Directed Acyclic Graphs in Decision-Analytic Modeling: Bridging Causal Inference and Effective Model Design in Medical Decision Making.

Our commentary proposes the application of directed acyclic graphs (DAGs) in the design of decision-analytic models, offering researchers a valuable and structured tool to enhance transparency and accuracy by bridging the gap between causal inference and model design in medical decision making.The practical examples in this article showcase the transformative effect DAGs can have on model structure, parameter selection, and the resulting conclusions on effectiveness and cost-effectiveness.This methodological article invites a broader conversation on decision-modeling choices grounded in causal assumptions.

Synergistic combination of orally available safe-in-man pleconaril, AG7404, and mindeudesivir inhibits enterovirus infections in human cell and organoid cultures.

Enteroviruses can infect various human organs, causing diseases such as meningitis, the common cold, hand-foot-and-mouth disease, myocarditis, pancreatitis, hepatitis, poliomyelitis, sepsis, and type 1 diabetes. Currently, there are no approved treatments for enterovirus infections. In this study, we identified a synergistic combination of orally available, safe-in-man pleconaril, AG7404, and mindeudesivir, that at non-toxic concentrations effectively inhibited enterovirus replication in human cell and organoid cultures.

Variable temocillin protein binding and pharmacokinetics in different clinical conditions: Implications for target attainment.

Aims: The beta-lactam antibiotic temocillin is increasingly used to treat extended-spectrum beta-lactamase (ESBL-producing) strains; however, its protein binding is complex. This study aims to predict unbound temocillin concentrations in various participant groups to determine its impact on the probability of target attainment (PTA) and to improve dosing recommendations.

Methods: The plasma pharmacokinetics were analysed using non-linear mixed-effects modelling.

Unloader brace or high tibial osteotomy in the treatment of the young patient with medial knee osteoarthritis: a randomized controlled trial.

Background And Purpose:  For medial knee osteoarthritis (OA), operative and nonoperative treatment options are available. Two widely applied unloading therapies are a valgus unloader brace and a high tibial osteotomy (HTO). We aimed to compare the effects of a valgus unloader knee brace with an HTO on knee pain after 1 year in patients with symptomatic medial knee OA.

Corrigendum: Cipaglucosidase alfa plus miglustat: linking mechanism of action to clinical outcomes in late-onset Pompe disease.

[This corrects the article DOI: 10.3389/fneur.2024.

HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design.

Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation.

Does Nocturnal Blood Pressure Matter in Retinal Small Vessels? A Systematic Review and Meta-Analysis of the Literature.

Purpose Of The Review: Τhe association between nocturnal blood pressure (BP) and alterations in the retinal microvasculature remains understudied, with few available studies to provide conflicting results. Therefore, we conducted a systematic review and meta-analysis to determine whether an association exists between retinal microvascular alterations and nocturnal BP patterns, determined by 24h ambulatory BP measurement.

Recent Findings: Our search concluded to 1002 patients (6 studies).

Finding a constrained number of predictor phenotypes for multiple outcome prediction.

Background: Prognostic models help aid medical decision-making. Various prognostic models are available via websites such as MDCalc, but these models typically predict one outcome, for example, stroke risk. Each model requires individual predictors, for example, age, lab results and comorbidities.

Discovery of a DNA methylation profile in individuals with Sifrim-Hitz-Weiss syndrome.

Pathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear.

Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation.

Background: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and recurrent infections. Significant morbidity and mortality are caused by immune dysregulation complications (CVIDid), which affect around one-third of CVID patients and have a poorly understood etiology. Here, we investigate the hypothesis that gut microbial dysbiosis contributes to the inflammation underlying CVIDid.

Promoting Global Cardiovascular Health to Advance the Sustainable Development Agenda.

The burden of cardiovascular disease has declined in high-income countries in the past 3 decades but is growing in low- and middle-income countries due to epidemiological, demographic, and socioeconomic shifts. A range of cost-effective policies and interventions are available for advancing cardiovascular health (CVH) through primordial, primary, and secondary prevention. We showcase multifaceted challenges that stifle the global progress of CVH including shortcomings in financial protection, health systems, primary health care, national health policies, service coverage, and surveillance.

