bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-time PCR on skin biopsies for super-spreaders’ detection in bovine besnoitiosis
Authors: Grisez Christelle , Bottari Leslie , Prévot Françoise , Alzieu Jean-Pierre , Liénard Emmanuel , Corbière Fabien , Rameil Marie , Desclaux Xavier , Lacz Christophe , Boulon Christian , Petermann Julie , Le Mével Jeanne , Vilardell Carine , Jacquiet Philippe 
Published: October 2020

Abstract
Background
Bovine besnoitiosis, an emerging disease in Europe that can be transmitted by vectors, is caused by the apicomplexan Besnoitia besnoiti. Bovine besnoitiosis is difficult to control due to the complexity of its diagnosis in the acute stage of the disease, poor treatment success and chronically asymptomatic cattle acting as parasite reservoirs. When serological prevalence is low, detection and specific culling of seropositive cattle is feasible; however, economic considerations preclude this approach when serological prevalence is high. The aims of this study were to evaluate the accuracy of detection of super-spreaders in highly infected herds and to test their selective elimination as a new control strategy for bovine besnoitiosis.

Methods
Previous real-time PCR analyses performed on skin tissues from 160 asymptomatic animals sampled at slaughterhouses showed that the tail base was the best location to evaluate the dermal parasite DNA load. All seropositive animals (n = 518) from eight dairy or beef cattle farms facing a high serological prevalence of besnoitiosis were sampled at the tail base and their skin sample analysed by real-time PCR. A recommendation of rapid and selective culling of super-spreaders was formulated and provided to the cattle breeders. Subsequent serological monitoring of naïve animals was used to evaluate the interest of this control strategy over time.

Results
Among the 518 seropositive animals, a low proportion of individuals (14.5%) showed Cq values below 36, 17.8% had doubtful results (36 < Cq ≤ 40) and 67.8% had negative PCR results. These proportions were grossly similar on the eight farms, regardless of their production type (beef or dairy cattle), size, geographical location or history of besnoitiosis. Within two weeks of the biopsy, the rapid culling of super-spreaders was implemented on only three farms. The numbers of newly infected animals were lower on these farms compared to those where super-spreaders were maintained in the herd.

Conclusions
Real-time PCR analyses performed on skin biopsies of seropositive cattle showed huge individual variabilities in parasite DNA load. The rapid culling of individuals considered as super-spreaders seems to be a new and encouraging strategy for bovine besnoitiosis control.
Wnt-regulated lncRNA discovery enhanced by in vivo identification and CRISPRi functional validation
Authors: Liu Shiyang , Harmston Nathan , Glaser Trudy Lee , Wong Yunka , Zhong Zheng , Madan Babita , Virshup David M. , Petretto Enrico 
Published: October 2020

Abstract
Background
Wnt signaling is an evolutionarily conserved developmental pathway that is frequently hyperactivated in cancer. While multiple protein-coding genes regulated by Wnt signaling are known, the functional lncRNAs regulated by Wnt signaling have not been systematically characterized.

Methods
We comprehensively mapped Wnt-regulated lncRNAs from an orthotopic Wnt-addicted pancreatic cancer model and examined the response of lncRNAs to Wnt inhibition between in vivo and in vitro cancer models. We further annotated and characterized these Wnt-regulated lncRNAs using existing genomic classifications (using data from FANTOM5) in the context of Wnt signaling and inferred their role in cancer pathogenesis (using GWAS and expression data from the TCGA). To functionally validate Wnt-regulated lncRNAs, we performed CRISPRi screens to assess their role in cancer cell proliferation both in vivo and in vitro.

Results
We identified 3633 lncRNAs, of which 1503 were regulated by Wnt signaling in an orthotopic Wnt-addicted pancreatic cancer model. These lncRNAs were much more sensitive to changes in Wnt signaling in xenografts than in cultured cells. Our analysis suggested that Wnt signaling inhibition could influence the co-expression relationship of Wnt-regulated lncRNAs and their eQTL-linked protein-coding genes. Wnt-regulated lncRNAs were also implicated in specific gene networks involved in distinct biological processes that contribute to the pathogenesis of cancers. Consistent with previous genome-wide lncRNA CRISPRi screens, around 1% (13/1503) of the Wnt-regulated lncRNAs were found to modify cancer cell growth in vitro. This included CCAT1 and LINC00263, previously reported to regulate cancer growth. Using an in vivo CRISPRi screen, we doubled the discovery rate, identifying twice as many Wnt-regulated lncRNAs (25/1503) that had a functional effect on cancer cell growth.

