Expected impact of MRI-targeted biopsy interreader variability among uropathologists on ProScreen prostate cancer screening trial: a pre-trial validation study.

PURPOSE: Prostate cancer (PCa) histology, particularly the Gleason score, is an independent prognostic predictor in PCa. Little is known about the inter-reader variability in grading of targeted prostate biopsy based on magnetic resonance imaging (MRI). The aim of this study was to assess inter-reader variability in Gleason grading of MRI-targeted biopsy among uropathologists and its potential impact on a population-based randomized PCa screening trial (ProScreen). METHODS: From June 2014 to May 2018, 100 men with clinically suspected PCa were retrospectively selected. All men underwent prostate MRI and 86 underwent targeted prostate of the prostate. Six pathologists individually reviewed the pathology slides of the prostate biopsies. The five-tier ISUP (The International Society of Urological Pathology) grade grouping (GG) system was used. Fleiss' weighted kappa (κ) and Model-based kappa for associations were computed to estimate the combined agreement between individual pathologists. RESULTS: GG reporting of targeted prostate was highly consistent among the trial pathologists. Inter-reader agreement for cancer (GG1-5) vs. benign was excellent (Model-based kappa 0.90, Fleiss' kappa κ = 0.90) and for clinically significant prostate cancer (csPCa) (GG2-5 vs. GG0 vs. GG1), it was good (Model-based kappa 0.70, Fleiss' kappa κ 0.67). CONCLUSIONS: Inter-reader agreement in grading of MRI-targeted biopsy was good to excellent, while it was fair to moderate for MRI in the same cohort, as previously shown. Importantly, there was wide consensus by pathologists in assigning the contemporary GG on MRI-targeted biopsy suggesting high reproducibility of pathology reporting in the ProScreen trial.

Mental health service diversity and work disability: associations of mental health service system characteristics and mood disorder disability pensioning in Finland.

PURPOSE: Public mental health services (MHS) are crucial in preventing psychiatric disability pensions (DP). We studied the associations between mood disorder DP risk and the characteristics of Finnish municipalities' MHS provision using the ESMS-R mapping tool and Finnish population registers, based on first-time granted mood disorder DPs between 2010 and 2015. METHODS: The final data set included 13,783 first-time mood disorder DP recipients and 1088 mental health service units in 104 municipalities. We focused on five different MHS types: all MHS, outpatient care provision, local services without and with gatekeeping, and centralized services. Three factors for each MHS type were studied: service resources, richness, and diversity index. Negative binomial regression models were used in the analysis. RESULTS: In all the municipalities, higher service richness and diversity regarding all MHS, outpatient care and local services with gatekeeping were associated with a lower DP risk. In urban municipalities, service richness was mainly associated with lower DP risk, and in semi-urban municipalities service diversity and resources were primarily associated with lower DP risk in outpatient care and local services with gatekeeping. In rural municipalities, DP risk indicated no association with MHS factors. CONCLUSION: The organization and structure of MHS play a role in psychiatric disability pensioning. MHS richness and diversity are associated with lower mood disorder DP in specific societal contexts indicating their role as quality indicators for regional MHS. The diversity of service provision should be accounted for in MHS planning to offer services matching population needs.

Patterns of mental health services and mood disorder disability pensions: a standard comparison of Finland's three largest hospital districts.

