hypothesis that enhancement of innate immunosurveillance against tumors may result from infection with common infectious agents through modulation of the host immune microenvironment.
Dynamic nature of somatic chromosomal mosaicism, genetic-environmental interactions and therapeutic opportunities in disease and aging
Authors: Vorsanova Svetlana G. , Yurov Yuri B. , Iourov Ivan Y.
Published: May 2020

Background

Somatic chromosomal mosaicism is the presence of cell populations differing with respect to the chromosome complements (e.g. normal and abnormal) in an individual. Chromosomal mosaicism is associated with a wide spectrum of disease conditions and aging. Studying somatic genome variations has indicated that amounts of chromosomally abnormal cells are likely to be unstable. As a result, dynamic changes of mosaicism rates occur through ontogeny. Additionally, a correlation between disease severity and mosaicism rates appears to exist. High mosaicism rates are usually associated with severe disease phenotypes, whereas low-level mosaicism is generally observed in milder disease phenotypes or in presumably unaffected individuals. Here, we hypothesize that dynamic nature of somatic chromosomal mosaicism may result from genetic-environmental interactions creating therapeutic opportunities in the associated diseases and aging.

Conclusion

Genetic-environmental interactions seem to contribute to the dynamic nature of somatic mosaicism. Accordingly, an external influence on cellular populations may shift the ratio of karyotypically normal and abnormal cells in favor of an increase in the amount of cells without chromosome rearrangements. Taking into account the role of somatic chromosomal mosaicism in health and disease, we have hypothesized that artificial changing of somatic mosaicism rates may be beneficial in individuals suffering from the associated diseases and/or behavioral or reproductive problems. In addition, such therapeutic procedures might be useful for anti-aging strategies (i.e. possible rejuvenation through a decrease in levels of chromosomal mosaicism) increasing the lifespan. Finally, the hypothesis appears to be applicable to any type of somatic mosacism.
Autophagy pathway upregulation in a human iPSC-derived neuronal model of Cohen syndrome with VPS13B missense mutations
Authors: Lee You-Kyung , Lee Soo-Kyeong , Choi Suin , Huh Yang Hoon , Kwak Ji-Hye , Lee Yong-Seok , Jang Deok-Jin , Lee Jae-Hyung , Lee Kyungmin , Kaang Bong-Kiun , Lim Chae-Seok , Lee Jin-A
Published: May 2020

Significant clinical symptoms of Cohen syndrome (CS), a rare autosomal recessive disorder, include intellectual disability, facial dysmorphism, postnatal microcephaly, retinal dystrophy, and intermittent neutropenia. CS has been associated with mutations in the VPS13B (vacuolar protein sorting 13 homolog B) gene, which regulates vesicle-mediated protein sorting and transport; however, the cellular mechanism underlying CS pathogenesis in patient-derived neurons remains uncertain. This report states that autophagic vacuoles accumulate in CS fibroblasts and the axonal terminals of CS patient-specific induced pluripotent stem cells (CS iPSC)-derived neurons; additionally, autophagic flux was significantly increased in CS-derived neurons compared to control neurons. VPS13B knockout HeLa cell lines generated using the CRISPR/Cas9 genome editing system showed significant upregulation of autophagic flux, indicating that VSP13B may be associated with autophagy in CS. Transcriptomic analysis focusing on the autophagy pathway revealed that genes associated with autophagosome organization were dysregulated in CS-derived neurons. ATG4C is a mammalian ATG4 paralog and a crucial regulatory component of the autophagosome biogenesis/recycling pathway. ATG4C was significantly upregulated in CS-derived neurons, indicating that autophagy is upregulated in CS neurons. The autophagy pathway in CS neurons may be associated with the pathophysiology exhibited in the neural network of CS patients.
Different effects of methylphenidate and atomoxetine on the behavior and brain transcriptome of zebrafish
Authors: Suzuki Shiho , Kimura Ryo , Maegawa Shingo , Nakata Masatoshi , Hagiwara Masatoshi
Published: May 2020

Attention deficit-hyperactivity disorder (ADHD) is a prevalent neuropsychiatric disorder found in children. It is characterized by inattention, hyperactivity, and impulsivity. Methylphenidate (MPH) and atomoxetine (ATX) are commonly prescribed for the treatment of ADHD. In the present study, we examined the behavioral and brain transcriptome changes in MPH-treated and ATX-treated zebrafish. In behavioral analysis, zebrafish showed opposite response to each treatment. MPH-treated fish showed higher anxiety-like behavior while ATX-treated fish showed lower anxiety-like behavior. Further, we performed RNA sequencing analysis of zebrafish brain to elucidate the underlying biological pathways associated with MPH and ATX treatment. Interestingly, we found that shared differentially expressed genes in MPH-treated and ATX-treated fish were instrumental in cholesterol biosynthesis pathway and were regulated in opposite manner. Our findings highlight the contrast between MPH and ATX, and may suggest the alterations in clinical practice for these medications and drug development for ADHD.
Inositol hexakisphosphate kinase-1 is a key mediator of prepulse inhibition and short-term fear memory
Authors: Kim Min-Gyu , Zhang Seungjae , Park Hoyong , Park Seung Ju , Kim Seyun , Chung ChiHye
Published: May 2020

