Digital twins to personalize medicine Björnsson, Bergthor; Borrebaeck, Carl; Elander, Nils ...
Genome medicine,
12/2019, Letnik:
12, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are ...high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.
Purpose
In recent years, epidemiological studies have revealed the relationship between gestational diabetes mellitus (GDM) and cardiovascular disease (CVD). In this study, we utilized Mendelian ...randomization (MR) to investigate the potential causal impact of GDM on cardiovascular disease for the first time.
Methods
We retrieved summary statistics from published genome-wide association studies. MR was first performed using significant SNPs extracted from the eighth data release of the FinnGen study. Next, a replication analysis for coronary artery disease (CAD) was conducted in another European ancestry population to validate our findings. Finally, mediation analysis was carried out to assess potential mediation effects.
Results
Our data analysis revealed that genetically predicted GDM was significantly associated with increased CAD risk (OR 1.10, 95% CI 1.02–1.18,
p
0.006). Replication analysis confirmed a significant genetic association between GDM and CAD (OR 1.07, 95% CI 1.02–1.12,
p
0.003) in another European ancestry population. Mediation analysis indicated no significant mediation effect by type 2 diabetes mellitus (T2DM) on the GDM–CAD relationship (mediation effect β 95% CI: 0.005 −0.003, −0.017).
Conclusion
Women with a prior history of GDM face an elevated risk of future CAD. This increased risk of CAD cannot be solely attributed to the subsequent onset of diabetes. Regular CAD risk assessment and primary prevention strategies are of paramount importance for women with a history of GDM.
Aims
The study aimed to perform a systematic investigation of the effects of quercetin on biofilm formation and virulence factors in Pseudomonas aeruginosa.
Methods and Results
The Ps. aeruginosa ...strain PAO1 was selected as the test strain. The results indicated that quercetin did not impact the growth of PAO1 as determined by MIC and growth curve analysis. However, this compound significantly inhibited (P < 0·05) biofilm formation and production of virulence factors including pyocyanin, protease and elastase at a lower concentration than those for most previously reported plant extracts and substances. Considering the central role of quorum sensing (QS) in the regulation of biofilm and virulence factor, we further detected the transcriptional changes associated with QS and found that the expression levels of lasI, lasR, rhlI and rhlR were significantly reduced (P < 0·05) by 34, 68, 57 and 50%, respectively, in response to 16 μg ml−1 quercetin.
Conclusions
This study indicated that quercetin is an effective inhibitor of biofilm formation and virulence factors in Ps. aeruginosa.
Significance and Impact of the Study
This is the first study to demonstrate that quercetin is an effective inhibitor of QS, biofilm formation and virulence factors in Ps. aeruginosa. Furthermore, quercetin might have potential in fighting biofilm‐related infections.
Cardiovascular adverse conditions are caused by coronavirus disease 2019 (COVID-19) infections and reported as side-effects of the COVID-19 vaccines. Enriching current vaccine safety surveillance ...systems with additional data sources may improve the understanding of COVID-19 vaccine safety. Using a unique dataset from Israel National Emergency Medical Services (EMS) from 2019 to 2021, the study aims to evaluate the association between the volume of cardiac arrest and acute coronary syndrome EMS calls in the 16-39-year-old population with potential factors including COVID-19 infection and vaccination rates. An increase of over 25% was detected in both call types during January-May 2021, compared with the years 2019-2020. Using Negative Binomial regression models, the weekly emergency call counts were significantly associated with the rates of 1st and 2nd vaccine doses administered to this age group but were not with COVID-19 infection rates. While not establishing causal relationships, the findings raise concerns regarding vaccine-induced undetected severe cardiovascular side-effects and underscore the already established causal relationship between vaccines and myocarditis, a frequent cause of unexpected cardiac arrest in young individuals. Surveillance of potential vaccine side-effects and COVID-19 outcomes should incorporate EMS and other health data to identify public health trends (e.g., increased in EMS calls), and promptly investigate potential underlying causes.
Objective
Social frailty is related to adverse health-related outcomes. However, the measurement thereof is controversial and research into the relationship between social frailty and physical ...functioning remains limited. This study aimed to determine social frailty status via developing a simple self-reported screening tool, termed the HALFT scale, and to examine the association between social frailty and physical functioning, cognition, depression, and mortality among community-dwelling older adults.
Design
Prospective cohort study.
Setting
Community.
Participants
1697 community-dwelling adults aged ≥60 years from Beijing Longitudinal Study of Aging were included.
Measurements
The HALFT scale was developed based on 5 items: unhelpful to others, limited social participation, loneliness, financial difficulty, and not having anyone to talk to. Socioeconomic and demographic data were collected, and physical functioning, frailty index, cognition, and depression were assessed.
Results
The prevalence of social frailty was 7.7% (weighted, 4.5%). Participants with physical frailty, low levels of physical activity, and poor physical functioning had a higher prevalence of social frailty. Social frailty was associated with dementia, subjective memory decline, depression, cognitive impairment, and having experienced a recent significant life event. After adjusting for age and sex, the 8-year mortality hazard ratios were 2.5-4.3 and 1.6-2.3, respectively, for those with social frailty or pre-social frailty. Each component of the HALFT scale predicted 8-year mortality.
