Black Women's Perspectives on Breast Cancer Risk Assessment.

PURPOSE: The aim of this study was to gather the perspectives of Black women on breast cancer risk assessment through a series of one-on-one interviews. METHODS: The authors conducted a cross-sectional qualitative study consisting of one-on-one semistructured telephone interviews with Black women in Tennessee between September 2020 and November 2020. Guided by the Health Belief Model, qualitative analysis of interview data was performed in an iterative inductive and deductive approach and resulted in the development of a conceptual framework to depict influences on a woman's decision to engage with breast cancer risk assessment. RESULTS: A total of 37 interviews were completed, and a framework of influences on a woman's decision to engage in breast cancer risk assessment was developed. Study participants identified several emerging themes regarding women's perspectives on breast cancer risk assessment and potential influences on women's decisions to engage with risk assessment. Much of women's decision context was based on risk appraisal (perceived severity of cancer and susceptibility of cancer), emotions (fear and trust), and perceived risks and benefits of having risk assessment. The decision was further influenced by modifiers such as communication, the risk assessment protocol, access to health care, knowledge, and health status. Perceived challenges to follow-up if identified as high risk also influenced women's decisions to pursue risk assessment. CONCLUSIONS: Black women in this study identified several barriers to engagement with breast cancer risk assessment. Efforts to overcome these barriers and increase the use of breast cancer risk assessment can potentially serve as a catalyst to address existing breast cancer disparities. Continued work is needed to develop patient-centric strategies to overcome identified barriers.

Barriers to Implementation of Breast Cancer Risk Assessment: The Health Care Team Perspective.

PURPOSE: To assess health care professionals' perceptions of barriers to the utilization of breast cancer risk assessment tools in the public health setting through a series of one-on-one interviews with health care team members. METHODS: We conducted a cross-sectional qualitative study consisting of one-on-one semistructured telephone interviews with health care team members in the public health setting in the state of Tennessee between May 2020 and October 2020. An iterative inductive-deductive approach was used for qualitative analysis of interview data, resulting in the development of a conceptual framework to depict influences of provider behavior in the utilization of breast cancer risk assessment. RESULTS: A total of 24 interviews were completed, and a framework of influences of provider behavior in the utilization of breast cancer risk assessment was developed. Participants identified barriers to the utilization of breast cancer risk assessment (knowledge and understanding of risk assessment tools, workflow challenges, and availability of personnel); patient-level barriers as perceived by health care team members (psychological, economic, educational, and environmental); and strategies to increase the utilization of breast cancer risk assessment at the provider level (leadership buy-in, training, supportive policies, and incentives) and patient level (improved communication and better understanding of patients' perceived cancer risk and severity of cancer). CONCLUSIONS: Understanding barriers to implementation of breast cancer risk assessment and strategies to overcome these barriers as perceived by health care team members offers an opportunity to improve implementation of risk assessment and to identify a racially, geographically, and socioeconomically diverse population of young women at high risk for breast cancer.

Functional maturation of kidney organoid tubules: PIEZO1-mediated Ca2+ signaling.

