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  • Ganel, Liron; Chen, Lei; Christ, Ryan; Vangipurapu, Jagadish; Young, Erica; Das, Indraniel; Kanchi, Krishna; Larson, David; Regier, Allison; Abel, Haley; Kang, Chul J.; Scott, Alexandra; Havulinna, Aki; Chiang, Charleston W. K.; Service, Susan; Freimer, Nelson; Palotie, Aarno; Ripatti, Samuli; Kuusisto, Johanna; Boehnke, Michael; Laakso, Markku; Locke, Adam; Stitziel, Nathan O.; Hall, Ira M. (BioMed Central, 2021)
    Abstract Background Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell-type composition. Here, we studied MT-CN variation in blood-derived DNA from 19184 Finnish individuals using a combination of genome (N = 4163) and exome sequencing (N = 19034) data as well as imputed genotypes (N = 17718). Results We identified two loci significantly associated with MT-CN variation: a common variant at the MYB-HBS1L locus (P = 1.6 × 10−8), which has previously been associated with numerous hematological parameters; and a burden of rare variants in the TMBIM1 gene (P = 3.0 × 10−8), which has been reported to protect against non-alcoholic fatty liver disease. We also found that MT-CN is strongly associated with insulin levels (P = 2.0 × 10−21) and other metabolic syndrome (metS)-related traits. Using a Mendelian randomization framework, we show evidence that MT-CN measured in blood is causally related to insulin levels. We then applied an MT-CN polygenic risk score (PRS) derived from Finnish data to the UK Biobank, where the association between the PRS and metS traits was replicated. Adjusting for cell counts largely eliminated these signals, suggesting that MT-CN affects metS via cell-type composition. Conclusion These results suggest that measurements of MT-CN in blood-derived DNA partially reflect differences in cell-type composition and that these differences are causally linked to insulin and related traits.
  • Viljanen, Anna; Salminen, Marika; Irjala, Kerttu; Heikkilä, Elisa; Isoaho, Raimo; Kivelä, Sirkka-Liisa; Korhonen, Päivi; Vahlberg, Tero; Viitanen, Matti; Wuorela, Maarit; Löppönen, Minna; Viikari, Laura (BioMed Central, 2021)
    Abstract Background Objective health measures, such as registered illnesses or frailty, predict mortality and institutionalization in older adults. Also, self-reported assessment of health by simple self-rated health (SRH) has been shown to predict mortality and institutionalization. The aim of this study was to assess the association of objective and subjective health with mortality and institutionalization in Finnish community-dwelling older adults. Methods In this prospective study with 10- and 18-year follow-ups, objective health was measured by registered illnesses and subjective health was evaluated by simple SRH, self-reported walking ability (400 m) and self-reported satisfaction in life. The participants were categorized into four groups according to their objective and subjective health: 1. subjectively and objectively healthy, 2. subjectively healthy and objectively unhealthy, 3. subjectively unhealthy and objectively healthy and 4. subjectively and objectively unhealthy. Cox regression model was used in the analyses. Death was used as a competing factor in the institutionalization analyses. Results The mean age of the participants (n = 1259) was 73.5 years (range 64.0–100.0). During the 10- and 18-year follow-ups, 466 (37%) and 877 (70%) died, respectively. In the institutionalization analyses (n = 1106), 162 (15%) and 328 (30%) participants were institutionalized during the 10- and 18-year follow-ups, respectively. In both follow-ups, being subjectively and objectively unhealthy, compared to being subjectively and objectively healthy, was significantly associated with a higher risk of institutionalization in unadjusted models and with death both in unadjusted and adjusted models. Conclusions The categorization of objective and subjective health into four health groups was good at predicting the risk of death during 10- and 18-year follow-ups, and seemed to also predict the risk of institutionalization in the unadjusted models during both follow-ups. Poor subjective health had an additive effect on poor objective health in predicting mortality and could therefore be used as part of an older individual’s health evaluation when screening for future adverse outcomes.
