ABSTRACT
Chimeric antigen receptor (CAR)-T cell therapy is a groundbreaking immunotherapy for cancer. However, the intricate and costly manufacturing process remains a hurdle. Improving the transduction rate is a potential avenue to cut down costs and boost therapeutic efficiency. Peptide nanofibrils (PNFs) serve as one such class of transduction enhancers. PNFs bind to negatively charged virions, facilitating their active engagement by cellular protrusions, which enhances virion attachment to cells, leading to increased cellular entry and gene transfer rates. While first-generation PNFs had issues with aggregate formation and potential immunogenicity, our study utilized in silico screening to identify short, endogenous, and non-immunogenic peptides capable of enhancing transduction. This led to the discovery of an 8-mer peptide, RM-8, which forms PNFs that effectively boost T cell transduction rates by various retroviral vectors. A subsequent structure-activity relationship (SAR) analysis refined RM-8, resulting in the D4 derivative. D4 peptide is stable and assembles into smaller PNFs, avoiding large aggregate formation, and demonstrates superior transduction rates in primary T and NK cells. In essence, D4 PNFs present an economical and straightforward nanotechnological tool, ideal for refining ex vivo gene transfer in CAR-T cell production and potentially other advanced therapeutic applications.
Subject(s)
Killer Cells, Natural , T-Lymphocytes , Transduction, Genetic , Peptides , Immunotherapy, Adoptive/methodsABSTRACT
African Americans (AAs) have higher prevalence of uncontrolled hypertension than Whites, which leads to reduced life expectancy. Barriers to achieving blood pressure control in AAs include mistrust of healthcare and poor adherence to medication and dietary recommendations. We conducted a pilot study of a church-based community health worker (CHW) intervention to reduce blood pressure among AAs by providing support and strategies to improve diet and medication adherence. To increase trust and cultural concordance, we hired and trained church members to serve as CHWs. AA adults (n = 79) with poorly controlled blood pressure were recruited from churches in a low-income, segregated neighborhood of Chicago. Participants had an average of 7.5 visits with CHWs over 6 months. Mean change in systolic blood pressure across participants was - 5 mm/Hg (p = 0.029). Change was greater among participants (n = 45) with higher baseline blood pressure (- 9.2, p = 0.009). Medication adherence increased at follow-up, largely due to improved timeliness of medication refills, but adherence to the DASH diet decreased slightly. Intervention fidelity was poor. Recordings of CHW visits revealed that CHWs did not adhere closely to the intervention protocol, especially with regard to assisting participants with action plans for behavior change. Participants gave the intervention high ratings for acceptability and appropriateness, and slightly lower ratings for feasibility of achieving intervention behavioral targets. Participants valued having the intervention delivered at their church and preferred a church-based intervention to an intervention conducted in a clinical setting. A church-based CHW intervention may be effective at reducing blood pressure in AAs.
ABSTRACT
Heart-to-Heart (H2H) is a church-based behavioral cluster randomized trial to measure the effectiveness of a lifestyle education program for reducing blood pressure (BP) in African American adults with uncontrolled BP. Design and implementation of this study were informed by our ALIVE pilot study conducted with church pastors and leaders using a community-based participatory research methodology. The current study employs a cross-over design in which all participants receive two 6-month programs in different orders: the intervention arm receives the H2H program first, followed by a financial education program, and the comparator arm receives the programs in the reverse order. Approximately 34 churches will be randomized with the aim of including at least 272 participants across churches. The H2H program consists of 24 weekly dietitian-led diet and lifestyle virtual education sessions, 12 Bible studies taught by the church pastor reinforcing positive dietary behaviors from a biblical perspective, daily self-monitoring of BP, and, as needed, one-on-one support from a community health worker to assist with medication adherence. The Money Smart program consists of 14 financial education sessions and 12 Bible studies teaching the biblical basis of good financial management over a 6-month period. The primary outcome measure is systolic BP at 6 months with a follow-up at 12 months. Secondary outcome measures include medication adherence, Dietary Approaches to Stop Hypertension (DASH) diet adherence, self-efficacy for hypertension self-care, social support for eating a healthy diet, hypertension and nutrition knowledge, beliefs about medicines, barriers to medication use, depression, and financial knowledge and behaviors.
Subject(s)
Black or African American , Hypertension , Adult , Humans , Blood Pressure , Pilot Projects , DietABSTRACT
Many consumers nowadays wish to reduce their smartphone usage in the hope of improving productivity and well-being. We conducted a pre-registered field experiment (N = 112) over a period of several weeks to test the effectiveness of two widely available digital strategies for screen time reduction. The effectiveness of a design friction intervention (i.e., activating grayscale mode) was compared with a goal-setting intervention (i.e., self-commitment to time limits) and a control condition (i.e., self-monitoring). The design friction intervention led to an immediate, significant reduction of objectively measured screen time compared with the control condition. Conversely, the goal-setting intervention led to a smaller and more gradual screen time reduction. In contrast to the popular belief that reducing screen time has broad benefits, we found no immediate causal effect of reducing usage on subjective well-being and academic performance.
Subject(s)
Screen Time , Smartphone , HumansABSTRACT
PURPOSE: Sagittal malalignment is a risk factor for mechanical complications after surgery for adult spinal deformity (ASD). Spinal loads, modulated by sagittal alignment, may explain this relationship. The aims of this study were to investigate the relationships between: (1) postoperative changes in loads at the proximal segment and realignment, and (2) absolute postoperative loads and postoperative alignment measures. METHODS: A previously validated musculoskeletal model of the whole spine was applied to study a clinical sample of 205 patients with ASD. Based on clinical and radiographic data, pre-and postoperative patient-specific alignments were simulated to predict loads at the proximal segment adjacent to the spinal fusion. RESULTS: Weak-to-moderate associations were found between pre-to-postop changes in lumbar lordosis, LL (r = - 0.23, r = - 0.43; p < 0.001), global tilt, GT (r = 0.26, r = 0.38; p < 0.001) and the Global Alignment and Proportion score, GAP (r = 0.26, r = 0.37; p < 0.001), and changes in compressive and shear forces at the proximal segment. GAP score parameters, thoracic kyphosis measurements and the slope of upper instrumented vertebra were associated with changes in shear. In patients with T10-pelvis fusion, moderate-to-strong associations were found between postoperative sagittal alignment measures and compressive and shear loads, with GT showing the strongest correlations (r = 0.75, r = 0.73, p < 0.001). CONCLUSIONS: Spinal loads were estimated for patient-specific full spinal alignment profiles in a large cohort of patients with ASD pre-and postoperatively. Loads on the proximal segments were greater in association with sagittal malalignment and malorientation of proximal vertebra. Future work should explore whether they provide a causative mechanism explaining the associated risk of proximal junction complications.
Subject(s)
Kyphosis , Lordosis , Spinal Fusion , Humans , Adult , Lumbar Vertebrae/surgery , Retrospective Studies , Lordosis/diagnostic imaging , Lordosis/surgery , Kyphosis/diagnostic imaging , Kyphosis/surgery , Pelvis , Spinal Fusion/adverse effects , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgeryABSTRACT
BACKGROUND: Given the widespread and concerted efforts to propagate health misinformation on social media, particularly centered around vaccination during the pandemic, many groups of clinicians and scientists were organized on social media to tackle misinformation and promote vaccination, using a national or international lens. Although documenting the impact of such social media efforts, particularly at the community level, can be challenging, a more hyperlocal or "place-based approach" for social media campaigns could be effective in tackling misinformation and improving public health outcomes at a community level. OBJECTIVE: We aimed to describe and document the effectiveness of a place-based strategy for a coordinated group of Chicago health care workers on social media to tackle misinformation and improve vaccination rates in the communities they serve. METHODS: The Illinois Medical Professionals Action Collaborative Team (IMPACT) was founded in March 2020 in response to the COVID-19 pandemic, with representatives from major academic teaching hospitals in Chicago (eg, University of Chicago, Northwestern University, University of Illinois, and Rush University) and community-based organizations. Through crowdsourcing on multiple social media platforms (eg, Facebook, Twitter, and Instagram) with a place-based approach, IMPACT engaged grassroots networks of thousands of Illinois health care workers and the public to identify gaps, needs, and viewpoints to improve local health care delivery during the pandemic. RESULTS: To address vaccine misinformation, IMPACT created 8 "myth debunking" infographics and a "vaccine information series" of 14 infographics that have generated >340,000 impressions and informed the development of vaccine education for the Chicago Public Libraries. IMPACT delivered 13 policy letters focusing on different topics, such as health care worker personal protective equipment, universal masking, and vaccination, with >4000 health care workers signatures collected through social media and delivered to policy makers; it published over 50 op-eds on COVID-19 topics in high-impact news outlets and contributed to >200 local and national news features. Using the crowdsourcing approach on IMPACT social media channels, IMPACT mobilized health care and lay volunteers to staff >400 vaccine events for >120,000 individuals, many in Chicago's hardest-hit neighborhoods. The group's recommendations have influenced public health awareness campaigns and initiatives, as well as research, advocacy, and policy recommendations, and they have been recognized with local and national awards. CONCLUSIONS: A coordinated group of health care workers on social media, using a hyperlocal place-based approach, can not only work together to address misinformation but also collaborate to boost vaccination rates in their surrounding communities.
Subject(s)
COVID-19 , Social Media , COVID-19/epidemiology , COVID-19/prevention & control , Health Personnel , Humans , Pandemics/prevention & control , Power, Psychological , Trust , VaccinationABSTRACT
Do regularly physically active individuals differ in their decision-making from people who are not regularly physically active? Across five studies, we document a novel benefit of being regularly physically active for decisions that require the appropriate weighing of goal-relevant versus goal-irrelevant information. Usually, when faced with a mix of relevant and irrelevant attribute information, decision makers find it difficult to ignore the irrelevant information, and as such, "dilute" their judgments (i.e., judgments become less extreme). Such a dilution effect has been amply documented in past research. In contrast, we find that people who engage in regular leisure physical activity are less susceptible to dilution effects. Beyond the dilution effect, we also find similar benefits of being regularly physically active for decisions involving desirability-feasibility trade-offs. The results hold across multiple replicates, diverse samples, and different measures of regular physical activity. We also rule out several potential alternative accounts (e.g., demographics, personality traits). The results cannot be explained by physical effort alone as these benefits are observed only for regular leisure physical activity and not for occupational physical activity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Subject(s)
Exercise , Leisure Activities , Humans , JudgmentABSTRACT
Spatial skills support STEM learning and achievement. However, children from low-socioeconomic (SES) backgrounds typically lag behind their middle- and high-SES peers. We asked whether a digital educational app-designed to mirror an already successful, spatial assembly training program using concrete materials-would be as effective for facilitating spatial skills in under-resourced preschoolers as the concrete materials. Three-year-olds (N = 61) from under-resourced backgrounds were randomly assigned to a business-as-usual control group or to receive 5 weeks of spatial training using either concrete, tangible materials or a digital app on a tablet. The spatial puzzles used were an extension of items from the Test of Spatial Assembly (TOSA). Preschoolers were pretested and posttested on new two-dimensional (2D) TOSA trials. Results indicate that both concrete and digital spatial training increased performance on the 2D-TOSA compared to the control group. The two trainings did not statistically differ from one another suggesting that educational spatial apps may be one route to providing early foundational skills to children from under-resourced backgrounds.
Subject(s)
Mobile Applications , Spatial Navigation , Achievement , Child, Preschool , Educational Status , HumansABSTRACT
BACKGROUND: Visual communication strategies are becoming increasingly prevalent for conveying information to health professionals as well as to the general public. The potential of social media for rapid knowledge dissemination using infographics was recognized early in the coronavirus disease (COVID-19) pandemic by health professionals. OBJECTIVE: The purpose of this study was to describe a coalition of health professionals' approach to developing infographics about COVID-19 vaccines and the reach and engagement of those infographics when shared through social media. METHODS: Infographics were created by a core team within the coalition following a stepwise approach. Each underwent a multistep review process, readability evaluation, and translation into Spanish. Infographics were then shared through multiple social media platforms. They were grouped into 1 of 3 categories for this analysis: COVID-19 vaccine series, myth debunkers, or other. RESULTS: All infographics had greater outreach, impressions, and engagement on Twitter than they did on other platforms. When comparing the 3 groups, no 1 infographic type was consistently performing higher than the others. CONCLUSION: Each infographic reached thousands to tens of thousands of people. We do not know whether those who viewed these infographics changed their perspective on vaccination, so we are unable to draw a conclusion about their impact on vaccine hesitancy based on this study alone.
Subject(s)
COVID-19 , Social Media , COVID-19 Vaccines , Communication , Data Visualization , Humans , SARS-CoV-2 , Vaccination , Vaccination HesitancyABSTRACT
Bone morphogenic proteins (BMPs) are important growth regulators in embryogenesis and postnatal homeostasis. Their tight regulation is crucial for successful embryonic development as well as tissue homeostasis in the adult organism. BMP inhibition by natural extracellular biologic antagonists represents the most intensively studied mechanistic concept of BMP growth factor regulation. It was shown to be critical for numerous developmental programs, including germ layer specification and spatiotemporal gradients required for the establishment of the dorsal-ventral axis and organ formation. The importance of BMP antagonists for extracellular matrix homeostasis is illustrated by the numerous human connective tissue disorders caused by their mutational inactivation. Here, we will focus on the known functional interactions targeting BMP antagonists to the ECM and discuss how these interactions influence BMP antagonist activity. Moreover, we will provide an overview about the current concepts and investigated molecular mechanisms modulating BMP inhibitor function in the context of development and disease.
ABSTRACT
Bone morphogenetic proteins (BMPs) belong to the TGF-ß superfamily of signaling ligands which comprise a family of pluripotent cytokines regulating a multitude of cellular events. Although BMPs were originally discovered as potent factors extractable from bone matrix that are capable to induce ectopic bone formation in soft tissues, their mode of action has been mostly studied as soluble ligands in absence of the physiologically relevant cellular microenvironment. This micro milieu is defined by supramolecular networks of extracellular matrix (ECM) proteins that specifically target BMP ligands, present them to their cellular receptors, and allow their controlled release. Here we focus on functional interactions and mechanisms that were described to control BMP bioavailability in a spatio-temporal manner within the respective tissue context. Structural disturbance of the ECM architecture due to mutations in ECM proteins leads to dysregulated BMP signaling as underlying cause for connective tissue disease pathways. We will provide an overview about current mechanistic concepts of how aberrant BMP signaling drives connective tissue destruction in inherited and chronic diseases.
Subject(s)
Bone Morphogenetic Proteins , Extracellular Matrix , Bone Morphogenetic Proteins/metabolism , Extracellular Matrix/metabolism , Extracellular Matrix Proteins/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Transforming Growth Factor beta/metabolismABSTRACT
Since their discovery as pluripotent cytokines extractable from bone matrix, it has been speculated how bone morphogenetic proteins (BMPs) become released and activated from the extracellular matrix (ECM). In contrast to TGF-ßs, most investigated BMPs are secreted as bioactive prodomain (PD)-growth factor (GF) complexes (CPLXs). Recently, we demonstrated that PD-dependent targeting of BMP-7 CPLXs to the extracellular fibrillin microfibril (FMF) components fibrillin-1 and -2 represents a BMP sequestration mechanism by rendering the GF latent. Understanding how BMPs become activated from ECM scaffolds such as FMF is crucial to elucidate pathomechanisms characterized by aberrant BMP activation and ECM destruction. Here, we describe a new MMP-dependent BMP-7 activation mechanism from ECM-targeted pools via specific PD degradation. Using Edman sequencing and mutagenesis, we identified a new and conserved MMP-13 cleavage site within the BMP-7 PD. A degradation screen with different BMP family PDs and representative MMP family members suggested utilization of the identified site in a general MMP-driven BMP activation mechanism. Furthermore, sandwich ELISA and solid phase cleavage studies in combination with bioactivity assays, single particle TEM, and in silico molecular docking experiments provided evidence that PD cleavage by MMP-13 leads to BMP-7 CPLX disintegration and bioactive GF release.
Subject(s)
Bone Morphogenetic Proteins/metabolism , Extracellular Matrix/metabolism , Matrix Metalloproteinases/physiology , Amino Acid Motifs , Animals , Bone Morphogenetic Protein 7/chemistry , Bone Morphogenetic Protein 7/metabolism , Bone Morphogenetic Proteins/chemistry , HEK293 Cells , Humans , Matrix Metalloproteinase 13/physiology , Mice , Molecular Docking Simulation , Protein DomainsABSTRACT
Working memory (WM) develops rapidly during early childhood. In the present study, visual WM (VSM) was measured using the well-established Spin the Pots task (Hughes & Ensor, 2005), a complex non-verbal eight-location object occlusion task. A self-ordered hiding procedure was adopted to allow for an examination of children's strategy use during a VWM task. Participants (N = 640) between the ages of 2 and 4 years were tested under semi-naturalistic conditions, in the home or in a museum. Computational modeling was used to estimate an expected value for the total trials to complete Spin the Pots via a random search and child performance was compared to expected values. Based on this approach, we determined that children who found six stickers retrieved them in significantly fewer trials than the expected value, excluding chance performance and implicating VWM. Results also showed age-related and sex-related changes in VWM. Between 2 and 4 years of age, 4-year-olds performed significantly better than younger children and girls out-performed the boys. Spontaneous use of a color matching hiding strategy was associated with a higher success rate on the task. Implications of these findings for early development of VWM are discussed.
Subject(s)
Memory, Short-Term , Child , Child, Preschool , Computer Simulation , Female , Humans , MaleABSTRACT
Humans imitate patently irrelevant actions known as overimitation, and rather than decreasing with age, overimitation increases with age. Whereas most overimitation research has focused on social factors associated with overimitation, comparatively little is known about the cognitive- and task-specific features that influence overimitation. Specifically, developmental contrasts between imitation and overimitation are confounded by the addition of irrelevant actions to causally necessary actions, increasing sequence length, cognitive load, and processing costs-variables known to be age dependent. We constructed a novel puzzle box task such that a four-step imitation, four-step overimitation, and two-step efficient sequence could be demonstrated using the same apparatus on video. In Experiments 1 and 2, 2.5- to 5-year-olds randomly assigned to imitation and overimitation groups performed significantly more target actions than baseline control groups. Rates of imitation and overimitation increased as a function of age, with older preschoolers outperforming younger preschoolers in both conditions. In Experiment 3, preschoolers were shown a video of an efficient two-step demonstration prior to testing. After they responded, they were shown a four-step overimitation video and were tested on the same puzzle box. Children imitated the efficient demonstration, but after watching the overimitation video, they also overimitated the irrelevant actions. Once again, older children overimitated more than younger children. Together, results show that preschoolers are faithful, flexible, and persistent overimitators. The fidelity and flexibility of overimitation are constrained not only by social factors but also by basic cognitive processes that vary across age groups. As these constraints diminish, overimitation and flexible (optimal) imitation increases.
Subject(s)
Goals , Imitative Behavior , Child Behavior , Child, Preschool , Cognition , Humans , Infant , LearningABSTRACT
OBJECTIVE: To test whether a previously tested, small-changes weight loss program could be translated for use in African American churches. METHODS: The program consisted of 12 group sessions held weekly at a partner church. Key intervention messages were disseminated via Facebook. A single-arm pretest-posttest evaluation included assessments at baseline, program completion (3-month), and after three months with no contact (6-month). RESULTS: Participants (N = 17; 16 women, age 57.5±12.1 years, body mass index 36.5 kg/m2±5.4, hemoglobin A1c 6.3±0.5, blood pressure 132±14/82±7) attended an average of 77% (mdn=9) of treatment sessions and 94% and 100% completed the 3- and 6-month assessment visits. All participants reported they were "somewhat" or "very satisfied" with the program. There was minimal interaction with Facebook with an average of 0.5 comments and 3.9 reactions per post. Three- and six-month reductions (all p's≤.01) were observed for weight (mdn=-2.7 kg; mdn=-2.6 kg), waist circumference (mdn=-3.8cm; mdn=-5.1cm), and hemoglobin A1c (mdn=-0.5; mdn=-0.3). At 3-months, there were significant reductions in systolic (mdn=-10.7 mmHg) and diastolic blood pressure (mdn=-8.0) but not at 6 months. CONCLUSIONS: This study suggests that a faith-based, faith-placed intervention utilizing a small-changes approach in African American churches may achieve sustained weight loss in parishioners with obesity.
ABSTRACT
Early spatial skills predict the development of later spatial and mathematical skills. Yet, it is unclear how comprehension of the words that capture spatial relations, words like behind and under, might be associated with children's early spatial and mathematics skills. The current study addressed this question by conducting a moderated mediation model to test the potential moderating effects of group factors, such as socioeconomic status (SES) and gender, on the possible mediation of spatial language comprehension on the association between spatial skill and mathematics performance. In total, 192 3-year-olds were tested on a battery of assessments, including a novel Spatial Language Comprehension Task, a test of spatial skills (2- and 3-dimensional trials of the Test of Spatial Assembly [2D and 3D TOSA, respectively]), and a composite of 2 mathematical assessments. The results indicate that this novel Spatial Language Comprehension Task is a reliable measure useful for examining group differences and the early space-math link. Specifically, higher-SES preschoolers and females had higher spatial language comprehension compared with their lower-SES peers and males, respectively. These SES and gender disparities in spatial language comprehension are concerning, given the strong association between spatial language comprehension and mathematics skills. Additionally, spatial language comprehension mediated the association between spatial skill and mathematics performance for females only. Future work should examine the potential causal role that spatial language comprehension may have in concurrent and later spatial and mathematics skills. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Subject(s)
Comprehension , Social Class , Child , Child, Preschool , Female , Humans , Male , MathematicsABSTRACT
BACKGROUND: Low-dose computed tomography (LDCT) scan for lung cancer screening is underutilized. Studies suggest that up to one-third of providers do not know the current lung cancer screening guidelines. Thus, identifying the barriers to utilization of LDCT scan is essential. METHODS: Primary care providers in three different healthcare settings in the United States were surveyed to assess provider knowledge of LDCT scan screening criteria, lung cancer screening practices, and barriers to the utilization of LDCT scan screening. Fisher's Exact, Chi-Squared, and Kruskal-Wallis tests were used to compare provider responses. Multivariable logistic regression was used to test the association between provider characteristics and the likelihood of utilizing LDCT scan for lung cancer screening. RESULTS: The survey was sent to 614 providers, with a 15.7% response rate. Overall, 29.2% of providers report never ordering LDCT scans for eligible patients. Providers practicing at a community or academic hospital more frequently order LDCT scans than those practicing at a safety net hospital. Academic- and community-based providers received a significantly higher mean knowledge score than safety net-based providers [academic 6.84 (SD 1.33), community 6.72 (SD 1.46), safety net 5.85 (SD 1.38); P<0.01]. Overall, only 6.2% of respondents correctly identified all six Centers for Medicare and Medicaid Services eligibility criteria when challenged with three incorrect criteria. Common barriers to utilization of LDCT scan included failure of the electronic medical record (EMR) to notify providers of eligible patients (54.7%), patient refusal (37%), perceived high false-positive rate leading to unnecessary procedures (18.9%), provider time constraints (16.8%), and lack of insurance coverage (13.7%). CONCLUSIONS: Provider knowledge of lung cancer screening guidelines varies, perhaps contributing to underutilization of LDCT scan for lung cancer screening. Improved provider education at safety net hospitals and improving EMR-based best practice alerts may improve the rate of lung cancer screening.
ABSTRACT
Spatial skills are associated with mathematics skills, but it is unclear if spatial training transfers to mathematics skills for preschoolers, especially from underserved communities. The current study tested (a) whether spatial training benefited preschoolers' spatial and mathematics skills, (b) if the type of feedback provided during spatial training differentially influenced children's spatial and mathematics skills, and (c) if the spatial training's effects varied by socioeconomic status (SES). Preschoolers (N = 187) were randomly assigned to either a 'business-as-usual' control or one of three spatial training groups (modeling and feedback [MF]; gesture feedback [GF]; spatial language feedback [SLF]). Three-year-olds were trained to construct puzzles to match a model composed of various geometric shapes. New models were created similar to the 2-dimensional trials of the Test of Spatial Assembly (TOSA). Training was given once per week for 5 weeks. Preschoolers were pretested and posttested on 2D and 3D TOSA trials, spatial vocabulary, shape identification, and 2 mathematics assessments. Results indicate that first, any spatial training improved preschoolers' 2D TOSA performance, although a significant interaction with SES indicated improvement was driven by low-SES children. Furthermore, low-SES children showed greatest gains on the 2D TOSA with MF and GF. Second, MF and GF improved low-SES children's performance on the 3D TOSA. Third, only low-SES children with MF saw improvements in far-transfer to mathematics (Woodcock-Johnson: Applied Problems, but not the Test of Early Mathematical Ability). Results indicate that, especially for low-income learners, spatial training can improve children's early spatial and mathematics skills. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Subject(s)
Early Intervention, Educational , Feedback, Physiological/physiology , Gestures , Mathematical Concepts , Mathematics/education , Psychomotor Performance/physiology , Social Class , Space Perception/physiology , Transfer, Psychology/physiology , Vocabulary , Child, Preschool , Female , Humans , MaleABSTRACT
Display of short peptides on the surface of adeno-associated viruses (AAVs) is a powerful technology for the generation of gene therapy vectors with altered cell specificities and/or transduction efficiencies. Following its extensive prior use in the best characterized AAV serotype 2 (AAV2), recent reports also indicate the potential of other AAV isolates as scaffolds for peptide display. In this study, we systematically explored the respective capacities of 13 different AAV capsid variants to tolerate 27 peptides inserted on the surface followed by production of reporter-encoding vectors. Single-round screening in pre-arrayed 96-well plates permitted rapid and simple identification of superior vectors in >90 cell types, including T cells and primary cells. Notably, vector performance depended not only on the combination of capsid, peptide, and cell type, but also on the position of the inserted peptide and the nature of flanking residues. For optimal data availability and accessibility, all results were assembled in a searchable online database offering multiple output styles. Finally, we established a reverse-transduction pipeline based on vector pre-spotting in 96- or 384-well plates that facilitates high-throughput library panning. Our comprehensive illustration of the vast potential of alternative AAV capsids for peptide display should accelerate their in vivo screening and application as unique gene therapy vectors.