Kidney organoids cultured on adherent matrices in the presence of superfusate flow generate vascular networks and exhibit more mature podocyte and tubular compartments compared with static controls (Homan KA, Gupta N, Kroll KT, Kolesky DB, Skylar-Scott M, Miyoshi T, Mau D, Valerius MT, Ferrante T, Bonventre JV, Lewis JA, Morizane R. Nat Methods 16: 255-262, 2019; Takasato M, Er PX, Chiu HS, Maier B, Baillie GJ, Ferguson C, Parton RG, Wolvetang EJ, Roost MS, Chuva de Sousa Lopes SM, Little MH. Nature 526: 564-568, 2015.). However, their physiological function has yet to be systematically investigated. Here, we measured mechano-induced changes in intracellular Ca2+ concentration ([Ca2+]i) in tubules isolated from organoids cultured for 21-64 days, microperfused in vitro or affixed to the base of a specimen chamber, and loaded with fura-2 to measure [Ca2+]i. A rapid >2.5-fold increase in [Ca2+]i from a baseline of 195.0 ± 22.1 nM (n = 9; P ≤ 0.001) was observed when microperfused tubules from organoids >40 days in culture were subjected to luminal flow. In contrast, no response was detected in tubules isolated from organoids <30 days in culture. Nonperfused tubules (41 days) subjected to a 10-fold increase in bath flow rate also exhibited a threefold increase in [Ca2+]i from baseline (P < 0.001). Mechanosensitive PIEZO1 channels contribute to the flow-induced [Ca2+]i response in mouse distal tubule (Carrisoza-Gaytan R, Dalghi MG, Apodaca GL, Kleyman TR, Satlin LM. The FASEB J 33: 824.25, 2019.). Immunodetectable apical and basolateral PIEZO1 was identified in tubular structures by 21 days in culture. Basolateral PIEZO1 appeared to be functional as basolateral exposure of nonperfused tubules to the PIEZO1 activator Yoda 1 increased [Ca2+]i (P ≤ 0.001) in segments from organoids cultured for >30 days, with peak [Ca2+]i increasing with advancing days in culture. These results are consistent with a maturational increase in number and/or activity of flow/stretch-sensitive Ca2+ channels, including PIEZO1, in tubules of static organoids in culture.

Using the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) to study adaptations in lung cancer screening delivery in the Veterans Health Administration: a cohort study.

BACKGROUND: Lung cancer screening is a complex clinical process that includes identification of eligible individuals, shared decision-making, tobacco cessation, and management of screening results. Adaptations to the delivery process for lung cancer screening in situ are understudied and underreported, with the potential loss of important considerations for improved implementation. The Framework for Reporting Adaptations and Modifications-Expanded (FRAME) allows for a systematic enumeration of adaptations to implementation of evidence-based practices. We applied FRAME to study adaptations in lung cancer screening delivery processes implemented by lung cancer screening programs in a Veterans Health Administration (VHA) Enterprise-Wide Initiative. METHODS: We prospectively conducted semi-structured interviews at baseline and 1-year intervals with lung cancer screening program navigators at 10 Veterans Affairs Medical Centers (VAMCs) between 2019 and 2021. Using this data, we developed baseline (1st) process maps for each program. In subsequent years (year 1 and year 2), each program navigator reviewed the process maps. Adaptations in screening processes were identified, documented, and mapped to FRAME categories. RESULTS: We conducted a total of 16 interviews across 10 VHA lung cancer screening programs (n=6 in year 1, n=10 in year 2) to collect adaptations. In year 1 (2020), six programs were operational and eligible. Of these, three reported adaptations to their screening process that were planned or in response to COVID-19. In year 2 (2021), all 10 programs were operational and eligible. Programs reported 14 adaptations in year 2. These adaptations were planned and unplanned and often triggered by increased workload; 57% of year 2 adaptations were related to the identification and eligibility of Veterans and 43% were related to follow-up with Veterans for screening results. Throughout the 2 years, adaptations related to data management and patient tracking occurred in 60% of programs to improve the data collection and tracking of Veterans in the screening process. CONCLUSIONS: Using FRAME, we found that adaptations occurred primarily in the areas of patient identification and communication of results due to increased workload. These findings highlight navigator time and resource considerations for sustainability and scalability of existing and future lung cancer screening programs as well as potential areas for future intervention.

Embedded 3D Printing of Architected Ceramics via Microwave-Activated Polymerization.

Light- and ink-based 3D printing methods have vastly expanded the design space and geometric complexity of architected ceramics. However, light-based methods are typically confined to a relatively narrow range of preceramic and particle-laden resins, while ink-based methods are limited in geometric complexity due to layerwise assembly. Here, embedded 3D printing is combined with microwave-activated curing to generate architected ceramics with spatially controlled composition in freeform shapes. Aqueous colloidal inks are printed within a support matrix, rapidly cured via microwave-activated polymerization, and subsequently dried and sintered into dense architectures composed of one or more oxide materials. This integrated manufacturing method opens new avenues for the design and fabrication of complex ceramic architectures with programmed composition, density, and form for myriad applications.

Rotational multimaterial printing of filaments with subvoxel control.

