Guidance and Considerations When Performing Data-Validity Checks.

This response to a Commentary by Delgado-Ron, Jeyabalan, Watt, and Salway (2024) on Cimpian, Timmer, and Kim's (2023) paper discusses and clarifies some key issues in applying the new data-validity sensitivity analysis proposed by Cimpian et al. (2023). The differences in the applications of the method by Delgado-Ron et al.

Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy.

Autophagy is a key cellular quality control mechanism. Nutrient stress triggers bulk autophagy, which nonselectively degrades cytoplasmic material upon formation and liquid-liquid phase separation of the autophagy-related gene 1 (Atg1) complex. In contrast, selective autophagy eliminates protein aggregates, damaged organelles and other cargoes that are targeted by an autophagy receptor.

Evaluation and clinical applicability of angiography-derived assessment of coronary microcirculatory resistance: a [O]HO PET study.

The introduction of wire-free microcirculatory resistance index from functional angiography (angio-IMR) promises swift detection of coronary microvascular dysfunction, however it has not been properly validated. We sought to validate angio-IMR against invasive IMR and PET derived microvascular resistance (MVR). Moreover, we studied if angio-IMR could aid in the detection of ischemia with non-obstructive coronary arteries (INOCA).

Making waves: How to clean surface water with photogranules.

Global surface waters are in a bad ecological and chemical state, which has detrimental effects on entire ecosystems. To prevent further deterioration of ecosystems and ecosystem services, it is vital to minimize environmental pollution and come up with ways to keep surface water healthy and clean. Recently, photogranules have emerged as a promising platform for wastewater treatment to remove organic matter and nutrients with reduced or eliminated mechanical aeration, while also facilitating CO capture and production of various bioproducts.

Intraindividual time-varying dynamic network of affects: linear autoregressive mixed-effects models for ecological momentary assessment.

An interesting recent development in emotion research and clinical psychology is the discovery that affective states can be modeled as a network of temporally interacting moods or emotions. Additionally, external factors like stressors or treatments can influence the mood network by amplifying or dampening the activation of specific moods. Researchers have turned to multilevel autoregressive models to fit these affective networks using intensive longitudinal data gathered through ecological momentary assessment.

Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.

Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable; however, designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated drug product for targeting CD33+ tumors called dimerizaing agent-regulated immunoreceptor complex (DARIC33). T cell products demonstrated target-specific and rapamycin-dependent cytokine release, transcriptional responses, cytotoxicity, and in vivo antileukemic activity in the presence of as little as 1 nM rapamycin.

Basal MET phosphorylation is an indicator of hepatocyte dysregulation in liver disease.

Chronic liver diseases are worldwide on the rise. Due to the rapidly increasing incidence, in particular in Western countries, metabolic dysfunction-associated steatotic liver disease (MASLD) is gaining importance as the disease can develop into hepatocellular carcinoma. Lipid accumulation in hepatocytes has been identified as the characteristic structural change in MASLD development, but molecular mechanisms responsible for disease progression remained unresolved.

Design of a Biohybrid Materials Circuit with Binary Decoder Functionality.

Synthetic biology applies concepts from electrical engineering and information processing to endow cells with computational functionality. Transferring the underlying molecular components into materials and wiring them according to topologies inspired by electronic circuit boards has yielded materials systems that perform selected computational operations. However, the limited functionality of available building blocks is restricting the implementation of advanced information-processing circuits into materials.

Likelihood-ratio test statistic for the finite-sample case in nonlinear ordinary differential equation models.

Likelihood ratios are frequently utilized as basis for statistical tests, for model selection criteria and for assessing parameter and prediction uncertainties, e.g. using the profile likelihood.

Activator-blocker model of transcriptional regulation by pioneer-like factors.

Zygotic genome activation (ZGA) in the development of flies, fish, frogs and mammals depends on pioneer-like transcription factors (TFs). Those TFs create open chromatin regions, promote histone acetylation on enhancers, and activate transcription. Here, we use the panel of single, double and triple mutants for zebrafish genome activators Pou5f3, Sox19b and Nanog, multi-omics and mathematical modeling to investigate the combinatorial mechanisms of genome activation.

Uncovering specific mechanisms across cell types in dynamical models.

Ordinary differential equations are frequently employed for mathematical modeling of biological systems. The identification of mechanisms that are specific to certain cell types is crucial for building useful models and to gain insights into the underlying biological processes. Regularization techniques have been proposed and applied to identify mechanisms specific to two cell types, e.

Investigating two mobile just-in-time adaptive interventions to foster psychological resilience: research protocol of the DynaM-INT study.

Background: Stress-related disorders such as anxiety and depression are highly prevalent and cause a tremendous burden for affected individuals and society. In order to improve prevention strategies, knowledge regarding resilience mechanisms and ways to boost them is highly needed. In the Dynamic Modelling of Resilience - interventional multicenter study (DynaM-INT), we will conduct a large-scale feasibility and preliminary efficacy test for two mobile- and wearable-based just-in-time adaptive interventions (JITAIs), designed to target putative resilience mechanisms.

