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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 2+]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.

Although the phloem is a highly specialized tissue, certain pathogens, including phytoplasmas, spiroplasmas, and viruses, have evolved to access and live in this sequestered and protected environment, causing substantial economic harm. In particular, Candidatus Liberibacter spp. are devastating citrus in many parts of the world. Given that most phloem pathogens are vectored, they are not exposed to applied chemicals and are therefore difficult to control. Furthermore, pathogens use the phloem network to escape mounted defenses. Our review summarizes the current knowledge of phloem anatomy, physiology, and biochemistry relevant to phloem/pathogen interactions. We focus on aspects of anatomy specific to pathogen movement, including sieve plate structure and phloem-specific proteins. Phloem sampling techniques are discussed. Finally, pathogens that cause particular harm to the phloem of crop species are considered in detail.

Organic chemistry is one of the most feared and failed courses due to its complex and fast-paced nature. Investigating affective metrics that relate to achievement in these courses can be worthwhile, particularly when these metrics show predictive relationships to achievement. Attitude toward chemistry has been investigated utilizing a variety of instruments. We present herein an instrument related to the well-established Attitude toward the Subject of Chemistry Inventory (ASCIv2). This new instrument was developed utilizing The Standards of Psychological and Educational Measurement, which describe five aspects of validity evidence that should be gathered when using instruments in research. Content validity was gathered through consultation with experts. Response process validity was gathered through student interviews. Internal structural validity was collected through confirmatory factor analysis. Relations to other variables were investigated through correlation analysis and structural equation modeling. Consequential validity was studied through measurement invariance testing before comparing scores for subgroups (high- and low-achieving students). Additionally, reliability evidence was tested with Omega coefficients for each of the factors. We showed that all tests and analyses were done with high rigor, and that this new instrument, ASCI-UE, measuring utility and e motional satisfaction, can provide interesting results and implications for research and practice.

Implantable tubes, shunts, and other medical conduits are crucial for treating a wide range of conditions from ears and eyes to brain and liver but often impose serious risks of device infection, obstruction, migration, unreliable function, and tissue damage. Efforts to alleviate these complications remain at an impasse because of fundamentally conflicting design requirements: Millimeter-scale size is required to minimize invasiveness but exacerbates occlusion and malfunction. Here, we present a rational design strategy that reconciles these trade-offs in an implantable tube that is even smaller than the current standard of care. Using tympanostomy tubes (ear tubes) as an exemplary case, we developed an iterative screening algorithm and show how unique curved lumen geometries of the liquid-infused conduit can be designed to co-optimize drug delivery, effusion drainage, water resistance, and biocontamination/ingrowth prevention in a single subcapillary–length-scale device. Through extensive in vitro studies, we demonstrate that the engineered tubes enabled selective uni- and bidirectional fluid transport; nearly eliminated adhesion and growth of common pathogenic bacteria, blood, and cells; and prevented tissue ingrowth. The engineered tubes also enabled complete eardrum healing and hearing preservation and exhibited more efficient and rapid antibiotic delivery to the middle ear in healthy chinchillas compared with current tympanostomy tubes, without resulting in ototoxicity at up to 24 weeks. The design principle and optimization algorithm presented here may enable tubes to be customized for a wide range of patient needs.

Expression studies have consistently identified tumor protein D52 (TPD52) overexpression in tumor cells. Murine TPD52 (mD52) shares 86% identity with the human orthologue. To study a possible role for TPD52 in transformation, 3T3 fibroblasts were transfected with the full-length cDNA for mD52. Expression of mD52 was confirmed by reverse transcription-PCR (RT-PCR), real-time PCR, and Western blot analysis compared with 3T3 and vector-transfected 3T3 (3T3.V), and the resultant cell line was designated 3T3.mD52. At 4 weeks, 3T3.mD52 gained a 2-fold increase in growth rate, lost contact inhibition, and exhibited a marked phenotype change. Further characterization revealed an acquired ability for anchorage-independent cell growth. To determine whether 3T3.mD52 had become tumorigenic, naïve, healthy, immunocompetent syngeneic mice were inoculated subcutaneously with varying cell doses. Tumors measuring >1 cm2 were detected 60 days postinoculation with 3T3.mD52, and a 50% subcutaneous tumor incidence was obtained with as few as 5 × 105 3T3.mD52 cells. Remarkably, when lungs from 3T3.mD52 tumor-bearing mice were analyzed, numerous tumor nodules were observed, ranging from nodules less than 10 to nodules too numerous to count (inoculation with 1 × 105 and 5 × 106 cells, respectively). Further support for the metastatic capacity of 3T3.mD52 was the demonstration that transforming growth factor (TGF)-βR1 (receptor) expression decreased and TGF-β1 secretion increased in 3T3.mD52 compared with 3T3 controls. cDNA microarray analysis showed a gene expression pattern that further supported mD52-induced transformation and metastasis. Together, these data suggest that mD52 expression in 3T3 cells initiated cellular transformation, tumorigenesis, and progression to metastasis. (Mol Cancer Res 2007;5(2):133–44)

