Severity of COVID-19 Patients Predicted by Serum Sphingolipids Signature

The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient’s outcome is poorly understood. The present study targets the sphingolipid profile of twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry and ELISA. Results indicated a progressive increase in dihydrosphingosine, dihydroceramides, ceramides, sphingosine, and a decrease in sphingosine-1-phosphate. These changes are associated with a serine palmitoyltransferase long chain base subunit 1 (SPTLC1) increase in relation to COVID-19 severity. Severe patients showed a decrease in sphingomyelins and a high level of acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical patients are characterized by high levels of dihydrosphingosine and dihydroceramide but not of glycosphingolipids. In severe and critical patients, unbalanced lipid metabolism induces lipid raft remodeling, leads to cell apoptosis and immunoescape, suggesting active sphingolipid participation in viral infection. Furthermore, results indicated that the sphingolipid and glycosphingolipid metabolic rewiring promoted by aSMase and GM3 is age-dependent but also characteristic of severe and critical patients influencing prognosis and increasing viral load. AUCs calculated from ROC curves indicated ceramides C16:0, C18:0, C24:1, sphingosine and SPTLC1 as putative biomarkers of disease evolution.

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A Dansyl-Modified Sphingosine Kinase Inhibitor Dpf-543 Enhanced de Novo Ceramide Generation

10.20944/preprints202108.0100.v1 ◽

2021 ◽

Author(s):

Maftuna Shamshiddinova ◽

Shokhid Gulyamov ◽

Hee Jung Kim ◽

Seo Hyeon Jung ◽

Dong Jae Baek ◽

...

Keyword(s):

Cancer Metastasis ◽

Kinase Inhibitor ◽

De Novo ◽

Sphingosine Kinase ◽

Acid Sphingomyelinase ◽

Sphingolipid Metabolism ◽

Ceramide Synthase ◽

Serine Palmitoyltransferase ◽

Comparative Efficiency ◽

Sphingosine 1 Phosphate

Sphingosine-1-phosphate (S1P) synthesized by sphingosine kinase (SPHK) is a signaling molecule, involved in cell proliferation, growth, differentiation, and survival. Indeed, a sharp increase of S1P was linked to the pathological outcome with inflammation, cancer metastasis or angiogenesis etc. In this regard, the SPHK/S1P axis regulation has been a specific issue in anticancer strategy to turn accumulated sphingosine (SPN) into cytotoxic ceramides (Cers). For these purposes, there have been numerous chemicals synthesized for SPHK inhibition. In this study, we investigated the comparative efficiency of dansylated PF-543 (DPF-543) on the Cers synthesis along with PF-543. DPF-543 deserved attention in strong cytotoxicity, due to the cytotoxic Cers accumulation by ceramide synthase (CerSs). DPF-543 exhibited dual actions on Cers synthesis by enhance the serine palmitoyltransferase (SPT) activity, and by inhibiting SPHKs which eventually induced an unusual environment of the high amount of 3-ketosphinganine and sphinganine (SPA). SPA in turn was consumed to synthesize Cers via de novo pathway. Interestingly, PF-543 increased only the SPN level, but not for SPA. In addition, DPF-543 mildly activates acid sphingomyelinase (aSMase) that contributes a partial increase on Cers. Collectively, a dansyl-modified DPF-543 relatively en-hanced Cers accumulation via de novo pathway which was not observed in PF-543. Our results demonstrated that the structural modification on SPHK inhibitors is still an attractive anticancer strategy by regulating sphingolipid metabolism.

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A Dansyl-Modified Sphingosine Kinase Inhibitor DPF-543 Enhanced De Novo Ceramide Generation

International Journal of Molecular Sciences ◽

10.3390/ijms22179190 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9190

Author(s):

Maftuna Shamshiddinova ◽

Shokhid Gulyamov ◽

Hee-Jung Kim ◽

Seo-Hyeon Jung ◽

Dong-Jae Baek ◽

...

Keyword(s):