  • Husu, Henrik L.; Leppäniemi, Ari K.; Mentula, Panu J. (BioMed Central, 2021)
    Abstract Background Selection of patients for open abdomen (OA) treatment in severe acute pancreatitis (SAP) is challenging. Treatment related morbidity and risk of adverse events are high; however, refractory abdominal compartment syndrome (ACS) is potentially lethal. Factors influencing the decision to initiate OA treatment are clinically important. We aimed to study these factors to help understand what influences the selection of patients for OA treatment in SAP. Methods A single center study of patients with SAP that underwent OA treatment compared with conservatively treated matched controls. Results Within study period, 47 patients treated with OA were matched in a 1:1 fashion with conservatively treated control patients. Urinary output under 20 ml/h (OR 5.0 95% CI 1.8-13.7) and ACS (OR 4.6 95% CI 1.4-15.2) independently associated with OA treatment. Patients with OA treatment had significantly more often visceral ischemia (34%) than controls (6%), P = 0.002. Mortality among patients with visceral ischemia was 63%. Clinically meaningful parameters predicting developing ischemia were not found. OA treatment associated with higher overall 90-day mortality rate (43% vs 17%, P = 0.012) and increased need for necrosectomy (55% vs 21%, P = 0.001). Delayed primary fascial closure was achieved in 33 (97%) patients that survived past OA treatment. Conclusion Decreased urine output and ACS were independently associated with the choice of OA treatment in patients with SAP. Underlying visceral ischemia was strikingly common in patients undergoing OA treatment, but predicting ischemia in these patients seems difficult.
  • Tuominen, Leena; Ritmala-Castrén, Marita; Nikander, Pia; Mäkelä, Siru; Vahlberg, Tero; Leino-Kilpi, Helena (BioMed Central, 2021)
    Abstract Background Chemotherapy-induced side effects may have a negative effect on nutrition intake, thus increasing the risk of malnutrition and consequently, other serious complications for patients with cancer. The prevalence of malnutrition is common among patients with colorectal cancer. Nurse-led empowering education may have a positive effect on self-care activity in this patient group. Therefore, our purpose is to develop an empowering educational nursing intervention and test its effect on self-care activation and knowledge level among patients with colorectal cancer during chemotherapy. Secondary outcomes are quality of life and risk of malnutrition. Methods An interdisciplinary expert group developed a face-to-face empowering educational intervention using teach-back method. A two-arm, single-centre, superiority trial with stratified randomisation (1:1) and pre-post measures will be used to assess the effect of the intervention compared to standard care. Patients (N = 40 + 40) will be recruited in one university hospital outpatient clinic in Finland. Eligibility criteria are adult patients diagnosed with colorectal cancer starting oral fluoropyrimidine or combination chemotherapy treatment. A registered nurse experienced in oncology will deliver the intervention 2 weeks after the first chemotherapy. Outcomes are measured before intervention (M0) and after a two-month follow-up period (M1). Discussion This study will assess whether nurse-led empowering education using teach-back method is effective on self-care activity among patients with colorectal cancer. If the intervention has a positive effect, it may be implemented into patient education in a corresponding context. Trial registration ClinicalTrials.gov : NCT04160650 Registered 12 November 2019 - retrospectively registered
  • Breidenbach, Johannes; McRoberts, Ronald E.; Alberdi, Iciar; Antón-Fernández, Clara; Tomppo, Erkki (Springer Singapore, 2021)
    Abstract In 2019, 100 years had elapsed since the first National Forest Inventory (NFI) was established in Norway. Motivated by a fear of over-exploitation of timber resources, NFIs today enable informed policy making by providing data vital to decision support at international, national, regional, and local scales. This Collection of articles celebrates the 100th anniversary of NFIs with a description of past, present, and future research aiming at improving the monitoring of forest and other terrestrial ecosystems.
