Brittle and ductile yielding in soft materials.

Many soft materials yield under mechanical loading, but how this transition from solid-like behavior to liquid-like behavior occurs can vary significantly. Understanding the physics of yielding is of great interest for the behavior of biological, environmental, and industrial materials, including those used as inks in additive manufacturing and muds and soils. For some materials, the yielding transition is gradual, while others yield abruptly. We refer to these behaviors as being ductile and brittle. The key rheological signatures of brittle yielding include a stress overshoot in steady-shear-startup tests and a steep increase in the loss modulus during oscillatory amplitude sweeps. In this work, we show how this spectrum of yielding behaviors may be accounted for in a continuum model for yield stress materials by introducing a parameter we call the brittility factor. Physically, an increased brittility decreases the contribution of recoverable deformation to plastic deformation, which impacts the rate at which yielding occurs. The model predictions are successfully compared to results of different rheological protocols from a number of real yield stress fluids with different microstructures, indicating the general applicability of the phenomenon of brittility. Our study shows that the brittility of soft materials plays a critical role in determining the rate of the yielding transition and provides a simple tool for understanding its effects under various loading conditions.

Unbiased construction of constitutive relations for soft materials from experiments via rheology-informed neural networks.

The ability to concisely describe the dynamical behavior of soft materials through closed-form constitutive relations holds the key to accelerated and informed design of materials and processes. The conventional approach is to construct constitutive relations through simplifying assumptions and approximating the time- and rate-dependent stress response of a complex fluid to an imposed deformation. While traditional frameworks have been foundational to our current understanding of soft materials, they often face a twofold existential limitation: i) Constructed on ideal and generalized assumptions, precise recovery of material-specific details is usually serendipitous, if possible, and ii) inherent biases that are involved by making those assumptions commonly come at the cost of new physical insight. This work introduces an approach by leveraging recent advances in scientific machine learning methodologies to discover the governing constitutive equation from experimental data for complex fluids. Our rheology-informed neural network framework is found capable of learning the hidden rheology of a complex fluid through a limited number of experiments. This is followed by construction of an unbiased material-specific constitutive relation that accurately describes a wide range of bulk dynamical behavior of the material. While extremely efficient in closed-form model discovery for a real-world complex system, the model also provides insight into the underpinning physics of the material.

Direct-ink-write cross-linkable bottlebrush block copolymers for on-the-fly control of structural color.

Additive manufacturing capable of controlling and dynamically modulating structures down to the nanoscopic scale remains challenging. By marrying additive manufacturing with self-assembly, we develop a UV (ultra-violet)-assisted direct ink write approach for on-the-fly modulation of structural color by programming the assembly kinetics through photo-cross-linking. We design a photo-cross-linkable bottlebrush block copolymer solution as a printing ink that exhibits vibrant structural color (i.e., photonic properties) due to the nanoscopic lamellar structures formed post extrusion. By dynamically modulating UV-light irradiance during printing, we can program the color of the printed material to access a broad spectrum of visible light with a single ink while also creating color gradients not previously possible. We unveil the mechanism of this approach using a combination of coarse-grained simulations, rheological measurements, and structural characterizations. Central to the assembly mechanism is the matching of the cross-linking timescale with the assembly timescale, which leads to kinetic trapping of the assembly process that evolves structural color from blue to red driven by solvent evaporation. This strategy of integrating cross-linking chemistry and out-of-equilibrium processing opens an avenue for spatiotemporal control of self-assembled nanostructures during additive manufacturing.

Investigation of the yielding transition in concentrated colloidal systems via rheo-XPCS.

We probe the microstructural yielding dynamics of a concentrated colloidal system by performing creep/recovery tests with simultaneous collection of coherent scattering data via X-ray Photon Correlation Spectroscopy (XPCS). This combination of rheology and scattering allows for time-resolved observations of the microstructural dynamics as yielding occurs, which can be linked back to the applied rheological deformation to form structure-property relations. Under sufficiently small applied creep stresses, examination of the correlation in the flow direction reveals that the scattering response recorrelates with its predeformed state, indicating nearly complete microstructural recovery, and the dynamics of the system under these conditions slows considerably. Conversely, larger creep stresses increase the speed of the dynamics under both applied creep and recovery. The data show a strong connection between the microstructural dynamics and the acquisition of unrecoverable strain. By comparing this relationship to that predicted from homogeneous, affine shearing, we find that the yielding transition in concentrated colloidal systems is highly heterogeneous on the microstructural level.