Helical structures are ubiquitous in nature and impart unique mechanical properties and multifunctionality1. So far, synthetic architectures that mimic these natural systems have been fabricated by winding, twisting and braiding of individual filaments1-7, microfluidics8,9, self-shaping1,10-13 and printing methods14-17. However, those fabrication methods are unable to simultaneously create and pattern multimaterial, helically architected filaments with subvoxel control in arbitrary two-dimensional (2D) and three-dimensional (3D) motifs from a broad range of materials. Towards this goal, both multimaterial18-23 and rotational24 3D printing of architected filaments have recently been reported; however, the integration of these two capabilities has yet to be realized. Here we report a rotational multimaterial 3D printing (RM-3DP) platform that enables subvoxel control over the local orientation of azimuthally heterogeneous architected filaments. By continuously rotating a multimaterial nozzle with a controlled ratio of angular-to-translational velocity, we have created helical filaments with programmable helix angle, layer thickness and interfacial area between several materials within a given cylindrical voxel. Using this integrated method, we have fabricated functional artificial muscles composed of helical dielectric elastomer actuators with high fidelity and individually addressable conductive helical channels embedded within a dielectric elastomer matrix. We have also fabricated hierarchical lattices comprising architected helical struts containing stiff springs within a compliant matrix. Our additive-manufacturing platform opens new avenues to generating multifunctional architected matter in bioinspired motifs.

Goal setting, goal attainment and quality of life of children following selective dorsal rhizotomy.

AIM: The aim of this study is to describe the individualized occupational performance issues identified by parents/carers and children prior to selective dorsal rhizotomy (SDR) surgery and analyse change up to 2 years post surgery in goal attainment and quality of life (QoL). METHOD: The Australian SDR Research Registry (trial registration: ACTRN12618000985280) was used to extract data for individualized goals, goal attainment and QoL based on the Canadian Occupational Performance Measure (COPM) and the Cerebral Palsy Quality of Life Questionnaire for Children (CP QOL-Child parent-proxy) at baseline and 1 and 2 years following SDR. Change in mean scores was analysed using linear mixed models. RESULTS: Fifty-two children had COPM scores at baseline and 1 and/or 2 years post, of which 28 had two QoL scores. COPM problem areas included leisure (n = 39), productivity (n = 37) and self-care (n = 173). The most common goals were walking (26.1%), participation in physical activities (17.7%) and transitions (14.1%). Mean COPM scores improved significantly between baseline to 1 year and baseline to 2 years (P < 0.001). Mean QoL scores improved between baseline to 1 year for functional QoL domains: participation and physical health (P = 0.003) and pain and impact of disability (P = 0.011). CONCLUSIONS: Collaborative goal setting is an integral part of family-centred rehabilitation practice. The COPM was an appropriate individualized outcome measure in identifying meaningful goals for our SDR cohort. Results demonstrate improved scores in goal attainment and improvement in functional QoL domains. This paper highlights the need to include outcomes that measure daily life experiences.

Embedded 3D printing of multimaterial polymer lattices via graph-based print path planning.

Recent advances in computational design and 3D printing enable fabrication of polymer lattices with high strength-to-weight ratio and tailored mechanics. To date, 3D lattices composed of monolithic materials have primarily been constructed due to limitations associated with most commercial 3D printing platforms. Here, we demonstrate freeform fabrication of multi-material polymer lattices via embedded three-dimensional (EMB3D) printing. We first developed an algorithm that generates print paths for each target lattice based on graph theory. We then investigated the effects of ink rheology on filamentary printing and effects of the print path on resultant mechanical properties. By co-printing multiple materials with different mechanical properties, a broad range of periodic and stochastic lattices with tailored mechanical responses can be realized opening new avenues for constructing architected matter. This article is protected by copyright. All rights reserved.

Organoid-on-a-chip model of human ARPKD reveals mechanosensing pathomechanisms for drug discovery.