  • Konttinen, Hanna; Halmesvaara, Otto; Fogelholm, Mikael; Saarijärvi, Hannu; Nevalainen, Jaakko; Erkkola, Maijaliisa (BioMed Central, 2021)
    Abstract Background Although sociodemographic differences in dietary intake have been widely studied, the up-to-date evidence on the corresponding variations in motives for food selection is limited. We investigated how sociodemographic characteristics and special diets in households are associated with the relative importance of various food motives. Methods Participants were members of the S Group loyalty card program across Finland who consented to release their grocery purchase data to be used for research purposes and responded to a web-based questionnaire in 2018 (LoCard study). Self-reported information on sociodemographic factors (age, gender, marital status, living situation, education, household income), special diets in household and food motives (Food Choice Questionnaire) were utilized in the present analyses (N = 10,795). Age- and gender-adjusted linear models were performed separately for each sociodemographic predictor and motive dimension (derived by factor analysis) outcome. The importance of each sociodemographic predictor was evaluated based on an increase in R2 value after adding the predictor to the age- and gender-adjusted model. Results Age emerged as a central determinant of food motives with the following strongest associations: young adults emphasized convenience (∆R2 = 0.09, P < 0.001) and mood control (∆R2 = 0.05, P < 0.001) motives more than middle-aged and older adults. The relative importance of cheapness decreased with increasing socioeconomic position (SEP) (∆R2 = 0.08, P < 0.001 for income and ∆R2 = 0.04, P < 0.001 for education). However, the price item (“is good value for money”) depicting the concept of worth did not distinguish between SEP categories. Considerations related to familiarity of food were more salient to men (∆R2 = 0.02, P < 0.001) and those with lower SEP (∆R2 = 0.03, P < 0.001 for education and ∆R2 = 0.01, P < 0.001 for income). Respondents living in households with a vegetarian, red-meat-free, gluten-free or other type of special diet rated ethical concern as relatively more important than households with no special diets (∆R2 = 0.02, P < 0.001). Conclusions We observed sociodemographic differences in a range of food motives that might act as barriers or drivers for adopting diets that benefit human and planetary health. Interventions aiming to narrow SEP and gender disparities in dietary intake should employ strategies that take into account higher priority of familiarity and price in daily food selection in lower-SEP individuals and males.
  • Mukherjee, Kingshuk; Rossi, Massimiliano; Salmela, Leena; Boucher, Christina (BioMed Central, 2021)
    Abstract Genome wide optical maps are high resolution restriction maps that give a unique numeric representation to a genome. They are produced by assembling hundreds of thousands of single molecule optical maps, which are called Rmaps. Unfortunately, there are very few choices for assembling Rmap data. There exists only one publicly-available non-proprietary method for assembly and one proprietary software that is available via an executable. Furthermore, the publicly-available method, by Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006), follows the overlap-layout-consensus (OLC) paradigm, and therefore, is unable to scale for relatively large genomes. The algorithm behind the proprietary method, Bionano Genomics’ Solve, is largely unknown. In this paper, we extend the definition of bi-labels in the paired de Bruijn graph to the context of optical mapping data, and present the first de Bruijn graph based method for Rmap assembly. We implement our approach, which we refer to as rmapper, and compare its performance against the assembler of Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006) and Solve by Bionano Genomics on data from three genomes: E. coli, human, and climbing perch fish (Anabas Testudineus). Our method was able to successfully run on all three genomes. The method of Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006) only successfully ran on E. coli. Moreover, on the human genome rmapper was at least 130 times faster than Bionano Solve, used five times less memory and produced the highest genome fraction with zero mis-assemblies. Our software, rmapper is written in C++ and is publicly available under GNU General Public License at https://github.com/kingufl/Rmapper .