Inositol phosphate metabolism has emerged as one of the key players in synaptic transmission. Previous studies have shown that the deletion of inositol hexakisphosphate kinase 1 (IP6K1), which is responsible for inositol pyrophosphate biosynthesis, alters probability of presynaptic vesicle release and short-term facilitation of glutamatergic synapses in mouse hippocampus. However, the behavioral and cognitive functions regulated by IP6K1 remain largely elusive. In this study, IP6K1-knockout mice exhibited decreased prepulse inhibition with no defects in Y-maze and elevated plus maze tests. Interestingly, IP6K1 knockout led to impaired short-term memory formation in a contextual fear memory retrieval test with no effect on long-term memory. Further, both hippocampal long-term potentiation and long-term depression in IP6K1-knockout mice were similar to those in the wild-type control. Taken together, the findings in this study suggest the physiological roles of IP6K1 and the associated inositol pyrophosphate metabolism in regulating sensorimotor gating as well as short-term memory.
A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk
Authors: Gentles Andrew J. , Hui Angela Bik-Yu , Feng Weiguo , Azizi Armon , Nair Ramesh V. , Bouchard Gina , Knowles David A. , Yu Alice , Jeong Youngtae , Bejnood Alborz , Forgó Erna , Varma Sushama , Xu Yue , Kuong Amanda , Nair Viswam S. , West Rob , van de Rijn Matt , Hoang Chuong D. , Diehn Maximilian , Plevritis Sylvia K.
Published: May 2020

Background

Tumors comprise a complex microenvironment of interacting malignant and stromal cell types. Much of our understanding of the tumor microenvironment comes from in vitro studies isolating the interactions between malignant cells and a single stromal cell type, often along a single pathway.

Result

To develop a deeper understanding of the interactions between cells within human lung tumors, we perform RNA-seq profiling of flow-sorted malignant cells, endothelial cells, immune cells, fibroblasts, and bulk cells from freshly resected human primary non-small-cell lung tumors. We map the cell-specific differential expression of prognostically associated secreted factors and cell surface genes, and computationally reconstruct cross-talk between these cell types to generate a novel resource called the Lung Tumor Microenvironment Interactome (LTMI). Using this resource, we identify and validate a prognostically unfavorable influence of Gremlin-1 production by fibroblasts on proliferation of malignant lung adenocarcinoma cells. We also find a prognostically favorable association between infiltration of mast cells and less aggressive tumor cell behavior.

Conclusion

These results illustrate the utility of the LTMI as a resource for generating hypotheses concerning tumor-microenvironment interactions that may have prognostic and therapeutic relevance.
Survive and Thrive in Brazil: The Boa Vista Early Childhood Program: study protocol of a stepped-wedge, randomized controlled trial
Authors: Brentani Alexandra , Ferrer Ana Paula Scolezze , Bessa Luana , Chang Susan , Walker Susan , Powell Christine , Hamadani Jena , Grisi Sandra , Fink Günther
Published: May 2020

Background

A growing body of evidence suggests that early life health and developmental outcomes can be improved through parental support programs. The objective of this project was to test the feasibility, impact, and relative cost-effectiveness of an adapted “Reach Up and Learn” program delivered through home-visiting programs as well as through center-based parenting groups on child health and development in the municipality of Boa Vista, Brazil.

Methods

A randomized, stepped-wedge design was used to roll out and evaluate the two parenting platforms in Boa Vista municipality. A total of 39 neighborhoods with a high Neighborhood Vulnerability Index were selected for the study. For the first phase of the program, nine neighborhoods were randomly selected for home visits, and two were randomly selected for the center-based parenting groups. In the second phase of the program, 10 neighborhoods were added to the home-visiting program, and eight were added to the center-based program. In the final phase of the program, the remaining 10 control areas will also be assigned to treatment. Study eligibility will be assessed through a baseline survey completed by all pregnant women in the 39 study areas. Pregnant women will be eligible to participate in the study if they are either classified as poor, were under age 20 years when they became pregnant, or if they indicate to have been exposed to domestic or sexual violence. To assess program impact, an endline survey will be conducted when children reach age 2 years. The primary study outcome is child development at age 2 years as measured by the PRIDI instrument. Secondary outcome will be infant mortality, which will be assessed linking municipal vital registration systems to the program rollout.

Discussion

This trial will assess the feasibility and impact of parenting programs rolled out at medium scale. The results from the trial should create evidence urgently needed for guiding Brazil’s national Criança Feliz program as well as similar efforts in other countries.

Trial registration

ClinicalTrials.gov, ID: NCT03386747. Registered on 13 December 2017. All items of the World Health Organization Trial Registration Data Set are available in this record.
An overview of malarial Anopheles mosquito survival estimates in relation to methodology
Authors: Matthews Justin , Bethel Alison , Osei Goldie
Published: May 2020

Background

The transmission of malaria is known to be sensitive to the survival (longevity, mortality) of its mosquito vector, yet there have been few reviews of estimates of this important population parameter in the malaria-carrying genusAnopheles.

Methods

We carried out a systematic search for and meta-analysis of survival estimates, framed around the methods of estimation, under the major groupings of ‛vertical’ (based on stable age or stage frequencies), ‛horizontal’ (based on recaptures of marked and released cohorts), and ‛parasitological’ (proportion of infectious mosquitoes). Because of the intricacies of the estimation process we provide an outline of these methods.

Results

By meta-analysis we quantify the average of the distribution of daily survival$$p$$pfor vertical (0.83, 95% CI: 0.80–0.86), horizontal (0.73, 95% CI: 0.66–0.79) and parasitological (0.92, 95% CI: 0.86–0.95) methods.

Conclusions

The meta-analysis demonstrates the anticipated result that horizontal estimates are lowest because they estimate apparent survival (survival and non-emigration) rather than true survival. On the other hand, vertical methods make strong assumptions about the stability or stationarity of the underlying populations. Further potential sources of methodological bias are mentioned. The substantial differences in estimates between methods indicates that methodological biases need to be considered when making use of available survival estimates.
Epidemiology of Taenia saginata taeniosis/cysticercosis: a systematic review of the distribution in East, Southeast and South Asia
Authors: Eichenberger Ramon M. , Thomas Lian F. , Gabriël Sarah , Bobić Branco , Devleesschauwer Brecht , Robertson Lucy J. , Saratsis Anastasios , Torgerson Paul R. , Braae Uffe C. , Dermauw Veronique , Dorny Pierre
Published: May 2020

Background

Taenia saginata is an important zoonotic parasite, causing taeniosis in humans and cysticercosis in bovines, the latter being a significant concern for the global beef industry. Many countries in East, Southeast and South Asia are experiencing rapid economic growth, and an increasing number of people in these countries are dependent on the livestock industry. Currently, however, an overview of the prevalence of T. saginata in this region is lacking. In this review, we analysed the available literature on T. saginata taeniosis and bovine cysticercosis for East, Southeast and South Asia.

Methods

A systematic review was conducted, based on both published and grey literature. Articles published between 1990 and 2017 were mined for information on the occurrence, prevalence, and geographical distribution of T. saginata taeniosis and bovine cysticercosis in East, Southeast and South Asia.

Results

The presence of T. saginata was described in 15 of 27 countries of the region, including Afghanistan, Cambodia, China, India, Indonesia, Japan, Lao PDR, Malaysia, Mongolia, Nepal, Pakistan, Philippines, South Korea, Thailand and Vietnam. The only country that reported an absence of T. saginata is Japan, although sporadic reports of imported cases and unconfirmed reports of autochthonous infections were identified. Nationwide surveys of taeniosis with systematic sample collection and high sample numbers were available for Cambodia, China, Lao PDR, and South Korea, although speciation of Taenia was not always performed. Regional prevalence of taeniosis and bovine cysticercosis in endemic regions ranged between 0.02–42.6%, and 0.76–46.7%, respectively. However, data for bovine cysticercosis were only available for five countries (Japan, Lao PDR, Mongolia, Pakistan and Vietnam).

Conclusions

The data indicate a widespread occurrence of T. saginata throughout East, Southeast and South Asia. Identification of Taenia spp. in human infections was frequently not performed, leading to gaps in knowledge about the distribution of human tapeworm infections, mainly in regions where different human Taenia species co-occur. A high prevalence of T. saginata taeniosis and bovine cysticercosis may reflect insufficiencies in sanitation, limited health education standards, and insufficient food safety measures. Therefore, there is a need to improve local surveillance, notification, and overall control systems.
The European Register of Cystic Echinococcosis, ERCE: state-of-the-art five years after its launch
Authors:   the ERCE network, Rossi Patrizia , Tamarozzi Francesca , Galati Fabio , Akhan Okan , Cretu Carmen Michaela , Vutova Kamenna , Siles-Lucas Mar , Brunetti Enrico , Casulli Adriano
Published: May 2020

Background

The real burden of human cystic echinococcosis (CE) remains elusive, due to the peculiar characteristics of the disease and the heterogeneous and incomplete data recording of clinical cases. Furthermore, official notification systems do not collect pivotal clinical information, which would allow the comparison of different treatment outcomes, and thus circumvent the difficulty of implementing clinical trials for CE. The Italian Register of CE (RIEC) was launched in 2012 and expanded in 2014 into the European Register of CE (ERCE). The primary aim of the ERCE was to highlight the magnitude of CE underreporting, through the recording of cases that were not captured by official records. We present an overview of data collated in the ERCE and discuss its future, five years after its inception.

Methods

The ERCE database was explored on March 31st 2019; data concerning participating centres and registered cases were descriptively analysed.

Results

Forty-four centres from 15 countries (7 non-European) were affiliated to the ERCE. Thirty-four centres (77%) registered at least one patient; of these, 18 (53%) recorded at least one visit within the past 18 months. A total of 2097 patients were registered, 19.9% of whom were immigrants. Cyst characteristics were reported for at least one cyst at least in one visit in 1643 (78.3%) patients, and cyst staging was used by 27 centres. In total, 3386 cysts were recorded at first registration; mostly located in the liver (75.5%). Data concerning clinical management could be analysed for 920 “cyst stage-location-management” observations, showing great heterogeneity in the implementation of the stage-specific management approach recommended by the WHO.