Organoids serve as a novel tool for disease modeling in three-dimensional multicellular contexts. Static organoids, however, lack the requisite biophysical microenvironment such as fluid flow, limiting their ability to faithfully recapitulate disease pathology. Here, we unite organoids with organ-on-a-chip technology to unravel disease pathology and develop therapies for autosomal recessive polycystic kidney disease. PKHD1-mutant organoids-on-a-chip are subjected to flow that induces clinically relevant phenotypes of distal nephron dilatation. Transcriptomics discover 229 signal pathways that are not identified by static models. Mechanosensing molecules, RAC1 and FOS, are identified as potential therapeutic targets and validated by patient kidney samples. On the basis of this insight, we tested two U.S. Food and Drug Administration-approved and one investigational new drugs that target RAC1 and FOS in our organoid-on-a-chip model, which suppressed cyst formation. Our observations highlight the vast potential of organoid-on-a-chip models to elucidate complex disease mechanisms for therapeutic testing and discovery.

3D proximal tubule-on-chip model derived from kidney organoids with improved drug uptake.

Three-dimensional, organ-on-chip models that recapitulate kidney tissue are needed for drug screening and disease modeling. Here, we report a method for creating a perfusable 3D proximal tubule model composed of epithelial cells isolated from kidney organoids matured under static conditions. These organoid-derived proximal tubule epithelial cells (OPTECs) are seeded in cylindrical channels fully embedded within an extracellular matrix, where they form a confluent monolayer. A second perfusable channel is placed adjacent to each proximal tubule within these reusable multiplexed chips to mimic basolateral drug transport and uptake. Our 3D OPTEC-on-chip model exhibits significant upregulation of organic cation (OCT2) and organic anion (OAT1/3) transporters, which leads to improved drug uptake, compared to control chips based on immortalized proximal tubule epithelial cells. Hence, OPTEC tubules exhibit a higher normalized lactate dehydrogenase (LDH) release, when exposed to known nephrotoxins, cisplatin and aristolochic acid, which are diminished upon adding OCT2 and OAT1/3 transport inhibitors. Our integrated multifluidic platform paves the way for personalized kidney-on-chip models for drug screening and disease modeling.

Using the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) to study lung cancer screening adaptations in the Veterans Health Administration.

Background: Lung cancer screening includes identification of eligible individuals, shared decision-making inclusive of tobacco cessation, and management of screening results. Adaptations to the implemented processes for lung cancer screening in situ are understudied and underreported, with potential loss of important considerations for improved implementation. The Framework for Reporting Adaptations and Modifications-Expanded (FRAME) allows for systematic enumeration of adaptations to implementations of evidence-based practices. We used FRAME to study adaptations in lung cancer screening processes that were implemented as part of a Veterans Health Administration (VHA) Enterprise-Wide Initiative. Methods: We conducted semi-structured interviews at baseline and 1-year intervals with lung cancer screening program navigators at 10 Veterans Affairs Medical Centers (VAMC) between 2019-2021. Using this data, we developed baseline (1st) process maps for each program. In subsequent years (year 1 and year 2), each program navigator reviewed the process maps. Adaptations in screening processes were identified, recorded and mapped to FRAME categories. Results: A total of 14 program navigators across 10 VHA lung cancer screening programs participated in 20 interviews. In year 1 (2019-2020), seven programs were operational and of these, three reported adaptations to their screening process that were either planned and in response to COVID-19. In year 2 (2020-2021), all 10 programs were operational. Programs reported 14 adaptations in year 2. These adaptations were both planned and unplanned and often triggered by increased workload; 57% of year 2 adaptations were related to identification and eligibility of Veterans and 43% were related to follow-up with Veterans for screening results. Throughout the 2 years, adaptations related to data management and patient tracking occurred in 6 of 10 programs to improve the data collection and tracking of Veterans in the screening process. Conclusions: Using FRAME, we found that adaptations occurred throughout the lung cancer screening process but primarily in the areas of patient identification and communication of results. These findings highlight considerations for lung cancer screening implementation and potential areas for future intervention.

Programmed shape-morphing into complex target shapes using architected dielectric elastomer actuators.