  • Hemminki, Kari; Försti, Asta; Hemminki, Akseli; Ljungberg, Börje; Hemminki, Otto (BioMed Central, 2021)
    Abstract Background The dominant risk factor for urinary bladder cancer has been cigarette smoking, but, as smoking prevalence is decreasing in many populations, other risk factors may become uncovered. Such new risk factors could be responsible for halting the declining incidence of bladder cancer. We hypothesize that snuff use by Swedish men may increase the rate for bladder cancer, as snuff contains carcinogenic nitrosamines. Methods We carried out an ecological study by comparing incidence trends in lung and bladder cancers between Danish, Finnish and Swedish men in order to test if the Swedish bladder cancer rate deviates from the Danish and Finnish ones. We used the NORDCAN database for cancer data from 1960 through 2016 to test the hypothesis. Results In the three countries, the incidence of lung cancer started to decrease after a peak incidence, and this was later followed by declining incidence in bladder cancer in Denmark from 1990 to 2016 by 14.3%, in Finland by 8.3% but not in Sweden (the decline of 1.4% was not significant). The difference in trends can be partly explained by the increasing incidence in Swedish men aged 70 or more years. Sweden differs from the two other countries by low male smoking prevalence but increasing use of snuff recorded by various surveys. Conclusion The stable bladder cancer trend for Swedish men was opposite to the declining trends in Denmark, Finland and globally. We suggest that this unusual finding may be related to the increasing use of snuff by Swedish men. Average users of snuff are exposed to at least 3 times higher levels of carcinogenic tobacco-specific nitrosamines than a smoker of one daily pack of cigarettes.
  • Scala, Giovanni; Federico, Antonio; Greco, Dario (BioMed Central, 2021)
    Abstract Background The investigation of molecular alterations associated with the conservation and variation of DNA methylation in eukaryotes is gaining interest in the biomedical research community. Among the different determinants of methylation stability, the DNA composition of the CpG surrounding regions has been shown to have a crucial role in the maintenance and establishment of methylation statuses. This aspect has been previously characterized in a quantitative manner by inspecting the nucleotidic composition in the region. Research in this field still lacks a qualitative perspective, linked to the identification of certain sequences (or DNA motifs) related to particular DNA methylation phenomena. Results Here we present a novel computational strategy based on short DNA motif discovery in order to characterize sequence patterns related to aberrant CpG methylation events. We provide our framework as a user-friendly, shiny-based application, CpGmotifs, to easily retrieve and characterize DNA patterns related to CpG methylation in the human genome. Our tool supports the functional interpretation of deregulated methylation events by predicting transcription factors binding sites (TFBS) encompassing the identified motifs. Conclusions CpGmotifs is an open source software. Its source code is available on GitHub https://github.com/Greco-Lab/CpGmotifs and a ready-to-use docker image is provided on DockerHub at https://hub.docker.com/r/grecolab/cpgmotifs .
  • Tiwari, Ananda; Hokajärvi, Anna-Maria; Domingo, Jorge S.; Elk, Michael; Jayaprakash, Balamuralikrishna; Ryu, Hodon; Siponen, Sallamaari; Vepsäläinen, Asko; Kauppinen, Ari; Puurunen, Osmo; Artimo, Aki; Perkola, Noora; Huttula, Timo; Miettinen, Ilkka T.; Pitkänen, Tarja (BioMed Central, 2021)
    Abstract Background Rivers and lakes are used for multiple purposes such as for drinking water (DW) production, recreation, and as recipients of wastewater from various sources. The deterioration of surface water quality with wastewater is well-known, but less is known about the bacterial community dynamics in the affected surface waters. Understanding the bacterial community characteristics —from the source of contamination, through the watershed to the DW production process—may help safeguard human health and the environment. Results The spatial and seasonal dynamics of bacterial communities, their predicted functions, and potential health-related bacterial (PHRB) reads within the Kokemäenjoki River watershed in southwest Finland were analyzed with the 16S rRNA-gene amplicon sequencing method. Water samples were collected from various sampling points of the watershed, from its major pollution sources (sewage influent and effluent, industrial effluent, mine runoff) and different stages of the DW treatment process (pre-treatment, groundwater observation well, DW production well) by using the river water as raw water with an artificial groundwater recharge (AGR). The beta-diversity analysis revealed that bacterial communities were highly varied among sample groups (R = 0.92, p <  0.001, ANOSIM). The species richness and evenness indices were highest in surface water (Chao1; 920 ± 10) among sample groups and gradually decreased during the DW treatment process (DW production well; Chao1: 320 ± 20). Although the phylum Proteobacteria was omnipresent, its relative abundance was higher in sewage and industrial effluents (66–80%) than in surface water (55%). Phyla Firmicutes and Fusobacteria were only detected in sewage samples. Actinobacteria was more abundant in the surface water (≥13%) than in other groups (≤3%). Acidobacteria was more abundant in the DW treatment process (≥13%) than in others (≤2%). In total, the share of PHRB reads was higher in sewage and surface water than in the DW treatment samples. The seasonal effect in bacterial communities was observed only on surface water samples, with the lowest diversity during summer. Conclusions The low bacterial diversity and absence of PHRB read in the DW samples indicate AGR can produce biologically stable and microbiologically safe drinking water. Furthermore, the significantly different bacterial communities at the pollution sources compared to surface water and DW samples highlight the importance of effective wastewater treatment for protecting the environment and human health.