INTRODUCTION: Mental disorders are one of the most common and disabling health conditions worldwide. There is however no consensus on the best practice of system level mental health services (MHS) provision, in order to prevent e.g. mood disorder disability pensions (DPs). We analyzed the MHS provision between Finland's three largest hospital districts Helsinki and Uusimaa (HUS), Southwest Finland and Pirkanmaa, with known differences in mood disorder DP risk but presumably equal rates of mood disorder prevalence. METHODS: We used public MHS data analyzed with the standardized DEscription and Evaluation of Services and DirectoriEs for Long Term Care (DESDE-LTC) mapping tool, focusing on all MHS, outpatient care provision, local services without and with gatekeeping, and centralized services. We also collected demographic data based on the European Socio-Demographic Schedule (ESDS). As a novel approach, the Gini-Simpson Diversity Index (GSDI) was calculated for the districts. RESULTS: Evident differences were observed regarding the districts' MHS factors. As the hospital district with lower DP risk, HUS was characterized by the highest level of regional socioeconomic prosperity as well as high service richness and diversity. With a nationally average DP risk, Southwest Finland had the highest number of MHS personnel in full-time equivalents (FTE) per 100 000 inhabitants. Pirkanmaa, with a higher DP risk, had overall the lowest service richness and the lowest FTE of the three districts in all MHS, outpatient care and local services with gatekeeping. CONCLUSIONS: Our findings indicate that greater richness and diversity of MHS, especially in outpatient and community-based settings, may serve as indicators of a balanced, high-quality service system that is more effective in preventing mood disorder DP and meeting the different needs of the population. In addition, the need for sufficient resourcing in all MHS and outpatient services is indicated. We suggest using diversity indices to complement the measuring and reporting of regional service variation.

Tensorial Principal Component Analysis in Detecting Temporal Trajectories of Purchase Patterns in Loyalty Card Data: Retrospective Cohort Study.

BACKGROUND: Loyalty card data automatically collected by retailers provide an excellent source for evaluating health-related purchase behavior of customers. The data comprise information on every grocery purchase, including expenditures on product groups and the time of purchase for each customer. Such data where customers have an expenditure value for every product group for each time can be formulated as 3D tensorial data. OBJECTIVE: This study aimed to use the modern tensorial principal component analysis (PCA) method to uncover the characteristics of health-related purchase patterns from loyalty card data. Another aim was to identify card holders with distinct purchase patterns. We also considered the interpretation, advantages, and challenges of tensorial PCA compared with standard PCA. METHODS: Loyalty card program members from the largest retailer in Finland were invited to participate in this study. Our LoCard data consist of the purchases of 7251 card holders who consented to the use of their data from the year 2016. The purchases were reclassified into 55 product groups and aggregated across 52 weeks. The data were then analyzed using tensorial PCA, allowing us to effectively reduce the time and product group-wise dimensions simultaneously. The augmentation method was used for selecting the suitable number of principal components for the analysis. RESULTS: Using tensorial PCA, we were able to systematically search for typical food purchasing patterns across time and product groups as well as detect different purchasing behaviors across groups of card holders. For example, we identified customers who purchased large amounts of meat products and separated them further into groups based on time profiles, that is, customers whose purchases of meat remained stable, increased, or decreased throughout the year or varied between seasons of the year. CONCLUSIONS: Using tensorial PCA, we can effectively examine customers' purchasing behavior in more detail than with traditional methods because it can handle time and product group dimensions simultaneously. When interpreting the results, both time and product dimensions must be considered. In further analyses, these time and product groups can be directly associated with additional consumer characteristics such as socioeconomic and demographic predictors of dietary patterns. In addition, they can be linked to external factors that impact grocery purchases such as inflation and unexpected pandemics. This enables us to identify what types of people have specific purchasing patterns, which can help in the development of ways in which consumers can be steered toward making healthier food choices.

Socioeconomic status, psychotherapy duration, and return to work from disability due to common mental disorders.

