The persistence of HIV-1 proviruses in latently infected cells allows viremia to resume upon treatment cessation. To characterize the resulting immune response, we compare plasma proteomics and single-cell transcriptomics of peripheral blood mononuclear cells (PBMCs) before, during, and after detectable plasma viremia. We observe unique transcriptional signatures prior to viral rebound including a significant increase in CD16 monocytes with increased anti-viral gene expression.
View Article and Find Full Text PDFBiodegradable plastics, primarily aliphatic polyesters, degrade to varying extents in different environments. However, the absence of easily implementable techniques for screening microbial biodegradation potential -coupled with the limitations of non-functional omics analyses- has restricted comparative studies across diverse polymer types and ecosystems. In this study, we optimized a novel airbrushing method that facilitates functional analyses by simplifying the preparation of polyester-coated plates for biodegradation screening.
View Article and Find Full Text PDFObjectives: The present study performed a systematic review of the scientific literature that deals with the academic performance of university students with ADHD, collecting the research conducted between 2018 and 2024. Likewise, we aimed to know the factors that influence on academic performance and evaluate the tools used in the collection of ADHD symptoms and educational data.
Methods: The electronic databases PubMed, PsycInfo, and Scopus were used to search studies using PRISMA guidelines.
Background: The WHO HIV testing algorithm for high prevalence populations recommends the use of three different serologic assays, though this approach may lead to diagnostic misclassification. The study objective was to compare dried blood spot (DBS)-based HIV-1 nucleic acid detection methods to determine their suitability to confirm the diagnosis of HIV-1 in adults generally with suppressed or low-level plasma HIV-1 RNA.
Methods: Four methods were evaluated: Cepheid Xpert HIV-1 Qual Assay (Xpert), Hologic Aptima HIV-1 Quant Dx assay (Aptima), Roche Cobas Ampliprep/Cobas TaqMan HIV-1 test, v.
Maximum likelihood inference can often become computationally intensive when performing joint modeling of longitudinal and time-to-event data, due to the intractable integrals in the joint likelihood function. The computational challenges escalate further when modeling HIV-1 viral load data, owing to the nonlinear trajectories and the presence of left-censored data resulting from the assay's lower limit of quantification. In this paper, for a joint model comprising a nonlinear mixed-effect model and a Cox Proportional Hazards model, we develop a computationally efficient Stochastic EM (StEM) algorithm for parameter estimation.
View Article and Find Full Text PDFOpen Forum Infect Dis
October 2024
The value of microbiology and histopathology in the diagnosis of neuropathic foot osteomyelitis remains poorly understood. In this retrospective cohort study, we evaluated the concordance of microbiology and histopathology results from bone resections and found similar proportions of bacterial growth in samples with and without histopathologic evidence of osteomyelitis.
View Article and Find Full Text PDFThis study aims to develop methods to design the complete magnetic system for a truly portable MRI scanner for neurological and musculoskeletal (MSK) applications, optimized for field homogeneity, field of view (FoV), and gradient performance compared to existing low-weight configurations. We explore optimal elliptic-bore Halbach configurations based on discrete arrays of permanent magnets. In this way, we seek to improve the field homogeneity and remove constraints to the extent of the gradient coils typical of Halbach magnets.
View Article and Find Full Text PDFKey HIV cure strategies involve reversing immune dysfunction and limiting the proliferation of infected T cells. We evaluate the safety of sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in people with HIV (PWH) and study the impact of sirolimus on HIV-1 reservoir size and HIV-1-specific immunity in a single-arm study of 20 weeks of treatment in PWH on antiretroviral therapy (ART). Sirolimus treatment does not impact HIV-1-specific CD8 T cell responses but leads to a significant decrease in CD4 T cell-associated HIV-1 DNA levels at 20 weeks of therapy in the primary efficacy population (n = 16; 31% decline, p = 0.
View Article and Find Full Text PDFBackground: Anemia is an independent predictor of mortality, which may be utilized as a signal of deteriorating health. We estimated the association between anemia severity categories and mortality following the initiation of antiretroviral therapy (ART) among people with HIV (PWH) in North America.
Methods: Within the NA-ACCORD, annual median hemoglobin measurements between 01/01/2007-12/31/2016 were categorized using World Health Organization criteria into mild (11.
CPT Pharmacometrics Syst Pharmacol
September 2024
Obesity has become a major public health concern worldwide. Pharmacological interventions with the glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising results in facilitating weight loss and improving metabolic outcomes in individuals with obesity. Quantifying drug effects of GLP-1RAs on energy intake (EI) and body weight (BW) using a QSP modeling approach can further increase the mechanistic understanding of these effects, and support obesity drug development.