Digital rheometer twins: Learning the hidden rheology of complex fluids through rheology-informed graph neural networks.

SignificanceScience-based data-driven methods that can describe the rheological behavior of complex fluids can be transformative across many disciplines. Digital rheometer twins, which are developed here, can significantly reduce the cost, time, and energy required to characterize complex fluids and predict their future behavior. This is made possible by combining two different methods of informing neural networks with the rheological underpinnings of a system, resulting in quantitative recovery of a gel's response to different flow protocols. The platform developed here is general enough that it can be extended to areas well beyond complex fluids modeling.

TopNEXt: automatic DDA exclusion framework for multi-sample mass spectrometry experiments.

MOTIVATION: Liquid Chromatography Tandem Mass Spectrometry experiments aim to produce high-quality fragmentation spectra, which can be used to annotate metabolites. However, current Data-Dependent Acquisition approaches may fail to collect spectra of sufficient quality and quantity for experimental outcomes, and extend poorly across multiple samples by failing to share information across samples or by requiring manual expert input. RESULTS: We present TopNEXt, a real-time scan prioritization framework that improves data acquisition in multi-sample Liquid Chromatography Tandem Mass Spectrometry metabolomics experiments. TopNEXt extends traditional Data-Dependent Acquisition exclusion methods across multiple samples by using a Region of Interest and intensity-based scoring system. Through both simulated and lab experiments, we show that methods incorporating these novel concepts acquire fragmentation spectra for an additional 10% of our set of target peaks and with an additional 20% of acquisition intensity. By increasing the quality and quantity of fragmentation spectra, TopNEXt can help improve metabolite identification with a potential impact across a variety of experimental contexts. AVAILABILITY AND IMPLEMENTATION: TopNEXt is implemented as part of the ViMMS framework and the latest version can be found at https://github.com/glasgowcompbio/vimms. A stable version used to produce our results can be found at 10.5281/zenodo.7468914.

Feature-based molecular networking in the GNPS analysis environment.

Molecular networking has become a key method to visualize and annotate the chemical space in non-targeted mass spectrometry data. We present feature-based molecular networking (FBMN) as an analysis method in the Global Natural Products Social Molecular Networking (GNPS) infrastructure that builds on chromatographic feature detection and alignment tools. FBMN enables quantitative analysis and resolution of isomers, including from ion mobility spectrometry.

Using topic modeling to detect cellular crosstalk in scRNA-seq.

Cell-cell interactions are vital for numerous biological processes including development, differentiation, and response to inflammation. Currently, most methods for studying interactions on scRNA-seq level are based on curated databases of ligands and receptors. While those methods are useful, they are limited to our current biological knowledge. Recent advances in single cell protocols have allowed for physically interacting cells to be captured, and as such we have the potential to study interactions in a complemantary way without relying on prior knowledge. We introduce a new method based on Latent Dirichlet Allocation (LDA) for detecting genes that change as a result of interaction. We apply our method to synthetic datasets to demonstrate its ability to detect genes that change in an interacting population compared to a reference population. Next, we apply our approach to two datasets of physically interacting cells to identify the genes that change as a result of interaction, examples include adhesion and co-stimulatory molecules which confirm physical interaction between cells. For each dataset we produce a ranking of genes that are changing in subpopulations of the interacting cells. In addition to the genes discussed in the original publications, we highlight further candidates for interaction in the top 100 and 300 ranked genes. Lastly, we apply our method to a dataset generated by a standard droplet-based protocol not designed to capture interacting cells, and discuss its suitability for analysing interactions. We present a method that streamlines detection of interactions and does not require prior clustering and generation of synthetic reference profiles to detect changes in expression.

Extracting microscopic insight from transient dielectric measurements during large amplitude oscillatory shear.

Probing the transient microstructure of soft matter far from equilibrium is an ongoing challenge to understanding material processing. In this work, we investigate inverse worm-like micelles undergoing large amplitude oscillatory shear using time-resolved dielectric spectroscopy. By controlling the Weissenburg number, we compare the non-linear microstructure response of branched and unbranched worm-like micelles and isolate distinct elastic effects that manifest near flow reversal. We validate our dielectric measurements with small angle neutron scattering and employ sequence of physical processes to disentangle the elastic and viscous contributions of the stress.

