• All non-adherence is equal, but is some more equal than others? TB in the digital era 

      Stagg, Helen; Flook, Mary; Martinecz, Antal; Kielmann, Karina; Abel zur Wiesch, Pia; Karat, Aaron; Lipman, Marc; Sloan, Derek; Walker, Elizabeth; Fielding, Katherine L (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-11-02)
      Adherence to treatment for tuberculosis (TB) has been a concern for many decades, resulting in the World Health Organization's recommendation of the direct observation of treatment in the 1990s. Recent advances in digital adherence technologies (DATs) have renewed discussion on how to best address nonadherence, as well as offering important information on dose-by-dose adherence patterns and their ...
    • Estimating treatment prolongation for persistent infections 

      Martinecz, Antal; Abel zur Wiesch, Pia (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-08-09)
      Treatment of infectious diseases is often long and requires patients to take drugs even after they have seemingly recovered. This is because of a phenomenon called persistence, which allows small fractions of the bacterial population to survive treatment despite being genetically susceptible. The surviving subpopulation is often below detection limit and therefore is empirically inaccessible but can ...
    • Fractional integral-like processing in retinal cones reduces noise and improves adaptation 

      Martinecz, Antal; Niitsuma, Mihoko (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-10-04)
      In the human retina, rod and cone cells detect incoming light with a molecule called rhodopsin. After rhodopsin molecules are activated (by photon impact), these molecules activate the rest of the signalling process for a brief period of time until they are deactivated by a multistage process. First, active rhodopsin is phosphorylated multiple times. Following this, they are further inhibited by the ...
    • High rifampicin peak plasma concentrations accelerate the slow phase of bacterial decline in tuberculosis patients: Evidence for heteroresistance 

      Martinecz, Antal; Boeree, Martin J.; Diacon, Andreas H.; Dawson, Rodney; Hemez, Colin; Arnoutse, Rob; Abel zur Wiesch, Pia (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-04-13)
      Background - Antibiotic treatments are often associated with a late slowdown in bacterial killing. This separates the killing of bacteria into at least two distinct phases: a quick phase followed by a slower phase, the latter of which is linked to treatment success. Current mechanistic explanations for the in vitro slowdown are either antibiotic persistence or heteroresistance. Persistence is defined ...
    • Mathematical Models of Optimal Antibiotic Treatment 

      Martinecz, Antal (Doctoral thesis; Doktorgradsavhandling, 2020-06-09)
      When bacteria are exposed to antibiotics, the rate of killing can slow down dramatically over time. This phenomenon can be observed both in vitro and in vivo. In vitro, the mechanistic explanations for this can be divided into two main categories: antibiotic persistence and heteroresistance. In vivo, both mechanisms thought to contribute to observed slowdowns in the elimination and as a result may ...
    • Multi-scale modeling of drug binding kinetics to predict drug efficacy 

      Clarelli, Fabrizio; Liang, Jingyi; Martinecz, Antal; Heiland, Ines; Wiesch, Pia Abel Zur (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-11-25)
      Optimizing drug therapies for any disease requires a solid understanding of pharmacokinetics (the drug concentration at a given time point in different body compartments) and pharmacodynamics (the effect a drug has at a given concentration). Mathematical models are frequently used to infer drug concentrations over time based on infrequent sampling and/or in inaccessible body compartments. Models are ...
    • Multi-scale modeling of drug binding kinetics to predict drug efficacy 

      Clarelli, Fabrizio; Liang, Jingyi; Martinecz, Antal; Heiland, Ines; Abel zur Wiesch, Pia (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-11-25)
      Optimizing drug therapies for any disease requires a solid understanding of pharmacokinetics (the drug concentration at a given time point in different body compartments) and pharmacodynamics (the effect a drug has at a given concentration). Mathematical models are frequently used to infer drug concentrations over time based on infrequent sampling and/or in inaccessible body compartments. Models are ...
    • Perspectives for systems biology in the management of tuberculosis 

      Kontsevaya, Irina; Lange, Christoph; Comella-Del-barrio, Patricia; Coarfa, Cristian; Dinardo, Andrew R.; Gillespie, Stephen H.; Hauptmann, Matthias; Leschczyk, Christoph; Mandalakas, Anna M.; Martinecz, Antal; Merker, Matthias; Niemann, Stefan; Reimann, Maja; Rzhepishevska, Olena; Schaible, Ulrich E.; Scheu, Katrin M.; Schurr, Erwin; Abel zur Wiesch, Pia; Heyckendorf, Jan (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-05-25)
      Standardised management of tuberculosis may soon be replaced by individualised, precision medicineguided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel ...
    • Reaction Kinetic Models of Antibiotic Heteroresistance 

      Martinecz, Antal; Clarelli, Fabrizio; Abel, Sören; Abel zur Wiesch, Pia (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08-15)
      Bacterial heteroresistance (i.e., the co-existence of several subpopulations with different antibiotic susceptibilities) can delay the clearance of bacteria even with long antibiotic exposure. Some proposed mechanisms have been successfully described with mathematical models of drug-target binding where the mechanism’s downstream of drug-target binding are not explicitly modeled and subsumed in ...
    • vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding 

      Tran, Vi Ngoc-Nha; Shams, Alireza; Ascioglu, Sinan; Martinecz, Antal; Liang, Jingyi; Clarelli, Fabrizio; Mostowy, Rafal; Cohen, Ted; Abel zur Wiesch, Pia (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-01-06)
      Background: As antibiotic resistance creates a signifcant global health threat, we need not only to accelerate the development of novel antibiotics but also to develop better treatment strategies using existing drugs to improve their efcacy and prevent the selection of further resistance. We require new tools to rationally design dosing regimens from data collected in early phases of antibiotic ...