Supplementary Data from Induction of Tumorigenesis and Metastasis by the Murine Orthologue of Tumor Protein D52

Background: Low-dose computed tomography (LDCT) screening reduces lung cancer–specific and overall mortality. We sought to assess lung cancer screening practices and attitudes among primary care providers (PCPs) in the era of new LDCT screening guidelines.Methods: In 2013, we surveyed PCPs at an academic medical center (60% response) and assessed: lung cancer screening use, perceived screening effectiveness, knowledge of screening guidelines, perceived barriers to LDCT use, and interest in LDCT screening education.Results: Few PCPs (n = 212) reported ordering lung cancer screening: chest X-ray (21%), LDCT (12%), and sputum cytology (3%). Only 47% of providers knew three or more of six guideline components for LDCT screening; 24% did not know any guideline components. In multiple logistic regression analysis, providers who knew three or more guideline components were more likely to order LDCT (OR, 7.1; 95% confidence intervals, 2.0–25.6). Many providers (30%) were unsure of the effectiveness of LDCT. Mammography, colonoscopy, and Pap smear were rated more frequently as effective in reducing cancer mortality compared with LDCT (all P values < 0.0001). Common perceived barriers included patient cost (86.9% major or minor barrier), harm from false positives (82.7%), patients' lack of awareness (81.3%), risk of incidental findings (81.3%), and insurance coverage (80.1%).Conclusions: LDCT lung cancer screening is currently an uncommon practice at an academic medical center. PCPs report ordering chest X-ray, a nonrecommended screening test, more often than LDCT. PCPs had a limited understanding of lung cancer screening guidelines and LDCT effectiveness. Provider educational interventions are needed to facilitate shared decision-making with patients.Impact: This study describes some of the first data available about PCPs' use of lung cancer screening tests since the publication of multiple professional guidelines endorsing LDCT. Knowledge gaps were identified that may hinder the uptake of evidence-based lung cancer screening guidelines. Cancer Epidemiol Biomarkers Prev; 24(4); 664–70. ©2015 AACR.

Supplementary Table 1. Items Assessing Lung Cancer Screening Guideline Knowledge

Society faces emerging challenges that require re-envisioning what it means to know and use science, technology, engineering, and mathematics (STEM) and who are STEM scientists. We advocate for a transdisciplinary framework for participatory STEM learning based on the culmination of the authors’ designing and complemented by reviews of extant works in youth STEM learning and engagement. Data literacy, geospatial reasoning, and community science are cornerstones in our framework because of their power to leverage and integrate the four STEM disciplines. Youth with their families are authors and designers in community problem-solving using data literacy and geospatial reasoning through participatory community science to question, analyze, and design solutions empowered by their lived experiences. Through partnerships with community organizations, families, youth, and STEM practitioners, we discuss how to develop and use tools and methods to design and build better spaces for youths’ communities. Our aim is for more authentic, inclusive, and empowering learning opportunities that broaden youths’ STEM participation. We describe our framework and the underlying commitments, design principles, expected outcomes, and limitations.

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.