Conclusions
Our study demonstrates the value of studying lncRNA functions in vivo, provides a valuable resource of lncRNAs regulated by Wnt signaling, and establishes a framework for systematic discovery of functional lncRNAs.
The presence of membrane bound CD99 ligands on leukocyte surface
Authors: Takheaw Nuchjira , Pata Supansa , Laopajon Witida , Roytrakul Sittiruk , Kasinrerk Watchara 
Published: October 2020

AbstractObjectiveCD99, a leukocyte surface molecule, reportedly plays an important role in several cellular processes. However, the role of CD99 in T cell regulation remains unclear, as the CD99 ligand associated with T-cell regulation has not yet been identified. Our previous study showed that recombinant CD99 bound to CD99 ligands was expressed on monocytes, NK cells and dendritic cells. This interaction regulates the expression of IL-6 and TNF-α in CD3 + T cells following T cell activation. In the present study, we confirmed the presence of CD99 ligands in immune cells.ResultsA recombinant CD99-human IgG fusion protein, CD99HIgG, was produced and used to search for CD99 ligand expression in various hematopoietic cell lines. Among several cell lines, THP-1 monocytic cell line showed strong positive reaction for CD99HIgG, and CD99 and CD99 ligand complexes were pulled-down using a DTSSP cross-linker. The study demonstrated the presence of the membrane bound CD99 ligand, and CD99 ligand candidates were identified via LC–MS/MS. These results may be useful to further identify the CD99 ligands, and to fully comprehend the role of CD99 in immunoregulation.
Genome-wide methylation analysis in Silver–Russell syndrome, Temple syndrome, and Prader–Willi syndrome
Authors: Hara-Isono Kaori , Matsubara Keiko , Fuke Tomoko , Yamazawa Kazuki , Satou Kazuhito , Murakami Nobuyuki , Saitoh Shinji , Nakabayashi Kazuhiko , Hata Kenichiro , Ogata Tsutomu , Fukami Maki , Kagami Masayo 
Published: October 2020

Abstract
Background
Imprinting disorders (IDs) show overlapping phenotypes, particularly in Silver–Russell syndrome (SRS), Temple syndrome (TS14), and Prader–Willi syndrome (PWS). These three IDs include fetal and postnatal growth failure, feeding difficulty, and muscular hypotonia as major clinical features. However, the mechanism that causes overlapping phenotypes has not been clarified. To investigate the presence or absence of methylation signatures associated with overlapping phenotypes, we performed genome-wide methylation analysis (GWMA).

Results
GWMA was carried out on 36 patients with three IDs (SRS [n = 16], TS14 [n = 7], PWS [n = 13]) and 11 child controls using HumanMethylation450 BeadChip including 475,000 CpG sites across the human genome. To reveal an aberrantly methylated region shared by SRS, TS14, and PWS groups, we compared genome-wide methylation data of the three groups with those of control subjects. All the identified regions were known as SRS-, TS14-, and PWS-related imprinting-associated differentially methylated regions (iDMRs), and there was no hypermethylated or hypomethylated region shared by different ID groups. To examine the methylation pattern shared by SRS, TS14, and PWS groups, we performed clustering analysis based on GWMA data. The result focusing on 620 probes at the 62 known iDMRs (except for SRS-, TS14-, and PWS-related iDMRs) classified patients into two categories: (1) category A, grossly normal methylation patterns mainly consisting of SRS group patients; and (2) category B, broad and mild hypermethylation patterns mainly consisting of TS14 and PWS group patients. However, we found no obvious relationship between these methylation patterns and phenotypes of patients.