  • Päivinen, Marja; Keskinen, Kari; Tikkanen, Heikki (BioMed Central, 2021)
    Abstract Background A special improvement in pulmonary function is found in swimmers. In clinical testing the airway reactivity is observed at certain exercise intensity and target ventilation. However, in highly trained swimmers exercising in water the reactions may not function the same way. The aim was to study the combined effects of the water environment and swimming on pulmonary function and the associations with perceived symptoms. Methods First, 412 competitive swimmers completed questionnaires concerning respiratory symptoms at different swimming intensities. Then, pulmonary function testing was performed in 14 healthy elite swimmers. Spirometry and maximal voluntary ventilation (MVV) were measured on land and in water before and after swimming. While swimming, minute ventilation (VE) tidal volume (VT) and breathing frequency (fb) were measured during competition speed swimming. Results Swimmers reported the most symptoms at competition speed intensity swimming. In the transition from the land into the water swimming body position, the ratio of forced expiratory volume in one second (FEV1) and forced expiratory capacity (FVC) (FEV1/FVC) decreased by a mean (SD) 5.3 % (3) in females and by 2.2 % (5) in males. During competition speed intensity swimming, the minute ventilation (VE) had a mean of 72 and 75 % of calculated maximal voluntary ventilation (cMVV) in females and in males, respectively. Conclusions Spirometry showed sex differences in water compared to land measurements. These differences should be considered when the effects of swimming are observed. During the intensity that triggered the symptoms the most, the VE was approximately 20 % higher than the target ventilations for clinical testing. These findings encourages specific modifications of clinical testing protocols for elite swimmers.
  • Toresson, L.; Steiner, J. M.; Suchodolski, J. S. (BioMed Central, 2021)
  • Sillanpää, Elina; Heikkinen, Aino; Kankaanpää, Anna; Paavilainen, Aini; Kujala, Urho M.; Tammelin, Tuija H.; Kovanen, Vuokko; Sipilä, Sarianna; Pietiläinen, Kirsi H.; Kaprio, Jaakko; Ollikainen, Miina; Laakkonen, Eija K. (BioMed Central, 2021)
    Abstract The aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 and N = 47) were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with questionnaires and accelerometers. Several tests were conducted to estimate cardiorespiratory fitness and muscle strength. Body composition was estimated by dual-energy X-ray absorptiometry. DNAmAge estimates from blood and muscle were highly correlated with chronological age, but different age acceleration estimates were weakly associated with each other. The monozygotic twin within-pair similarity of ageing pace was higher in blood (r = 0.617–0.824) than in muscle (r = 0.523–0.585). Associations of age acceleration estimates with PA, physical function and body composition were weak in both tissues and mostly explained by smoking and sex. The muscle-specific epigenetic clock MEAT was developed to predict chronological age, which may explain why it did not associate with functional phenotypes. The Horvath’s clock and GrimAge were weakly associated with PA and related phenotypes, suggesting that higher PA would be linked to accelerated biological ageing in muscle. This may, however, be more reflective of the low capacity of epigenetic clock algorithms to measure functional muscle ageing than of actual age acceleration. Based on our results, the investigated epigenetic clocks have rather low value in estimating muscle ageing with respect to the physiological adaptations that typically occur due to ageing or PA. Thus, further development of methods is needed to gain insight into muscle tissue-specific ageing and the underlying biological pathways.