Cancer Metastasis ◽

Kinase Inhibitor ◽

De Novo ◽

Sphingosine Kinase ◽

Acid Sphingomyelinase ◽

Sphingolipid Metabolism ◽

Ceramide Synthase ◽

Serine Palmitoyltransferase ◽

Comparative Efficiency ◽

Sphingosine 1 Phosphate

Sphingosine-1-phosphate (S1P) synthesized by sphingosine kinase (SPHK) is a signaling molecule, involved in cell proliferation, growth, differentiation, and survival. Indeed, a sharp increase of S1P is linked to a pathological outcome with inflammation, cancer metastasis, or angiogenesis, etc. In this regard, SPHK/S1P axis regulation has been a specific issue in the anticancer strategy to turn accumulated sphingosine (SPN) into cytotoxic ceramides (Cers). For these purposes, there have been numerous chemicals synthesized for SPHK inhibition. In this study, we investigated the comparative efficiency of dansylated PF-543 (DPF-543) on the Cers synthesis along with PF-543. DPF-543 deserved attention in strong cytotoxicity, due to the cytotoxic Cers accumulation by ceramide synthase (CerSs). DPF-543 exhibited dual actions on Cers synthesis by enhancing serine palmitoyltransferase (SPT) activity, and by inhibiting SPHKs, which eventually induced an unusual environment with a high amount of 3-ketosphinganine and sphinganine (SPA). SPA in turn was consumed to synthesize Cers via de novo pathway. Interestingly, PF-543 increased only the SPN level, but not for SPA. In addition, DPF-543 mildly activates acid sphingomyelinase (aSMase), which contributes a partial increase in Cers. Collectively, a dansyl-modified DPF-543 relatively enhanced Cers accumulation via de novo pathway which was not observed in PF-543. Our results demonstrated that the structural modification on SPHK inhibitors is still an attractive anticancer strategy by regulating sphingolipid metabolism.

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Accuracy of probabilistic and deterministic record linkage: the case of tuberculosis

Revista de Saúde Pública ◽

10.1590/s1518-8787.2016050006327 ◽

2016 ◽

Vol 50 (0) ◽

Cited By ~ 10

Author(s):

Gisele Pinto de Oliveira ◽

Ana Luiza de Souza Bierrenbach ◽

Kenneth Rochel de Camargo Júnior ◽

Cláudia Medina Coeli ◽

Rejane Sobrino Pinheiro

Keyword(s):

Record Linkage ◽

Missing Values ◽

Probabilistic Approach ◽

Roc Curves ◽

Cutoff Point ◽

Accurate Analysis ◽

Linkage Algorithm ◽

Probabilistic Linkage ◽

Key Variables ◽

High Level

ABSTRACT OBJECTIVE To analyze the accuracy of deterministic and probabilistic record linkage to identify TB duplicate records, as well as the characteristics of discordant pairs. METHODS The study analyzed all TB records from 2009 to 2011 in the state of Rio de Janeiro. A deterministic record linkage algorithm was developed using a set of 70 rules, based on the combination of fragments of the key variables with or without modification (Soundex or substring). Each rule was formed by three or more fragments. The probabilistic approach required a cutoff point for the score, above which the links would be automatically classified as belonging to the same individual. The cutoff point was obtained by linkage of the Notifiable Diseases Information System – Tuberculosis database with itself, subsequent manual review and ROC curves and precision-recall. Sensitivity and specificity for accurate analysis were calculated. RESULTS Accuracy ranged from 87.2% to 95.2% for sensitivity and 99.8% to 99.9% for specificity for probabilistic and deterministic record linkage, respectively. The occurrence of missing values for the key variables and the low percentage of similarity measure for name and date of birth were mainly responsible for the failure to identify records of the same individual with the techniques used. CONCLUSIONS The two techniques showed a high level of correlation for pair classification. Although deterministic linkage identified more duplicate records than probabilistic linkage, the latter retrieved records not identified by the former. User need and experience should be considered when choosing the best technique to be used.

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Deep learning based DNA:RNA triplex forming potential prediction

BMC Bioinformatics ◽

10.1186/s12859-020-03864-0 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Yu Zhang ◽

Yahui Long ◽

Chee Keong Kwoh

Keyword(s):

Machine Learning ◽

Neural Networks ◽

Cross Validation ◽

Roc Curves ◽

Triplex Dna ◽

Triplex Formation ◽

Machine Learning Model ◽

Non Coding Rnas ◽

High Level ◽

Integrated Program

Abstract Background Long non-coding RNAs (lncRNAs) can exert functions via forming triplex with DNA. The current methods in predicting the triplex formation mainly rely on mathematic statistic according to the base paring rules. However, these methods have two main limitations: (1) they identify a large number of triplex-forming lncRNAs, but the limited number of experimentally verified triplex-forming lncRNA indicates that maybe not all of them can form triplex in practice, and (2) their predictions only consider the theoretical relationship while lacking the features from the experimentally verified data. Results In this work, we develop an integrated program named TriplexFPP (Triplex Forming Potential Prediction), which is the first machine learning model in DNA:RNA triplex prediction. TriplexFPP predicts the most likely triplex-forming lncRNAs and DNA sites based on the experimentally verified data, where the high-level features are learned by the convolutional neural networks. In the fivefold cross validation, the average values of Area Under the ROC curves and PRC curves for removed redundancy triplex-forming lncRNA dataset with threshold 0.8 are 0.9649 and 0.9996, and these two values for triplex DNA sites prediction are 0.8705 and 0.9671, respectively. Besides, we also briefly summarize the cis and trans targeting of triplexes lncRNAs. Conclusions The TriplexFPP is able to predict the most likely triplex-forming lncRNAs from all the lncRNAs with computationally defined triplex forming capacities and the potential of a DNA site to become a triplex. It may provide insights to the exploration of lncRNA functions.