Conclusions

The ERCE achieved its goal in showing that CE is a relevant but neglected public health problem in Europe and beyond, since a proportion of patients reaching medical attention are not captured by official notification systems. The ERCE may provide a valuable starting platform to complement hospital-derived data, to obtain a better picture of the epidemiology of clinical CE, and to collect clinical data for the issue of evidence-based recommendations. The ERCE will be expanded into the International Register of CE (IRCE) and restructured aiming to overcome its current criticalities and fulfil these aims.
Biting rates and relative abundance of Simulium flies under different climatic conditions in an onchocerciasis endemic community in Ghana
Authors: Otabil Kenneth Bentum , Gyasi Samuel Fosu , Awuah Esi , Obeng-Ofori Daniels , Tenkorang Seth Boateng , Kessie Justice Amenyo , Schallig Henk D. F. H.
Published: May 2020

Background

Knowledge of the relative abundance and biting rates of riverine blackflies (vectors of onchocerciasis) is essential as these entomological indices affect transmission of the disease. However, transmission patterns vary from one ecological zone to another and this may be due to differences in species of blackfly vectors and the climatic conditions in the area. This study investigated the effects of climate variability on the relative abundance and biting rates of blackflies in the Tanfiano community (Nkoranza North District, Bono East Region, Ghana). Such information will help to direct policy on effective timing of the annual mass drug administration of ivermectin in the area.

Methods

The study employed human landing collections and locally built Esperanza window traps to collect blackflies from March 2018 to February 2019. The relative abundance and biting rates of the Simulium vectors as well as the monthly climatic conditions of the study area were monitored. Correlation analysis and Poisson regression were used to establish the relationships between the variables.

Results

The relative abundance and biting rates of the Simulium vectors were highest in the drier months of March, April and August, characterized by high temperatures, low humidity, longer hours of sunshine and stronger winds. The rainy months of May, June and July, characterized by low temperatures, high humidity, few hours of sunshine and weaker winds, had relatively low blackfly abundance and biting activity. Correlation analysis showed that only temperature was significantly, positively correlated with the relative abundance of blackflies (r = 0.617, n = 12, P = 0.033) and monthly biting rates (r = 0.612, n = 12, P = 0.034). A model to predict relative abundance and monthly biting rates using climatological variables was developed.

Conclusions

This study demonstrated that Simulium species in the study area preferred higher temperature, lower humidity and rainfall, more hours of sunshine and relatively stronger winds for survival. It is thus recommended that for the study district and others with similar climatological characteristics, mass drug administration of ivermectin should take place in April and September when the abundance of vectors has begun to decline after peaking.
Interactions between host biogenic amines and sand fly salivary yellow-related proteins
Authors: Spitzova Tatiana , Sumova Petra , Volfova Vera , Polanska Nikola , Poctova Luisa , Volf Petr
Published: May 2020

Background

During blood feeding, sand flies inoculate salivary proteins that interact with the host haemostatic system. The blocking of biogenic amines such as serotonin and histamine helps to limit vasodilatation and clot formation, and thus enables the insect to finish the blood-feeding process. In sand flies, an amine-binding ability is known only for the yellow-related proteins ofPhlebotomusandLutzomyiavectors, but not yet for members of the genusSergentomyia.

Methods

The ability ofPhlebotomus argentipesandSergentomyia schwetzirecombinant yellow-related salivary proteins to bind histamine and serotonin was measured by microscale thermophoresis. Both sand fly species were also fed through a chicken-skin membrane on blood mixed with histamine or serotonin in order to check the effects of biogenic amines on sand fly fitness. Additionally, fecundity and mortality were compared in two groups ofP. argentipesfemales fed on repeatedly-bitten and naive hamsters, respectively.

Results

TheP. argentipesrecombinant yellow-related protein PagSP04 showed high binding affinity to serotonin and low affinity to histamine. No binding activity was detected for two yellow-related proteins ofS. schwetzi. Elevated concentrations of serotonin significantly reduced the amount of eggs laid byP. argentipeswhen compared to the control. The fecundity ofS. schwetziand the mortality of both sand fly species were not impaired after the experimental membrane feeding. Additionally, there were no differences in oviposition or mortality betweenP. argentipesfemales fed on immunized or naive hamsters.

Conclusions

Our results suggest that in natural conditions sand flies are able to cope with biogenic amines or anti-saliva antibodies without any influence on their fitness. The serotonin binding by salivary yellow-related proteins may play an important role inPhlebotomusspecies feeding on mammalian hosts, but not inS. schwetzi, which is adapted to reptiles.
The absence of the drhm gene is not a marker for human-pathogenicity in European Anaplasma phagocytophilum strains
Authors: Langenwalder Denis B. , Schmidt Sabine , Silaghi Cornelia , Skuballa Jasmin , Pantchev Nikola , Matei Ioana A. , Mihalca Andrei D. , Gilli Urs , Zajkowska Joanna , Ganter Martin , Hoffman Tove , Salaneck Erik , Petrovec Miroslav , von Loewenich Friederike D.
Published: May 2020

Background

Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophil granulocytes. It is transmitted by ticks of the Ixodes ricinus complex and causes febrile illness in humans and animals. The geographical distribution of A. phagocytophilum spans the Americas, Europe, Africa and Asia. However, human disease predominantly occurs in North America but is infrequently reported from Europe and Asia. In North American strains, the absence of the drhm gene has been proposed as marker for pathogenicity in humans whereas no information on the presence or absence of the drhm gene was available for A. phagocytophilum strains circulating in Europe. Therefore, we tested 511 European and 21 North American strains for the presence of drhm and compared the results to two other typing methods: multilocus sequence typing (MLST) and ankA-based typing.