Conclusions
GWMA in three IDs found no methylation signatures shared by SRS, TS14, and PWS groups. Although clustering analysis showed similar mild hypermethylation patterns in TS14 and PWS groups, further study is needed to clarify the effect of methylation patterns on the overlapping phenotypes.
Novel presentation of intraocular metastases in a patient with penile squamous cell carcinoma: a case report
Authors: Li Shanshan , Zhao Haifeng , Qiu Cui , Wu Changfan 
Published: October 2020

Abstract

Background
The choroid is the most common site for intraocular tumor metastasis because of its abundant vascular supply. However, choroidal metastasis in penile cancer is highly unusual. Here, we report the first case of diagnosis of choroidal metastasis at presentation in a patient with penile squamous cell carcinoma.

Case presentation
A 43-year-old Asian man with a 3-year history of penile cancer presented with metastasis in the right intraocular sites. Magnetic resonance imaging showed hyperintensity in the T1-weighted images and hypointensity in the T2-weighted images of the right eye. After enucleation of his right eye, histopathological analysis led to a diagnosis of metastatic, moderately differentiated penile squamous cell carcinoma.

Conclusions
Penile cancer typically occurs as penile squamous cell carcinoma, and its most common metastatic sites are the inguinal lymph nodes. Hemorrhagic transfer of tumor cells is extremely rare, especially to intraocular sites. Intraocular metastatic tumors have a unique presentation on imaging, as observed on magnetic resonance imaging and histopathological analysis. This novel finding of intraocular metastasis in penile squamous cell carcinoma is of great significance to optic surgeons and oncologists as it has new implications in the diagnosis of and timely intervention for penile cancer metastasis.
Interactive effects of asparagine and aspartate homeostasis with sex and age for the risk of type 2 diabetes risk
Authors: Luo Hui-Huan , Feng Xiao-Fei , Yang Xi-Lin , Hou Rui-Qin , Fang Zhong-Ze 
Published: October 2020

Abstract
Background
Asparagine and aspartate homeostasis are linked with type 2 diabetes (T2D). This study aimed to explore whether asparagine and aspartate metabolism interacted with sex and age to increase the risk of T2D.

Methods
From 27 May 2015 to 3 August 2016, we consecutively retrieved 1032 T2D patients and 1522 subjects without T2D from a tertiary care hospital in Liaoning, China. Restricted cubic spline nested in the logistic regression was used to draw odds ratio curves of plasma asparagine to aspartate ratio for T2D by sex and age. Cut-off point was selected where curves went apart, indicating possible interaction. Addictive interactions of asparagine to aspartate ratio with sex or age and secondary interaction with copresence of unfavorable sex and age were further estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S).

Results
Ratio of asparagine to aspartate > 1.5 was associated with elevated risk of T2D (OR 7.99, 95%CI 5.50 to 11.6), which was enhanced by female gender to 13.6, (95%CI 8.10–22.9) and by > 50 years of age to 28.7 (14.6–56.3), with significant additive interactions. There was a significant secondary-interaction of copresence of female sex and > 50 years of age with high asparagine to aspartate ratio for increased T2D risk with the OR being further increased to 34.4 (20.5–57.5).

Conclusions
High asparagine to aspartate ratio was associated with markedly increased risk of T2D, which was further amplified by either female gender or > 50 years of age, and especially both.
Complementary NAD+ replacement strategies fail to functionally protect dystrophin-deficient muscle
Authors: Frederick David W. , McDougal Alan V. , Semenas Melisa , Vappiani Johanna , Nuzzo Andrea , Ulrich John C. , Becherer J. David , Preugschat Frank , Stewart Eugene L. , Sévin Daniel C. , Kramer H. Fritz 
Published: October 2020

AbstractBackgroundDuchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder stemming from a loss of functional dystrophin. Current therapeutic options for DMD are limited, as small molecule modalities remain largely unable to decrease the incidence or mitigate the consequences of repetitive mechanical insults to the muscle during eccentric contractions (ECCs).MethodsUsing a metabolomics-based approach, we observed distinct and transient molecular phenotypes in muscles of dystrophin-deficient MDX mice subjected to ECCs. Among the most chronically depleted metabolites was nicotinamide adenine dinucleotide (NAD), an essential metabolic cofactor suggested to protect muscle from structural and metabolic degeneration over time. We tested whether the MDX muscle NAD pool can be expanded for therapeutic benefit using two complementary small molecule strategies: provision of a biosynthetic precursor, nicotinamide riboside, or specific inhibition of the NAD-degrading ADP-ribosyl cyclase, CD38.ResultsAdministering a novel, potent, and orally available CD38 antagonist to MDX mice successfully reverted a majority of the muscle metabolome toward the wildtype state, with a pronounced impact on intermediates of the pentose phosphate pathway, while supplementing nicotinamide riboside did not significantly affect the molecular phenotype of the muscle. However, neither strategy sustainably increased the bulk tissue NAD pool, lessened muscle damage markers, nor improved maximal hindlimb strength following repeated rounds of eccentric challenge and recovery.ConclusionsIn the absence of dystrophin, eccentric injury contributes to chronic intramuscular NAD depletion with broad pleiotropic effects on the molecular phenotype of the tissue. These molecular consequences can be more effectively overcome by inhibiting the enzymatic activity of CD38 than by supplementing nicotinamide riboside. However, we found no evidence that either small molecule strategy is sufficient to restore muscle contractile function or confer protection from eccentric injury, undermining the modulation of NAD metabolism as a therapeutic approach for DMD.
On basic Horn hypergeometric functions $\mathbf{H}_{3}$ and $\mathbf{H}_{4}$
Authors: Shehata Ayman 
Published: October 2020

AbstractThe purpose of this work is to demonstrate several interesting contiguous function relations and q-differential formulas for basic Horn hypergeometric functions $\mathbf{H}_{3}$

H
3

and $\mathbf{H}_{4}$

H
4

. Some properties of our main results are also constructed.
Molecular drivers and cells of origin in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine carcinoma
Authors: Gao He-Li , Wang Wen-Quan , Yu Xian-Jun , Liu Liang 
Published: October 2020

AbstractPancreatic cancer is one of the most common causes of cancer-related deaths worldwide. The two major histological subtypes of pancreatic cancer are pancreatic ductal adenocarcinoma (PDAC), accounting for 90% of all cases, and pancreatic neuroendocrine neoplasm (PanNEN), which makes up 3–5% of all cases. PanNEN is classified into well-differentiated pancreatic neuroendocrine tumor and poorly-differentiated pancreatic neuroendocrine carcinoma (PanNEC). Although PDAC and PanNEN are commonly thought to be different diseases with distinct biology, cell of origin, and genomic abnormalities, the idea that PDAC and PanNEC share common cells of origin has been gaining support. This is substantiated by evidence that the molecular profiling of PanNEC is genetically and phenotypically related to PDAC. In the current review, we summarize published studies pointing to common potential cells of origin and speculate about how the distinct paths of differentiation are determined by the genomic patterns of each disease. We also discuss the overlap between PDAC and PanNEC, which has been noted in clinical observations.
Human genetic factors associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity
Authors: Anastassopoulou Cleo , Gkizarioti Zoi , Patrinos George P. , Tsakris Athanasios 
Published: October 2020

Abstract

Background
The emergence of the novel coronavirus in Wuhan, Hubei Province, China, in December 2019 marked the synchronization of the world to a peculiar clock that is counting infected cases and deaths instead of hours and minutes. The pandemic, highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has indeed caused considerable morbidity and mortality and drastically changed our everyday lives. As we continue to become acquainted with the seventh coronavirus known to infect our species, a number of its characteristics keep surprising us. Among those is the wide spectrum of clinical manifestations of the resulting coronavirus disease 2019 (COVID-19), which ranges from asymptomatic or mildly symptomatic infections to severe pneumonia, respiratory failure, and death.

Main body
Data, now from patient populations, are beginning to accumulate on human genetic factors that may contribute to the observed diversified disease severity. Therefore, we deemed it prudent to review the associations between specific human genetic variants and clinical disease severity or susceptibility to infection that have been reported in the literature to date (at the time of writing this article in early August 2020 with updates in mid-September). With this work, we hope (i) to assist the fast-paced biomedical research efforts to combat the virus by critically summarizing current knowledge on the potential role of host genetics, and (ii) to help guide current genetics and genomics research towards candidate gene variants that warrant further investigation in larger studies. We found that determinants of differing severity of COVID-19 predominantly include components of the immune response to the virus, while determinants of differing susceptibility to SARS-CoV-2 mostly entail genes related to the initial stages of infection (i.e., binding of the cell surface receptor and entry).