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Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine -1-phosphate therapy

Nature Medicine ◽

10.1038/80442 ◽

2000 ◽

Vol 6 (10) ◽

pp. 1109-1114 ◽

Cited By ~ 426

Author(s):

Yutaka Morita ◽

Gloria I. Perez ◽

Francois Paris ◽

Silvia R. Miranda ◽

Desiree Ehleiter ◽

...

Keyword(s):

Acid Sphingomyelinase ◽

Sphingosine 1 Phosphate

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Assessment of Performance-Related Experiences: An Individualized Approach

The Sport Psychologist ◽

10.1123/tsp.2015-0035 ◽

2016 ◽

Vol 30 (3) ◽

pp. 201-218 ◽

Cited By ~ 12

Author(s):

Montse C. Ruiz ◽

Yuri Hanin ◽

Claudio Robazza

Keyword(s):

Individual Variability ◽

Stimulus List ◽

Practical Utility ◽

Wide Range ◽

Item List ◽

Individualized Approach ◽

Item Content ◽

Perceived Impact ◽

High Level ◽

Individual Profiles

In this investigation we describe an individualized approach in the assessment of athletes’ experiences associated with successful and poor performances. Two studies were conducted to develop a profiling procedure to assess eight modalities of performance-related states. In Study 1, six high-level athletes assessed their states before most successful and unsuccessful performances using a preliminary 71-item stimulus list developed by a panel of four emotion researchers. They also rated the intensity of their states on a modified Borg’s CR-10 scale. In Study 2, five top-level divers assessed their states before multiple dives (three successful and three unsuccessful) using a revised 74-item list. The perceived impact on performance was also examined using an open-ended question. Individual profiles reflected two typical curves discriminating successful and unsuccessful performances. High individual variability in item content and intensity was found. Athletes reported a wide range of interrelated experiences associated with their performances. Our findings support the practical utility of individualized profiling to assess athletes’ performance-related states.

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Stroke Recovery: Surprising Influences and Residual Consequences

Advances in Medicine ◽

10.1155/2014/378263 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 33

Author(s):

Argye E. Hillis ◽

Donna C. Tippett

Keyword(s):

Individual Variability ◽

Written Language ◽

Stroke Recovery ◽

Time Points ◽

Report Data ◽

High Level ◽

Cortical Functions

There is startling individual variability in the degree to which people recover from stroke and the duration of time over which recovery of some symptoms occurs. There are a variety of mechanisms of recovery from stroke which take place at distinct time points after stroke and are influenced by different variables. We review recent studies from our laboratory that unveil some surprising findings, such as the role of education in chronic recovery. We also report data showing that the consequences that most plague survivors of stroke and their caregivers are loss of high level cortical functions, such as empathy or written language. These results have implications for rehabilitation and management of stroke.

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Viral and host factors related to the clinic outcome of the SARS-CoV-2 infection

10.21203/rs.3.rs-19344/v1 ◽

2020 ◽

Cited By ~ 2

Author(s):

Xiaonan Zhang ◽

Yun Tan ◽

Yun Ling ◽

Gang Lu ◽

Feng Liu ◽

...

Keyword(s):

Host Factors ◽

Wuhan City ◽

Cell Counts ◽

Disease Outcomes ◽

Rapid Spread ◽

Differential Exposure ◽

Critical Patients ◽

Global Initiative ◽

Novel Coronavirus ◽

High Level

Abstract At least three months have been passed since the outbreak of the severe acute respiratory disease, COVID-19 in Wuhan city, China in December 2019, caused by the infection of a novel coronavirus, SARS-CoV-2.1,2. Due to its rapid spread throughout China and abroad, knowledge sharing for both its epidemiology and clinic manifestations is urgently need. Here we analyzed the clinical, molecular and immunological data from 326 confirmed cases of SARS-CoV-2 infection in Shanghai. Genomic sequences assembled from 112 quality samples together with uploaded sequences in Global Initiative on Sharing All Influenza Data (GISAID) showed a stable evolution and suggested two major lineages with differential exposure history during the earliest outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes. Lymphocytopenia, especially the reduced CD4+ and CD8+ T cell counts upon admission, was predictive of disease progression. High level of IL-6 and IL-8 during treatment was observed in severe and critical patients and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such age, lymphocytopenia and its associated cytokine storm whereas viral genetic variation did not significantly affect the outcomes. This comprehensive analysis on the molecular, immunological and clinical data provides a panorama of the key determinants related to the disease outcomes which should be helpful for improving the current combat against this extremely aggressive pandemic.Authors Xiaonan Zhang, Yun Tan, Yun Ling, Gang Lu, Feng Liu, and Zhigang Yi contributed equally to this work.

