Articles from BioMed Central


Recent Submissions

  • 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.
  • 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.
  • 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.
  • Smyth, L. J; Kilner, J.; Nair, V.; Liu, H.; Brennan, E.; Kerr, K.; Sandholm, N.; Cole, J.; Dahlström, E.; Syreeni, A.; Salem, R. M; Nelson, R. G; Looker, H. C; Wooster, C.; Anderson, K.; McKay, G. J; Kee, F.; Young, I.; Andrews, D.; Forsblom, C.; Hirschhorn, J. N; Godson, C.; Groop, P. H; Maxwell, A. P; Susztak, K.; Kretzler, M.; Florez, J. C; McKnight, A. J (BioMed Central, 2021)
    Abstract Background A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina’s Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10–8 and fold change ± 2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM. Results Top-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation. Conclusions Epigenetic alterations provide a dynamic link between an individual’s genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.
  • Dieckmann, Linda; Lahti-Pulkkinen, Marius; Kvist, Tuomas; Lahti, Jari; DeWitt, Peter E; Cruceanu, Cristiana; Laivuori, Hannele; Sammallahti, Sara; Villa, Pia M; Suomalainen-König, Sanna; Eriksson, Johan G; Kajantie, Eero; Raikkönen, Katri; Binder, Elisabeth B; Czamara, Darina (BioMed Central, 2021)
    Abstract Background Epigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. However, so far, only few studies have examined epigenetic aging in newborns—especially regarding different gestational or perinatal tissues. In this study, we investigated which birth- and pregnancy-related variables are most important in predicting gestational epigenetic age acceleration or deceleration (i.e., the deviation between gestational epigenetic age estimated from the DNA methylome and chronological gestational age) in chorionic villus, placenta and cord blood tissues from two independent study cohorts (ITU, n = 639 and PREDO, n = 966). We further characterized the correspondence of epigenetic age deviations between these tissues. Results Among the most predictive factors of epigenetic age deviations in single tissues were child sex, birth length, maternal smoking during pregnancy, maternal mental disorders until childbirth, delivery mode and parity. However, the specific factors related to epigenetic age deviation and the direction of association differed across tissues. In individuals with samples available from more than one tissue, relative epigenetic age deviations were not correlated across tissues. Conclusion Gestational epigenetic age acceleration or deceleration was not related to more favorable or unfavorable factors in one direction in the investigated tissues, and the relative epigenetic age differed between tissues of the same person. This indicates that epigenetic age deviations associate with distinct, tissue specific, factors during the gestational and perinatal period. Our findings suggest that the epigenetic age of the newborn should be seen as a characteristic of a specific tissue, and less as a general characteristic of the child itself.
  • Singh, Pooja; Ahi, Ehsan P; Sturmbauer, Christian (BioMed Central, 2021)
    Abstract Background The oral and pharyngeal jaw of cichlid fishes are a classic example of evolutionary modularity as their functional decoupling boosted trophic diversification and contributed to the success of cichlid adaptive radiations. Most studies until now have focused on the functional, morphological, or genetic aspects of cichlid jaw modularity. Here we extend this concept to include transcriptional modularity by sequencing whole transcriptomes of the two jaws and comparing their gene coexpression networks. Results We show that transcriptional decoupling of gene expression underlies the functional decoupling of cichlid oral and pharyngeal jaw apparatus and the two units are evolving independently in recently diverged cichlid species from Lake Tanganyika. Oral and pharyngeal jaw coexpression networks reflect the common origin of the jaw regulatory program as there is high preservation of gene coexpression modules between the two sets of jaws. However, there is substantial rewiring of genetic architecture within those modules. We define a global jaw coexpression network and highlight jaw-specific and species-specific modules within it. Furthermore, we annotate a comprehensive in silico gene regulatory network linking the Wnt and AHR signalling pathways to jaw morphogenesis and response to environmental cues, respectively. Components of these pathways are significantly differentially expressed between the oral and pharyngeal jaw apparatus. Conclusion This study describes the concerted expression of many genes in cichlid oral and pharyngeal jaw apparatus at the onset of the independent life of cichlid fishes. Our findings suggest that – on the basis of an ancestral gill arch network—transcriptional rewiring may have driven the modular evolution of the oral and pharyngeal jaws, highlighting the evolutionary significance of gene network reuse. The gene coexpression and in silico regulatory networks presented here are intended as resource for future studies on the genetics of vertebrate jaw morphogenesis and trophic adaptation.