Newborn With Refractory Seizures Due To Hemimegalencephaly And Tuberous Sclerosis Complex: Case Report and Literature Review.

Background Hemimegalencephaly (HME) is a rare congenital disorder that is initiated during embryonic development with abnormal growth of one hemisphere. Tuberous sclerosis complex (TSC), a genetic disorder, is rarely associated with HME. Methods We present a case of a newborn with HME with a confirmed mutation in the TSC-1 gene and describe the clinical course, findings on (amplitude integrated) electroencephalography (aEEG), cranial ultrasound (CUS), MRI, and the postmortem evaluation.

Systematic review of machine learning applications using nonoptical motion tracking in surgery.

This systematic review explores machine learning (ML) applications in surgical motion analysis using non-optical motion tracking systems (NOMTS), alone or with optical methods. It investigates objectives, experimental designs, model effectiveness, and future research directions. From 3632 records, 84 studies were included, with Artificial Neural Networks (38%) and Support Vector Machines (11%) being the most common ML models.

Effectiveness of potent topical corticosteroids versus mild ones in primary care for children with moderate flare-ups of atopic dermatitis; results of a randomised controlled trial.

Objective: To assess the effectiveness of a potent topical corticosteroid (TCS) as an initial treatment in primary care for children with moderate flare-ups of atopic dermatitis (AD), compared to starting on a mild TCS.

Design: An observational prospective cohort study with an embedded pragmatic multicentre open-label randomised controlled trial.

Setting: A total of 53 general practices in the southwest of the Netherlands took part in the study.

Pharmacodynamics of NOSO-502 studied in vitro and in vivo: determination of the dominant pharmacodynamic index driver.

Background: NOSO-5O2 is the first clinical candidate of a new antimicrobial class-the odilorhabdins. The pharmacodynamics of NOSO-502 were studied in vitro and in vivo to establish the pharmacodynamic index (PDI) driver.

Methods: A dilutional pharmacokinetic system was used for in vitro experiments.

Predictors of hepatic flares after nucleos(t)ide analogue cessation - Results of a global cohort study (RETRACT-B study).

Background & Aims: Flares after nucleos(t)ide analogue (NA) cessation are common and potentially harmful. Predictors of flares are required for risk stratification and to guide off-treatment follow-up.

Method: This multicenter cohort study included virally suppressed patients with chronic hepatitis B (CHB) who were hepatitis B e antigen negative at NA cessation.

A Systematic Review and Meta-Analysis of an Angiotensin Receptor-Neprilysin Inhibitor in Patients Using a Durable Left Ventricular Assist Device.

Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) drug used to treat patients with heart failure and has shown improvement in outcomes. Different studies reported the use of an ARNI in patients using left ventricular assist devices (LVADs). However, there are limited data on the use of ARNIs in this population.

Understanding the dynamics driving obesity in socioeconomically deprived urban neighbourhoods: an expert-based systems map.

Background: Over the past decades, the prevalence of obesity among adults has rapidly increased, particularly in socioeconomically deprived urban neighbourhoods. To better understand the complex mechanisms behind this trend, we created a system map exposing the underlying system driving obesity prevalence in socioeconomically deprived urban neighbourhoods over the last three decades in the Netherlands.

Methods: We conducted Group Model Building (GMB) sessions with a group of thirteen interdisciplinary experts to develop a Causal Loop Diagram (CLD) of the obesogenic system.

Tract-specific white matter hyperintensities and neuropsychiatric syndromes: a multicentre memory clinic study.

Background: White matter hyperintensities (WMH) have been implicated in the pathogenesis of neuropsychiatric symptoms of dementia but the functional significance of WMH in specific white matter (WM) tracts is unclear. We investigate whether WMH burden within major WM fibre classes and individual WM tracts are differentially associated with different neuropsychiatric syndromes in a large multicentre study.

Method: Neuroimaging and neuropsychiatric data of seven memory clinic cohorts through the Meta VCI Map consortium were harmonised.

Oral Glucose-Lowering Agents vs Insulin for Gestational Diabetes: A Randomized Clinical Trial.

Importance: Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown.

Objective: To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants.