bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990–2019
Authors: Lawal Tokunbor A. , Wires Emily S. , Terry Nancy L. , Dowling James J. , Todd Joshua J. 
Published: May 2020

AbstractBackgroundPathogenic variations in the gene encoding the skeletal muscle ryanodine receptor (RyR1) are associated with malignant hyperthermia (MH) susceptibility, a life-threatening hypermetabolic condition andRYR1-related myopathies (RYR1-RM), a spectrum of rare neuromuscular disorders. InRYR1-RM, intracellular calcium dysregulation, post-translational modifications, and decreased protein expression lead to a heterogenous clinical presentation including proximal muscle weakness, contractures, scoliosis, respiratory insufficiency, and ophthalmoplegia. Preclinical model systems ofRYR1-RM and MH have been developed to better understand underlying pathomechanisms and test potential therapeutics.MethodsWe conducted a comprehensive scoping review of scientific literature pertaining toRYR1-RM and MH preclinical model systems in accordance with the PRISMA Scoping Reviews Checklist and the framework proposed by Arksey and O’Malley. Two major electronic databases (PubMed and EMBASE) were searched without language restriction for articles and abstracts published between January 1, 1990 and July 3, 2019.ResultsOur search yielded 5049 publications from which 262 were included in this review. A majority of variants tested inRYR1preclinical models were localized to established MH/central core disease (MH/CCD) hot spots. A total of 250 uniqueRYR1variations were reported in human/rodent/porcine models with 95% being missense substitutions. The most frequently reportedRYR1variant was R614C/R615C (human/porcine totaln = 39), followed by Y523S/Y524S (rabbit/mouse totaln = 30), I4898T/I4897T/I4895T (human/rabbit/mouse totaln = 20), and R163C/R165C (human/mouse totaln = 18). The dyspedic mouse was utilized by 47% of publications in the rodent category and its RyR1-null (1B5) myotubes were transfected in 23% of publications in the cellular model category. In studies of transfected HEK-293 cells, 57% ofRYR1variations affected the RyR1 channel and activation core domain. A total of 15RYR1mutant mouse strains were identified of which ten were heterozygous, three were compound heterozygous, and a further two were knockout. Porcine, avian, zebrafish,C. elegans, canine, equine, and drosophila model systems were also reported.ConclusionsOver the past 30 years, there were 262 publications on MH andRYR1-RM preclinical model systems featuring more than 200 uniqueRYR1variations tested in a broad range of species. Findings from these studies have set the foundation for therapeutic development for MH andRYR1-RM.
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

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

AbstractBackgroundSomatic 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.ConclusionGenetic-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

AbstractSignificant 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

AbstractAttention 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

AbstractInositol 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

Abstract
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

Abstract
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

AbstractBackgroundThe 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.MethodsWe 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.ResultsBy 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.ConclusionsThe 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

Abstract
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

Abstract
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.