  • Tuominen, Heidi; Rautava, Jaana; Kero, Katja; Syrjänen, Stina; Collado, Maria C; Rautava, Samuli (BioMed Central, 2021)
    Abstract Background Aberrant microbiota composition has been linked to disease development at numerous anatomical sites. Microbiota changes in reaction to viral infections, such as human papillomavirus (HPV), have been investigated almost exclusively in the female reproductive tract. However, HPV infection may also affect male health by reducing semen quality and fertility. The aim of this study was to investigate whether present HPV DNA is associated with detectable changes in semen bacterial microbiota composition and diversity. Methods This study relied on stored semen samples from 31 fertile healthy men who participated in the Finnish family HPV Study during the years 1998–2001. DNA was extracted from semen with PCR template preparation kit. HPV was genotyped using Luminex-based Multimetrix® assay. Microbiota was analyzed from the V3-V4 region of 16S rDNA gene following sequencing on an Illumina MiSeq platform. All statistical analyses were performed with Calypso software version 8.84. Results HPV DNA was detected in 19.4% (6/31) of the semen samples. HPV status in the semen did not impact the α-diversity estimations, as measured by Chao1 and Shannon indices, nor ß-diversity. Nevertheless, HPV-positive semen samples exhibited differences in the taxonomic composition of the bacterial microbiota including higher abundances of Moraxellaceae (p = 0.028), Streptococcus (p = 0.0058) and Peptostreptococcus (p = 0.012) compared to HPV-negative semen samples. Conclusion HPV infection is associated with altered bacterial microbiota composition in semen, and this might have in impact to male health in general. As of present, it is unclear whether these changes result from HPV infection or whether altered bacterial microbiota increases susceptibility to HPV infection. More research is needed on viral-bacterial interactions in the male reproductive system.
  • Bazzocco, Sarah; Dopeso, Higinio; Martínez-Barriocanal, Águeda; Anguita, Estefanía; Nieto, Rocío; Li, Jing; García-Vidal, Elia; Maggio, Valentina; Rodrigues, Paulo; de Marcondes, Priscila G; Schwartz, Simo; Aaltonen, Lauri A; Sánchez, Alex; Mariadason, John M; Arango, Diego (BioMed Central, 2021)
    Abstract Background Cancer initiation and progression are driven by genetic and epigenetic changes. Although genome/exome sequencing has significantly contributed to the characterization of the genetic driver alterations, further investigation is required to systematically identify cancer driver genes regulated by promoter hypermethylation. Results Using genome-wide analysis of promoter methylation in 45 colorectal cancer cell lines, we found that higher overall methylation levels were associated with microsatellite instability (MSI), faster proliferation and absence of APC mutations. Because epigenetically silenced genes could represent important oncogenic drivers, we used mRNA expression profiling of colorectal cancer cell lines and primary tumors to identify a subset of 382 (3.9%) genes for which promoter methylation was negatively associated with gene expression. Remarkably, a significant enrichment in zinc finger proteins was observed, including the transcriptional repressor ZBTB18. Re-introduction of ZBTB18 in colon cancer cells significantly reduced proliferation in vitro and in a subcutaneous xenograft mouse model. Moreover, immunohistochemical analysis revealed that ZBTB18 is frequently lost or reduced in colorectal tumors, and reduced ZBTB18 expression was found to be associated with lymph node metastasis and shorter survival of patients with locally advanced colorectal cancer. Conclusions We identified a set of 382 genes putatively silenced by promoter methylation in colorectal cancer that could significantly contribute to the oncogenic process. Moreover, as a proof of concept, we demonstrate that the epigenetically silenced gene ZBTB18 has tumor suppressor activity and is a novel prognostic marker for patients with locally advanced colorectal cancer.