Results

Altogether, 99% (478/484) of the analyzable European and 19% (4/21) of the North American samples from different hosts were drhm-positive. Regarding the strains from human granulocytic anaplasmosis cases, 100% (35/35) of European origin were drhm-positive and 100% (14/14) of North American origin were drhm-negative. Human strains from North America and Europe were both part of MLST cluster 1. North American strains from humans belonged to ankA gene clusters 11 and 12 whereas European strains from humans were found in ankA gene cluster 1. However, the North American ankA gene clusters 11 and 12 were highly identical at the nucleotide level to the European cluster 1 with 97.4% and 95.2% of identity, respectively.

Conclusions

The absence of the drhm gene in A. phagocytophilum does not seem to be associated with pathogenicity for humans per se, because all 35 European strains of human origin were drhm-positive. The epidemiological differences between North America and Europe concerning the incidence of human A. phagocytophilum infection are not explained by strain divergence based on MLST and ankA gene-based typing.
Comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approaches
Authors: Chairta Paraskevi , Nicolaou Paschalis , Sokratous Kleitos , Galant Christine , Houssiau Frédéric , Oulas Anastasis , Spyrou George M. , Alarcon-Riquelme Marta E. , Lauwerys Bernard R. , Christodoulou Kyproula
Published: May 2020

Background

Pathogenesis and aetiology of systemic sclerosis (SSc) are currently unclear, thus rendering disease prognosis, diagnosis and treatment challenging. The aim of this study was to use paired skin biopsy samples from affected and unaffected areas of the same patient, in order to compare the proteomes and identify biomarkers and pathways which are associated with SSc pathogenesis.

Methods

Biopsies were obtained from affected and unaffected skin areas of SSc patients. Samples were cryo-pulverised and proteins were extracted and analysed using mass spectrometry (MS) discovery analysis. Differentially expressed proteins were revealed after analysis with the Progenesis QIp software. Pathway analysis was performed using the Enrichr Web server. Using specific criteria, fifteen proteins were selected for further validation with targeted-MS analysis.

Results

Proteomic analysis led to the identification and quantification of approximately 2000 non-redundant proteins. Statistical analysis showed that 169 of these proteins were significantly differentially expressed in affected versus unaffected tissues. Pathway analyses showed that these proteins are involved in multiple pathways that are associated with autoimmune diseases (AIDs) and fibrosis. Fifteen of these proteins were further investigated using targeted-MS approaches, and five of them were confirmed to be significantly differentially expressed in SSc affected versus unaffected skin biopsies.

Conclusion

Using MS-based proteomics analysis of human skin biopsies from patients with SSc, we identified a number of proteins and pathways that might be involved in SSc progression and pathogenesis. Fifteen of these proteins were further validated, and results suggest that five of them may serve as potential biomarkers for SSc.
Host responses to Clostridium perfringens challenge in a chicken model of chronic stress
Authors: Zaytsoff Sarah J. M. , Lyons Sarah M. , Garner Alexander M. , Uwiera Richard R. E. , Zandberg Wesley F. , Abbott D. Wade , Inglis G. Douglas
Published: May 2020

Background

This study utilized a chicken model of chronic physiological stress mediated by corticosterone (CORT) administration to ascertain how various host metrics are altered upon challenge with Clostridium perfringens. Necrotic enteritis (NE) is a disease of the small intestine of chickens incited by C. perfringens, which can result in elevated morbidity and mortality. The objective of the current study was to investigate how physiological stress alters host responses and predisposes birds to subclinical NE.

Results

Birds administered CORT exhibited higher densities of C. perfringens in their intestine, and this corresponded to altered production of intestinal mucus. Characterization of mucus showed that C. perfringens treatment altered the relative abundance of five glycans. Birds inoculated with C. perfringens did not exhibit evidence of acute morbidity. However, histopathologic changes were observed in the small intestine of infected birds. Birds administered CORT showed altered gene expression of tight junction proteins (i.e. CLDN3 and CLDN5) and toll-like receptors (i.e. TLR2 and TLR15) in the small intestine. Moreover, birds administered CORT exhibited increased expression of IL2 and G-CSF in the spleen, and IL1β, IL2, IL18, IFNγ, and IL6 in the thymus. Body weight gain was impaired only in birds that were administered CORT and challenged with C. perfringens.

Conclusion

CORT administration modulated a number of host functions, which corresponded to increased densities of C. perfringens in the small intestine and weight gain impairment in chickens. Importantly, results implicate physiological stress as an important predisposing factor to NE, which emphasizes the importance of managing stress to optimize chicken health.
The association of low serum salivary and pancreatic amylases with the increased use of lipids as an energy source in non-obese healthy women
Authors: Nakajima Kei , Higuchi Ryoko , Iwane Taizo , Iida Ayaka
Published: May 2020

Objective

It is unknown whether low serum levels of salivary and pancreatic amylases are associated with the high combustion of carbohydrates or lipids for energy. Elevated blood ketones and a low respiratory quotient (RQ) can reflect the preferential combustion of lipids relative to carbohydrates. Therefore, using the data from our previous study, we investigated if low levels of serum amylases were associated with a high serum ketone level and low RQ in 60 healthy non-obese young women aged 20–39 years old.

