How does an intervention work?-English Version : Development of an effect model for a complex intervention to prevent recurring or persistent pain using the example of PAIN 2.0.

In addition to the usual evaluation approach (usually a clinical randomized trial in the sense of the question: does an intervention work), complex interventions require further systematic investigations to prove their effectiveness. The role of the context in which the intervention is delivered is essential here, as is consideration of the question of why an intervention works (or does not work). Detailed recommendations exist for the planning and implementation of effectiveness studies on complex interventions, to which interdisciplinary multimodal pain therapy undoubtedly belongs.

[How does an intervention work?-German Version. : Development of an effect model for a complex intervention to prevent recurring or persistent pain using the example of PAIN 2.0].

In addition to the usual evaluation approach (usually a clinical randomized trial in the sense of the question: does an intervention work), complex interventions require further systematic investigations to prove their effectiveness. The role of the context in which the intervention is delivered is essential here, as is consideration of the question of why an intervention works (or does not work). Detailed recommendations exist for the planning and implementation of effectiveness studies on complex interventions, to which interdisciplinary multimodal pain therapy undoubtedly belongs.

Of criminals and cancer: The importance of social bonds and innate morality on cellular societies.

The current dogma in cancer biology contends that cancer is an identity problem: mutations in a cell's DNA cause it to "go rogue" and proliferate out of control. However, this largely ignores the role of cell-cell interaction and fails to explain phenomena such as cancer reversion, the existence of cancers without mutations, and foreign-body carcinogenesis. In this proof-of-concept paper, we draw on criminology to propose that cancer may alternatively be conceptualized as a relational problem: Although a cell's genetics is essential, the influence of its interaction with other cells is equally important in determining its phenotype.

A modelling framework for cancer ecology and evolution.

Cancer incidence increases rapidly with age, typically as a polynomial. The somatic mutation theory explains this increase through the waiting time for enough mutations to build up to generate cells with the full set of traits needed to grow without control. However, lines of evidence ranging from tumour reversion and dormancy to the prevalence of presumed cancer mutations in non-cancerous tissues argue that this is not the whole story, and that cancer is also an ecological process, and that mutations only lead to cancer when the systems of control within and across cells have broken down.

Mathematical modeling of the evolution of resistance and aggressiveness of high-grade serous ovarian cancer from patient CA-125 time series.

A time-series analysis of serum Cancer Antigen 125 (CA-125) levels was performed in 791 patients with high-grade serous ovarian cancer (HGSOC) from the Australian Ovarian Cancer Study to evaluate the development of chemoresistance and response to therapy. To investigate chemoresistance and better predict the treatment effectiveness, we examined two traits: resistance (defined as the rate of CA-125 change when patients were treated with therapy) and aggressiveness (defined as the rate of CA-125 change when patients were not treated). We found that as the number of treatment lines increases, the data-based resistance increases (a decreased rate of CA-125 decay).

Toward mechanistic medical digital twins: some use cases in immunology.

A fundamental challenge for personalized medicine is to capture enough of the complexity of an individual patient to determine an optimal way to keep them healthy or restore their health. This will require personalized computational models of sufficient resolution and with enough mechanistic information to provide actionable information to the clinician. Such personalized models are increasingly referred to as medical digital twins.

Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis.

Airway inflammation underlies cystic fibrosis (CF) pulmonary exacerbations. In a prospective multicenter study of randomly selected, clinically stable adolescents and adults, we assessed relationships between 24 inflammation-associated molecules and the future occurrence of CF pulmonary exacerbation using proportional hazards models. We explored relationships for potential confounding or mediation by clinical factors and assessed sensitivities to treatments including CF transmembrane regulator (CFTR) protein synthesis modulators.

Forum on immune digital twins: a meeting report.

Medical digital twins are computational models of human biology relevant to a given medical condition, which are tailored to an individual patient, thereby predicting the course of disease and individualized treatments, an important goal of personalized medicine. The immune system, which has a central role in many diseases, is highly heterogeneous between individuals, and thus poses a major challenge for this technology. In February 2023, an international group of experts convened for two days to discuss these challenges related to immune digital twins.

CRISPR Screening Identifies Mechanisms of Resistance to KRASG12C and SHP2 Inhibitor Combinations in Non-Small Cell Lung Cancer.

Unlabelled: Although KRASG12C inhibitors show clinical activity in patients with KRAS G12C mutated non-small cell lung cancer (NSCLC) and other solid tumor malignancies, response is limited by multiple mechanisms of resistance. The KRASG12C inhibitor JDQ443 shows enhanced preclinical antitumor activity combined with the SHP2 inhibitor TNO155, and the combination is currently under clinical evaluation. To identify rational combination strategies that could help overcome or prevent some types of resistance, we evaluated the duration of tumor responses to JDQ443 ± TNO155, alone or combined with the PI3Kα inhibitor alpelisib and/or the cyclin-dependent kinase 4/6 inhibitor ribociclib, in xenograft models derived from a KRASG12C-mutant NSCLC line and investigated the genetic mechanisms associated with loss of response to combined KRASG12C/SHP2 inhibition.

A minimal model of learning: quantifying the cost and benefit of learning in changing environments.