  • Haftorn, Kristine L; Lee, Yunsung; Denault, William R P; Page, Christian M; Nustad, Haakon E; Lyle, Robert; Gjessing, Håkon K; Malmberg, Anni; Magnus, Maria C; Næss, Øyvind; Czamara, Darina; Räikkönen, Katri; Lahti, Jari; Magnus, Per; Håberg, Siri E; Jugessur, Astanand; Bohlin, Jon (BioMed Central, 2021)
    Abstract Background Gestational age is a useful proxy for assessing developmental maturity, but correct estimation of gestational age is difficult using clinical measures. DNA methylation at birth has proven to be an accurate predictor of gestational age. Previous predictors of epigenetic gestational age were based on DNA methylation data from the Illumina HumanMethylation 27 K or 450 K array, which have subsequently been replaced by the Illumina MethylationEPIC 850 K array (EPIC). Our aims here were to build an epigenetic gestational age clock specific for the EPIC array and to evaluate its precision and accuracy using the embryo transfer date of newborns from the largest EPIC-derived dataset to date on assisted reproductive technologies (ART). Methods We built an epigenetic gestational age clock using Lasso regression trained on 755 randomly selected non-ART newborns from the Norwegian Study of Assisted Reproductive Technologies (START)—a substudy of the Norwegian Mother, Father, and Child Cohort Study (MoBa). For the ART-conceived newborns, the START dataset had detailed information on the embryo transfer date and the specific ART procedure used for conception. The predicted gestational age was compared to clinically estimated gestational age in 200 non-ART and 838 ART newborns using MM-type robust regression. The performance of the clock was compared to previously published gestational age clocks in an independent replication sample of 148 newborns from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restrictions (PREDO) study—a prospective pregnancy cohort of Finnish women. Results Our new epigenetic gestational age clock showed higher precision and accuracy in predicting gestational age than previous gestational age clocks (R2 = 0.724, median absolute deviation (MAD) = 3.14 days). Restricting the analysis to CpGs shared between 450 K and EPIC did not reduce the precision of the clock. Furthermore, validating the clock on ART newborns with known embryo transfer date confirmed that DNA methylation is an accurate predictor of gestational age (R2 = 0.767, MAD = 3.7 days). Conclusions We present the first EPIC-based predictor of gestational age and demonstrate its robustness and precision in ART and non-ART newborns. As more datasets are being generated on the EPIC platform, this clock will be valuable in studies using gestational age to assess neonatal development.
  • Naghizadeh, Ayeh; Salamat, Mahdi; Hamzeian, Donya; Akbari, Shaghayegh; Rezaeizadeh, Hossein; Vaghasloo, Mahdi A; Karbalaei, Reza; Mirzaie, Mehdi; Karimi, Mehrdad; Jafari, Mohieddin (BioMed Central, 2021)
    Abstract Background Iranian traditional medicine, also known as Persian Medicine, is a holistic school of medicine with a long prolific history. It describes numerous concepts and the relationships between them. However, no unified language system has been proposed for the concepts of this medicine up to the present time. Considering the extensive terminology in the numerous textbooks written by the scholars over centuries, comprehending the totality of concepts is obviously a very challenging task. To resolve this issue, overcome the obstacles, and code the concepts in a reusable manner, constructing an ontology of the concepts of Iranian traditional medicine seems a necessity. Construction and content Makhzan al-Advieh, an encyclopedia of materia medica compiled by Mohammad Hossein Aghili Khorasani, was selected as the resource to create an ontology of the concepts used to describe medicinal substances. The steps followed to accomplish this task included (1) compiling the list of classes via examination of textbooks, and text mining the resource followed by manual review to ensure comprehensiveness of extracted terms; (2) arranging the classes in a taxonomy; (3) determining object and data properties; (4) specifying annotation properties including ID, labels (English and Persian), alternative terms, and definitions (English and Persian); (5) ontology evaluation. The ontology was created using Protégé with adherence to the principles of ontology development provided by the Open Biological and Biomedical Ontology (OBO) foundry. Utility and discussion The ontology was finalized with inclusion of 3521 classes, 15 properties, and 20,903 axioms in the Iranian traditional medicine General Ontology (IrGO) database, freely available at . An indented list and an interactive graph view using WebVOWL were used to visualize the ontology. All classes were linked to their instances in UNaProd database to create a knowledge base of ITM materia medica. Conclusion We constructed an ontology-based knowledge base of ITM concepts in the domain of materia medica to help offer a shared and common understanding of this concept, enable reuse of the knowledge, and make the assumptions explicit. This ontology will aid Persian medicine practitioners in clinical decision-making to select drugs. Extending IrGO will bridge the gap between traditional and conventional schools of medicine, helping guide future research in the process of drug discovery.