Results

Serum ketones [3-hydroxybutyric acid (3-HBA) and acetoacetic acid (AA)] were inversely correlated with RQs, but not body mass index (BMI) or glycated haemoglobin (HbA1c) levels. Logistic regression analysis showed that high levels of serum ketones (3-HBA ≥ 24 μmol/L and AA ≥ 17 μmol/L) and a low RQ (< 0.766) were significantly associated with low serum salivary (< 60 U/L) and pancreatic (< 29 U/L) amylase levels, respectively. These associations were not altered by further adjustments for age, BMI, HbA1c, and estimated glomerular filtration rate. These results confirm the high combustion of lipids for energy in individuals with low serum amylase levels, suggesting a close relationship between circulating amylases and internal energy production.
Risk stratification of HPV 16 DNA methylation combined with E6 oncoprotein in cervical cancer screening: a 10-year prospective cohort study
Authors: Dong Li , Zhang Li , Hu Shang-Ying , Feng Rui-Mei , Zhao Xue-Lian , Zhang Qian , Pan Qin-Jing , Zhang Xun , Qiao You-Lin , Zhao Fang-Hui
Published: May 2020

Background

How to best triage human papillomavirus (HPV) positive women remains controversial in an era of HPV primary screening of cervical cancer. Here, we assessed the long-term risk stratification for triaging HPV 16 positive women by standalone HPV 16 methylation and combined with E6 oncoprotein.

Methods

 A total of 1742 women underwent screening with HPV DNA testing, cytology, and visual inspection with acetic acid (VIA) in 2005 and were followed for 10 years. Seventy-seven women with HPV 16 positivity determined by HPV genotyping test were examined via E6 oncoprotein detection and bisulfite pyrosequencing for quantitative methylation of L1 and LCR genes of HPV 16.

Results

The 10-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 3 or severe (CIN3+) for HPV 16 positive women was 25.3% (95% CI 14.7–37.3%), which significantly increased in women with high methylation at six sites (CpG 5602, 6650, 7034, 7461, 31, and 37) and in women with positive E6 oncoprotein. A methylation panel based on the above six sites showed a competitive risk stratification compared to cytology (HR 11.5 vs. 8.1), with a higher 10-year CIR of CIN3+ in panel positives (57.2% vs 36.8%) and comparable low risk in panel negatives (5.7% vs 4.8%).The sensitivity and specificity for accumulative CIN3+ was 85.7% (95%CI 60.1–96.0%) and 78.4% (95%CI 62.8–88.6%) for a methylation panel and 57.1% (95%CI 32.6–78.6%) and 86.5% (95%CI 72.0–94.1%) for E6 oncoprotein. The AUC values of methylation standalone and the co-testing of methylation panel and E6 oncoprotein were around 0.80, comparable to 0.68 for cytology, 0.65 for viral load, and superior to 0.52 for VIA (p < 0.05).

Conclusions

Our findings indicated the promising use of HPV 16 methylation alone or combined with E6 oncoprotein for triaging HPV 16 positive women based on the long-term risk stratification ability.
Cord blood-endothelial colony forming cells are immunotolerated and participate at post-ischemic angiogenesis in an original dorsal chamber immunocompetent mouse model
Authors: Proust Richard , Ponsen Anne-Charlotte , Rouffiac Valérie , Schenowitz Chantal , Montespan Florent , Ser-Le Roux Karine , De Leeuw Frédéric , Laplace-Builhé Corinne , Mauduit Philippe , Carosella Edgardo D. , Banzet Sébastien , Lataillade Jean-Jacques , Rouas-Freiss Nathalie , Uzan Georges , Peltzer Juliette
Published: May 2020

Background

Cardiovascular diseases are the main cause of morbidity and mortality worldwide. Restoring blood supply to ischemic tissues is an essential goal for the successful treatment of these diseases. Growth factor or gene therapy efficacy remains controversial, but stem cell transplantation is emerging as an interesting approach to stimulate angiogenesis. Among the different stem cell populations, cord blood-endothelial progenitor cells (CB-EPCs) and more particularly cord blood-endothelial progenitor cell-derived endothelial colony forming cells (CB-ECFCs) have a great proliferative potential without exhibiting signs of senescence. Even if it was already described that CB-ECFCs were able to restore blood perfusion in hind-limb ischemia in an immunodeficient mouse model, until now, the immunogenic potential of allogenic CB-ECFCs remains controversial. Therefore, our objectives were to evaluate the immune tolerance potency of CB-ECFCs and their capacity to restore a functional vascular network under ischemic condition in immunocompetent mice.

Methods

In vitro, the expression and secretion of immunoregulatory markers (HLA-G, IL-10, and TGF-β1) were evaluated on CB-ECFCs. Moreover, CB-ECFCs were co-cultured with activated peripheral blood mononuclear cells (PBMCs) for 6 days. PBMC proliferation was evaluated by [3H]-thymidine incorporation on the last 18 h. In vivo, CB-ECFCs were administered in the spleen and muscle of immunocompetent mice. Tissues were collected at day 14 after surgery. Finally, CB-ECFCs were injected intradermally in C57BL/6JRj mice close to ischemic macrovessel induced by thermal cauterization. Mice recovered until day 5 and were imaged, twice a week until day 30.

Results

Firstly, we demonstrated that CB-ECFCs expressed HLA-G, IL-10, and TGF-β1 and secreted IL-10 and TGF-β1 and that they could display immunosuppressive properties in vitro. Secondly, we showed that CB-ECFCs could be tolerated until 14 days in immunocompetent mice. Thirdly, we revealed in an original ischemic model of dorsal chamber that CB-ECFCs were integrated in a new functional vascular network.