Abstract Instructional reform in STEM aims for the widespread adoption of evidence based instructional practices (EBIPS), practices that implement active learning. Research recognizes that faculty social networks regarding discussion or advice about teaching may matter to such efforts. But teaching is not the only priority for university faculty – meeting research expectations is at least as important and, often, more consequential for tenure and promotion decisions. We see value in understanding how research networks, based on discussion and advice about research matters, relate to teaching networks to see if and how such networks could advance instructional reform efforts. Our research examines data from three departments (biology, chemistry, and geosciences) at three universities that had recently received funding to enhance adoption of EBIPs in STEM fields. We evaluate exponential random graph models of the teaching network and find that (a) the existence of a research tie from one faculty member $$i$$ i to another $$j$$ j enhances the prospects of a teaching tie from $$i$$ i to $$j$$ j , but (b) even though faculty highly placed in the teaching network are more likely to be extensive EBIP users, faculty highly placed in the research network are not, dimming prospects for leveraging research networks to advance STEM instructional reforms.

Motivation helps drive students to success in general chemistry, and active learning environments with social interactions has consistently shown to improve motivation. However, analyzing student outcomes in an interactive environment is best done by considering students not as isolated units but as working together and influencing each other. Therefore, we used social network analysis with self-determination theory as a framework for understanding motivation and social comparison theory as a framework for understanding how students influence each other. When analyzing an undergraduate general chemistry course that has incorporated peer-led team learning using data from the Learning Climate Questionnaire and Intrinsic Motivation Inventory, a series of progressively sophisticated statistical models with data gathered from 270 students shows that perceived competence and relatedness predict student interest in the activities with their peer-led sessions. However, we also found evidence that students tend to become polarized in their interest toward peer-led team learning activities, which is one possible outcome of social comparisons with their peers. In addition to these findings, this project demonstrates how social network analysis can expand how chemistry education researchers consider relational data and the effects of non-independent data on statistical analysis.

Instructors make assessment decisions based on their knowledge and experiences. Assessment practice is an essential element of instruction, and the outcomes of assessments have a broad impact on both students and instructors. Efforts to provide strengths-focused, relevant professional development support regarding assessment are enhanced by greater understanding of the complex nature of assessment practices. In this study, the Teacher Assessment Literacy in Practice (TALiP) framework was used to guide our investigation of one biochemistry instructor's assessment literacy, relevant to her integration of a biochemistry threshold concept, the physical basis of interactions (PBI), into her course. Qualitative framework analysis was used to examine classroom artifacts and interview data to reveal that community support and self-reflection influenced the instructor's enactment of specific assessments aligned with her instructional goals. Additionally, the instructor was seen to leverage assets to develop her assessment literacy within a single semester.

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).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.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).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.

Oculomotor target selection often requires discriminating visual features, but it remains unclear how oculomotor substrates encoding saccade vectors functionally contribute to this process. One possibility is that oculomotor vector representations (observed directly as physiological activation or inferred from behavioral interference) of potential targets are continuously reweighted by task relevance computed elsewhere in specialized visual modules, whereas an alternative possibility is that oculomotor modules use local featural analyses to actively discriminate potential targets. Strengthening the former account, oculomotor vector representations have longer onset latencies for ventral- (i.e., color) than dorsal-stream features (i.e., luminance), suggesting that oculomotor vector representations originate from featurally relevant specialized visual modules. Here, we extended this reasoning by behaviorally examining whether the onset latency of saccadic interference elicited by visually complex stimuli is greater than is commonly observed for simple stimuli. We measured human saccade metrics (saccade curvature, endpoint deviations, saccade frequency, and error proportion) as a function of time after abrupt distractor onset. Distractors were novel, visually complex, and had to be discriminated from targets to guide saccades. The earliest saccadic interference latency was ∼110 ms, considerably longer than previous experiments, suggesting that sensory representations projected into the oculomotor system are gated to allow for sufficient featural processing to satisfy task demands. Surprisingly, initial oculomotor vector representations encoded features, as we manipulated the visual similarity between targets and distractors and observed increased vector modulation response magnitude and duration when the distractor was highly similar to the target. Oculomotor vector modulation was gradually extinguished over the time course of the experiment.

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.

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.