  • Amadi, Miracle; Shcherbacheva, Anna; Haario, Heikki (BioMed Central, 2021)
    Abstract Background Increasingly complex models have been developed to characterize the transmission dynamics of malaria. The multiplicity of malaria transmission factors calls for a realistic modelling approach that incorporates various complex factors such as the effect of control measures, behavioural impacts of the parasites to the vector, or socio-economic variables. Indeed, the crucial impact of household size in eliminating malaria has been emphasized in previous studies. However, increasing complexity also increases the difficulty of calibrating model parameters. Moreover, despite the availability of much field data, a common pitfall in malaria transmission modelling is to obtain data that could be directly used for model calibration. Methods In this work, an approach that provides a way to combine in situ field data with the parameters of malaria transmission models is presented. This is achieved by agent-based stochastic simulations, initially calibrated with hut-level experimental data. The simulation results provide synthetic data for regression analysis that enable the calibration of key parameters of classical models, such as biting rates and vector mortality. In lieu of developing complex dynamical models, the approach is demonstrated using most classical malaria models, but with the model parameters calibrated to account for such complex factors. The performance of the approach is tested against a wide range of field data for Entomological Inoculation Rate (EIR) values. Results The overall transmission characteristics can be estimated by including various features that impact EIR and malaria incidence, for instance by reducing the mosquito–human contact rates and increasing the mortality through control measures or socio-economic factors. Conclusion Complex phenomena such as the impact of the coverage of the population with long-lasting insecticidal nets (LLINs), changes in behaviour of the infected vector and the impact of socio-economic factors can be included in continuous level modelling. Though the present work should be interpreted as a proof of concept, based on one set of field data only, certain interesting conclusions can already be drawn. While the present work focuses on malaria, the computational approach is generic, and can be applied to other cases where suitable in situ data is available.
  • Duru, Ilhan C; Bucur, Florentina I; Andreevskaya, Margarita; Ylinen, Anne; Crauwels, Peter; Grigore-Gurgu, Leontina; Nikparvar, Bahareh; Rode, Tone M; Laine, Pia; Paulin, Lars; Løvdal, Trond; Riedel, Christian U; Bar, Nadav; Borda, Daniela; Nicolau, Anca I; Auvinen, Petri (BioMed Central, 2021)
    Abstract Objectives The study aims to generate the whole genome sequence of L. monocytogenes strain S2542 and to compare it to the genomes of strains RO15 and ScottA. In addition, we aimed to compare gene expression profiles of L. monocytogenes strains S2542, ScottA and RO15 after high-pressure processing (HPP) using ddPCR. Results The whole genome sequence of L. monocytogenes S2542 indicates that this strain belongs to serotype 4b, in contrast to the previously reported serotype 1/2a. Strain S2542 appears to be more susceptible to the treatment at 400 MPa compared to RO15 and ScottA strains. In contrast to RO15 and ScottA strains, viable cell counts of strain S2542 were below the limit of detection after HPP (400 MPa/8 min) when stored at 8 °C for 24 and 48 h. The transcriptional response of all three strains to HPP was not significantly different.