View Article and Find Full Text PDFAttention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) are strongly associated with educational attainment (EA), but little is known about their genetic relationship with school performance and whether these links are explained, in part, by the genetic liability of EA. Here, we aim to dissect the polygenic contribution of ADHD and ASD to school performance, early manifestation of psychopathology and other psychiatric disorders and related traits by their relationship with EA. To do so, we tested the association of polygenic scores for EA, ADHD and ASD with school performance, assessed whether the contribution of the genetic liability of ADHD and ASD to school performance is influenced by the genetic liability of EA, and evaluated the role of EA in the genetic overlap between ADHD and ASD with early manifestation of psychopathology and other psychiatric disorders and related traits in a sample of 4,278 school-age children.
View Article and Find Full Text PDFCPT Pharmacometrics Syst Pharmacol
July 2024
In pharmacometric modeling, it is often important to know whether the data is sufficiently rich to identify the parameters of a proposed model. While it may be possible to assess this based on the results of a model fit, it is often difficult to disentangle identifiability issues from other model fitting and numerical problems. Furthermore, it can be of value to ascertain identifiability beforehand.
View Article and Find Full Text PDFPancreatic β-cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here we report that the succinate receptor (SUCNR1) is expressed in β-cells and is up-regulated in hyperglycemic states in mice and humans. We found that succinate acts as a hormone-like metabolite and stimulates insulin secretion via a SUCNR1-Gq-PKC-dependent mechanism in human β-cells.
View Article and Find Full Text PDFBackground: Controversy has recently broken out over the potential carcinogenic risk associated with exposure to UV lamps for permanent nail polish. The new LED-based polymerization devices, and their potential biological effect has not been analyzed to this date.
Objective: To evaluate the emission power and its potential biological effects on the skin of 2 types of UV LED and fluorescent curing lamps under normal use conditions compared to doses of sunlight exposure.
Objectives: To describe the daily Physical Activity (PA) patterns of adolescents with Attention-deficit/hyperactivity disorder (ADHD), to analyze the differences in terms of PA patterns between adolescents with ADHD and those without ADHD, and to study the factors associated with achieving the daily PA recommendations.
Methods: The sample was composed of 778 adolescents who provided complete information on their PA patterns through the Physical Activity Questionnaire for Adolescents (PAQ-A). Of these, 97 had ADHD according to DSM-5 criteria.
Plastics are versatile materials that have the potential to propel humanity towards circularity and ultimate societal sustainability. However, the escalating concern surrounding plastic pollution has garnered significant attention, leading to widespread negative perceptions of these materials. Here, we question the role microbes may play in plastic pollution bioremediation by (i) defining polymer biodegradability (i.
View Article and Find Full Text PDFCausal indirect and direct effects provide an interpretable method for decomposing the total effect of an exposure on an outcome into the indirect effect through a mediator and the direct effect through all other pathways. A natural choice for a mediator in a randomized clinical trial is the treatment's targeted biomarker. However, when the mediator is a biomarker, values can be subject to an assay lower limit.
View Article and Find Full Text PDFHIV-1 infection greatly alters the NK cell phenotypic and functional repertoire. This is highlighted by the expansion of a rare population of FcRγ- NK cells exhibiting characteristics of traditional immunologic memory in people with HIV (PWH). Although current antiretroviral therapy (ART) effectively controls HIV-1 viremia and disease progression, its impact on HIV-1-associated NK cell abnormalities remains unclear.
View Article and Find Full Text PDFBackground: Acute microcirculatory perfusion disturbances and organ edema are important factors leading to organ dysfunction during cardiac surgery with cardiopulmonary bypass (CPB). Priming of the CPB system with crystalloid or colloid fluids, which inevitably leads to hemodilution, could contribute to this effect. However, there is yet no optimal evidence-based strategy for this type of priming.
View Article and Find Full Text PDFBackground: T cells in people with human immunodeficiency virus (HIV) demonstrate an exhausted phenotype, and HIV-specific CD4 T cells expressing programmed cell death 1 (PD-1) are enriched for latent HIV, making antibody to PD-1 a potential strategy to target the latent reservoir.
Methods: This was a phase 1/2, randomized (4:1), double-blind, placebo-controlled study in adults with suppressed HIV on antiretroviral therapy with CD4 counts ≥350 cells/μL who received 2 infusions of cemiplimab versus placebo. The primary outcome was safety, defined as any grade 3 or higher adverse event (AE) or any immune-related AE (irAE).