The incremental value of coronary artery calcium score in predicting long-term prognosis and defining the warranty period of normal adenosine stress-only myocardial perfusion imaging using CZT SPECT.

Background: Normal stress-only (SO) myocardial perfusion imaging (MPI) using SPECT reduces imaging time and radiation dose with a good prognosis. However, the long-term prognostic value of combining coronary artery calcium score (CACS) with SO MPI to determine the warranty period remains unknown. Hence, we assessed the incremental prognostic value of CACS and its impact on the warranty period of normal SO MPI using SPECT.

The diagnostic performance of quantitative flow ratio and perfusion imaging in patients with prior coronary artery disease.

Aims: In chronic coronary syndrome (CCS) patients with documented coronary artery disease (CAD), ischaemia detection by myocardial perfusion imaging (MPI) and an invasive approach are viable diagnostic strategies. We compared the diagnostic performance of quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance imaging (CMR) in patients with prior CAD [previous percutaneous coronary intervention (PCI) and/or myocardial infarction (MI)].

Methods And Results: This PACIFIC-2 sub-study evaluated 189 CCS patients with prior CAD for inclusion.

Dynamic Modelling of Mental Resilience in Young Adults: Protocol for a Longitudinal Observational Study (DynaM-OBS).

Background: Stress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psychological resilience in healthy but susceptible young adults over 9 months.

Mitigating invalid and mischievous survey responses: A registered report examining risk disparities between heterosexual and lesbian, gay, bisexual, or questioning youth.

In a Registered Report, the authors propose a new survey-bias-mitigation method-incorporating inverse probability weighting via boosted regression-to better understand lesbian, gay, bisexual, or questioning (LGBQ)-heterosexual youth risk disparities. This method is tested using the 2019 US Centers for Disease Control and Prevention-collected Youth Risk Behavior Survey (YRBS) national data, which contain 12,847 observations (ages 12-18 [M = 16, SD = 1.25]; 49.

Mutual repression between JNK/AP-1 and JAK/STAT stratifies senescent and proliferative cell behaviors during tissue regeneration.

Epithelial repair relies on the activation of stress signaling pathways to coordinate tissue repair. Their deregulation is implicated in chronic wound and cancer pathologies. Using TNF-α/Eiger-mediated inflammatory damage to Drosophila imaginal discs, we investigate how spatial patterns of signaling pathways and repair behaviors arise.

Engineering a material-genetic interface as safety switch for embedded therapeutic cells.

Encapsulated cell-based therapies involve the use of genetically-modified cells embedded in a material in order to produce a therapeutic agent in a specific location in the patient's body. This approach has shown great potential in animal model systems for treating diseases such as type I diabetes or cancer, with selected approaches having been tested in clinical trials. Despite the promise shown by encapsulated cell therapy, though, there are safety concerns yet to be addressed, such as the escape of the engineered cells from the encapsulation material and the resulting production of therapeutic agents at uncontrolled sites in the body.

AAPM Task Group Report 238: 3D C-arms with volumetric imaging capability.

This report reviews the image acquisition and reconstruction characteristics of C-arm Cone Beam Computed Tomography (C-arm CBCT) systems and provides guidance on quality control of C-arm systems with this volumetric imaging capability. The concepts of 3D image reconstruction, geometric calibration, image quality, and dosimetry covered in this report are also pertinent to CBCT for Image-Guided Radiation Therapy (IGRT). However, IGRT systems introduce a number of additional considerations, such as geometric alignment of the imaging at treatment isocenter, which are beyond the scope of the charge to the task group and the report.

INBRX-120, a CD8α-targeted detuned IL-2 that selectively expands and activates tumoricidal effector cells for safe and durable in vivo responses.

Background: As a major driver of lymphocyte proliferation and activation interleukin 2 (IL-2) is a crucial mediator for antitumor responses. Despite promising activity in a subset of patients, wider therapeutic utility of IL-2 (aldesleukin) has been hampered by severe dose-limiting toxicities, the expansion of immunosuppressive regulatory T cells and a poor pharmacokinetic (PK) profile. Recent engineering efforts, including non-α IL-2 variants, have lowered the toxicity profile, but have yet to induce meaningful antitumor activity in a wider patient population.

Detecting frequency modulation in stochastic time-series data.

We propose a statistical test to identify nonstationary frequency-modulated stochastic processes from time-series data. Our method uses the instantaneous phase as a discriminatory statistics with reliable critical values derived from surrogate data. We simulated an oscillatory second-order autoregressive process to evaluate the size and power of the test.

BlotIt-Optimal alignment of Western blot and qPCR experiments.

Biological systems are frequently analyzed by means of mechanistic mathematical models. In order to infer model parameters and provide a useful model that can be employed for systems understanding and hypothesis testing, the model is often calibrated on quantitative, time-resolved data. To do so, it is typically important to compare experimental measurements over broad time ranges and various experimental conditions, e.