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Spatial behavior of red deer (cervus elaphus) in northern apennines: are we managing them correctly?

10.21203/rs.3.rs-1074292/v1 ◽

2021 ◽

Author(s):

Riccardo Fontana ◽

Licia Calabrese ◽

Ambrogio Lanzi ◽

Elisa Armaroli ◽

Elisabetta Raganella Pelliccioni

Keyword(s):

Sample Size ◽

Cervus Elaphus ◽

Red Deer ◽

Individual Variability ◽

Spatial Behavior ◽

Spatial Behaviour ◽

Spatial Mismatch ◽

Management Level ◽

Management Actions ◽

High Level

Abstract Backgound Throughout its range, red deer is a well-studied species. In Italy the species occupies two ecologically different ranges: the Alps and the Apennine. Although several studies have described spatial behaviour of red deer in the Italian Alps, no data are available for the Apennine population. Results Spatial behaviour of 13 deer from Northern Apennine range was analysed for the first-time using GPS-GSM telemetry, from 2011 to 2017. Red deer displayed two different strategies coexisting in the population, i.e., migratory and stationary. Females tend to migrate more than males. We found a high level of inter individual variability in the date of migration/return, while each migratory deer is very conservative during the study period. Migration ranges are on average 12±4.2 km far apart from the resident range. Both migratory and resident deer displayed high site fidelity. No switch from migratory to stationary strategy was observed for any deer during the study period, which however could have been too short to detect any switch. At management level, a spatial mismatch was found between deer range and management units (districts) in 44.4% of the cases. Merging the districts belonging of each province to obtain an area of approximately 1.000 km 2 would partially solve such spatial mismatch reducing it to 22%. Conclusions Despite the low sample size, these results can provide guidance for future management actions. An in-dept study with a higher sample size is however required to better understand and manage the red deer Apennine population.

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PREHOSPITAL EMERGENCY MEDICAL SERVICES UTILIZATION FOR CRITICAL PATIENTS AND ITS DETERMINANTS IN THAILAND

Journal of Southwest Jiaotong University ◽

10.35741/issn.0258-2724.56.5.47 ◽

2021 ◽

Vol 56 (5) ◽

pp. 514-523

Author(s):

Songsak Poomsaidorn ◽

Wongsa Laohasiriwong ◽

Keopanha Soeung

Keyword(s):

Emergency Medical Services ◽

Linear Mixed Model ◽

Medical System ◽

Emergency Medical System ◽

Medical Services ◽

Factors Associated ◽

Emergency Medical ◽

Prehospital Emergency ◽

Critical Patients ◽

High Level

This research aimed to determine the situations and factors associated with prehospital emergency medical services (EMS) utilization for critical patients in Thailand. This cross-sectional study used the data of a survey conducted by the Information Technology for Emergency Medical System (ITEMS) of the National Institute of Emergency Medicine, Thailand. The survey collected the data among 1,145 participants using a structured questionnaire. The generalized linear mixed model (GLMM) was used to identify the factors associated with prehospital EMS utilization among critical patients when controlling the effects of covariates presenting adjusted OR and 95% confidence interval. Among 1,145 critical patients, 33.71 % reported using the prehospital EMS of the emergency medical system. Factors that were associated with prehospital EMS use had a high level of knowledge on prehospital EMS (adj. OR = 6.49; 95%CI: 3.78-11.12), high level of trust in quality and safety of prehospital EMS (adj. OR = 4.72; 95%CI: 3.50-6.36), low-moderate severity of perceived illness (adj. OR= 3.71; 95%CI: 2.54-5.42), critical condition occurred at workplace/building (adj. OR=3.57; 95%CI: 2.33-5.47), at home/residential building (adj. OR = 2.21; 95%CI: 1.37-3.58), had adequate services in the area (adj. OR= 1.94; 95%CI: 1.45-2.60), finished at least secondary school (adj. OR= 1.62; 95%CI: 1.11-2.37), less than 15km distance between scene and EMS service site (adj. OR= 1.47; 95%CI: 1.10-1.98), and were very satisfied with services (adj. OR = 1.15; 95%CI: 1.08-1.22) from the reasons mentioned.

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