Conclusion

These results open up new perspectives about using CB-ECFCs as an allogeneic cell therapy product and gives new impulse to the treatment of cardiovascular diseases.
One-year survival in acute stroke patients requiring mechanical ventilation: a multicenter cohort study
Authors:   OUTCOMEREA Study Group, de Montmollin Etienne , Terzi Nicolas , Dupuis Claire , Garrouste-Orgeas Maité , da Silva Daniel , Darmon Michaël , Laurent Virginie , Thiéry Guillaume , Oziel Johana , Marcotte Guillaume , Gainnier Marc , Siami Shidasp , Sztrymf Benjamin , Adrie Christophe , Reignier Jean , Ruckly Stephane , Sonneville Romain , Timsit Jean-François
Published: May 2020

Background

Most prognostic studies in acute stroke patients requiring invasive mechanical ventilation are outdated and have limitations such as single-center retrospective designs. We aimed to study the association of ICU admission factors, including the reason for intubation, with 1-year survival of acute stroke patients requiring mechanical ventilation.

Methods

We conducted a secondary data use analysis of a prospective multicenter database (14 ICUs) between 1997 and 2016 on consecutive ICU stroke patients requiring mechanical ventilation at admission. We excluded patients with stroke of traumatic origin, subdural hematoma or cerebral venous thrombosis. The primary outcome was survival 1 year after ICU admission. Factors associated with the primary outcome were identified using a multivariable Cox model stratified on inclusion center.

Results

We identified 419 patients (age 68 [58–76] years, males 60%) with a Glasgow coma score (GCS) of 4 [3–8] at admission. Stroke subtypes were acute ischemic stroke (AIS, 46%), intracranial hemorrhage (ICH, 42%) and subarachnoid hemorrhage (SAH, 12%). At 1 year, 96 (23%) patients were alive. Factors independently associated with decreased 1-year survival were ICH and SAH stroke subtypes, a lower GCS score at admission, a higher non-neurological SOFA score. Conversely, patients receiving acute-phase therapy had improved 1-year survival. Intubation for acute respiratory failure or coma was associated with comparable survival hazard ratios, whereas intubation for seizure was not associated with a worse prognosis than for elective procedure. Survival did not improve over the study period, but patients included in the most recent period had more comorbidities and presented higher severity scores at admission.

Conclusions

In acute stroke patients requiring mechanical ventilation, the reason for intubation and the opportunity to receive acute-phase stroke therapy were independently associated with 1-year survival. These variables could assist in the decision process regarding the initiation of mechanical ventilation in acute stroke patients.
Big data security access control algorithm based on memory index acceleration in WSNs
Authors: Peng Jianhua , Zhou Hui , Meng Qingjie , Yang Jingli
Published: May 2020

The access control is used to ensure these data security when WSN (wireless sensor network) with a large number of base stations transmits huge amount of data to a data center server. Meanwhile big data systems are used to efficiently store, manage, and use data from large-scale WSNs. In big data systems for WSNs, the traditional access control technology will greatly affect the system performance. This paper first analyzes the data processing flow of the traditional access control strategy in big data systems, analyzes its time complexity, and explores how it affects system performance. Then, we propose the big data security access control algorithm based on memory index acceleration in WSNs which has better performance over the traditional ones. In our experiments, under the same test environment and security strategy, the performance has been greatly improved with the proposed algorithm.
Endpoint boundedness for commutators of singular integral operators on weighted generalized Morrey spaces
Authors: Qi Jinyun , Yan Xuefang , Li Wenming
Published: May 2020

In this paper, we obtain the endpoint boundedness for the commutators of singular integral operators with BMO functions and the associated maximal operators on weighted generalized Morrey spaces. We also get similar results for the commutators of fractional integral operators with BMO functions and the associated maximal operators.
New inequalities between the inverse hyperbolic tangent and the analogue for corresponding functions
Authors: Chen Xiao-Diao , Nie Long , Huang Wangkang
Published: May 2020

In this paper, we present new inequalities which reveal further relationship for both the inverse tangent function $\arctan (x)$arctan(x) and the inverse hyperbolic function $\operatorname{arctanh}(x)$arctanh(x). At the same time, we give the analogue for inverse hyperbolic tangent and other corresponding functions.
Evolution of field-aligned current in the meridional plane during substorm: multipoint observations from satellites and ground stations
Authors: Imajo Shun , Nosé Masahito , Aida Mari , Higashio Nana , Matsumoto Haruhisa , Kiyokazu Koga , Smith Charles , MacDowall Robert J. , Yoshikawa Akimasa
Published: May 2020