Dielectric elastomer actuators (DEAs) are among the fastest and most energy-efficient, shape-morphing materials. To date, their shapes have been controlled using patterned electrodes or stiffening elements. While their actuated shapes can be analyzed for prescribed configurations of electrodes or stiffening elements (the forward problem), the design of DEAs that morph into target shapes (the inverse problem) has not been fully addressed. Here, we report a simple analytical solution for the inverse design and fabrication of programmable shape-morphing DEAs. To realize the target shape, two mechanisms are combined to locally control the actuation magnitude and direction by patterning the number of local active layers and stiff rings of varying shapes, respectively. Our combined design and fabrication strategy enables the creation of complex DEA architectures that shape-morph into simple target shapes, for instance, those with zero, positive, and negative Gaussian curvatures as well as complex shapes, such as a face.

Kidney organoids: a pioneering model for kidney diseases.

The kidney is a vital organ that regulates the bodily fluid and electrolyte homeostasis via tailored urinary excretion. Kidney injuries that cause severe or progressive chronic kidney disease have driven the growing population of patients with end-stage kidney disease, leading to substantial patient morbidity and mortality. This irreversible kidney damage has also created a huge socioeconomical burden on the healthcare system, highlighting the need for novel translational research models for progressive kidney diseases. Conventional research methods such as in vitro 2D cell culture or animal models do not fully recapitulate complex human kidney diseases. By contrast, directed differentiation of human induced pluripotent stem cells enables in vitro generation of patient-specific 3D kidney organoids, which can be used to model acute or chronic forms of hereditary, developmental, and metabolic kidney diseases. Furthermore, when combined with biofabrication techniques, organoids can be used as building blocks to construct vascularized kidney tissues mimicking their in vivo counterpart. By applying gene editing technology, organoid building blocks may be modified to minimize the process of immune rejection in kidney transplant recipients. In the foreseeable future, the universal kidney organoids derived from HLA-edited/deleted induced pluripotent stem cell (iPSC) lines may enable the supply of bioengineered organotypic kidney structures that are immune-compatible for the majority of the world population. Here, we summarize recent advances in kidney organoid research coupled with novel technologies such as organoids-on-chip and biofabrication of 3D kidney tissues providing convenient platforms for high-throughput drug screening, disease modelling, and therapeutic applications.

Biomanufacturing human tissues via organ building blocks.

The construction of human organs on demand remains a tantalizing vision to solve the organ donor shortage. Yet, engineering tissues that recapitulate the cellular and architectural complexity of native organs is a grand challenge. The use of organ building blocks (OBBs) composed of multicellular spheroids, organoids, and assembloids offers an important pathway for creating organ-specific tissues with the desired cellular-to-tissue-level organization. Here, we review the differentiation, maturation, and 3D assembly of OBBs into functional human tissues and, ultimately, organs for therapeutic repair and replacement. We also highlight future challenges and areas of opportunity for this nascent field.

Programming Cellular Alignment in Engineered Cardiac Tissue via Bioprinting Anisotropic Organ Building Blocks.

The ability to replicate the 3D myocardial architecture found in human hearts is a grand challenge. Here, the fabrication of aligned cardiac tissues via bioprinting anisotropic organ building blocks (aOBBs) composed of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is reported. A bioink composed of contractile cardiac aOBBs is first generated and aligned cardiac tissue sheets with linear, spiral, and chevron features are printed. Next, aligned cardiac macrofilaments are printed, whose contractile force and conduction velocity increase over time and exceed the performance of spheroid-based cardiac tissues. Finally, the ability to spatially control the magnitude and direction of contractile force by printing cardiac sheets with different aOBB alignment is highlighted. This research opens new avenues to generating functional cardiac tissue with high cell density and complex cellular alignment.

The Association of Health Care System Resources With Lung Cancer Screening Implementation: A Cohort Study.