  • Anttila, Heidi; Tallqvist, Susanna; Muñoz, Minna; Leppäjoki-Tiistola, Sanna; Mäkitie, Outi; Hiekkala, Sinikka (BioMed Central, 2021)
    Abstract Background Little is known about the spectrum of everyday challenges that people with skeletal dysplasia face because of their health and functioning. We aimed to identify factors related to health, functioning and disability in people with skeletal dysplasia, and their challenges with accessibility in order to form a self-reported questionnaire for national data collection. The comprehensive musculoskeletal post-acute core set of the International Classification of Functioning, Disability and Health (ICF) was used as a framework. Methods An iterative, participatory and qualitative process was used to formulate a questionnaire. Items were searched from Patient-Reported Outcomes Measurement Information System and from other self-report instruments, additional items were formulated using ICF linking rules. Expert panels from the target population assessed the face and content validity in thematic interviews. Results The questionnaire demonstrated its relevance, comprehensiveness and feasibility for people with skeletal dysplasia. The ICF linkages showed the contents’ correspondence to the construct. Expert panels added 15 categories and one on chapter level to the core set and confirmed content validity. The final survey covers 86 ICF categories and 173 ICF-linked items that were grouped to 33 questions. Conclusions The content of the questionnaire proved to be sufficiently valid for people with skeletal dysplasia. It can be used to explore their health, functioning, disability and accessibility to develop care and rehabilitation policies, to plan services and to provide information to various parties involved.
  • De Simone, Belinda; Davies, Justin; Chouillard, Elie; Di Saverio, Salomone; Hoentjen, Frank; Tarasconi, Antonio; Sartelli, Massimo; Biffl, Walter L; Ansaloni, Luca; Coccolini, Federico; Chiarugi, Massimo; De’Angelis, Nicola; Moore, Ernest E; Kluger, Yoram; Abu-Zidan, Fikri; Sakakushev, Boris; Coimbra, Raul; Celentano, Valerio; Wani, Imtiaz; Pintar, Tadeja; Sganga, Gabriele; Di Carlo, Isidoro; Tartaglia, Dario; Pikoulis, Manos; Cardi, Maurizio; De Moya, Marc A; Leppaniemi, Ari; Kirkpatrick, Andrew; Agnoletti, Vanni; Poggioli, Gilberto; Carcoforo, Paolo; Baiocchi, Gian L; Catena, Fausto (BioMed Central, 2021)
    Abstract Background Despite the current therapeutic options for the treatment of inflammatory bowel disease, surgery is still frequently required in the emergency setting, although the number of cases performed seems to have decreased in recent years. The World Society of Emergency Surgery decided to debate in a consensus conference of experts, the main pertinent issues around the management of inflammatory bowel disease in the emergent situation, with the need to provide focused guidelines for acute care and emergency surgeons. Method A group of experienced surgeons and gastroenterologists were nominated to develop the topics assigned and answer the questions addressed by the Steering Committee of the project. Each expert followed a precise analysis and grading of the studies selected for review. Statements and recommendations were discussed and voted at the Consensus Conference of the 6th World Society of Emergency Surgery held in Nijmegen (The Netherlands) in June 2019. Conclusions Complicated inflammatory bowel disease requires a multidisciplinary approach because of the complexity of this patient group and disease spectrum in the emergency setting, with the aim of obtaining safe surgery with good functional outcomes and a decreasing stoma rate where appropriate.