OBJECTIVE: Low socioeconomic status (SES) is a risk factor for work disability due to common mental disorders (CMDs), one possible reason being inequal use of services. Psychotherapy is an evidence-based treatment for CMDs. This study examines socioeconomic and sociodemographic differences in psychotherapy attendance and an association of psychotherapy duration with return to work (RTW). METHODS: The study subjects (N = 12,263) were all Finnish citizens granted a disability pension (DP) due to CMDs in 2010-2012. Numbers of psychotherapy sessions (maximum 200) were collected from the nine-year interval around the DP grant. Socioeconomic and sociodemographic differences in psychotherapy duration (dependent variable) among DP recipients were studied using multinomial logistic regression models, likewise, the association between psychotherapy duration and RTW (dependent variable) among temporary DP recipients was examined. RESULTS: Higher SES, female gender, and younger age were positively associated with attending longer psychotherapies and surpassing the early treatment termination level (>10 sessions). Attending 11-60 psychotherapy sessions was positively associated with full RTW and partial RTW, whereas longer psychotherapies were not. Early termination was positively associated with partial RTW only. CONCLUSION: This study demonstrates varying tendencies among CMD patients from different backgrounds to attend long rehabilitative psychotherapies, which may create inequalities in RTW.

Socioeconomic factors and use of psychotherapy in common mental disorders predisposing to disability pension.

BACKGROUND: Research in high-income countries has identified low socioeconomic status as a risk factor for disability pension (DP) due to common mental disorders (CMDs). Psychotherapy is an evidence-based treatment for the majority of CMDs along with medication and it is often targeted to prevent work disability. This study examines socioeconomic differences in the use of rehabilitative psychotherapy in Finland, where citizens have universal health coverage, but psychotherapy is partly dependent on personal finance. METHODS: The study subjects (N = 22,501) were all the Finnish citizens granted a DP due to CMD between 2010 and 2015 and a comparison group (N = 57,732) matched based on age, gender, and hospital district. Socioeconomic differences in psychotherapy use were studied using logistic regression models. Socioeconomic status was defined by education, income, and occupation. Age, gender, and family status were also examined. RESULTS: A lower level of education, lower occupational status (blue-collar worker), male gender, and older age, were associated with less frequent psychotherapy use, in both groups. Education was the strongest component of socioeconomic status associated with psychotherapy use, but the role of income was not straightforward. Unemployment when approaching DP, but not otherwise, was a risk factor for not receiving rehabilitative psychotherapy. Socioeconomic disparities were not any smaller among CMD patients approaching DP than in the comparison group. CONCLUSION: This study demonstrates the disparity in the provision of psychotherapy for CMD patients, even on the verge of DP with an acute need for services. This disparity is partly related to a complex interplay of socioeconomic factors and the service system characteristics. Factors predisposing to unequal access to mental health services are presumably diverse and should be studied further.

Health check attendance association with health and study-related factors: a register-based cohort study of Finnish university entrants.

BACKGROUND: General health checks are an established component of preventive health care in many countries. Declining participation rates have raised concerns in health care providers. Understanding the reasons for attendance and non-attendance is necessary to improve the preventive health care system. The aim of this study was to examine health- and study-related factors associated with university entrants' health check attendance. METHODS: Since 2009, an electronic health questionnaire (eHQ) has been conducted yearly to all Finnish university entrants by the Finnish Student Health Service (FSHS) to screen students for a general health check. The questionnaire comprises 26 questions about health, health habits and studying. The study population consisted of the 3346 entrants from the 2011-2012 academic year who were referred to a health check based on their eHQ responses. The eHQ data were linked with health check attendance information. Multivariable logistic regression was used to study the associations between the questionnaire responses and non-attendance of the health check. RESULTS: Male sex (OR 1.6, 95% CI % 1.4-1.9) and low engagement with studies (OR 1.5, 95% CI 1.2-2.0) were the variables most strongly associated with non-attendance. Having low state of mind was negatively associated with health check non-attendance thus enhanced the health-check attendance (OR 0.6, 95% CI 0.5-0.8). CONCLUSIONS: The results suggest that providing health checks in student health care may serve as a way of reaching students with health concerns. However, motivating males and smokers to attend general health checks continue to be a challenge also in a university student population. That low engagement with studies associates with health check non-attendance points to need to improve collaboration between universities and student health care.

Serum fatty acids and risk of developing islet autoimmunity: A nested case-control study within the TRIGR birth cohort.

