Impact of a Conformite Europeenne (CE) Certification-Marked Medical Software Sensor on COVID-19 Pandemic Progression Prediction : Register-Based Study Using Machine Learning Methods

Publisher Copyright: © 2022 JMIR Publications Inc.. All Rights Reserved.Background: To address the current COVID-19 and any future pandemic, we need robust, real-time, and population-scale collection and analysis of data. Rapid and comprehensive knowledge on the trends in reported symptoms in populations provides an earlier window into the progression of viral spread, and helps to predict the needs and timing of professional health care. Objective: The objective of this study was to use a Conformité Européenne (CE)-marked medical online symptom checker service, Omaolo, and validate the data against the national demand for COVID-19-related care to predict the pandemic progression in Finland. Methods: Our data comprised real-time Omaolo COVID-19 symptom checker responses (414,477 in total) and daily admission counts in nationwide inpatient and outpatient registers provided by the Finnish Institute for Health and Welfare from March 16 to June 15, 2020 (the first wave of the pandemic in Finland). The symptom checker responses provide self-triage information input to a medically qualified algorithm that produces a personalized probability of having COVID-19, and provides graded recommendations for further actions. We trained linear regression and extreme gradient boosting (XGBoost) models together with F-score and mutual information feature preselectors to predict the admissions once a week, 1 week in advance. Results: Our models reached a mean absolute percentage error between 24.2% and 36.4% in predicting the national daily patient admissions. The best result was achieved by combining both Omaolo and historical patient admission counts. Our best predictor was linear regression with mutual information as the feature preselector. Conclusions: Accurate short-term predictions of COVID-19 patient admissions can be made, and both symptom check questionnaires and daily admissions data contribute to the accuracy of the predictions. Thus, symptom checkers can be used to estimate the progression of the pandemic, which can be considered when predicting the health care burden in a future pandemic.Peer reviewe

Work-Related Exposures and Sickness Absence Trajectories: A Nationally Representative Follow-up Study among Finnish Working-Aged People

The contribution of physically demanding work to the developmental trajectories of sickness absence (SA) has seldom been examined. We analyzed the associations of 12 physical work exposures, individually and in combination, with SA trajectories among the occupationally active in the Finnish nationally representative Health 2000 survey. We included 3814 participants aged 30–59 years at baseline, when exposure history to work-related factors was reported. The survey and interview responses were linked with the annual number of medically confirmed SA spells through 2002–2008 from national registries. Trajectory analyses identified three SA subgroups: 1 = low (54.6%), 2 = slowly increasing (33.7%), and 3 = high (11.7%). After adjustments, sitting or use of keyboard >1 year was inversely associated with the high SA trajectory (odds ratio, OR, 0.57; 95% 95% confidence interval, CI, 0.43–0.77). The odds of belonging to the trajectory of high SA increased with an increasing number of risk factors, and was highest for those with ≥4 physical workload factors (OR 2.71; 95% CI 1.99–3.69). In conclusion, these findings highlight the need to find ways to better maintain the work ability of those in physically loading work, particularly when there occurs exposure to several workload factors

Work-Related Exposures and Sickness Absence Trajectories: A Nationally Representative Follow-up Study among Finnish Working-Aged People

The contribution of physically demanding work to the developmental trajectories of sickness absence (SA) has seldom been examined. We analyzed the associations of 12 physical work exposures, individually and in combination, with SA trajectories among the occupationally active in the Finnish nationally representative Health 2000 survey. We included 3814 participants aged 30–59 years at baseline, when exposure history to work-related factors was reported. The survey and interview responses were linked with the annual number of medically confirmed SA spells through 2002–2008 from national registries. Trajectory analyses identified three SA subgroups: 1 = low (54.6%), 2 = slowly increasing (33.7%), and 3 = high (11.7%). After adjustments, sitting or use of keyboard >1 year was inversely associated with the high SA trajectory (odds ratio, OR, 0.57; 95% 95% confidence interval, CI, 0.43–0.77). The odds of belonging to the trajectory of high SA increased with an increasing number of risk factors, and was highest for those with ≥4 physical workload factors (OR 2.71; 95% CI 1.99–3.69). In conclusion, these findings highlight the need to find ways to better maintain the work ability of those in physically loading work, particularly when there occurs exposure to several workload factors

The Early-Onset Myocardial Infarction Associated PHACTR1 Gene Regulates Skeletal and Cardiac Alpha-Actin Gene Expression.