Concerns raised by people treated for head and neck cancer: a secondary analysis of audiotaped consultations in a health services follow-up clinic.

PURPOSE: People treated for head and neck cancer (HNC) face various barriers in communicating concerns with consultants. Our aim was to investigate the number of concerns raised between patients using the Patient Concerns Inventory (PCI) and those who did not. The PCI is a 57-item prompt list used in routine HNC follow-up clinics. Additionally, we aimed to examine whether who initiated the concerns differed between groups and the factors that may predict this initiation. METHODS: Secondary data analysis included 67 participants across 15 HNC consultants from specialist cancer centres in Liverpool and Leeds. Seven consultants utilised the PCI and eight did not, assigned by preferential and random assignment. RESULTS: Patients in the PCI group raised on average 2.5 more concerns than patients in the non-PCI group (p < .001). There was no significant relationship between group and who initiated the first concern (p = .28). A mixed-effects logistic regression was found to significantly predict who initiated the first concern in consultations (p < .05). DISCUSSION: The number of concerns raised by patients increased when the PCI was introduced pre-HNC consultation. A number of factors were shown to predict the number of concerns raised in consultations by both patient and consultant. As concerns may not be raised further following the concern mentioned, we propose that the discussion of concerns needs to be maintained by the clinician throughout the consultation and not solely at the start. CONCLUSION: The PCI promoted the sharing of concerns in follow-up consultations between patient and consultant.

Barriers to and facilitators of physical activity in adults living with and beyond cancer, with special emphasis on head and neck cancer: a systematic review of qualitative and mixed methods studies.

PURPOSE: Physical activity can improve health outcomes for cancer patients; however, only 30% of patients are physically active. This review explored barriers to and facilitators of physical activity promotion and participation in patients living with and beyond cancer. Secondary aims were to (1) explore similarities and differences in barriers and facilitators experienced in head and neck cancer versus other cancers, and (2) identify how many studies considered the influence of socioeconomic characteristics on physical activity behaviour. METHODS: CINAHL Plus, MEDLINE, PsycINFO, Scopus and Cochrane (CDSR) were searched for qualitative and mixed methods evidence. Quality assessment was conducted using the Mixed Methods Appraisal Tool and a Critical Appraisal Skills Programme Tool. Thematic synthesis and frequency of reporting were conducted, and results were structured using the Capability-Opportunity-Motivation-Behaviour model and Theoretical Domains Framework. RESULTS: Thirty qualitative and six mixed methods studies were included. Socioeconomic characteristics were not frequently assessed across the included studies. Barriers included side effects and comorbidities (physical capability; skills) and lack of knowledge (psychological capability; knowledge). Having a dry mouth or throat and choking concerns were reported in head and neck cancer, but not across other cancers. Facilitators included improving education (psychological capability; knowledge) on the benefits and safety of physical activity. CONCLUSION: Educating patients and healthcare professionals on the benefits and safety of physical activity may facilitate promotion, uptakeand adherence. Head and neck cancer patients experienced barriers not cited across other cancers, and research exploring physical activity promotion in this patient group is required to improve physical activity engagement.

Elucidating the G″ overshoot in soft materials with a yield transition via a time-resolved experimental strain decomposition.

Materials that exhibit yielding behavior are used in many applications, from spreadable foods and cosmetics to direct write three-dimensional printing inks and filled rubbers. Their key design feature is the ability to transition behaviorally from solid to fluid under sufficient load or deformation. Despite its widespread applications, little is known about the dynamics of yielding in real processes, as the nonequilibrium nature of the transition impedes understanding. We demonstrate an iteratively punctuated rheological protocol that combines strain-controlled oscillatory shear with stress-controlled recovery tests. This technique provides an experimental decomposition of recoverable and unrecoverable strains, allowing for solid-like and fluid-like contributions to a yield stress material's behavior to be separated in a time-resolved manner. Using this protocol, we investigate the overshoot in loss modulus seen in materials that yield. We show that this phenomenon is caused by the transition from primarily solid-like, viscoelastic dissipation in the linear regime to primarily fluid-like, plastic flow at larger amplitudes. We compare and contrast this with a viscoelastic liquid with no yielding behavior, where the contribution to energy dissipation from viscous flow dominates over the entire range of amplitudes tested.

