Associations of polygenic risk scores for preeclampsia and blood pressure with hypertensive disorders of pregnancy.

Background: Preexisting hypertension increases risk for preeclampsia. We examined whether a generic blood pressure polygenic risk score (BP-PRS), compared with a preeclampsia-specific polygenic risk score (PE-PRS), could better predict hypertensive disorders of pregnancy.

Methods: Our study sample included 141 298 genotyped FinnGen study participants with at least one childbirth and followed from 1969 to 2021.

Stress-Related Exhaustion, Polygenic Cognitive Potential, and Cognitive Test Performance - A General Population Study.

Background: We investigated whether stress-related exhaustion (chronic or short-term, and co-occurring with depression or not) is related to cognitive performance and whether polygenic cognitive potential modifies these associations.

Methods: The participants were from the Young Finns Study (N = 541-1273). Stress-related exhaustion was assessed using the Maastricht Questionnaire, depressive symptoms with the Beck Depression Inventory, and cognitive performance with subtests of the Cambridge Neuropsychological Test Automated Battery, measuring visuospatial learning, reaction time, sustained attention, and executive function.

Increasing circulating levels of Tenascin C in response to the Wingate anaerobic test.

Aim: Tenascin C (TNC) is a large extracellular matrix glycoprotein. It is involved in development and upregulated both during tissue repair and in several pathological conditions, including cardiovascular disease. Extracellular matrix proteins play a role in promoting exercise responses, leading to adaptation, regeneration, and repair.

hexanucleotide repeat allele tagging SNPs: Associations with ALS risk and longevity.

hexanucleotide repeat expansion is a common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The locus may harbor residual risk outside the hexanucleotide repeat expansion, but the evidence is conflicting. Here, we first compared 683 unrelated amyotrophic lateral sclerosis cases and 3,196 controls with Finnish ancestry to find best single nucleotide polymorphisms that tag the hexanucleotide repeat expansion and intermediate-length alleles.

Comparison of two supporting matrices for patient-derived cancer cells in 3D drug sensitivity and resistance testing assay (3D-DSRT).

Central to the success of functional precision medicine of solid tumors is to perform drug testing of patient-derived cancer cells (PDCs) in tumor-mimicking ex vivo conditions. While high throughput (HT) drug screening methods have been well-established for cells cultured in two-dimensional (2D) format, this approach may have limited value in predicting clinical responses. Here, we describe the results of the optimization of drug sensitivity and resistance testing (DSRT) in three-dimensional (3D) growth supporting matrices in a HT mode (3D-DSRT) using the hepatocyte cell line (HepG2) as an example.

Controlled release of enhanced cross-hybrid IgGA Fc PD-L1 inhibitors using oncolytic adenoviruses.

Immune checkpoint inhibitors have clinical success in prolonging the life of many cancer patients. However, only a minority of patients benefit from such therapy, calling for further improvements. Currently, most PD-L1 checkpoint inhibitors in the clinic do not elicit Fc effector mechanisms that would substantially increase their efficacy.

OSCAR: Optimal subset cardinality regression using the L0-pseudonorm with applications to prognostic modelling of prostate cancer.

In many real-world applications, such as those based on electronic health records, prognostic prediction of patient survival is based on heterogeneous sets of clinical laboratory measurements. To address the trade-off between the predictive accuracy of a prognostic model and the costs related to its clinical implementation, we propose an optimized L0-pseudonorm approach to learn sparse solutions in multivariable regression. The model sparsity is maintained by restricting the number of nonzero coefficients in the model with a cardinality constraint, which makes the optimization problem NP-hard.

Genetic and Environmental Factors Underlying Parallel Changes in Body Mass Index and Alcohol Consumption: A 36-Year Longitudinal Study of Adult Twins.

Introduction: While the genetic and environmental underpinnings of body weight and alcohol use are fairly well-known, determinants of simultaneous changes in these traits are still poorly known. We sought to quantify the environmental and genetic components underlying parallel changes in weight and alcohol consumption and to investigate potential covariation between them.

Methods: The analysis comprised 4,461 adult participants (58% women) from the Finnish Twin Cohort with four measures of alcohol consumption and body mass index (BMI) over a 36-year follow-up.

Novel therapeutic approaches for pleural mesothelioma identified by functional ex vivo drug sensitivity testing.

Objectives: Pleural mesothelioma (PM) is an aggressive malignancy with limited treatment options. The first-line therapy has remained unchanged for two decades and consists of pemetrexed in combination with cisplatin. Immune-checkpoint inhibitors (nivolumab plus ipilimumab) have high response rates, resulting in recent updates in treatment recommendations by the U.