  • Söderhäll, Cilla; Reinius, Lovisa E; Salmenperä, Pertteli; Gentile, Massimiliano; Acevedo, Nathalie; Konradsen, Jon R; Nordlund, Björn; Hedlin, Gunilla; Scheynius, Annika; Myllykangas, Samuel; Kere, Juha (BioMed Central, 2021)
    Abstract Background Methylation of DNA at CpG sites is an epigenetic modification and a potential modifier of disease risk, possibly mediating environmental effects. Currently, DNA methylation is commonly assessed using specific microarrays that sample methylation at a few % of all methylated sites. Methods To understand if significant information on methylation can be added by a more comprehensive analysis of methylation, we set up a quantitative method, bisulfite oligonucleotide-selective sequencing (Bs-OS-seq), and compared the data with microarray-derived methylation data. We assessed methylation at two asthma-associated genes, IL13 and ORMDL3, in blood samples collected from children with and without asthma and fractionated white blood cell types from healthy adult controls. Results Our results show that Bs-OS-seq can uncover vast amounts of methylation variation not detected by commonly used array methods. We found that high-density methylation information from even one gene can delineate the main white blood cell lineages. Conclusions We conclude that high-resolution methylation studies can yield clinically important information at selected specific loci missed by array-based methods, with potential implications for future studies of methylation-disease associations.
  • Sjöblom, Nelli; Boyd, Sonja; Manninen, Anniina; Knuuttila, Anna; Blom, Sami; Färkkilä, Martti; Arola, Johanna (BioMed Central, 2021)
    Abstract Background The objective was to build a novel method for automated image analysis to locate and quantify the number of cytokeratin 7 (K7)-positive hepatocytes reflecting cholestasis by applying deep learning neural networks (AI model) in a cohort of 210 liver specimens. We aimed to study the correlation between the AI model’s results and disease progression. The cohort of liver biopsies which served as a model of chronic cholestatic liver disease comprised of patients diagnosed with primary sclerosing cholangitis (PSC). Methods In a cohort of patients with PSC identified from the PSC registry of the University Hospital of Helsinki, their K7-stained liver biopsy specimens were scored by a pathologist (human K7 score) and then digitally analyzed for K7-positive hepatocytes (K7%area). The digital analysis was by a K7-AI model created in an Aiforia Technologies cloud platform. For validation, values were human K7 score, stage of disease (Metavir and Nakunuma fibrosis score), and plasma liver enzymes indicating clinical cholestasis, all subjected to correlation analysis. Results The K7-AI model results (K7%area) correlated with the human K7 score (0.896; p < 2.2e− 16). In addition, K7%area correlated with stage of PSC (Metavir 0.446; p < 1.849e− 10 and Nakanuma 0.424; p < 4.23e− 10) and with plasma alkaline phosphatase (P-ALP) levels (0.369, p < 5.749e− 5). Conclusions The accuracy of the AI-based analysis was comparable to that of the human K7 score. Automated quantitative image analysis correlated with stage of PSC and with P-ALP. Based on the results of the K7-AI model, we recommend K7 staining in the assessment of cholestasis by means of automated methods that provide fast (9.75 s/specimen) quantitative analysis.
  • Boman, Nea; Fernandez-Luque, Luis; Koledova, Ekaterina; Kause, Marketta; Lapatto, Risto (BioMed Central, 2021)
    Abstract Background A range of factors can reduce the effectiveness of treatment prescribed for the long-term management of chronic health conditions, such as growth disorders. In particular, prescription medications may not achieve the positive outcomes expected because approximately half of patients adhere poorly to the prescribed treatment regimen. Methods Adherence to treatment has previously been assessed using relatively unreliable subjective methods, such as patient self-reporting during clinical follow-up, or counting prescriptions filled or vials returned by patients. Here, we report on a new approach, the use of electronically recorded objective evidence of date, time, and dose taken which was obtained through a comprehensive eHealth ecosystem, based around the easypod™ electromechanical auto-injection device and web-based connect software. The benefits of this eHealth approach are also illustrated here by two case studies, selected from the Finnish cohort of the easypod™ Connect Observational Study (ECOS), a 5-year, open-label, observational study that enrolled children from 24 countries who were being treated with growth hormone (GH) via the auto-injection device. Results Analyses of data from 9314 records from the easypod™ connect database showed that, at each time point studied, a significantly greater proportion of female patients had high adherence (≥ 85%) than male patients (2849/3867 [74%] vs 3879/5447 [71%]; P < 0.001). Furthermore, more of the younger patients (< 10 years for girls, < 12 years for boys) were in the high adherence range (P < 0.001). However, recursive partitioning of data from ECOS identified subgroups with lower adherence to GH treatment ‒ children who performed the majority of injections themselves at an early age (~ 8 years) and teenagers starting treatment aged ≥ 14 years. Conclusions The data and case studies presented herein illustrate the importance of adherence to GH therapy and how good growth outcomes can be achieved by following treatment as described. They also show how the device, software, and database ecosystem can complement normal clinical follow-up by providing HCPs with reliable information about patient adherence between visits and also providing researchers with real-world evidence of adherence and growth outcomes across a large population of patients with growth disorders treated with GH via the easypod™ device.