Development of the stroke patient concerns inventory: A modified Delphi study.

OBJECTIVES: Stroke survivors often have unmet physical, psychological and/or social concerns. Patient Concerns Inventories (PCIs) have been developed for other health conditions to address concerns. Our objective was to develop a PCI for stroke care. METHODS: This was a development study, including Modified Delphi study design, with academic and healthcare professionals with stroke care expertise. In Stage 1, a draft Stroke PCI (Version 1a) was created through identifying patient-reported concerns post-stroke from three previous studies and through expert panel discussions using Nominal Group Technique. In Stage 2, Version 1a was sent to 92 academic and healthcare professionals with stroke care expertise. Participants ranked their top 20 Stroke PCI items in order of importance and provided feedback. Rankings were converted into scores, and, with the feedback, used to amend the Stroke PCI. Two further rounds of feedback followed until consensus was reached between participants. A final draft of the Stroke PCI was created. RESULTS: In stage 1, 64 potential Stroke PCI items were generated. In Stage 2, 38 participants (41.3%) responded to the request to rank Stroke PCI items. The three highest ranked items were 'Risk of another stroke', 'Walking', 'Recovery'. After three rounds of feedback and amendments, the final draft of the Stroke PCI consisted of 53 items. CONCLUSIONS: A Stroke PCI has been developed using patient-reported concerns in previous studies and input from academic and healthcare professionals. Future work will involve gathering further feedback on the tool and exploring its acceptability and usability in a pilot study.

Treatment priorities and regret in older adults with head and neck cancer: A systematic review.

BACKGROUND: The majority of head and neck cancer (HNC) diagnoses are seen in people aged 70 and older; these numbers are set to increase. Greater understanding of treatment needs of older patients with HNC is essential. These older patients often have co-existing health conditions, are prone to frailty and may not prioritise survival when considering treatment options. This systematic review examines the current research with regard to priorities and factors influencing treatment regret in older people with HNC. METHODS: Studies were eligible for inclusion if they (i) reported data from patients with a mean age of 65 years or older who had a confirmed diagnosis of HNC and had been treated using surgery, chemotherapy and/or radiotherapy with either palliative or curative intent, (ii) considered patient's priorities or preferences or examined treatment regret as one of the primary outcomes of the study (iii) were published in English. RESULTS: Pilot search identified n = 7222 articles; however, following screening, only four papers met the inclusion criteria. Narrative synthesis was indicated to analyse quantitative and qualitative evidence in parallel, as meta-analyses were not possible. DISCUSSION: There is a paucity in the literature examining older adults with HNC. There is an indication that older adults prioritise maintaining independence when making treatment decisions and treatment regret is seen in those with high levels of depression with level of frailty also a contributing factor. Clinicians should consider patient's social circumstances, premorbid status and priorities in maintaining independence and managing symptoms when making treatment decisions in this cohort.

Patient preference for commonly-used, head and neck cancer-specific quality of life questionnaires in the follow-up setting (Determin): A multi-centre randomised controlled trial and mixed methods study.

BACKGROUND: Quality of life (QoL) assessment forms an integral part of modern cancer care and research. The aim of this study is to determine patients' preferences and willingness to complete commonly used head-and-neck cancer (HNC) QoL questionnaires (QLQs) in routine follow-up clinics. METHODS: This is a randomised control trial of 583 subjects from 17 centres during follow-up after treatment for oral, oropharyngeal or laryngeal cancer. Subjects completed three structured validated questionnaires: EORTC QLQ-HN35; FACT-HN and UW-QOL, and an unstructured patient-generated list. The order of questionnaire presentation was randomised, and subjects were stratified by disease site and stage. Patients self-rated the questionnaires they found most helpful to communicate their health concerns to their clinicians. RESULTS: Of the 558 respondents, 82% (457) found QLQs useful to communicate their health concerns to their clinician (OR = 15.76; 95% CI 10.83-22.94). Patients preferred the structured disease-specific instruments (OR 8.79; 95% CI 5.99-12.91), while the open list was the most disliked (OR = 4.25; 95% CI 3.04-5.94). There was no difference in preference by treatment modality. More women preferred the FACT-HN (OR = 3.01, 95% CI 1.05-8.62), and patients under 70 preferred EORTC QLQ-HN35 (OR = 3.14, 95% CI 1.3-7.59). However, only 55% of patients expressed preference to complete questionnaires routinely at the clinic. CONCLUSIONS: Most patients found QLQs helpful during their follow-up and 55% supported routine questionnaires in follow-up clinics. Males and people over 70 years old were the least willing to complete the routine questionnaires and preferred shorter questionnaires (e.g., UW-QOL). Women preferred FACT-HN, and younger patients preferred EORTC QLQ-HN35. Reasons for the reluctance to complete questionnaires require elucidation.