BACKGROUND: Circulating fatty acids have been linked to development of type 1 diabetes. OBJECTIVES: To study the prospective associations of serum fatty acids with the risk of islet autoimmunity in high-risk children. METHODS: A nested case-control selection was carried out within the TRIGR cohort, which included infants with HLA (DQB1 or DQA1)-conferred disease susceptibility and a first-degree relative with type 1 diabetes, born between 2002 and 2007 in 15 countries and followed-up until 2017. The present study included 244 case children positive for at least two islet autoantibodies (ICA, IAA, GADA, and IA-2A) and two control children were matched for country and age. Proportions of 26 serum fatty acids at cord blood and at 6, 12, and 18 months of age were assessed using gas-chromatography. RESULTS: The average proportions of the following fatty acids were associated with an increased risk of islet autoimmunity, adjusted for sex, HLA risk, and maternal type 1 diabetes: pentadecanoic acid (15:0) (OR 3.41: 95% CI 1.70, 6.85), heptadecanoic acid (iso 17:0) (2.64: 1.62, 4.28) and (anteiso 17:0) (2.27: 1.39, 3.70), stearic acid (18:0) (23.8: 2.32, 244.6), and conjugated linoleic acid (18:2n-7) (2.60: 1.47, 4.59). Breastfeeding and not having maternal type 1 diabetes were positively associated with levels of the above-mentioned fatty acids. N-3 fatty acids were not consistently associated with islet autoimmunity. CONCLUSIONS: We found direct associations of pentadecanoic acid, heptadecanoic acid, stearic acid, and conjugated linoleic acid with the risk of islet autoimmunity. Further studies are needed to understand the complex role of fatty acids in the development of type 1 diabetes.

Contextual and mental health service factors in mental disorder-based disability pensioning in Finland - a regional comparison.

BACKGROUND: We investigated the regional differences in all mental disorder disability pensions (DP) between 2010 and 2015 in Finland, and separately in mood disorders and non-affective psychotic disorder DP. We also studied the contribution of several district-level contextual and mental health service factors to mental disorder DP. METHODS: Subjects were all those granted mental disorder DP for the first time between 2010 and 2015 in Finland (N = 36,879). Associations between the district-level contextual and mental health service factors and regional DP risks collected from the year 2015 were studied with negative binomial regression analysis in the Finnish hospital districts. The population number on the age (18 to 65 years), gender, occupational status and residential hospital district of the Finnish population from 2015 was used as exposure in the model. RESULTS: Significant differences in the regional mental disorder DP risks between and within hospital districts did not appear to follow the traditional Finnish health differences. A lower risk of DP was associated with contextual indicators of higher regional socioeconomic level. Furthermore, population density as a proxy for access to mental health services indicated a higher regional DP risk for lower density in all mental (IRR 1.10; 95% CI 1.06-1.14) and mood disorder (IRR 1.12; 95% CI 1.08-1.16) DP. Both the highest and the lowest regional numbers of all mental health outpatient visits were associated with a higher DP risk in all mental and mood disorder DP, whereas particularly low regional numbers of inpatient treatment periods and of patients were associated with a lower risk of DP. CONCLUSIONS: In this comprehensive population-level study, we found evidence of significant regional variation in mental disorder DP and related district-level factors. This variation may at least partly relate to differences in regional mental health service systems and treatment practices. Adapting to the needs of the local population appears to be indicated for both regional mental health service systems and treatment practices to achieve optimal performance.

Socioeconomic factors in disability retirement due to mental disorders in Finland.

BACKGROUND: Previous research has identified low socioeconomic status (SES) as an epidemiological risk factor for early retirement and disability pension (DP) due to mental disorders. This study aims to examine these associations in greater detail, with separate consideration of the risk factors for mood disorders (F30-39) and non-affective psychotic disorder (F20-29) DP. METHODS: In this case-control setting the subjects (N = 36 879) were all those granted DP due to a mental disorder for the first time between 2010 and 2015 in Finland. All the subjects were matched with three controls for their gender, age and hospital district (N = 94 388). Three measures of dimensions of SES were used: education, income and occupational status, as well as family type as a control factor. Differences between DP recipients and controls, and between diagnostic groups, were studied using calculated characteristics and conditional logistic regression models. RESULTS: DP recipients often lived alone and had low educational and income levels. These characteristics were more prominent in non-affective psychotic disorder than in mood disorder DP. In white-collar occupational groups, the risk of DP was greater compared with blue-collar workers. Students were associated with the highest level of risk for all mental and mood disorder DPs. CONCLUSIONS: We found evidence of SES factors associating with mental disorder-related severe loss of working and studying ability in a disorder-specific way. Notably, white-collar workers had an increased risk of mental disorder DP. This could be related to the psychosocially demanding contemporary working life in non-manual work.

Vipie: web pipeline for parallel characterization of viral populations from multiple NGS samples.

BACKGROUND: Next generation sequencing (NGS) technology allows laboratories to investigate virome composition in clinical and environmental samples in a culture-independent way. There is a need for bioinformatic tools capable of parallel processing of virome sequencing data by exactly identical methods: this is especially important in studies of multifactorial diseases, or in parallel comparison of laboratory protocols. RESULTS: We have developed a web-based application allowing direct upload of sequences from multiple virome samples using custom parameters. The samples are then processed in parallel using an identical protocol, and can be easily reanalyzed. The pipeline performs de-novo assembly, taxonomic classification of viruses as well as sample analyses based on user-defined grouping categories. Tables of virus abundance are produced from cross-validation by remapping the sequencing reads to a union of all observed reference viruses. In addition, read sets and reports are created after processing unmapped reads against known human and bacterial ribosome references. Secured interactive results are dynamically plotted with population and diversity charts, clustered heatmaps and a sortable and searchable abundance table. CONCLUSIONS: The Vipie web application is a unique tool for multi-sample metagenomic analysis of viral data, producing searchable hits tables, interactive population maps, alpha diversity measures and clustered heatmaps that are grouped in applicable custom sample categories. Known references such as human genome and bacterial ribosomal genes are optionally removed from unmapped ('dark matter') reads. Secured results are accessible and shareable on modern browsers. Vipie is a freely available web-based tool whose code is open source.

Imbalance of bacteriome profiles within the Finnish Diabetes Prediction and Prevention study: Parallel use of 16S profiling and virome sequencing in stool samples from children with islet autoimmunity and matched controls.

BACKGROUND: We set out to explore associations between the stool bacteriome profiles and early-onset islet autoimmunity, taking into account the interactions with the virus component of the microbiome. METHODS: Serial stool samples were longitudinally collected from 18 infants and toddlers with early-onset islet autoimmunity (median age 17.4 months) followed by type 1 diabetes, and 18 tightly matched controls from the Finnish Diabetes Prediction and Prevention (DIPP) cohort. Three stool samples were analyzed, taken 3, 6, and 9 months before the first detection of serum autoantibodies in the case child. The risk of islet autoimmunity was evaluated in relation to the composition of the bacteriome 16S rDNA profiles assessed by mass sequencing, and to the composition of DNA and RNA viromes. RESULTS: Four operational taxonomic units were significantly less abundant in children who later on developed islet autoimmunity as compared to controls-most markedly the species of Bacteroides vulgatus and Bifidobacterium bifidum. The alpha or beta diversity, or the taxonomic levels of bacterial phyla, classes or genera, showed no differences between cases and controls. A correlation analysis suggested a possible relation between CrAssphage signals and quantities of Bacteroides dorei. No apparent associations were seen between development of islet autoimmunity and sequences of yet unknown origin. CONCLUSIONS: The results confirm previous findings that an imbalance within the prevalent Bacteroides genus is associated with islet autoimmunity. The detected quantitative relation of the novel "orphan" bacteriophage CrAssphage with a prevalent species of the Bacteroides genus may exemplify possible modifiers of the bacteriome.

Copy number variation and selection during reprogramming to pluripotency.

The mechanisms underlying the low efficiency of reprogramming somatic cells into induced pluripotent stem (iPS) cells are poorly understood. There is a clear need to study whether the reprogramming process itself compromises genomic integrity and, through this, the efficiency of iPS cell establishment. Using a high-resolution single nucleotide polymorphism array, we compared copy number variations (CNVs) of different passages of human iPS cells with their fibroblast cell origins and with human embryonic stem (ES) cells. Here we show that significantly more CNVs are present in early-passage human iPS cells than intermediate passage human iPS cells, fibroblasts or human ES cells. Most CNVs are formed de novo and generate genetic mosaicism in early-passage human iPS cells. Most of these novel CNVs rendered the affected cells at a selective disadvantage. Remarkably, expansion of human iPS cells in culture selects rapidly against mutated cells, driving the lines towards a genetic state resembling human ES cells.

Changes in global gene expression of Vibrio parahaemolyticus induced by cold- and heat-stress.

BACKGROUND: Vibrio (V.) parahaemolyticus causes seafood-borne gastro-intestinal bacterial infections in humans worldwide. It is widely found in marine environments and is isolated frequently from seawater, estuarine waters, sediments and raw or insufficiently cooked seafood. Throughout the food chain, V. parahaemolyticus encounters different temperature conditions that might alter metabolism and pathogenicity of the bacterium. In this study, we performed gene expression profiling of V. parahaemolyticus RIMD 2210633 after exposure to 4, 15, 20, 37 and 42 °C to describe the cold and heat shock response. METHODS: Gene expression profiles of V. parahaemolyticus RIMD 2210633 after exposure to 4, 15, 20, 37 and 42 °C were investigated via microarray. Gene expression values and RT-qPCR experiments were compared by plotting the log2 values. Moreover, volcano plots of microarray data were calculated to visualize the distribution of differentially expressed genes at individual temperatures and to assess hybridization qualities and comparability of data. Finally, enriched terms were searched in annotations as well as functional-related gene categories using the Database for Annotation, Visualization and Integrated Discovery. RESULTS: Analysis of 37 °C normalised transcriptomics data resulted in differential expression of 19 genes at 20 °C, 193 genes at 4 °C, 625 genes at 42 °C and 638 genes at 15 °C. Thus, the largest number of significantly expressed genes was observed at 15 and 42 °C with 13.3 and 13%, respectively. Genes of many functional categories were highly regulated even at lower temperatures. Virulence associated genes (tdh1, tdh2, toxR, toxS, vopC, T6SS-1, T6SS-2) remained mostly unaffected by heat or cold stress. CONCLUSION: Along with folding and temperature shock depending systems, an overall temperature-dependent regulation of expression could be shown. Particularly the energy metabolism was affected by changed temperatures. Whole-genome gene expression studies of food related pathogens such as V. parahaemolyticus reveal how these pathogens react to stress impacts to predict its behaviour under conditions like storage and transport.

Complications after pediatric percutaneous endoscopic gastrostomy: comparison of the push and pull technique.

Purpose: Various complications are associated with percutaneous endoscopic gastrostomy (PEG) procedures in children. The push technique is being increasingly used, but its complications are insufficiently characterized. We aimed to assess all complications related to PEG procedures and compare the safety of the pull and push techniques. Methods: Retrospective review of consecutive pediatric patients who underwent PEG between 2002 and 2020. Results: In total, 216 children underwent 217 PEG procedures. The push technique was used in 138 (64%) cases, and the pull technique in 79 (36%) cases. The median follow-up time was 6.1 (0.1-18.3) years. The complication rate was high (57%) and patients experienced complications years after the procedure. Overall, 51% and 67% of patients experienced complications in the push and pull groups, respectively. The rates of minor and major complications were higher in the pull group than in the push group (63% vs 48%, p=0.028; and 11% vs 6%, p=0.140, respectively). Reoperation was also more common in the pull group (17% vs 7%, p=0.020). Conclusions: The overall complication rate of PEG procedures is high. Fortunately, most complications are mild and do not require reoperations. The increasing push technique appears to be safer than the traditional pull technique. Significant long-term morbidity is related to gastrostomies in children.

Selective Classes and Early Health Inequalities in Comprehensive Schools in Finland.

BACKGROUND: The origin of inequalities in health outcomes has been explained by health selection and social causation models. Health selection processes operate particularly at school age. We study, if student allocation to teaching groups with aptitude tests (selective vs general class) differentiates adolescents by health behaviors and mental health. METHODS: Finnish schoolchildren 12-13 years from 12 selective classes, n = 248; 41 general classes, n = 703 answered a questionnaire on addictive products (tobacco, snus, alcohol, and energy drinks), digital media use, and mental health (health complaints, anxiety, and depression). Structural equation modeling was conducted to identify structures between outcomes, SEP (socioeconomic position), class type, and academic performance. RESULTS: Students in the selective classes reported less addictive digital media and addictive products use than students in the general classes. Differences in academic performance or SEP between the class types did not solely explain these differences. Mental health was not related to the class type. SEP was indirectly associated with health behaviors via the class type and academic performance. CONCLUSIONS: Selecting students to permanent teaching groups with aptitude tests differentiates students according to risky health behaviors. The impact of education policies using student grouping should also be evaluated in terms of students' health.

POMO--Plotting Omics analysis results for Multiple Organisms.

BACKGROUND: Systems biology experiments studying different topics and organisms produce thousands of data values across different types of genomic data. Further, data mining analyses are yielding ranked and heterogeneous results and association networks distributed over the entire genome. The visualization of these results is often difficult and standalone web tools allowing for custom inputs and dynamic filtering are limited. RESULTS: We have developed POMO (http://pomo.cs.tut.fi), an interactive web-based application to visually explore omics data analysis results and associations in circular, network and grid views. The circular graph represents the chromosome lengths as perimeter segments, as a reference outer ring, such as cytoband for human. The inner arcs between nodes represent the uploaded network. Further, multiple annotation rings, for example depiction of gene copy number changes, can be uploaded as text files and represented as bar, histogram or heatmap rings. POMO has built-in references for human, mouse, nematode, fly, yeast, zebrafish, rice, tomato, Arabidopsis, and Escherichia coli. In addition, POMO provides custom options that allow integrated plotting of unsupported strains or closely related species associations, such as human and mouse orthologs or two yeast wild types, studied together within a single analysis. The web application also supports interactive label and weight filtering. Every iterative filtered result in POMO can be exported as image file and text file for sharing or direct future input. CONCLUSIONS: The POMO web application is a unique tool for omics data analysis, which can be used to visualize and filter the genome-wide networks in the context of chromosomal locations as well as multiple network layouts. With the several illustration and filtering options the tool supports the analysis and visualization of any heterogeneous omics data analysis association results for many organisms. POMO is freely available and does not require any installation or registration.

RNA-binding protein L1TD1 interacts with LIN28 via RNA and is required for human embryonic stem cell self-renewal and cancer cell proliferation.

Human embryonic stem cells (hESC) have a unique capacity to self-renew and differentiate into all the cell types found in human body. Although the transcriptional regulators of pluripotency are well studied, the role of cytoplasmic regulators is still poorly characterized. Here, we report a new stem cell-specific RNA-binding protein L1TD1 (ECAT11, FLJ10884) required for hESC self-renewal and cancer cell proliferation. Depletion of L1TD1 results in immediate downregulation of OCT4 and NANOG. Furthermore, we demonstrate that OCT4, SOX2, and NANOG all bind to the promoter of L1TD1. Moreover, L1TD1 is highly expressed in seminomas, and depletion of L1TD1 in these cancer cells influences self-renewal and proliferation. We show that L1TD1 colocalizes and interacts with LIN28 via RNA and directly with RNA helicase A (RHA). LIN28 has been reported to regulate translation of OCT4 in complex with RHA. Thus, we hypothesize that L1TD1 is part of the L1TD1-RHA-LIN28 complex that could influence levels of OCT4. Our results strongly suggest that L1TD1 has an important role in the regulation of stemness.

