Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

Background: For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis.

Methods: We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z).

Time-varying reproduction number estimation: fusing compartmental models with generalized additive models.

The reproduction number, the mean number of secondary cases infected by each primary case, gives an indication of the effort required to control the disease. Beyond the well-known reproduction number, there are two natural extensions, namely the and reproduction numbers. As behaviour, population immunity and viral characteristics can change with time, these reproduction numbers can vary over time.

Characterization of patients with clonal mast cells in the bone marrow with clinical significance not otherwise specified.

Background: Systemic mastocytosis (SM) diagnosis requires the presence of 3 minor criteria or 1 major and 1 minor criterion according to the WHO 2016 classification. The aim of this study was to characterize patients with 1 or 2 minor SM criteria including mutation and/or aberrant expression of CD2 and/or CD25 on bone marrow (BM) mast cells (MCs), but without MC activation syndrome (MCAS) criteria.

Methods: We included eligible patients from two countries diagnosed between 2011 and 2021.

Photobioreactor design utilizing procedural three-dimensional modelling and ray tracing.

The design of photobioreactors for microalgae cultivation aims to achieve an architecture that allows the most efficient photosynthetic growth. The availability of light at wavelengths that are important for photosynthesis is therefore particularly crucial for reactor design. While testing different reactor types in practice is expensive, simulations could effectively limit the range of material and reactor design options.

Multicellular PID control for robust regulation of biological processes.

This article presents the first implementation of a proportional-integral-derivative (PID) biomolecular controller within a consortium of different cell populations, aimed at robust regulation of biological processes. By leveraging the modularity and cooperative dynamics of multiple engineered cell populations, we develop a comprehensive analysis of the performance and robustness of P, PD, PI and PID control architectures. Our theoretical findings, validated through experiments using the BSim agent-based simulation platform for bacterial populations, demonstrate the robustness and effectiveness of our multicellular PID control strategy.

Robust undulatory locomotion through neuromechanical adjustments in a dissipative medium.

Dissipative environments are ubiquitous in nature, from microscopic swimmers in low-Reynolds-number fluids to macroscopic animals in frictional media. In this study, we consider a mathematical model of a slender elastic locomotor with an internal rhythmic neural pattern generator to examine various undulatory locomotion such as swimming and crawling behaviours. By using local mechanical load as mechanosensory feedback, we have found that undulatory locomotion robustly emerges in different rheological media.

Mechanistic models of humoral kinetics following COVID-19 vaccination.

COVID-19 vaccine programmes must account for variable immune responses and waning protection. Existing descriptions of antibody responses to COVID-19 vaccination convey limited information about the mechanisms of antibody production and maintenance. We describe antibody dynamics after COVID-19 vaccination with two biologically motivated mathematical models.

Cooperative bots exhibit nuanced effects on cooperation across strategic frameworks.

The positive impact of cooperative bots on cooperation within evolutionary game theory is well-documented. However, prior studies predominantly use discrete strategic frameworks with deterministic actions. This article explores continuous and mixed strategic approaches.

Biomechanics of soft biological tissues and organs, mechanobiology, homeostasis and modelling.

The human body consists of many different soft biological tissues that exhibit diverse microstructures and functions and experience diverse loading conditions. Yet, under many conditions, the mechanical behaviour of these tissues can be described well with similar nonlinearly elastic or inelastic constitutive relations, both in health and some diseases. Such constitutive relations are essential for performing nonlinear stress analyses, which in turn are critical for understanding physiology, pathophysiology and even clinical interventions, including surgery.

Can spatial self-organization inhibit evolutionary adaptation?

Plants often respond to drier climates by slow evolutionary adaptations from fast-growing to stress-tolerant species. These evolutionary adaptations increase the plants' resilience to droughts but involve productivity losses that bear on agriculture and food security. Plants also respond by spatial self-organization, through fast vegetation patterning involving differential plant mortality and increased water availability to the surviving plants.

Capacity and limitations of microfluidic flow to increase solute transport in three-dimensional cell cultures.

Culturing living cells in three-dimensional environments increases the biological relevance of laboratory experiments, but requires solutes to overcome a diffusion barrier to reach the centre of cellular constructs. We present a theoretical and numerical investigation that brings a mechanistic understanding of how microfluidic culture conditions, including chamber size, inlet fluid velocity and spatial confinement, affect solute distribution within three-dimensional cellular constructs. Contact with the chamber substrate reduces the maximally achievable construct radius by 15%.

