Multi-Omic Atlas reveals cytotoxic phenotype and ROS-linked metabolic quiescence as key features of CTL-resistant HIV-infected CD4 T-cells.

Cytotoxic T-lymphocytes (CTL) exert sustained pressure on reservoirs of HIV-infected cells that persist through years of antiretroviral therapy (ART). This selects for latently infected cells, but also potentially for cells that express HIV but possess intrinsic CTL resistance. We demonstrate that such resistance exists in HIV-infected CD4 T-cells that survive rigorous CTL attack and map CTL susceptibility to cell identities and states defined by single-cell multi-omics and functional metabolic profiling.

Case report: First reported case of spondylodiscitis caused by Gemella morbillorum in South Africa.

Pyogenic spondylodiscitis is an uncommon but important clinical condition that often requires medical and/or surgical management. We report a case of spondylodiscitis caused by a rare pathogen, Gemella morbillorum. To date, worldwide, only six such cases of confirmed spondylodiscitis infection with this rare pathogen have been documented, and this is the first reported case in South Africa.

Pediatric oncology nutritional practices in high-income countries: A survey from the International Society of Paediatric Oncology (SIOP).

Background: Optimal nutrition in pediatric oncology can influence cancer-related outcomes. To establish an understanding of nutrition practice and perceptions of best practice, we queried nutrition providers practicing in pediatric oncology care centers in high-income countries.

Methods: An electronic, multidisciplinary, cross-sectional survey of nutrition practices was conducted among pediatric oncology nutrition practitioners.

Transcription of HIV-1 at sites of intact latent provirus integration.

HIV-1 antiretroviral therapy is highly effective but fails to eliminate a reservoir of latent proviruses, leading to a requirement for life-long treatment. How the site of integration of authentic intact latent proviruses might impact their own or neighboring gene expression or reservoir dynamics is poorly understood. Here, we report on proviral and neighboring gene transcription at sites of intact latent HIV-1 integration in cultured T cells obtained directly from people living with HIV, as well as engineered primary T cells and cell lines.

Improving emergency department flow by introducing four interventions simultaneously. A quality improvement project.

Background: Emergency department (ED) crowding is a widespread issue with adverse effects on patient care and outcomes.

Local Problem: ED crowding exacerbates wait times and compromises patient care, prompting opportunities for internal process improvement.

Method: Over one week, the ED flow project team implemented four interventions, including an additional triage station, to optimize patient flow.

Transcription of HIV-1 at sites of intact latent provirus integration.

HIV-1 anti-retroviral therapy is highly effective but fails to eliminate a reservoir of latent proviruses leading to a requirement for life-long treatment. How the site of integration of authentic intact latent proviruses might impact their own or neighboring gene expression or reservoir dynamics is poorly understood. Here we report on proviral and neighboring gene transcription at sites of intact latent HIV-1 integration in cultured T cells obtained directly from people living with HIV, as well as engineered primary T cells and cell lines.

Validating Health Economic Models With the Probabilistic Analysis Check dashBOARD.

Objectives: Health economic (HE) models are often considered as "black boxes" because they are not publicly available and lack transparency, which prevents independent scrutiny of HE models. Additionally, validation efforts and validation status of HE models are not systematically reported. Methods to validate HE models in absence of their full underlying code are therefore urgently needed to improve health policy making.

Quantifying hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNF-α inhibitors in juvenile idiopathic arthritis.

Objective: To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNF-α inhibitors (TNFi) in JIA patients.

Methods: This was a retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalization) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal).

Bayesian parameter estimation for the inclusion of uncertainty in progressive damage simulation of composites.

Despite gradual progress over the past decades, the simulation of progressive damage in composite laminates remains a challenging task, in part due to inherent uncertainties of material properties. This paper combines three computational methods - finite element analysis (FEA), machine learning and Markov Chain Monte Carlo - to estimate the probability density of FEA input parameters while accounting for the variation of mechanical properties. First, 15,000 FEA simulations of open-hole tension tests are carried out with randomly varying input parameters by applying continuum damage mechanics material models.

Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial.

Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3.

The latency-reversing agent HODHBt synergizes with IL-15 to enhance cytotoxic function of HIV-specific T cells.

IL-15 is under clinical investigation toward the goal of curing HIV infection because of its abilities to reverse HIV latency and enhance immune effector function. However, increased potency through combination with other agents may be needed. 3-Hydroxy-1,2,3-benzotriazin-4(3H)-one (HODHBt) enhances IL-15-mediated latency reversal and NK cell function by increasing STAT5 activation.

The impact of prehospital blood sampling on the emergency department process of patients with chest pain: a pragmatic non-randomized controlled trial.

Background: In patients with chest pain who arrive at the emergency department (ED) by ambulance, venous access is frequently established prehospital, and could be utilized to sample blood. Prehospital blood sampling may save time in the diagnostic process. In this study, the association of prehospital blood draw with blood sample arrival times, troponin turnaround times, and ED length of stay (LOS), number of blood sample mix-ups and blood sample quality were assessed.

A Review of Laser-Induced Crystallization from Solution.

Crystallization abounds in nature and industrial practice. A plethora of indispensable products ranging from agrochemicals and pharmaceuticals to battery materials are produced in crystalline form in industrial practice. Yet, our control over the crystallization process across scales, from molecular to macroscopic, is far from complete.