  • Uhlen, M. M; Tseveenjav, B.; Wuollet, E.; Furuholm, J.; Ansteinsson, V.; Mulic, A.; Valen, H. (BioMed Central, 2021)
    Abstract Background Stainless-steel crowns (SSCs) are recommended for restorative treatment of young teeth severely affected by caries, fractures or dental developmental disorders (DDDs). However, despite recommendations and clinical evidence, SSCs are not widely used by general dentists, who favour extraction and more conventional restorations. The present study aimed to investigate the views of and use of SSCs among Norwegian and Finnish dentists. Methods The present study was a cross-sectional survey among Norwegian and Finnish dentists. An electronic questionnaire was sent to Norwegian and Finnish dentists asking whether they used SSCs and on which indications. In addition, the questionnaire assessed reasons for non-use and dentists’ perceptions regarding advantages and challenges in the use of SSCs, as well as the need for additional training. Distributions of background characteristics, use of and views on SSCs were calculated, and statistical significance of the associations between respondents’ background and their answers were evaluated. Results Of the 574 Norwegian and 765 Finnish respondents, only 12.0% and 12.9% reported to use SSCs, respectively. The most frequently reported barrier reported by those who did not use SSCs was lack of practical training. The most frequent challenge reported by those using SSCs was difficulties in crown adjustment followed by aesthetic issues, and the most frequently reported advantage was that SSCs maintain the function and occlusion. The majority of respondents reported a need for more information and practical training in the use of SSCs, with hands-on course as their most frequently preferred education type. Conclusion Although the value of SSCs for restoring young molars is recognized by Norwegian and Finnish dentists, SSCs are rarely used by general dentists. The majority of the respondents reported lack of training and materials and was interested in receiving more information and education.
  • Nikparvar, Bahareh; Andreevskaya, Margarita; Duru, Ilhan C; Bucur, Florentina I; Grigore-Gurgu, Leontina; Borda, Daniela; Nicolau, Anca I; Riedel, Christian U; Auvinen, Petri; Bar, Nadav (BioMed Central, 2021)
    Abstract Background The pathogen Listeria (L.) monocytogenes is known to survive heat, cold, high pressure, and other extreme conditions. Although the response of this pathogen to pH, osmotic, temperature, and oxidative stress has been studied extensively, its reaction to the stress produced by high pressure processing HPP (which is a preservation method in the food industry), and the activated gene regulatory network (GRN) in response to this stress is still largely unknown. Results We used RNA sequencing transcriptome data of L. monocytogenes (ScottA) treated at 400 MPa and 8∘C, for 8 min and combined it with current information in the literature to create a transcriptional regulation database, depicting the relationship between transcription factors (TFs) and their target genes (TGs) in L. monocytogenes. We then applied network component analysis (NCA), a matrix decomposition method, to reconstruct the activities of the TFs over time. According to our findings, L. monocytogenes responded to the stress applied during HPP by three statistically different gene regulation modes: survival mode during the first 10 min post-treatment, repair mode during 1 h post-treatment, and re-growth mode beyond 6 h after HPP. We identified the TFs and their TGs that were responsible for each of the modes. We developed a plausible model that could explain the regulatory mechanism that L. monocytogenes activated through the well-studied CIRCE operon via the regulator HrcA during the survival mode. Conclusions Our findings suggest that the timely activation of TFs associated with an immediate stress response, followed by the expression of genes for repair purposes, and then re-growth and metabolism, could be a strategy of L. monocytogenes to survive and recover extreme HPP conditions. We believe that our results give a better understanding of L. monocytogenes behavior after exposure to high pressure that may lead to the design of a specific knock-out process to target the genes or mechanisms. The results can help the food industry select appropriate HPP conditions to prevent L. monocytogenes recovery during food storage.
  • Turjanmaa, Elina; Jasinskaja-Lahti, Inga (Springer International Publishing, 2021)
    An amendment to this paper has been published and can be accessed via the original article.
  • von Hintze, Jake; Niemeläinen, Mika; Sintonen, Harri; Nieminen, Jyrki; Eskelinen, Antti (BioMed Central, 2021)
    Abstract Background The purpose of this study was to determine the mid-term clinical, radiographic and health-related quality of life (HRQoL) outcomes and define the survival rate in patients who had undergone revision total knee arthroplasty (TKA) using the single rotating hinged knee (RHK) design. Methods Between January 2004 and December 2013, 125 revision TKAs were performed at our institution using the single RHK implant. We conducted both a retrospective analysis of prospectively collected outcome data of these patients and a prospective follow-up study of all 39 living patients (41 knees). The follow-up phase included an optional extra follow-up visit, PROM questionnaires, and plain radiographs. Results The ten-year Kaplan-Meier survival rate of the revision RHK knees was 81.7% (95% CI 71.9–91.6%) with re-revision for any reason as the endpoint. Overall, 15 knees (12% of the total) underwent re-revision surgery during the follow-up. The median follow-up was 6.2 years (range, 0–12.7 years) post-operatively for the baseline group. One mechanical hinge mechanism-related failure occurred without any history of trauma or infection. At the time of the final follow-up, the majority of patients evinced a fairly good clinical outcome measured with patient-reported outcome measures and none of the components were radiographically loose. Conclusion We found that in patients undergoing complex revision TKA, fairly good functional outcome and quality of life can be achieved using an RHK implant. Further, it seems that in this type of patient cohort, revision TKA using an RHK implant relieves pain more than it improves ability to function. The NexGen® RHK design can be regarded as a suitable option in complex revision TKA.
  • Viertiö, Satu; Kiviruusu, Olli; Piirtola, Maarit; Kaprio, Jaakko; Korhonen, Tellervo; Marttunen, Mauri; Suvisaari, Jaana (BioMed Central, 2021)
    Abstract Background Psychological distress refers to non-specific symptoms of stress, anxiety and depression, and it is more common in women. Our aim was to investigate factors contributing to psychological distress in the working population, with a special reference to gender differences. Methods We used questionnaire data from the nationally representative Finnish Regional Health and Well-being Study (ATH) collected in the years 2012–2016 (target population participants aged 20 +, n = 96,668, response rate 53%), restricting the current analysis to those persons who were working full-time and under 65 of age (n = 34,468). Psychological distress was assessed using the Mental Health Inventory-5 (MHI-5) (cut-off value <=52). We studied the following factors potentially associated with psychological distress: sociodemographic factors, living alone, having children under18 years of age, lifestyle-related factors, social support, helping others outside of the home and work-related factors. We used logistic regression analysis to examine association between having work-family conflict with the likelihood for psychological distress. We first performed the models separately for men and women. Then interaction by gender was tested in the combined data for those independent variables where gender differences appeared probable in the analyses conducted separately for men and women. Results Women reported more psychological distress than men (11.0% vs. 8.8%, respectively, p < 0.0001). Loneliness, job dissatisfaction and family-work conflict were associated with the largest risk of psychological distress. Having children, active participation, being able to successfully combine work and family roles, and social support were found to be protective factors. A significant interaction with gender was found in only two variables: ignoring family due to being absorbed in one’s work was associated with distress in women (OR 1.30 (95% CI 1.00–1.70), and mental strain of work in men (OR 2.71 (95% CI 1.66–4.41). Conclusions Satisfying work, family life and being able to successfully combine the two are important sources of psychological well-being for both genders in the working population.