Many organisms have the ability to learn, but the costs and benefits of learning are difficult to quantify. We construct a minimal mathematical model of learning in which a forager attempts to maximize the amount of resources (food) it collects in a changing environment. Our model has two learning parameters: , corresponding to the duration of the forager's memory, and [Formula: see text], corresponding to how much the forager explores the environment to learn more about it.

Mathematical Modeling of Field Cancerization through the Lens of Cancer Behavioral Ecology.

Field cancerization is a process in which a normal tissue is replaced with pre-cancerous but histologically normal tissue. This transformed field can give rise to malignancy and contribute to tumor relapse. In this paper, we create a mathematical model of field cancerization from the perspective of cancer behavioral ecology.

Biomarkers or biotargets? Using competition to lure cancer cells into evolutionary traps.

Background And Objectives: Cancer biomarkers provide information on the characteristics and extent of cancer progression and help inform clinical decision-making. However, they can also play functional roles in oncogenesis, from enabling metastases and inducing angiogenesis to promoting resistance to chemotherapy. The resulting evolution could bias estimates of cancer progression and lead to suboptimal treatment decisions.

Cell facilitation promotes growth and survival under drug pressure in breast cancer.

The interplay of positive and negative interactions between drug-sensitive and resistant cells influences the effectiveness of treatment in heterogeneous cancer cell populations. Here, we study interactions between estrogen receptor-positive breast cancer cell lineages that are sensitive and resistant to ribociclib-induced cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition. In mono- and coculture, we find that sensitive cells grow and compete more effectively in the absence of treatment.

Exploring pig farmers' decision-making concerning biosecurity measures against African Swine Fever.

African Swine Fever (ASF) is a growing threat to the German pig production sector. Rigorous biosecurity measures can prevent the introduction of ASF in domestic pig farms. Increased efforts have been made to inform pig farmers and other stakeholders in the industry regarding disease prevention measures for ASF.

Modeling collective cell behavior in cancer: Perspectives from an interdisciplinary conversation.

Collective cell behavior contributes to all stages of cancer progression. Understanding how collective behavior emerges through cell-cell interactions and decision-making will advance our understanding of cancer biology and provide new therapeutic approaches. Here, we summarize an interdisciplinary discussion on multicellular behavior in cancer, draw lessons from other scientific disciplines, and identify future directions.

A survey of open questions in adaptive therapy: Bridging mathematics and clinical translation.

Adaptive therapy is a dynamic cancer treatment protocol that updates (or 'adapts') treatment decisions in anticipation of evolving tumor dynamics. This broad term encompasses many possible dynamic treatment protocols of patient-specific dose modulation or dose timing. Adaptive therapy maintains high levels of tumor burden to benefit from the competitive suppression of treatment-sensitive subpopulations on treatment-resistant subpopulations.

Strategy maps: Generalised giving-up densities for optimal foraging.

Finding a common currency for benefits and hazards is a major challenge in optimal foraging theory, often requiring complex computational methods. We present a new analytic approach that builds on the Marginal Value Theorem and giving-up densities while incorporating the nonlinear effect of predation risk. We map the space of all possible environments into strategy regions, each corresponding to a discrete optimal strategy.

Large-scale assessment of German dairy farmers´ personality and resulting ideas for improving veterinary consultancy.

The here presented investigation was part of a cross-sectional study on dairy cattle health aiming to identify risk factors for animal health and welfare. Within this setting, we chose a social-science related approach to explore German dairy farmers' personality composition in a variable-centered and person-centered approach. We have assessed German dairy farmers' personalities based on the HEXACO model of personality in three representative regional samples.

Are Staphylococcus aureus Carrier Types Evidence of Population Heterogeneity?

Asymptomatic colonization by Staphylococcus aureus is a precursor for infection, so identifying the mode and source of transmission which leads to colonization could help in targeting interventions. Longitudinal studies have shown that some people are persistently colonized for years, while others seem to carry S. aureus for weeks or less, and conventional wisdom attributes this disparity to an underlying risk factor in the persistently colonized.

Uncertainty quantification for ecological models with random parameters.

There is often considerable uncertainty in parameters in ecological models. This uncertainty can be incorporated into models by treating parameters as random variables with distributions, rather than fixed quantities. Recent advances in uncertainty quantification methods, such as polynomial chaos approaches, allow for the analysis of models with random parameters.

Getting Better or Getting Worse? A Population-Based Study on Trends in Self-Rated Health among Single Mothers in Germany between 1994 and 2018.

Background: While numerous studies suggest that single motherhood is associated with socioeconomic disadvantages and poor health, few studies have analyzed how these conditions have evolved over time. Addressing this gap, we examined the temporal development of self-rated health (SRH) among single compared to partnered mothers, and the role of socioeconomic factors that may have influenced this trend.

Methods: We used representative longitudinal data from the German Socioeconomic Panel Survey (G-SOEP) between 1994 and 2018, consisting of 83,843 women with children, aged 30-49 years (13,664 single and 70,179 partnered mothers).

2,3-Difunctionalized Indoles via Radical Acylation or Trifluoromethylation of -Alkynylphenyl Isonitriles.

A radical cascade to 2,3-disubstituted indoles proceeding via acylation or trifluoromethylation of -alkynylphenyl isonitriles is presented. In these cascades, two C-C bonds and one C-O bond are formed using an inexpensive oxidant and a catalytic copper or iron salt. The starting isonitriles are easily accessible, and commercially available aldehydes and fluoromethylation reagents serve as reaction partners.