Both inhibition and enhanced expression of miR-31 lead to reduced migration and invasion of pancreatic cancer cells.

MicroRNAs (miRNAs) are short single-stranded RNA molecules that have a critical role in the regulation of gene expression. Alterations in miRNA expression levels have been observed in multiple tumor types and there is clear evidence on their active involvement in cancer development. Here, a comprehensive miRNA expression profiling in 16 pancreatic cancer cell lines and four normal pancreatic samples provided a specific molecular signature for pancreatic cancer and enabled us to identify 72 differentially expressed miRNAs with approximately half of them being up- and half downregulated in cancer cells as compared with normal samples. Of these, miR-31 was selected for further functional analyses based on its interesting "on-off" type expression profile, i.e., very low or even absent expression in normal pancreas and in six of the pancreatic cancer samples but extremely high expression in the remaining 10 cell lines. Quite unexpectedly, both the inhibition of miR-31 in AsPC-1 and HPAF-II pancreatic cancer cells with high endogenous expression and forced expression of miR-31 in MIA PaCa-2 with low endogenous levels led to reduced cell proliferation, migration, and invasion. More importantly, in AsPC-1 cells further enhancement of miR-31 also resulted in reduced cell migration and invasion, implicating that the level of miR-31 is critical for these phenotypes. This study highlights a specific miRNA expression pattern in pancreatic cancer and reveals that manipulation of miR-31 expression leads to reduced cell migration and invasion in pancreatic cancer.

Impact of the first response unit on prehospital on-scene time among paramedic-suspected stroke patients: a retrospective before-after cohort study in Finland.

BACKGROUND: Revascularization of an occluded artery by either thrombolysis or mechanical thrombectomy is a time-critical intervention in ischaemic stroke. Each link in the stroke chain of survival should minimize the delay to definitive treatment in every possible way. In this study, we investigated the effect of routine dispatch of a first response unit (FRU) on prehospital on-scene time (OST) on stroke missions. METHODS: Medical dispatch of FRU together with an emergency medical service (EMS) ambulance was a routine strategy in the Tampere University Hospital area before 3 October 2018, after which the FRU has only been dispatched to medical emergencies on the decision of an EMS field commander. This study presents a retrospective before-after analysis of 2,228 paramedic-suspected strokes transported by EMSs to Tampere University Hospital. We collected data from EMS medical records from April 2016 to March 2021, and used statistical tests and binary logistic regression to detect the associations between the variables and the shorter and longer half of OSTs. RESULTS: The median OST of stroke missions was 19 min, IQR [14-25] min. The OST decreased when the routine use of the FRU was discontinued (19 [14-26] min vs. 18 [13-24] min, p < 0.001). The median OST with the FRU being the first at the scene (n = 256, 11%) was shorter than in cases where the FRU arrived after the ambulance (16 [12-22] min vs. 19 [15-25] min, p < 0.001). The OST with a stroke dispatch code was shorter than with non-stroke dispatches (18 [13-23] min vs. 22 [15-30] min, p < 0.001). The OST for thrombectomy candidates was shorter than that for thrombolysis candidates (18 [13-23] min vs. 19 [14-25], p = 0.01). The shorter half of OSTs were associated with the FRU arriving first at the scene, stroke dispatch code, thrombectomy transportation and urban location. CONCLUSION: The routine dispatch of the FRU to stroke missions did not decrease the OST unless the FRU was first to arrive at the scene. In addition, a correct stroke identification in the dispatch centre and thrombectomy candidate status decreased the OST.