2,415 results match your criteria: "Institute for Molecular Medicine Finland[Affiliation]"

Background: Infections caused by soil-transmitted helminths (STHs) are the most prevalent neglected tropical diseases and result in a major disease burden in low- and middle-income countries, especially in school-aged children. Improved diagnostic methods, especially for light intensity infections, are needed for efficient, control and elimination of STHs as a public health problem, as well as STH management. Image-based artificial intelligence (AI) has shown promise for STH detection in digitized stool samples.

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Background: The gut microbiome is a complex system within the human gastrointestinal tract. The bacteria play a significant role in human health, and some can promote inflammation and pathologic processes through chemical interactions or metabolites. Gut microbiome dysbiosis has been linked to some neurological and other diseases.

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Lipidomic data often exhibit missing data points, which can be categorized as missing completely at random (MCAR), missing at random, or missing not at random (MNAR). In order to utilize statistical methods that require complete datasets or to improve the identification of potential effects in statistical comparisons, imputation techniques can be employed. In this study, we investigate commonly used methods such as zero, half-minimum, mean, and median imputation, as well as more advanced techniques such as k-nearest neighbor and random forest imputation.

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Low-dose decitabine enhances the efficacy of viral cancer vaccines for immunotherapy.

Mol Ther Oncol

March 2024

Drug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland.

Cancer immunotherapy requires a specific antitumor CD8 T cell-driven immune response; however, upon genetic and epigenetic alterations of the antigen processing and presenting components, cancer cells escape the CD8 T cell recognition. As a result, poorly immunogenic tumors are refractory to conventional immunotherapy. In this context, the use of viral cancer vaccines in combination with hypomethylating agents represents a promising strategy to prevent cancer from escaping immune system recognition.

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Truncating NFKB1 variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis.

Cell Rep Med

April 2024

Faculty of Medicine, Clinicum, Translational Immunology Research Program, Research Program Unit (RPU), University of Helsinki (UH), 00014 Helsinki, Finland; Department of Rheumatology, HUH and UH, 00029 Helsinki, Finland; Orton Orthopaedic Hospital, 00280 Helsinki, Finland. Electronic address:

Article Synopsis
  • Mutations in genes involved in innate immune responses can lead to severe autoinflammatory diseases, causing a dangerous overactivation of inflammasome pathways and type I interferon responses.* -
  • Research identifies six families with members suffering from necrotizing fasciitis linked to a specific genetic variant (NFKB1) that disrupts immune regulation in macrophages.* -
  • Patients showed improvement with anti-inflammatory treatments, suggesting that focusing on blocking IL-1β or IFN-I signaling could offer new therapeutic options.*
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Objective: The number of computer-based cognitive tests has increased in recent years, but there is a need for tests focusing on the assessment of executive function (EF), as it can be crucial for the identification of early-onset neurodegenerative disorders. This study aims to examine the ability of the Flexible Attention Test (FAT), a new computer-based test battery for detecting executive dysfunction of early-onset cognitive impairment and dementia patients.

Method: We analyzed the FAT subtask results in memory clinic patients with cognitive symptom onset at ≤65 years.

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Antipsychotic medications and sleep problems in patients with schizophrenia.

Schizophr Res

May 2024

Finnish Institute for Health and Welfare, Finland; Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Finland.

Background: Sleep problems are common and related to a worse quality of life in patients with schizophrenia. Almost all patients with schizophrenia use antipsychotic medications, which usually increase sleep. Still, the differences in subjective sleep outcomes between different antipsychotic medications are not entirely clear.

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Detection and measurement of amyloid-beta (Aβ) in the brain is a key factor for early identification and diagnosis of Alzheimer's disease (AD). We aimed to develop a deep learning model to predict Aβ cerebrospinal fluid (CSF) concentration directly from amyloid PET images, independent of tracers, brain reference regions or preselected regions of interest. We used 1870 Aβ PET images and CSF measurements to train and validate a convolutional neural network ("ArcheD").

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Background: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression.

Methods: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites.

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Article Synopsis
  • Human centromeres are challenging to sequence due to their large size and repetitive nature, limiting our understanding of their variation and evolutionary function.
  • Using long-read sequencing, researchers completely sequenced and assembled all centromeres from a second human genome, revealing a significant increase in genetic variation and size differences between centromeres.
  • Comparative analysis of centromeric sequences across species, including humans and great apes, highlights the rapid evolution of α-satellite DNA and suggests limited recombination between chromosome arms, aiding in studying centromeric DNA evolution.
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Article Synopsis
  • The study examines the use of intravenous thrombolysis (IVT) and endovascular thrombectomy for treating ischemic strokes in pregnant women, highlighting a lack of previous research in this area.
  • Data was collected from national registers in Finland over nearly three decades, comparing the outcomes of 12 IVT-treated maternal stroke patients to a control group of young females with non-pregnancy-related strokes.
  • Results indicate that while IVT-treated patients showed significant neurological improvement, their overall functional outcomes were less favorable compared to controls, suggesting that maternal strokes should not be dismissed from potential recanalization therapies.
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Characterization of circulating leptin-receptor levels following acute sleep restriction: A pilot study on healthy adult females.

Physiol Behav

May 2024

Notre Dame University-Louaize (NDU), Faculty of Natural and Applied Sciences, Department of Sciences, Zouk Mosbeh, Lebanon; The American University of Iraq-Baghdad (AUIB), College of Arts and Sciences, Department of Natural and Applied Sciences, Baghdad, Iraq. Electronic address:

Background: Insufficient sleep adversely affects energy homeostasis by decreasing leptin levels. The underlying physiological mechanisms; however, remain unclear. Circulating leptin is well described to be regulated by its soluble receptor (sOB-R).

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Article Synopsis
  • Genome-wide association studies (GWASs) analyzed data from over 41,000 infertility cases and 687,000 controls, identifying 21 genetic risk loci for infertility, with 12 previously unreported.
  • The study found significant genetic correlations between female infertility and conditions like endometriosis and polycystic ovary syndrome, suggesting interactions between genetic risk factors.
  • Exome sequencing revealed that women with rare testosterone-lowering variants are at higher risk for infertility, yet no general correlation between reproductive hormones and infertility was found, highlighting a complex genetic landscape.
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To uncover the intricate, chemotherapy-induced spatiotemporal remodeling of the tumor microenvironment, we conducted integrative spatial and molecular characterization of 97 high-grade serous ovarian cancer (HGSC) samples collected before and after chemotherapy. Using single-cell and spatial analyses, we identify increasingly versatile immune cell states, which form spatiotemporally dynamic microcommunities at the tumor-stroma interface. We demonstrate that chemotherapy triggers spatial redistribution and exhaustion of CD8+ T cells due to prolonged antigen presentation by macrophages, both within interconnected myeloid networks termed "Myelonets" and at the tumor stroma interface.

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CD33 (Siglec-3) is a cell surface receptor expressed in approximately 90% of acute myeloid leukemia (AML) blasts, making it an attractive target for therapy of AML. Although previous CD33-targeting antibody-drug conjugates (ADC) like gemtuzumab ozogamicin (GO, Mylotarg) have shown efficacy in AML treatment, they have suffered from toxicity and narrow therapeutic window. This study aimed to develop a novelADCwith improved tolerability and a wider therapeutic window.

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Genetic factors contribute to the susceptibility of psychotic disorders, but less is known how they affect psychotic disease-course development. Utilizing polygenic scores (PGSs) in combination with longitudinal healthcare data with decades of follow-up we investigated the contributing genetics to psychotic disease-course severity and diagnostic shifts in the SUPER-Finland study, encompassing 10 403 genotyped individuals with a psychotic disorder. To longitudinally track the study participants' past disease-course severity, we created a psychiatric hospitalization burden metric using the full-coverage and nation-wide Finnish in-hospital registry (data from 1969 and onwards).