Correction: Bayesian parameter estimation for dynamical models in systems biology.

[This corrects the article DOI: 10.1371/journal.pcbi.

Effects of process changes on emergency department crowding in a changing world: an interrupted time-series analysis.

Background: During a 6-year period, several process changes were introduced at the emergency department (ED) to decrease crowding, such as the implementation of a general practitioner cooperative (GPC) and additional medical staff during peak hours. In this study, we assessed the effects of these process changes on three crowding measures: patients' length of stay (LOS), the modified National ED OverCrowding Score (mNEDOCS), and exit block while taking into account changing external circumstances, such as the COVID-19 pandemic and centralization of acute care.

Methods: We determined time points of the various interventions and external circumstances and built an interrupted time-series (ITS) model per outcome measure.

Association between Covid-19 surge and emergency department patient flow and experience.

Background: Preparations for Covid-19 in the Netherlands included hospital reconfigurations to increase capacity for the expected surge at the emergency department (ED). We describe patients' ED length of stay (LOS), crowding and experiences of patients with respiratory complaints during the first Covid-19 peak.

Methods: Retrospective analysis of demand, ED LOS, crowding, and a patient experience survey during a 12-week period in 2020 and similar periods in 2018 and 2019.

Bayesian parameter estimation for dynamical models in systems biology.

Dynamical systems modeling, particularly via systems of ordinary differential equations, has been used to effectively capture the temporal behavior of different biochemical components in signal transduction networks. Despite the recent advances in experimental measurements, including sensor development and '-omics' studies that have helped populate protein-protein interaction networks in great detail, modeling in systems biology lacks systematic methods to estimate kinetic parameters and quantify associated uncertainties. This is because of multiple reasons, including sparse and noisy experimental measurements, lack of detailed molecular mechanisms underlying the reactions, and missing biochemical interactions.

Potential multi-modal effects of provirus integration on HIV-1 persistence: lessons from other viruses.

Despite antiretroviral therapy (ART), HIV-1 persists as proviruses integrated into the genomic DNA of CD4 T cells. The mechanisms underlying the persistence and clonal expansion of these cells remain incompletely understood. Cases have been described in which proviral integration can alter host gene expression to drive cellular proliferation.

Promising effect of multi-family therapy on BMI, eating disorders and perceived family functioning in adolescent anorexia nervosa: an uncontrolled longitudinal study.

This contribution reports on the results of an uncontrolled longitudinal study investigating the effects of a Multi-Family Therapy (MFT) as treatment for adolescent Anorexia Nervosa (AN) and the role played by perceived family functioning in these effects. 150 patients (144 females) and their families took part in an MFT and were assessed at the beginning, middle, end of the therapy, as well as 6 and 12 months after the end of therapy. BMI, eating disorders symptomatology (EDI-II) and perceived family functioning (FAD) all improved over the time of MFT, and these benefits remained at both times of follow-up.

Social control and solidarity during the COVID-19 pandemic: The direct and indirect effects of causal attribution of insufficient compliance through perceived anomie.

The COVID-19 pandemic is a crisis which called for two crucial modes of social regulation: and . In the present pre-registered study, we examine how the perceived relates to attitudes towards these modes of social regulation, as well as to the role played by the perception of disintegrated and disregulated society (). Using data from an online cross-sectional survey conducted in Belgium in April 2020 ( = 717), results show that the causal attribution of the crisis to insufficient compliance was differentially associated with support for social control and social solidarity behaviours.

Dissociation of β2m from MHC class I triggers formation of noncovalent transient heavy chain dimers.

At the plasma membrane of mammalian cells, major histocompatibility complex class I molecules (MHC-I) present antigenic peptides to cytotoxic T cells. Following the loss of the peptide and the light chain beta-2 microglobulin (β2m, encoded by B2M), the resulting free heavy chains (FHCs) can associate into homotypic complexes in the plasma membrane. Here, we investigate the stoichiometry and dynamics of MHC-I FHCs assemblies by combining a micropattern assay with fluorescence recovery after photobleaching (FRAP) and with single-molecule co-tracking.

Health care cost of crusted scabies in Aboriginal communities in the Northern Territory, Australia.

Background: Crusted scabies is a debilitating dermatological condition. Although still relatively rare in the urban areas of Australia, rates of crusted scabies in remote Aboriginal communities in the Northern Territory (NT) are reported to be among the highest in the world.

Objective: To estimate the health system costs associated with diagnosing, treating and managing crusted scabies.

Go with the FLOW: visualizing spatiotemporal dynamics in optical widefield calcium imaging.

Widefield calcium imaging has recently emerged as a powerful experimental technique to record coordinated large-scale brain activity. These measurements present a unique opportunity to characterize spatiotemporally coherent structures that underlie neural activity across many regions of the brain. In this work, we leverage analytic techniques from fluid dynamics to develop a visualization framework that highlights features of flow across the cortex, mapping wavefronts that may be correlated with behavioural events.

The role of metacognitive competences in the development of school achievement among gifted adolescents.

Gifted underachievers perform worse in school than would be expected based on their high intelligence. Possible causes for underachievement are low motivational dispositions (need for cognition) and metacognitive competences. This study tested the interplay of these variables longitudinally with gifted and non-gifted students from Germany (N = 341, 137 females) in Grades 6 (M = 12.