BACKGROUND: The Veterans Health Administration issued policy for lung cancer screening resources at eight Veterans Affairs Medical Centers (VAMCs) in a demonstration project (DP) from 2013 through 2015. RESEARCH QUESTION: Do policies that provide resources increase lung cancer screening rates? STUDY DESIGN AND METHODS: Data from eight DP VAMCs (DP group) and 20 comparable VAMCs (comparison group) were divided into before DP (January 2011-June 2013), DP (July 2013-June 2015), and after DP (July 2015-December 2018) periods. Coprimary outcomes were unique veterans screened per 1,000 eligible per month and those with 1-year (9-15 months) follow-up screening. Eligible veterans were estimated using yearly counts and the percentage of those with eligible smoking histories. Controlled interrupted time series and difference-in-differences analyses were performed. RESULTS: Of 27,746 veterans screened, the median age was 66.5 years and most were White (77.7%), male (95.6%), and urban dwelling (67.3%). During the DP, the average rate of unique veterans screened at DP VAMCs was 17.7 per 1,000 eligible per month, compared with 0.3 at comparison VAMCs. Adjusted analyses found a higher rate increase at DP VAMCs by 0.93 screening per 1,000 eligible per month (95% CI, 0.25-1.61) during this time, with an average facility-level difference of 17.4 screenings per 1,000 eligible per month (95% CI, 12.6-22.3). Veterans with 1-year follow-up screening also increased more rapidly at DP VAMCs during the DP, by 0.39 screening per 1,000 eligible per month (95% CI, 0.18-0.60), for an average facility-level difference of 7.2 more screenings per 1,000 eligible per month (95% CI, 5.2-9.2). Gains were not maintained after the DP. INTERPRETATION: In this cohort, provision of resources for lung cancer screening implementation was associated with an increase in veterans screened and those with 1-year follow-up screening. Screening gains associated with the DP were not maintained.

Biomimetic and Biologically Compliant Soft Architectures via 3D and 4D Assembly Methods: A Perspective.

Recent progress in soft material chemistry and enabling methods of 3D and 4D fabrication-emerging programmable material designs and associated assembly methods for the construction of complex functional structures-is highlighted. The underlying advances in this science allow the creation of soft material architectures with properties and shapes that programmably vary with time. The ability to control composition from the molecular to the macroscale is highlighted-most notably through examples that focus on biomimetic and biologically compliant soft materials. Such advances, when coupled with the ability to program material structure and properties across multiple scales via microfabrication, 3D printing, or other assembly techniques, give rise to responsive (4D) architectures. The challenges and prospects for progress in this emerging field in terms of its capacities for integrating chemistry, form, and function are described in the context of exemplary soft material systems demonstrating important but heretofore difficult-to-realize biomimetic and biologically compliant behaviors.

Orthogonally induced differentiation of stem cells for the programmatic patterning of vascularized organoids and bioprinted tissues.

The generation of organoids and tissues with programmable cellular complexity, architecture and function would benefit from the simultaneous differentiation of human induced pluripotent stem cells (hiPSCs) into divergent cell types. Yet differentiation protocols for the overexpression of specific transcription factors typically produce a single cell type. Here we show that patterned organoids and bioprinted tissues with controlled composition and organization can be generated by simultaneously co-differentiating hiPSCs into distinct cell types via the forced overexpression of transcription factors, independently of culture-media composition. Specifically, we used such orthogonally induced differentiation to generate endothelial cells and neurons from hiPSCs in a one-pot system containing either neural or endothelial stem-cell-specifying media, and to produce vascularized and patterned cortical organoids within days by aggregating inducible-transcription-factor and wild-type hiPSCs into randomly pooled or multicore-shell embryoid bodies. Moreover, by leveraging multimaterial bioprinting of hiPSC inks without extracellular matrix, we generated patterned neural tissues with layered regions composed of neural stem cells, endothelium and neurons. Orthogonally induced differentiation of stem cells may facilitate the fabrication of engineered tissues for biomedical applications.

Towards enduring autonomous robots via embodied energy.

Autonomous robots comprise actuation, energy, sensory and control systems built from materials and structures that are not necessarily designed and integrated for multifunctionality. Yet, animals and other organisms that robots strive to emulate contain highly sophisticated and interconnected systems at all organizational levels, which allow multiple functions to be performed simultaneously. Herein, we examine how system integration and multifunctionality in nature inspires a new paradigm for autonomous robots that we call Embodied Energy. Whereas most untethered robots use batteries to store energy and power their operation, recent advancements in energy-storage techniques enable chemical or electrical energy sources to be embodied directly within the structures and materials used to create robots, rather than requiring separate battery packs. This perspective highlights emerging examples of Embodied Energy in the context of developing autonomous robots.