BackgroundChange strategies may leverage interpersonal relationships and conversations to spread teaching innovations among science faculty. Knowledge sharing refers to the process by which individuals transfer information and thereby spread innovative ideas within an organization. We use knowledge sharing as a lens for identifying factors that encourage productive teaching-related conversations between individuals, characterizing the context and content of these discussions, and understanding how peer interactions may shape instructional practices. In this study, we interview 19 science faculty using innovative teaching practices about the teaching-focused conversations they have with different discussion partners.ResultsThis qualitative study describes characteristics of the relationship between discussion partners, what they discuss with respect to teaching, the amount of help-seeking that occurs, and the perceived impacts of these conversations on their teaching. We highlight the role of office location and course overlap in bringing faculty together and characterize the range of topics they discuss, such as course delivery and teaching strategies. We note the tendency of faculty to seek out partners with relevant expertise and describe how faculty perceive their discussion partners to influence their instructional practices and personal affect. Finally, we elaborate on how these themes vary depending on the relationship between discussion partners.ConclusionsThe knowledge sharing framework provides a useful lens for investigating how various factors affect faculty conversations around teaching. Building on this framework, our results lead us to propose two hypotheses for how to promote sharing teaching knowledge among faculty, thereby identifying productive directions for further systematic inquiry. In particular, we propose that productive teaching conversations might be cultivated by fostering collaborative teaching partnerships and developing departmental structures to facilitate sharing of teaching expertise. We further suggest that social network theories and other examinations of faculty behavior can be useful approaches for researching the mechanisms that drive teaching reform.

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.

Background Many institutional and departmentally focused change efforts have sought to improve teaching in STEM through the promotion of evidence-based instructional practices (EBIPs). Even with these efforts, EBIPs have not become the predominant mode of teaching in many STEM departments. To better understand institutional change efforts and the barriers to EBIP implementation, we developed the Cooperative Adoption Factors Instrument (CAFI) to probe faculty member characteristics beyond demographic attributes at the individual level. The CAFI probes multiple constructs related to institutional change including perceptions of the degree of mutual advantage of taking an action (strategic complements), trust and interconnectedness among colleagues (interdependence), and institutional attitudes toward teaching (climate). Results From data collected across five STEM fields at three large public research universities, we show that the CAFI has evidence of internal structure validity based on exploratory and confirmatory factor analysis. The scales have low correlations with each other and show significant variation among our sampled universities as demonstrated by ANOVA. We further demonstrate a relationship between the strategic complements and climate factors with EBIP adoption through use of a regression analysis. In addition to these factors, we also find that indegree, a measure of opinion leadership, correlates with EBIP adoption. Conclusions The CAFI uses the CACAO model of change to link the intended outcome of EBIP adoption with perception of EBIPs as mutually reinforcing (strategic complements), perception of faculty having their fates intertwined (interdependence), and perception of institutional readiness for change (climate). Our work has established that the CAFI is sensitive enough to pick up on differences between three relatively similar institutions and captures significant relationships with EBIP adoption. Our results suggest that the CAFI is likely to be a suitable tool to probe institutional change efforts, both for change agents who wish to characterize the local conditions on their respective campuses to support effective planning for a change initiative and for researchers who seek to follow the progression of a change initiative. While these initial findings are very promising, we also recommend that CAFI be administered in different types of institutions to examine the degree to which the observed relationships hold true across contexts.

Background Effective treatment of longstanding Complex Regional Pain Syndrome (CRPS) is a challenge, as causal mechanisms remain elusive. People with CRPS frequently report distorted subjective perceptions of their affected limb. Evidence of pain reduction when the affected limb is visually altered in size suggests that visual illusions used to target central processing could restore coherence of this disrupted limb representation. We hypothesized that using virtual reality that alters hand image to match the patient's desired hand appearance would improve body perception disturbance and pain. Also, repeated exposure would maintain any therapeutic effect. Methods A blinded randomized controlled trial of 45 participants with refractory upper-limb CRPS and body perception disturbance (BPD) viewed a digital image of their affected hand for 1 min. The image was digitally altered according to the patient's description of how they desired their hand to look in the experimental group and unaltered in the control group. BPD and pain were measured pre- and post-intervention. A subgroup was followed up 2 weeks after a course of repeated interventions. Results BPD (mean-6, ±SD 7.9, p = 0.036, effect size [ES] = 0.6) and pain intensity (mean-0.43, ±SD 1.3, p = 0.047, ES = 0.5) reduced in 23 participants after single exposure compared to controls (n = 22). At follow-up, the subgroup (experimental n = 21; control n = 18) showed sustained pain reduction only (p = 0.037, ±SD 1.9, ES = 0.7), with an overall 1.2 decrease on an 11-point scale. Conclusions Visually changing the CRPS hand to a desired appearance modulates BPD and pain suggesting therapeutic potential for those with refractory CRPS. Further research to optimize this therapeutic effect is required. Significance Visual bodily illusions that change the shape and appearance of the painful CRPS hand to that desired by the patient result in a rapid amelioration of pain and body perception disturbance in people with longstanding CRPS. These findings highlight the future potential of this drug-free approach in the treatment of refractory CRPS.