Probabilistic framework for integration of mass spectrum and retention time information in small molecule identification.

MOTIVATION: Identification of small molecules in a biological sample remains a major bottleneck in molecular biology, despite a decade of rapid development of computational approaches for predicting molecular structures using mass spectrometry (MS) data. Recently, there has been increasing interest in utilizing other information sources, such as liquid chromatography (LC) retention time (RT), to improve identifications solely based on MS information, such as precursor mass-per-charge and tandem mass spectrometry (MS2). RESULTS: We put forward a probabilistic modelling framework to integrate MS and RT data of multiple features in an LC-MS experiment. We model the MS measurements and all pairwise retention order information as a Markov random field and use efficient approximate inference for scoring and ranking potential molecular structures. Our experiments show improved identification accuracy by combining MS2 data and retention orders using our approach, thereby outperforming state-of-the-art methods. Furthermore, we demonstrate the benefit of our model when only a subset of LC-MS features has MS2 measurements available besides MS1. AVAILABILITY AND IMPLEMENTATION: Software and data are freely available at https://github.com/aalto-ics-kepaco/msms_rt_score_integration. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Rheological Characteristics of Ionic Liquids under Nanoconfinement.

While the dynamic properties of ionic liquids (ILs) in nanoconfinement play a crucial role in the performance of IL-based electrochemical and mechanical devices, experimental work mostly falls short at reporting "solid-like" versus "liquid-like" behavior of confined ILs. The present work is the first to conduct frequency-sweep oscillatory-shear rheology on IL nanofilms, reconciling the solid-versus-liquid debate and revealing the importance of shear rate in the behavior. We disentangle and analyze the viscoelasticity of nanoconfined ILs and shed light on their relaxation mechanisms. Furthermore, a master curve describes the scaling of the dynamic behavior of four (non-hydrogen-bonding) ILs under nanoconfinement and reveals the role of the compressibility of the flow units.

Designing Multicomponent Polymer Colloids for Self-Stratifying Films.

Aqueous polymer colloids known as latexes are widely used in coating applications. Multicomponent latexes comprised of two incompatible polymeric species organized into a core-shell particle morphology are a promising system for self-stratifying coatings that spontaneously partition into multiple layers, thereby yielding complex structured coatings requiring only a single application step. Developing new materials for self-stratifying coatings requires a clear understanding of the thermodynamic and kinetic properties governing phase separation and polymeric species transport. In this work, we study phase separation and self-stratification in polymer films based on multicomponent acrylic (shell) and acrylic-silicone (core) latex particles. Our results show that the molecular weight of the shell polymer and heat aging conditions of the film critically determine the underlying transport phenomena, which ultimately controls phase separation in the film. Unentangled shell polymers result in efficient phase separation within hours with heat aging at reasonable temperatures, whereas entangled shell polymers effectively inhibit phase separation even under extensive heat aging conditions over a period of months due to kinetic limitations. Transmission electron microscopy is used to track morphological changes as a function of thermal aging. Interestingly, our results show that the rheological properties of the latex films are highly sensitive to morphology, and linear shear rheology is used to understand morphological changes. Overall, these results highlight the importance of bulk rheology as a simple and effective tool for understanding changes in morphology in multicomponent latex films.

PIEZO1 and the mechanism of the long circulatory longevity of human red blood cells.

