The dynamics of three-dimensional (3D) genome organization are essential to transcriptional regulation. While enhancers regulate spatiotemporal gene expression, chromatin looping is a means for enhancer-promoter interactions yielding cell-type-specific gene expression. Further, non-canonical DNA secondary structures, such as G-quadruplexes (G4s), are related to increased gene expression.
View Article and Find Full Text PDFThe COVID-19 pandemic has caused substantial worldwide disruptions in health, economy, and society, manifesting symptoms such as loss of smell (anosmia) and loss of taste (ageusia), that can result in prolonged sensory impairment. Establishing the host genetic etiology of anosmia and ageusia in COVID-19 will aid in the overall understanding of the sensorineural aspect of the disease and contribute to possible treatments or cures. By using human genome sequencing data from the University of Iowa (UI) COVID-19 cohort (N=187) and the National Institute of Health All of Us (AoU) Research Program COVID-19 cohort (N=947), we investigated the genetics of anosmia and/or ageusia by employing feature selection techniques to construct a novel variant and gene prioritization pipeline, utilizing machine learning methods for the classification of patients.
View Article and Find Full Text PDFUrinary tract infections are among the most frequently occurring forms of infection, and inflammation and tissue damage contribute significantly to symptoms, e.g., dysuria and urge.
View Article and Find Full Text PDFBackground: Hematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy for individuals with blood diseases, but involves a challenging recovery process that requires dedicated caregivers. The complex interplay between emotional distress, care partner (or unpaid caregiver) burden, and treatment outcomes necessitates comprehensive physiological and psychological measurements to fully understand these dynamics.
Findings: We collected longitudinal data from 166 HCT caregiver-patient dyads over 120 days post-transplant as part of a randomized controlled trial ( NCT04094844 ).
Results from randomized control trials (RCTs) may not be representative when individuals refuse to be randomized or are excluded for having a preference for which treatment they receive. If trial designs do not allow for participant treatment preferences, trials can suffer in accrual, adherence, retention, and external validity of results. Thus, there is interest surrounding clinical trial designs that incorporate participant treatment preferences.
View Article and Find Full Text PDFChronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy with limited therapeutic options. Single-cell analysis of clonal architecture demonstrates early clonal dominance with few residual WT hematopoietic stem cells. Circulating myeloid cells of the leukemic clone and the cytokines they produce generate a deleterious inflammatory climate.
View Article and Find Full Text PDFDoberman Pinschers are known for their increased susceptibility to dilated cardiomyopathy (DCM) relative to other domestic dogs. This makes the Doberman Pinscher a key model for gene-disease investigations. We conducted a genome-wide association study (GWAS) leveraging a database of genetic profiles obtained through collaboration with the Doberman Diversity Project (DDP).
View Article and Find Full Text PDFObjective: Noise reduction during surgical procedures leads to improved surgical performance and results. The caesarean birth (CB) is an exceptional operation and a life changing experience. Through the introduction of staff education and implementation of audiovisual feedback, we intended to reduce noise, and subsequently reduce surgical complications and increase the well-being of patients and staff.
View Article and Find Full Text PDFBackground: Humanized mice transplanted with CD34 hematopoietic cells (HPCs) are broadly used to study human immune responses and infections in vivo and for testing therapies pre-clinically. However, until now, it was not clear whether interactions between the mouse major histocompatibility complexes (MHCs) and/or the human leukocyte antigens (HLAs) were necessary for human T-cell development and immune reactivity.
Methods: We evaluated the long-term (20-week) human hematopoiesis and human T-cell development in NOD Scid Gamma (NSG) mice lacking the expression of MHC class I and II (NSG-DKO).
B lymphopoiesis is orchestrated by lineage-specific transcription factors. In B cell progenitors, lineage commitment is mediated by Pax5, which is commonly mutated in B cell acute lymphoblastic leukemia. Despite its essential role in immunity, the mechanisms regulating Pax5 function remain largely unknown.
View Article and Find Full Text PDFNon-communicable diseases (NCDs) represent a high burden for the society and affected individuals. Conservative non-pharmacological interventions play a first-line role in the treatment and management of most NCDs. Systematic reviews (SRs) provide the highest level of evidence and significantly influence clinical decision-making.
View Article and Find Full Text PDFIncarceration represents an opportune moment to improve self-management of anger and aggression. A hatha yoga-based intervention (YBI) could serve as a useful adjunctive intervention for anger within prisons. We enrolled 40 people with elevated levels of anger who were incarcerated (20 in a women's facility, and 20 in a men's facility) in a 10-week pilot randomized controlled trial of a YBI versus.
View Article and Find Full Text PDFa commensal species of the human gut, is an opportunistic pathogen that can reach extra-intestinal compartments, including the bloodstream and the bladder, among others. In non-immunosuppressed patients, purifying or neutral evolution of populations has been reported in the gut. Conversely, it has been suggested that when migrating to extra-intestinal compartments, genomes undergo diversifying selection as supported by strong evidence for adaptation.
View Article and Find Full Text PDFActa Obstet Gynecol Scand
September 2024
Retinitis pigmentosa (RP) is a genetic blinding disease with over 80 causative genes. Disease progression varies between patients with similar genetic backgrounds. We assessed the association between environment, gut microbiota, and retinal degeneration in the RP rat model Royal College of Surgeons (RCS).
View Article and Find Full Text PDFCaspases, well-known for their role in executing apoptosis, also participate in various non-apoptotic processes. Despite this, their involvement in promoting compensatory proliferation - a key aspect of tissue regeneration following extensive cell death - has been a subject of ongoing ambiguity. In our study, we investigate compensatory proliferation in the wing imaginal disc following ionizing radiation, a model epithelial tissue that has been a pioneering system for studying this regenerative response.
View Article and Find Full Text PDFPatients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are highly susceptible to infections. The consequent use of masks on wards for allo-HSCT has been controversial in the past decades and was not common before the COVID-19 pandemic. We retrospectively compared incidence and outcomes of viral respiratory infections during allo-HSCT on our specialized ward between 01/2018 and 09/2020 to the era of FFP2 masking between 10/2020 and 10/2022 covering similar seasons of the year.
View Article and Find Full Text PDFActa Obstet Gynecol Scand
September 2024
Introduction: The main goal of placenta accreta spectrum (PAS) screening is to enable delivery in an expert center in the presence of an experienced team at an appropriate time. Our study aimed to identify independent risk factors for emergency deliveries within the IS-PAS 2.0 database cohort and establish a multivariate predictive model.
View Article and Find Full Text PDFBackground And Aims: We previously identified small molecules predicted to reverse an ileal gene signature for future Crohn's Disease (CD) strictures. Here we used a new human intestinal organoid (HIO) model system containing macrophages to test a lead candidate, eicosatetraynoic acid (ETYA).
Methods: Induced pluripotent stem cell lines (iPSC) were derived from CD patients and differentiated into macrophages and HIOs.
The molecular mechanisms of progressive right heart failure are incompletely understood. In this study, we systematically examined transcriptomic changes occurring over months in isolated cardiomyocytes or whole heart tissues from failing right and left ventricles in rat models of pulmonary artery banding (PAB) or aortic banding (AOB). Detailed bioinformatics analyses resulted in the identification of gene signature, protein and transcription factor networks specific to ventricles and compensated or decompensated disease states.
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