The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium’s plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled—along with validated datasets—into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit—and the knowledge generated by its applications—as a means to accelerate the clinical development of new therapies for a wide range of conditions., This Perspective discusses how the Somatic Cell Genome Editing Consortium aims to accelerate the implementation of safe and effective genome-editing therapies in the clinic.

Background The harm caused by tobacco use is primarily attributable to cigarette smoking. Switching completely to non-combustible products may reduce disease risks in adult cigarette smokers who are unable or unwilling to quit. Before a new tobacco product can enter the market or can be marketed as a modified risk tobacco product, the manufacturer must determine the impact that the product will have on the likelihood of changes in tobacco use behavior among both tobacco users and nonusers. One way to estimate change in tobacco use behavior is to assess tobacco users’ and nonusers’ behavioral intentions toward the product and its marketing, including intentions to try, use, dual use, and switch to the product from cigarettes. The purpose of this study was to develop and validate behavioral intention metrics appropriate for use with current, former, and never adult tobacco users. Methods Preliminary items were subjected to cognitive testing with adult (1) smokers planning to quit cigarettes in the next 30 days, (2) smokers not planning to quit cigarettes in the next 30 days, (3) e-vapor users, (4) former tobacco users, and (5) never tobacco users. Items were iteratively revised based on feedback during cognitive testing, and surviving items were administered to a large sample of adults (N = 2943) representing the aforementioned sub-groups. Rating scale functioning, reliability, validity, bias, and ability to detect change were evaluated. Results Examination of the response category thresholds generated by the Rasch model provided evidence that the rating scales were functioning appropriately. Results revealed good stability and excellent internal consistency and person reliability and provided evidence of unidimensionality and convergent validity. Estimates of reliability and validity were similar across sub-groups. A cross-validation sample generally confirmed findings from the validation sample. No items were discarded due to differential item function. Exploratory analyses provided support for ability to detect change. Conclusions Results from this rigorous, empirical evaluation using large validation and cross-validation samples provide strong support for the psychometric properties of the Intention to Try, Use, Dual Use, and Switch scales with current, former, and never adult tobacco users.

Phytopathogens use secreted effector proteins to suppress host immunity and promote pathogen virulence, and there is increasing evidence that the host-pathogen interactome comprises a complex network. To identify novel interactors of the Pseudomonas syringae effector HopZ1a, we performed a yeast two-hybrid screen that identified a previously uncharacterized Arabidopsis protein that we designate HopZ1a interactor 1 (ZIN1). Additional analyses in yeast and in planta revealed that ZIN1 also interacts with several other P. syringae effectors. We show that an Arabidopsis loss-of-function zin1 mutant is less susceptible to infection by certain strains of P. syringae, while overexpression of ZIN1 results in enhanced susceptibility. Functionally, ZIN1 exhibits topoisomerase-like activity in vitro. Transcriptional profiling of wild-type and zin1 Arabidopsis plants inoculated with P. syringae indicated that while ZIN1 regulates a wide range of pathogen-responsive biological processes, the list of genes more highly expressed in zin1 versus wild-type plants is particularly enriched for ribosomal protein genes. Altogether, these data illuminate ZIN1 as a potential susceptibility hub that interacts with multiple effectors to influence the outcome of plant-microbe interactions. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Hierarchically porous ceramics with a high specific surface area and interconnected porosity may find potential application as particulate filters, catalyst supports, and battery electrodes. We report the design and programmable assembly of cellular ceramic architectures with controlled pore size, volume, and interconnectivity across multiple length scales via direct foam writing. Specifically, binary colloidal gel foams are created that contain entrained bubbles stabilized by the irreversible adsorption of attractive alumina and carbon (porogen) particles at their air-water interfaces. Composition effects on foam ink rheology and printing behavior are investigated. Sintered ceramic foams exhibited specific permeabilities that increased from 2 × 10-13 to 1 × 10-12 m2 and compressive strengths that decreased from 40 to 1 MPa, respectively, with increasing specific interfacial area. Using direct foam writing, 3D ceramic lattices composed of open-cell foam struts were fabricated with tailored mechanical properties and interconnected porosity across multiple length scales.