The phosphatase and actin regulator 1 (PHACTR1) locus is a very commonly identified hit in genome-wide association studies investigating coronary artery disease and myocardial infarction (MI). However, the function of PHACTR1 in the heart is still unknown. We characterized the mechanisms regulating Phactr1 expression in the heart, used adenoviral gene delivery to investigate the effects of Phactr1 on cardiac function, and analyzed the relationship between MI associated PHACTR1 allele and cardiac function in human subjects. Phactr1 mRNA and protein levels were markedly reduced (60%, P<0.01 and 90%, P<0.001, respectively) at 1 day after MI in rats. When the direct myocardial effects of Phactr1 were studied, the skeletal α-actin to cardiac α-actin isoform ratio was significantly higher (1.5-fold, P<0.05) at 3 days but 40% lower (P<0.05) at 2 weeks after adenovirus-mediated Phactr1 gene delivery into the anterior wall of the left ventricle. Similarly, the skeletal α-actin to cardiac α-actin ratio was lower at 2 weeks in infarcted hearts overexpressing Phactr1. In cultured neonatal cardiac myocytes, adenovirus-mediated Phactr1 overexpression for 48 hours markedly increased the skeletal α-actin to cardiac α-actin ratio, this being associated with an enhanced DNA binding activity of serum response factor. Phactr1 overexpression exerted no major effects on the expression of other cardiac genes or LV structure and function in normal and infarcted hearts during 2 weeks' follow-up period. In human subjects, MI associated PHACTR1 allele was not associated significantly with cardiac function (n = 1550). Phactr1 seems to regulate the skeletal to cardiac α-actin isoform ratio

Characterization of the Regulatory Mechanisms of Activating Transcription Factor 3 by Hypertrophic Stimuli in Rat Cardiomyocytes

Peer reviewe

Kaivosten jätevakuuden alan laajentamisen ympäristönsuojelullinen vaikuttavuus ja kustannukset

Kaivosten jätevakuuden alan laajentamisen ympäristönsuojelullinen vaikuttavuus ja kustannuksetHankkeen taustalla on hallitusohjelman kirjaus kaivosten ympäristönsuojelun parantamisesta muun ohella vakuussääntelyä kehittämällä. Nykytilanteessa vakuussääntely ei kata useita olennaisia vesijakeita ja niihin liittyviä vastuita, kuten louhosten ylivuotovesien hallintaa. Hankkeessa tuotettiin tietoa kaivoksilla syntyvien vesijakeiden määrästä ja laadusta sekä kaivosten vesienhallinta- ja käsittelytekniikoista, tarkkailusta ja lopettamis- ja jälkihoitovaiheen kustannuksista. Hankkeessa tuotettiin myös tietoa tekijöistä, jotka vaikuttavat vesijakeiden ominaisuuksiin, vesienkäsittelytavan valintaan, tarkkailuun ja kustannuksiin. Hankkeessa analysoitiin myös vakuussääntelyn nykytila katvealueineen kaivosten vesienhallinnan, vesienkäsittelyn ja ympäristötarkkailun näkökulmista sekä kehitettiin sääntelymalli näihin vastaamiseksi. Sääntelymallissa YSL:n mukaisen vakuuden ala laajenisi jätteiden käsittelytoiminnasta koko kaivostoimintaan. Malliin sisältyisi sääntelyä kaivostoiminnan sulkemissuunnitelmasta, vesienhallinta- ja vesienkäsittelysuunnitelmasta, seuranta- ja tarkkailusuunnitelmasta sekä uudesta kaivostoiminnan vakuudesta. Vakuuden laajentamisen taloudellisen merkityksen suuruusluokka voi yksittäisellä kaivoksella jäädä pienimmillään alle sadantuhannen. Suurimmillaan, lähinnä ääritapauksissa, lisäkustannukset voivat olla kymmenen miljoonan suuruusluokkaa.Tämä julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa (tietokayttoon.fi). Julkaisun sisällöstä vastaavat tiedon tuottajat, eikä tekstisisältö välttämättä edusta valtioneuvoston näkemystä

WDR12, a Member of Nucleolar PeBoW-Complex, Is Up-Regulated in Failing Hearts and Causes Deterioration of Cardiac Function

Aims In a recent genome-wide association study, WD-repeat domain 12 (WDR12) was associated with early-onset myocardial infarction (MI). However, the function of WDR12 in the heart is unknown. Methods and Results We characterized cardiac expression of WDR12, used adenovirus-mediated WDR12 gene delivery to examine effects of WDR12 on left ventricular (LV) remodeling, and analyzed relationship between MI associated WDR12 allele and cardiac function in human subjects. LV WDR12 protein levels were increased in patients with dilated cardiomyopathy and rats post-infarction. In normal adult rat hearts, WDR12 gene delivery into the anterior wall of the LV decreased interventricular septum diastolic and systolic thickness and increased the diastolic and systolic diameters of the LV. Moreover, LV ejection fraction (9.1%, P Conclusions WDR12 triggers distinct deterioration of cardiac function in adult rat heart and the MI associated WDR12 variant is associated with diastolic dysfunction in human subjects.Peer reviewe

Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006)

p38 mitogen-activated protein kinase and transcription factor GATA-4 in the regulation of cardiomyocyte function

Abstract Cardiovascular diseases are the leading causes of death in the developed countries and their incidence is not expected to decrease in the future. There is a lifetime risk of one in five of developing heart failure, which still has poor prognosis and current treatments only cover part of the pathophysiology behind this syndrome. Pathological processes contributing to heart failure include cardiac hypertrophy and remodeling, which involves neurohumoral activation, reactivation of fetal genes, impaired Ca2+ cycling, increased apoptosis, and increased fibrosis. Intracellular signalling pathways and transcription factors mediating the response to various extracellular stresses have a key role in the regulation of myocardial remodeling and they are investigated in order to develop new approaches for the treatment of heart failure. The aim of this thesis was to elucidate roles of mitogen-activated protein kinases (MAPKs) and transcription factor GATA-4 in the regulation of cardiomyocyte function in cell cultures, and in hearts ex vivo and in vivo. The main findings were that (i) Inhibition of p38α MAPK enhanced function of sarco/endoplasmic reticulum Ca2+ -ATPase and thus cardiac contractility by increasing phosphorylation of protein phosphatase inhibitor-1 and phospholamban, (ii) p38 MAPK isoforms p38α and p38β regulated promoter activity of B-type natriuretic peptide via distinct pathways, (iii) p38α and p38β MAPKs also had different effects on gene expressions related to fibrosis and hypertrophy, and (iv) p38 and ERK1/2 MAPKs mediated stretch-induced activation of GATA-4 by phosphorylation at Ser 105. GATA-4 also seems to be regulated by ubiquitination. This study provides novel data of p38 MAPK and GATA-4 in the regulation of cardiomyocyte function. Inhibition of p38α MAPK could be beneficial in the treatment of heart failure. Also GATA-4 is a potential target for treatment of cardiovascular diseases.Tiivistelmä Sydän- ja verisuonisairaudet ovat yleisin kuolinsyy länsimaissa, eikä niiden ilmaantuvuus tule vähenemään lähitulevaisuudessa. Elinikäinen riski sairastua sydämen vajaatoimintaan on 20 %, ja sydämen vajaatoiminnan ennuste on edelleen huono. Nykyisillä hoitomuodoilla voidaan puuttua vain osittain sydämen vajaatoiminnan patofysiologisiin mekanismeihin. Sydämen vajaatoiminnan kehittymiseen liittyvät sydänlihaksen liikakasvu ja uudelleenmuovautumisprosessi, johon liittyy neurohumoraalinen aktivaatio, sikiöaikaisten geenien uudelleenilmentyminen, häiriöt solunsisäisessä Ca2+-viestinnässä sekä lisääntynyt ohjelmoitu solukuolema ja sidekudoksen muodostuminen sydämeen. Solunsisäisillä viestinvälitysketjuilla sekä transkriptiotekijöillä, jotka vastaavat solunulkoisten ärsykkeiden välittämisestä solun sisällä, on keskeinen rooli edellämainittujen prosessien säätelyssä. Uusien lähestymistapojen kehittäminen sydämen vajaatoiminnan hoitoon edellyttää myös solunsisäisen viestinvälityksen ja geenien säätelyn mekanismien selvittämistä. Tämän väitöstyön tavoite oli selvittää p38 mitogeeniaktivoituvan proteiinikinaasin (p38 MAPK) ja transkriptiotekijä GATA-4:n merkitystä sydämen vajaatoiminnan patogeneesissä soluviljelymalleissa. Päälöydöksiä olivat: (i) p38α MAPK -isoformin estäminen paransi kalsiumia solulimakalvostoon pumppaavan SERCA2a:n toimintaa ja sydänlihassolun supistumiskykyä lisäämällä fosfolambaanin ja proteiinifosfataasi-inhibiittori-1:n fosforylaatiota. (ii) p38 MAPK isoformit p38α ja p38β säätelivät B-tyypin natriureettisen peptidin geenin promoottorialuetta erillisten reittien kautta. (iii) p38α ja p38β isoformit vaikuttivat myös eri tavoin sydämen sidekudoksen muodostumiseen ja hypertrofiaan liittyvien geenien ilmentymiseen. (iv) p38 ja ERK1/2 välittävät venytyksen aiheuttaman GATA-4:n aktivaation fosforyloimalla seriini-105 fosforylaatiopaikan. Lisäksi GATA-4:n toimintaa säädellään ubiquitinaation avulla. Tämä tutkimus tuo uutta tietoa p38 MAPK:n ja GATA-4:n rooleista sydämen vajaatoiminnan kehittymisessä. p38α-isoformin toiminnan estäminen voisi olla hyödyllinen hoitomuoto sydämen vajaatoiminnassa. Myös GATA-4 on potentiaalinen lääkehoidon kohde sydänsairauksien hoidossa