  • Almangush, Alhadi; Alabi, Rasheed O; Troiano, Giuseppe; Coletta, Ricardo D; Salo, Tuula; Pirinen, Matti; Mäkitie, Antti A; Leivo, Ilmo (BioMed Central, 2021)
    Abstract Background The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck cancer. Methods Four databases (Scopus, Medline, PubMed and Web of Science) were searched using the term tumo(u)r-stroma ratio. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed. Results TSR was studied in nine studies of different subsites (including cohorts of nasopharyngeal, oral, laryngeal and pharyngeal carcinomas). In all studies, TSR was evaluated using hematoxylin and eosin staining. Classifying tumors based on TSR seems to allow for identification of high-risk cases. In oral cancer, specifically, our meta-analysis showed that TSR is significantly associated with both cancer-related mortality (HR 2.10, 95%CI 1.56–2.84) and disease-free survival (HR 1.84, 95%CI 1.38–2.46). Conclusions The assessment of TSR has a promising prognostic value and can be implemented with minimum efforts in routine head and neck pathology.
  • Simonsen, Nina; Koponen, Anne M; Suominen, Sakari (BioMed Central, 2021)
    Abstract Background Rising prevalence of type 2 diabetes (T2D), also among younger adults, constitutes a growing public health challenge. According to the person-centred Chronic Care Model, proactive care and self-management support in combination with community resources enhance quality of healthcare and health outcomes for patients with T2D. However, research is scarce concerning the importance of person-centred care and community resources for such outcomes as empowerment, and the relative impact of various patient support sources for empowerment is not known. Moreover, little is known about the association of age with these variables in this patient-group. This study, carried out among patients with T2D, examined in three age-groups (27–54, 55–64 and 65–75 years) whether person-centred care and diabetes-related social support, including community support and possibilities to influence community health issues, are associated with patient empowerment, when considering possible confounding factors, such as other quality of care indicators and psychosocial wellbeing. We also explored age differentials in empowerment and in the proposed correlates of empowerment. Method Individuals from a register-based sample with T2D participated in a cross-sectional survey (participation 56%, n = 2866). Data were analysed by descriptive statistics and multivariate logistic regression analyses. Results Respondents in the youngest age-group were more likely to have low empowerment scores, less continuity of care, and lower wellbeing than the other age-groups, and to perceive less social support, but a higher level of person-centred care than the oldest group. Community support, including possibilities to influence community health issues, was independently and consistently associated with high empowerment in all three age-groups, as was person-centred care in the two older age-groups. Community support was the social support variable with the strongest association with empowerment across age-groups. Moreover, vitality was positively and diabetes-related distress negatively associated with high empowerment in all age-groups, whereas continuity of care, i.e. having a family/regular nurse, was independently associated in the youngest age-group only. Conclusion Person-centred care and community support, including possibilities to influence community health issues, supports empowerment among adults with T2D. Findings suggest that age is related to most correlates of empowerment, and that younger adults with T2D have specific healthcare needs.

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