Conclusion
Social frailty is associated with physical functioning, cognition, and depression, and predicts mortality. The HALFT scale could be a useful screening tool for determining social frailty in older adults. Interventions aimed at preventing or delaying social frailty are warranted.
Objective
To identify novel clinically relevant genes in papillary thyroid carcinoma from public databases.
Methods
Four original microarray datasets, GSE3678, GSE3467, GSE33630 and GSE58545, were ...downloaded. Differentially expressed genes (DEGs) were filtered from integrated data. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, followed by protein–protein interaction (PPI) network construction. The CentiScape pug-in was performed to scale degree. The genes at the top of the degree distribution (≥ 95% percentile) in the significantly perturbed networks were defined as central genes. UALCAN and The Cancer Genome Atlas Clinical Explorer were used to verify clinically relevant genes and perform survival analysis.
Result
225 commonly changed DEGs (111 up-regulated and 114 down-regulated) were identified. The DEGs were classified into three groups by GO terms. KEGG pathway enrichment analysis showed DEGs mainly enriched in the PI3K–Akt signaling pathway, pathways in cancer, focal adhesion and proteoglycans in cancer. DEGs’ protein–protein interaction (PPI) network complex was developed; six central genes (
BCL2
,
CCND1
,
FN1
,
IRS1
,
COL1A1
,
CXCL12
) were identified. Among them,
BCL2
,
CCND1
and
COL1A1
were identified as clinically relevant genes.
Conclusion
BCL2
,
CCND1
and
COL1A1
may be key genes for papillary thyroid carcinoma. Further molecular biological experiments are required to confirm the function of the identified genes.
Abstract Background The plasma protease factor XIa (FXIa) has become a target of interest for therapeutics designed to prevent or treat thrombotic disorders. Methods We used a solution-based, ...directed evolution approach called systematic evolution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers that target the FXIa catalytic domain. Results Two aptamers, designated 11.16 and 12.7, were identified that bound to previously identified anion binding and serpin bindings sites on the FXIa catalytic domain. The aptamers were non-competitive inhibitors of FXIa cleavage of a tripeptide chromogenic substrate and of FXIa activation of factor IX. In normal human plasma, aptamer 12.7 significantly prolonged the aPTT clotting time. Conclusions The results show that novel inhibitors of FXIa can be prepared using SELEX techniques. RNA aptamers can bind to distinct sites on the FXIa catalytic domain and noncompetitively inhibit FXIa activity toward its primary macromolecular substrate factor IX with different levels of potency. Such compounds can be developed for use as therapeutic inhibitors.
In this paper we describe the OpenGeoSys (OGS) project, which is a scientific open-source initiative for numerical simulation of thermo-hydro-mechanical-chemical processes in porous media. The basic ...concept is to provide a flexible numerical framework (using primarily the Finite Element Method (FEM)) for solving multifield problems in porous and fractured media for applications in geoscience and hydrology. To this purpose OGS is based on an object-oriented FEM concept including a broad spectrum of interfaces for pre- and postprocessing. The OGS idea has been in development since the mid-eighties. We provide a short historical note about the continuous process of concept and software development having evolved through Fortran, C, and C++ implementations. The idea behind OGS is to provide an open platform to the community, outfitted with professional software-engineering tools such as platform-independent compiling and automated benchmarking. A comprehensive benchmarking book has been prepared for publication. Benchmarking has been proven to be a valuable tool for cooperation between different developer teams, for example, for code comparison and validation purposes (DEVOVALEX and CO
2
BENCH projects). On one hand, object-orientation (OO) provides a suitable framework for distributed code development; however, the parallelization of OO codes still lacks efficiency. High-performance-computing efficiency of OO codes is subject to future research.
To investigate the effect of combined treatment with gonadotropin-releasing hormone (GnRH) agonist and menstrual blood-derived stem cell (MenSC) transplantation on ovarian function in mice.
We tested ...the effect of GnRH agonist and MenSC transplantation, either alone or in combination, in a mouse model of premature ovarian failure (POF) induced by daily intraperitoneal injection of 120 mg/kg cyclophosphamide (CTX) for 15 days. Venirelin was administered at the daily dose of 0.1 mg via intravenous infusion, starting at 14 days before modeling; MenSC suspension (2× 106 cells) was injected into the ovarium 1 day after modeling. HE staining was used to observe ovarian pathologies of the mice. ELISA was used to detect serum levels of LH, FSH, AMH and E2. The expression levels of ki-67, Bcl-2, BAX, caspase 9, caspase 3, their cleavages, P-PI3K, PI3K, P-Akt and Akt proteins in ovarian granulosa cells were determined with Western blotting.
The mouse models of POF showed obvious ovarian fibrosis with increased atresia
PDF