  • Zarei-Ghobadi, Mohadeseh; Sheikhi, Mohsen; Teymoori-Rad, Majid; Yaslianifard, Sahar; Norouzi, Mehdi; Yaslianifard, Somayeh; Faraji, Reza; Farahmand, Mohammad; Bayat, Shiva; Jafari, Mohieddin; Mozhgani, Sayed-Hamidreza (BioMed Central, 2021)
    Abstract Objectives Human T cell leukemia virus-1 (HTLV-1) infection may lead to one or both diseases including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T cell leukemia lymphoma (ATLL). The complete interactions of the virus with host cells in both diseases is yet to be determined. This study aims to construct an interaction network for distinct signaling pathways in these diseases based on finding differentially expressed genes (DEGs) between HAM/TSP and ATLL. Results We identified 57 hub genes with higher criteria scores in the primary protein–protein interaction network (PPIN). The ontology-based enrichment analysis revealed following important terms: positive regulation of transcription from RNA polymerase II promoter, positive regulation of transcription from RNA polymerase II promoter involved in meiotic cell cycle and positive regulation of transcription from RNA polymerase II promoter by histone modification. The upregulated genes TNF, PIK3R1, HGF, NFKBIA, CTNNB1, ESR1, SMAD2, PPARG and downregulated genes VEGFA, TLR2, STAT3, TLR4, TP53, CHUK, SERPINE1, CREB1 and BRCA1 were commonly observed in all the three enriched terms in HAM/TSP vs. ATLL. The constructed interaction network was then visualized inside a mirrored map of signaling pathways for ATLL and HAM/TSP, so that the functions of hub genes were specified in both diseases.
  • Mai, The T; Turner, Paul; Corander, Jukka (BioMed Central, 2021)
    Abstract Background Heritability is a central measure in genetics quantifying how much of the variability observed in a trait is attributable to genetic differences. Existing methods for estimating heritability are most often based on random-effect models, typically for computational reasons. The alternative of using a fixed-effect model has received much more limited attention in the literature. Results In this paper, we propose a generic strategy for heritability inference, termed as “boosting heritability”, by combining the advantageous features of different recent methods to produce an estimate of the heritability with a high-dimensional linear model. Boosting heritability uses in particular a multiple sample splitting strategy which leads in general to a stable and accurate estimate. We use both simulated data and real antibiotic resistance data from a major human pathogen, Sptreptococcus pneumoniae, to demonstrate the attractive features of our inference strategy. Conclusions Boosting is shown to offer a reliable and practically useful tool for inference about heritability.
  • Yohannes, Dawit A; Kaukinen, Katri; Kurppa, Kalle; Saavalainen, Päivi; Greco, Dario (BioMed Central, 2021)
    Abstract Background Deep immune receptor sequencing, RepSeq, provides unprecedented opportunities for identifying and studying condition-associated T-cell clonotypes, represented by T-cell receptor (TCR) CDR3 sequences. However, due to the immense diversity of the immune repertoire, identification of condition relevant TCR CDR3s from total repertoires has mostly been limited to either “public” CDR3 sequences or to comparisons of CDR3 frequencies observed in a single individual. A methodology for the identification of condition-associated TCR CDR3s by direct population level comparison of RepSeq samples is currently lacking. Results We present a method for direct population level comparison of RepSeq samples using immune repertoire sub-units (or sub-repertoires) that are shared across individuals. The method first performs unsupervised clustering of CDR3s within each sample. It then finds matching clusters across samples, called immune sub-repertoires, and performs statistical differential abundance testing at the level of the identified sub-repertoires. It finally ranks CDR3s in differentially abundant sub-repertoires for relevance to the condition. We applied the method on total TCR CDR3β RepSeq datasets of celiac disease patients, as well as on public datasets of yellow fever vaccination. The method successfully identified celiac disease associated CDR3β sequences, as evidenced by considerable agreement of TRBV-gene and positional amino acid usage patterns in the detected CDR3β sequences with previously known CDR3βs specific to gluten in celiac disease. It also successfully recovered significantly high numbers of previously known CDR3β sequences relevant to each condition than would be expected by chance. Conclusion We conclude that immune sub-repertoires of similar immuno-genomic features shared across unrelated individuals can serve as viable units of immune repertoire comparison, serving as proxy for identification of condition-associated CDR3s.

View more