We report the propagation of substorm-associated magnetic fluctuations by multipoint magnetic observations from ground and space in the same meridional plane. The first Quasi-Zenith Satellite (QZS-1), which has a unique orbit of quasi-zenith orbit with an inclination of $$41^\circ$$41∘, an apogee of 7.1 $$R_E$$RE radial distance, and an orbital period of 24 h, can stay for a long time in the near-earth magnetotail away from the magnetic equator. We examined a substorm event during 15:00–16:00 UT on July 09, 2013 when QZS-1 was located at $$31^\circ$$31∘ dipole latitude and 23.5 h dipole magnetic local time. The Engineering Test Satellite VIII (ETS-VIII), Time History of Events and Macroscale Interactions during Substorms D (THEMIS-D) at a radial distance of $$\sim 10$$∼10$$R_E$$RE, and THEMIS-E at a radial distance of $$\sim 7$$∼7$$R_E$$RE were located near the equator in the similar magnetic meridian. The dipolarization was first observed at THEMIS-D at 15:14:30 UT. Then, $$\sim 1$$∼1 min later, magnetic fluctuations were observed by ETS-VIII and THEMIS-E. At the same time, the magnetic bay and Pi2 pulsation were observed at low-latitude magnetic observatories and the Radiation Belt Storm Probes B satellite in the inner magnetosphere. We found that QZS-1 away from the equator observed a strong azimuthal magnetic field fluctuation with a long delay of 15 min from the first dipolarization at THEMIS-D near the equator. The speed of the poleward propagating magnetic fluctuation between the ionospheric footprints is calculated to be 310 $$\left[ \mathrm{m}/\mathrm{s}\right]$$m/s, which is consistent with a typical speed of auroral poleward expansion. A similar time delay of the onset of the negative bay was observed between the Tixie (AACGM $$\hbox {MLAT}=66.8^\circ$$MLAT=66.8∘) and Kotelny (AACGM $$\hbox {MLAT}=71.0^\circ$$MLAT=71.0∘) observatories near the ionospheric footprint of satellites. We suggest that the long delay time of the magnetic fluctuation at QZS-1 was associated with the crossing of field-aligned current during the poleward expansion of the substorm current system. The distribution of azimuthal magnetic field variations in the magnetosphere indicates that the east side downward current extended more west side in the higher latitude part of the current wedge.
A case study of correspondence between Pc1 activity and ionospheric irregularities at polar latitudes
Authors: Francia P. , Regi M. , De Lauretis M. , Pezzopane M. , Cesaroni C. , Spogli L. , Raita T.
Published: May 2020

A possible driver of precipitation of magnetospheric energetic electrons in the high-latitude atmosphere is represented by electromagnetic ion-cyclotron (EMIC) magnetospheric waves. The precipitating particles produce variations, by collision, in the ionized component of the atmosphere, altering its chemistry and electrical conductivity, with a significant impact on the atmospheric processes. In this framework, it would be significant to find experimental evidence of a correspondence between ionospheric electron density irregularities and the occurrence of Ultra-Low-Frequency (ULF) Pc1 geomagnetic pulsations, i.e., the ground signatures of EMIC waves, at high latitudes. In this work, we face this subject by considering a specific case study occurred on 22 February 2007 during quiet magnetospheric conditions. The study is based on the analysis of simultaneous ULF geomagnetic field and Total Electron Content (TEC) measurements recorded at Mario Zucchelli Station in Antarctica. We show that Pc1 pulsations occur in correspondence to solar wind pressure increases and that, at the same time, the ionosphere is characterized by the presence of ionospheric irregularities. We suggest that a possible link between the Pc1 activity and the ionospheric irregularities may be energetic electron precipitations, driven by EMIC waves generated in the compressed magnetosphere, which produce density variations in the ionized component of the atmosphere.
Unclassified hepatocellular adenoma with histological brown pigment deposition and serum PIVKA-II level elevation: a case report
Authors: Hoshino Kouki , Harimoto Norifumi , Muranushi Ryo , Hagiwara Kei , Yamanaka Takahiro , Ishii Norihiro , Tsukagoshi Mariko , Igarashi Takamichi , Watanabe Akira , Kubo Norio , Araki Kenichiro , Tomomasa Ran , Nobusawa Sumihito , Aishima Shinichi , Nakashima Osamu , Shirabe Ken
Published: May 2020

Background

Hepatocellular adenoma (HCA) is conventionally considered a rare benign liver tumor, but advanced studies have revealed that HCA is heterogeneous, and may include a type that is prone to malignant transformations. Differentiation between well-differentiated hepatocellular carcinoma and focal nodular hyperplasia is necessary to diagnose hepatocellular adenoma through imaging; however, the tumor marker of hepatocellular carcinoma, protein induced by vitamin K absence, or antagonist II (PIVKA-II), is rarely positive in hepatocellular adenoma.

Case presentation

A 44-year-old woman presented to our hospital with complaints of loss of appetite and weight loss. Multidetector row computed tomography revealed a liver tumor (diameter, 80 mm) that was enhanced in the arterial phase. Her serum PIVKA-II level was very high (3327 mAU/mL). Based on the enlargement of the mass and the results of the diagnostic imaging, hepatocellular adenoma or hepatocellular carcinoma was suspected, and we considered the possibility of a malignant transformation due to the high level of serum PIVKA-II; thus, we performed hepatectomy. Histological examination showed brown pigment deposition in the hepatocytes, which was determined to be lipofuscin granules. Based on immunohistochemical findings, the diagnosis was unclassified hepatocellular adenoma. Immunohistochemical examinations revealed that the adenoma cells in the tumor were positive for PIVKA-II. Her serum PIVKA-II level returned to normal after the resection.

Conclusions

We present a case of unclassified hepatocellular adenoma with brown pigment deposition and elevation of serum PIVKA-II level. For the differentiation of liver tumors with high levels of PIVKA-II and hypervascular mass, hepatocellular adenoma should be considered.