Pathogens secrete effector proteins into host cells to suppress host immunity and promote pathogen virulence, although many features at the molecular interface of host-pathogen interactions remain to be characterized. In a yeast two-hybrid assay, we found that the Pseudomonas syringae effector HopZ1a interacts with the Arabidopsis transcriptional regulator Abscisic Acid Repressor 1 (ABR1). Further analysis revealed that ABR1 interacts with multiple P. syringae effectors, suggesting that it may be targeted as a susceptibility hub. Indeed, loss-of-function abr1 mutants exhibit reduced susceptibility to a number of P. syringae strains. The ABR1 protein comprises a conserved APETALA2 (AP2) domain flanked by long regions of predicted structural disorder. We verified the DNA-binding activity of the AP2 domain and demonstrated that the disordered domains act redundantly to enhance DNA binding and to facilitate transcriptional activation by ABR1. Finally, we compared gene expression profiles from wild-type and abr1 plants following inoculation with P. syringae, which suggested that the reduced susceptibility of abr1 mutants is due to the loss of a virulence target rather than an enhanced immune response. These data highlight ABR1 as a functionally important component at the host-pathogen interface.

BackgroundA systems-level approach to smoking cessation treatment may optimize healthcare provider adherence to guidelines. Institutions such as the Veterans Health Administration (VHA) are unique in their systematic approach, but comparisons of provider behavior in different healthcare systems are limited.MethodsWe surveyed general medicine providers and specialists in a large academic health center (AHC) and its affiliated VHA in the Mid-South in 2017 to determine the cross-sectional association of healthcare system in which the provider practiced (exposure: AHC versus VHA) with self-reported provision of evidence-based smoking cessation treatment (delivery of counseling plus smoking cessation medication or referral) at least once in the past 12 months (composite outcome). Multivariable logistic regression with adjustment for specialty was performed in 2017–2019.ResultsOf 625 healthcare providers surveyed, 407 (65%) responded, and 366 (59%) were analyzed. Most respondents practiced at the AHC (273[75%] vs VHA 93[25%]) and were general internists (215[59%]); pulmonologists (39[11%]); hematologists/oncologists (69[19%]); and gynecologists (43[12%]). Most respondents (328[90%]) reported the primary outcome. The adjusted odds of evidence-based smoking cessation treatment were higher among VHA vs. AHC healthcare providers (aOR = 4.3; 95% CI 1.3–14.4;p = .02). Health systems differed by provision of individual treatment components, including smoking cessation medication use (98% VHA vs. 90% AHC,p = 0.02) and referral to smoking cessation services (91% VHA vs. 65% AHCp = 0.001).ConclusionsVHA healthcare providers were significantly more likely to provide evidence-based smoking cessation treatment compared to AHC healthcare providers. Healthcare systems’ prioritization of and investment in smoking cessation treatment is critical to improving providers’ adherence to guidelines.

Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for almost a fifth of all cancer-related deaths. Annual computed tomographic lung cancer screening (CTLS) detects lung cancer at earlier stages and reduces lung cancer-related mortality among high-risk individuals. Many medical organizations, including the U.S. Preventive Services Task Force, recommend annual CTLS in high-risk populations. However, fewer than 5% of individuals worldwide at high risk for lung cancer have undergone screening. In large part, this is owing to delayed implementation of CTLS in many countries throughout the world. Factors contributing to low uptake in countries with longstanding CTLS endorsement, such as the United States, include lack of patient and clinician awareness of current recommendations in favor of CTLS and clinician concerns about CTLS-related radiation exposure, false-positive results, overdiagnosis, and cost. This review of the literature serves to address these concerns by evaluating the potential risks and benefits of CTLS. Review of key components of a lung screening program, along with an updated shared decision aid, provides guidance for program development and optimization. Review of studies evaluating the population considered "high-risk" is included as this may affect future guidelines within the United States and other countries considering lung screening implementation.