Quantifying the configurational complexity of biological systems in multivariate 'complexity space'.

An increasing number of evolutionary studies seek to quantify the morphological complexity of organisms, particularly those comprising serially homologous elements at different hierarchical levels of organization. Numerous operational frameworks have been proposed for doing this, but most focus on one or multiple conflated aspects of what is really a multidimensional concept. Here, we advocate the use of 'complexity spaces': multidimensional spaces defined by different vectors of complexity.

Differential Associations of Cigar, Pipe, and Smokeless Tobacco Use Versus Combustible Cigarette Use With Subclinical Markers of Inflammation, Thrombosis, and Atherosclerosis: The Cross-Cohort Collaboration-Tobacco Working Group.

Background: Understanding the association of tobacco product use with subclinical markers is essential in evaluating health effects to inform regulatory policy. This is particularly relevant for noncigarette products (eg, cigars, pipes, and smokeless tobacco), which have been understudied because of their low prevalence in individual cohort studies.

Methods: This cross-sectional study included 98 450 participants from the Cross-Cohort Collaboration-Tobacco data set.

Early identification of dropouts during the special forces selection program.

Recruits are exposed to high levels of psychological and physical stress during the special forces selection period, resulting in dropout rates of up to 80%. To identify who likely drops out, we assessed a group of 249 recruits, every week of the selection program, on their self-efficacy, motivation, experienced psychological and physical stress, and recovery. Using linear regression as well as state-of-the-art machine learning techniques, we aimed to build a model that could meaningfully predict dropout while remaining interpretable.

The α-globin super-enhancer acts in an orientation-dependent manner.

Individual enhancers are defined as short genomic regulatory elements, bound by transcription factors, and able to activate cell-specific gene expression at a distance, in an orientation-independent manner. Within mammalian genomes, enhancer-like elements may be found individually or within clusters referred to as locus control regions or super-enhancers (SEs). While these behave similarly to individual enhancers with respect to cell specificity, distribution and distance, their orientation-dependence has not been formally tested.

The Construction of a Standard Karyotype of Intermediate Wheatgrass and Its Potential Progenitor Species.

The genome composition of intermediate wheatgrass (IWG; (Host) Barkworth and D.R. Dewey; 2n = 6x = 42) is complex and remains to be a subject of ongoing investigation.

Sustainable Skincare Innovation: Cork Powder Extracts as Active Ingredients for Skin Aging.

: An emerging practice within the concept of circular beauty involves the upcycling of agro-industrial by-products. Cork processing, for instance, yields by-products like cork powder, which presents an opportunity to create value-added cosmetic ingredients. Building upon our previous research, demonstrating the antioxidant potential of hydroalcoholic extracts derived from two distinct cork powders (P0 and P1), in this work, aqueous extracts were prepared and analyzed.

Pradofloxacin Minimum Inhibitory Concentration Profiling of Isolates: Insights into Antimicrobial Susceptibility in Swine.

This study evaluated the minimum inhibitory concentration (MIC) of pradofloxacin against various swine respiratory pathogens, including , , , , and (), associated with disease in swine. This research was conducted in two phases: the initial phase examined isolates from the lungs that could be either commensal or pathogenic, while the second phase focused on systemic strains that spread from the respiratory tract to the brain. The pradofloxacin MIC values of the second phase were within the MIC range of the initial phase, with MIC and MIC values highlighting its potential as an effective antimicrobial agent.

Multi-assay assessment of cytotoxicity reveals multiple mechanisms of action in 3D microtissues.

Cell viability assays are an integral component of toxicology and high-throughput drug screening studies; however, many assays rely on a single biomarker of cell death which provides an incomplete assessment of cell viability. Here, we introduce an innovative approach that combines data from multiple assays using a linear mixed effects regression model and principal component analysis. We explored the cytotoxic response of various assay-treatment combinations using four assays with distinct mechanisms of action and seven different treatments across three types of microtissue cultures.

An essential role for TASL in mouse autoimmune pathogenesis and Toll-like receptor signaling.

TASL is an immune adaptor that binds to the solute carrier SLC15A4 and facilitates activation of the transcription factor IRF5 during Toll-like receptor (TLR) signaling. Similar to IRF5 and SLC15A4, single nucleotide polymorphisms (SNPs) within TASL have been implicated in increased susceptibility to systemic lupus erythematosus (SLE) in patients. However, the biological function of TASL in vivo and how SLE-associated SNPs increase disease risk is unknown.