Stromal FAP Expression is Associated with MRI Visibility and Patient Survival in Prostate Cancer.

Unlabelled: Some clinically significant prostate cancers are missed by MRI. We asked whether the tumor stroma in surgically treated localized prostate cancer lesions positive or negative with MRI are different in their cellular and molecular properties, and whether the differences are reflected to the clinical course of the disease. We profiled the stromal and immune cell composition of MRI-classified tumor lesions by applying multiplexed fluorescence IHC (mfIHC) and automated image analysis in a clinical cohort of 343 patients (cohort I).

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

linemodels: clustering effects based on linear relationships.

Summary: Estimation of effects of multiple explanatory variables on multiple outcome measures has become routine across life sciences with high-throughput molecular technologies. The linemodels R-package allows a probabilistic clustering of variables based on their observed effect sizes on two outcomes.

Availability And Implementation: An open source implementation in R available at github.

Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes.

Acute myeloid leukaemia (AML) patients harbouring certain chromosome abnormalities have particularly adverse prognosis. For these patients, targeted therapies have not yet made a significant clinical impact. To understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres (in UK and Finland) at the proteomic, phosphoproteomic and drug response phenotypic levels.

Examining the causal effect of type 2 diabetes on ischemic heart disease - A longitudinal study with four measurements (1980-2017).

Objective: This longitudinal study examines a possible causal effect between type 2 diabetes and ischemic heart disease (IHD) by using measurements on four occasions from the Swedish Statistics on Income and Living Conditions (SILC) together with nationwide healthcare registers.

Methods: This was a longitudinal study based on a random sample of men and women (n = 2014) from the Swedish population with four measurements in the SILC every eight years. Baseline was 1980/81 and the participants were followed for up to 37 years.

Self-reported sleep bruxism and mortality in 1990-2020 in a nationwide twin cohort.

Background: The association of sleep bruxism with mortality has not been studied.

Objectives: Altogether 12 040 subjects from the nationwide Finnish twin cohort were included in the analyses. We examined whether self-reported sleep bruxism is associated with increased risk of mortality, and if so, whether the effect is independent of known common risk factors.

Correlative Fluorescence and Raman Microscopy to Define Mitotic Stages at the Single-Cell Level: Opportunities and Limitations in the AI Era.

Nowadays, morphology and molecular analyses at the single-cell level have a fundamental role in understanding biology better. These methods are utilized for cell phenotyping and in-depth studies of cellular processes, such as mitosis. Fluorescence microscopy and optical spectroscopy techniques, including Raman micro-spectroscopy, allow researchers to examine biological samples at the single-cell level in a non-destructive manner.

Development of a Syrian hamster anti-PD-L1 monoclonal antibody enables oncolytic adenoviral immunotherapy modelling in an immunocompetent virus replication permissive setting.

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, but preclinical testing of hypotheses such as combination therapies has been complicated, in part due to species incompatibility issues. For example, one of few known permissive animal models for oncolytic adenoviruses is the Syrian hamster, for which an ICI, mainly an anti-PD-L1 monoclonal antibody (mAb) was not previously available. In this study, we developed an anti-Syrian hamster PD-L1 mAb to enable the evaluation of safety and efficacy, when combining anti-PD-L1 with an oncolytic adenovirus encoding tumour necrosis factor alpha (TNFα) and interleukin-2 (IL-2) (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2 or TILT-123).

An in vitro approach to understand contribution of kidney cells to human urinary extracellular vesicles.

Extracellular vesicles (EV) are membranous particles secreted by all cells and found in body fluids. Established EV contents include a variety of RNA species, proteins, lipids and metabolites that are considered to reflect the physiological status of their parental cells. However, to date, little is known about cell-type enriched EV cargo in complex EV mixtures, especially in urine.

Functional Characterization of Six (OATP1B1) Variants Observed in Finnish Individuals with a Psychotic Disorder.

Variants in the (solute carrier organic anion transporter family member 1B1) gene encoding the OATP1B1 (organic anion transporting polypeptide 1B1) protein are associated with altered transporter function that can predispose patients to adverse drug effects with statin treatment. We explored the effect of six rare single nucleotide variants (SNVs) occurring in Finnish individuals with a psychotic disorder on expression and functionality of the OATP1B1 protein. The SUPER-Finland study has performed exome sequencing on 9381 individuals with at least one psychotic episode during their lifetime.