Human red blood cells (RBCs) have a circulatory lifespan of about four months. Under constant oxidative and mechanical stress, but devoid of organelles and deprived of biosynthetic capacity for protein renewal, RBCs undergo substantial homeostatic changes, progressive densification followed by late density reversal among others, changes assumed to have been harnessed by evolution to sustain the rheological competence of the RBCs for as long as possible. The unknown mechanisms by which this is achieved are the subject of this investigation. Each RBC traverses capillaries between 1000 and 2000 times per day, roughly one transit per minute. A dedicated Lifespan model of RBC homeostasis was developed as an extension of the RCM introduced in the previous paper to explore the cumulative patterns predicted for repetitive capillary transits over a standardized lifespan period of 120 days, using experimental data to constrain the range of acceptable model outcomes. Capillary transits were simulated by periods of elevated cell/medium volume ratios and by transient deformation-induced permeability changes attributed to PIEZO1 channel mediation as outlined in the previous paper. The first unexpected finding was that quantal density changes generated during single capillary transits cease accumulating after a few days and cannot account for the observed progressive densification of RBCs on their own, thus ruling out the quantal hypothesis. The second unexpected finding was that the documented patterns of RBC densification and late reversal could only be emulated by the implementation of a strict time-course of decay in the activities of the calcium and Na/K pumps, suggestive of a selective mechanism enabling the extended longevity of RBCs. The densification pattern over most of the circulatory lifespan was determined by calcium pump decay whereas late density reversal was shaped by the pattern of Na/K pump decay. A third finding was that both quantal changes and pump-decay regimes were necessary to account for the documented lifespan pattern, neither sufficient on their own. A fourth new finding revealed that RBCs exposed to levels of PIEZO1-medited calcium permeation above certain thresholds in the circulation could develop a pattern of early or late hyperdense collapse followed by delayed density reversal. When tested over much reduced lifespan periods the results reproduced the known circulatory fate of irreversible sickle cells, the cell subpopulation responsible for vaso-occlusion and for most of the clinical manifestations of sickle cell disease. Analysis of the results provided an insightful new understanding of the mechanisms driving the changes in RBC homeostasis during circulatory aging in health and disease.

Up-down biphasic volume response of human red blood cells to PIEZO1 activation during capillary transits.

In this paper we apply a novel JAVA version of a model on the homeostasis of human red blood cells (RBCs) to investigate the changes RBCs experience during single capillary transits. In the companion paper we apply a model extension to investigate the changes in RBC homeostasis over the approximately 200000 capillary transits during the ~120 days lifespan of the cells. These are topics inaccessible to direct experimentation but rendered mature for a computational modelling approach by the large body of recent and early experimental results which robustly constrain the range of parameter values and model outcomes, offering a unique opportunity for an in depth study of the mechanisms involved. Capillary transit times vary between 0.5 and 1.5s during which the red blood cells squeeze and deform in the capillary stream transiently opening stress-gated PIEZO1 channels allowing ion gradient dissipation and creating minuscule quantal changes in RBC ion contents and volume. Widely accepted views, based on the effects of experimental shear stress on human RBCs, suggested that quantal changes generated during capillary transits add up over time to develop the documented changes in RBC density and composition during their long circulatory lifespan, the quantal hypothesis. Applying the new red cell model (RCM) we investigated here the changes in homeostatic variables that may be expected during single capillary transits resulting from transient PIEZO1 channel activation. The predicted quantal volume changes were infinitesimal in magnitude, biphasic in nature, and essentially irreversible within inter-transit periods. A sub-second transient PIEZO1 activation triggered a sharp swelling peak followed by a much slower recovery period towards lower-than-baseline volumes. The peak response was caused by net CaCl2 and fluid gain via PIEZO1 channels driven by the steep electrochemical inward Ca2+ gradient. The ensuing dehydration followed a complex time-course with sequential, but partially overlapping contributions by KCl loss via Ca2+-activated Gardos channels, restorative Ca2+ extrusion by the plasma membrane calcium pump, and chloride efflux by the Jacobs-Steward mechanism. The change in relative cell volume predicted for single capillary transits was around 10-5, an infinitesimal volume change incompatible with a functional role in capillary flow. The biphasic response predicted by the RCM appears to conform to the quantal hypothesis, but whether its cumulative effects could account for the documented changes in density during RBC senescence required an investigation of the effects of myriad transits over the full four months circulatory lifespan of the cells, the subject of the next paper.