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Patient-Reported Outcomes to Inform Tolerability Characterization in Cancer Trials:A Critical Perspective on Unresolved Methodological Issues
No full textPatient-reported outcomes assessing treatment toxicity and its impact, and aspects of quality of life, have become increasingly important components of oncology drug development including early phase dose optimization studies. Despite insights from these data, there are limitations on drawing inferences about whether a treatment is tolerable or intolerable, which requires understanding individual risk-benefit assessments that vary between patients, cancer types, and stages of disease. This commentary examines unresolved methodological issues requiring more research rigor and attention: the development of tolerability thresholds based upon toxicity severity data; the direct measurement of tolerability through specific patient self-report measures; and overcoming the challenge of baseline value assessment in important measures such as single item side-effect bother assessments. We call for further research to resolve these challenges and drive more robust inference-making from patient-reported outcomes data collected in cancer clinical trials
Thermal Energy Storage integration with Nuclear Power:Material challenges and Innovation pathways towards Flexible Low-Carbon Systems
No full textRecent accelerated shift towards deep decarbonisation demands nuclear power to evolve from baseload generation into flexible one with multi services. The integration of thermal energy storage (TES) with nuclear reactors provides a promising pathway to decouple heat and power functions, enabling steady-state reactor operation while allowing the delivery of dispatchable electricity and industrial process heat. This perspective paper outlines the material, component, and system-level challenges constraining TES deployment under the nuclear contexts - particularly corrosion, thermal fatigue, and irradiation effects under high-temperature molten salt and phase-change environments. Advances in alloy design, redox-controlled salt chemistry, modular TES architectures, and predictive control strategies are identified as critical innovation levers. Drawing on lessons from concentrated solar power and small modular reactor development, the paper proposes a roadmap for cross-sector collaboration and standardised materials qualification. Overcoming these barriers could reposition nuclear power plants as flexible, carbon-neutral energy hubs, bridging clean energy generation with heat and power applications across future integrated energy systems
Tankyrases and Their Binding Proteins:Origins of Their Roles in Diverse Cellular Pathways
No full textTankyrases (TNKS1 and TNKS2) are multifunctional enzymes of the poly(ADP-ribose) polymerase (PARP) family that regulate cellular homeostasis by catalyzing poly(ADP-ribosyl)ation and stabilizing protein–protein interactions through their ankyrin repeat clusters. By engaging with diverse sets of proteins, TNKSs act as central hubs that coordinate signaling and metabolic pathways. In this review, we discuss how TNKS –protein interactions underpin their roles across multiple biological pathways, including Wnt/β-catenin, YAP and SRC signaling, mTORC1 signaling, DNA damage repair (via PARP crosstalk and recruitment of repair factors), telomere maintenance, cell-cycle regulation, glucose metabolism, cytoskeleton rearrangement, autophagy, proteasomal degradation, and apoptosis. We highlight the structural basis of these interactions, emphasizing ankyrin repeat domain recognition motifs and the consequences of TNKS-mediated PARylation on protein stability and localization. By integrating findings from oncology, virology, and metabolism, we illustrate how TNKS functions as a nodal regulator linking genome stability, signaling fidelity, and metabolic control. The interplay between TNKS and these varied pathways is essential for the well-being of the organism, with its dysregulation having severe biological and clinical consequences, which are discussed here. Finally, we consider therapeutic implications of disrupting TNKS–protein interactions, with particular attention paid to selective small-molecule inhibitors and their translational potential in cancer, viral infections, and degenerative diseases
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