Conclusion
Elucidating the genetic determinants of COVID-19 severity and susceptibility to SARS-CoV-2 infection would allow for the stratification of individuals according to risk so that those at high risk would be prioritized for immunization, for example, if or when safe and effective vaccines are developed. Our enhanced understanding of the underlying biological mechanisms could also guide personalized therapeutics. Such knowledge is already beginning to provide clues that help explain, at least in part, current epidemiologic observations regarding the typically more severe or benign disease course in older males and children, respectively.
Spatial and spatio-temporal analysis of malaria cases in Zimbabwe
Authors: Gwitira Isaiah , Mukonoweshuro Munashe , Mapako Grace , Shekede Munyaradzi D. , Chirenda Joconiah , Mberikunashe Joseph 
Published: October 2020

Abstract
Background
Although effective treatment for malaria is now available, approximately half of the global population remain at risk of the disease particularly in developing countries. To design effective malaria control strategies there is need to understand the pattern of malaria heterogeneity in an area. Therefore, the main objective of this study was to explore the spatial and spatio-temporal pattern of malaria cases in Zimbabwe based on malaria data aggregated at district level from 2011 to 2016.

Methods
Geographical information system (GIS) and spatial scan statistic were applied on passive malaria data collected from health facilities and aggregated at district level to detect existence of spatial clusters. The global Moran’s I test was used to infer the presence of spatial autocorrelation while the purely spatial retrospective analyses were performed to detect the spatial clusters of malaria cases with high rates based on the discrete Poisson model. Furthermore, space-time clusters with high rates were detected through the retrospective space-time analysis based on the discrete Poisson model.

Results
Results showed that there is significant positive spatial autocorrelation in malaria cases in the study area. In addition, malaria exhibits spatial heterogeneity as evidenced by the existence of statistically significant (P < 0.05) spatial and space-time clusters of malaria in specific geographic regions. The detected primary clusters persisted in the eastern region of the study area over the six year study period while the temporal pattern of malaria reflected the seasonality of the disease where clusters were detected within particular months of the year.

Conclusions
Geographic regions characterised by clusters of high rates were identified as malaria high risk areas. The results of this study could be useful in prioritizing resource allocation in high-risk areas for malaria control and elimination particularly in resource limited settings such as Zimbabwe. The results of this study are also useful to guide further investigation into the possible determinants of persistence of high clusters of malaria cases in particular geographic regions which is useful in reducing malaria burden in such areas.
Agroresidues enhanced peroxidase activity expression by Bacillus sp. MABINYA-1 under submerged fermentation
Authors: Falade Ayodeji O. , Mabinya Leonard V. , Okoh Anthony I. , Nwodo Uchechukwu U. 
Published: October 2020

AbstractAgroresidues have continued to gain preference over conventional carbon sources for microbial enzyme production due to the low price and abundance in the environment. Therefore, this study aimed at improving peroxidase yield by Bacillus sp. MABINYA-1 (BMAB-1) using agroresidues under submerged fermentation. The culture parameters that support maximum peroxidase yield by BMAB-1 was initially determined and the results showed that peroxidase activity expression was optimum at pH 5, 30 °C and 150 rpm while veratryl alcohol and ammonium sulphate served as the best peroxidase-inducer and inorganic nitrogen source, respectively. BMAB-1 exhibited maximum peroxidase expression (17.50 ± 0.10 U/mg) at 72 h using kraft lignin liquid medium (KLLM) under the optimized culture conditions. Upon utilization of selected agroresidues (sawdust, wheat straw and maize stover) as sole carbon sources by BMAB-1 in the fermentation process, peroxidase activity was significantly enhanced when compared with glucose (14.91 ± 0.31 U/mg) and kraft lignin (17.50 ± 0.10 U/mg). Sawdust produced the highest peroxidase yield (47.14 ± 0.41 U/mg), followed by maize stover (37.09 ± 0.00 U/mg) while wheat straw yielded the lowest peroxidase specific activity (21.65 ± 0.35 U/mg). This indicates that utilization of sawdust by BMAB-1 resulted in 3.2- and 2.7-fold increase in peroxidase activity expression as compared to glucose and kraft lignin, respectively. The aptitude of BMAB-1 to utilize agroresidues would reduce the cost of peroxidase production by the bacteria since the substrates are cheaper than the conventional carbon sources and are, as well, more readily available.