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Background: Smokers are at increased risk of type 2 diabetes (T2D), but the underlying mechanisms are unclear. We investigated if the smoking-T2D association is mediated by alterations in the metabolome and assessed potential interaction with genetic susceptibility to diabetes or insulin resistance.

Methods: In UK Biobank (n = 93,722), cross-sectional analyses identified 208 metabolites associated with smoking, of which 131 were confirmed in Mendelian Randomization analyses, including glycoprotein acetyls, fatty acids, and lipids.

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Purpose: TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration and cytotoxicity in solid tumors.

Patients And Methods: TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose-escalation trial designed to assess the safety of TILT-123 in advanced solid cancers refractory to standard therapy. Patients received intravenous and intratumoral TILT-123.

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Purpose: To examine age-related macular degeneration (AMD) and retinal pigment epithelium (RPE)-Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs.

Methods: In this study, 106 elderly twins (53 twin pairs) from the Finnish Twin Cohort study were recruited. Each participant underwent dilated 35-degree digital colour fundus photography (CFP), and spectral domain optical coherence tomography (OCT) and replied to a structured study questionnaire.

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Integration of polygenic and gut metagenomic risk prediction for common diseases.

Nat Aging

April 2024

Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Article Synopsis
  • This study explores the effectiveness of combining genomic and gut metagenomic assessments to better predict the risk of diseases like coronary artery disease, type 2 diabetes, Alzheimer’s, and prostate cancer, using data from a long-term health record follow-up.
  • The researchers found that using polygenic risk scores (PRSs) significantly enhances disease prediction compared to traditional risk factors alone.
  • By integrating PRSs with gut microbiome scores and conventional risk factors, they achieved the best predictive outcomes for the diseases studied, highlighting the potential of multiomics in early disease detection and risk profiling.
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Outline and background for the EU-OS solubility prediction challenge.

SLAS Discov

June 2024

Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Schnackenburgallee 114, Hamburg 22525, Germany; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD), Theodor Stern Kai 7, Frankfurt 60590, Germany. Electronic address:

In June 2022, EU-OS came to the decision to make public a solubility data set of 100+K compounds obtained from several of the EU-OS proprietary screening compound collections. Leveraging on the interest of SLAS for screening scientific development it was decided to launch a joint EUOS-SLAS competition within the chemoinformatics and machine learning (ML) communities. The competition was open to real world computation experts, for the best, most predictive, classification model of compound solubility.

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SCGB1D2 inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease.

Nat Commun

March 2024

Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.

Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding for Secretoglobin family 1D member 2 (SCGB1D2) protein that increases the susceptibility for Lyme disease.

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Article Synopsis
  • Rheumatic diseases significantly affect reproductive health, leading to increased rates of childlessness and fewer children, particularly observed in conditions like systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA).
  • A nationwide study evaluated over 5 million Finnish citizens, comparing individuals with 19 immune-mediated diseases (IMDs) against matched controls on reproductive health metrics, including adverse maternal and perinatal outcomes.
  • The findings highlighted that patients with rheumatic diseases face higher risks for complications such as pre-eclampsia and preterm delivery, with SLE and Sjögren's syndrome showing the largest increases in adverse pregnancy outcomes.
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  • The study examines the impact of double heterozygosity (DH) for factor V Leiden and prothrombin G20210A polymorphisms on the risk of venous thromboembolism (VTE), finding a strong association with increased risk.
  • Analysis of data from over 937,000 individuals revealed that DH carriers have a significantly higher odds ratio (OR = 5.24) for developing VTE compared to non-carriers.
  • The findings suggest DH genotype could occur as often as FVL homozygosity, indicating that it may pose a comparable risk for VTE, but does not significantly affect the risk for arterial thrombosis events like stroke or heart attack.
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