Examining the normality assumption of a design-comparable effect size in single-case designs.

What Works Clearinghouse (WWC, 2022) recommends a design-comparable effect size (D-CES; i.e., gAB) to gauge an intervention in single-case experimental design (SCED) studies, or to synthesize findings in meta-analysis. So far, no research has examined gAB's performance under non-normal distributions. This study expanded Pustejovsky et al. (2014) to investigate the impact of data distributions, number of cases (m), number of measurements (N), within-case reliability or intra-class correlation (ρ), ratio of variance components (λ), and autocorrelation (ϕ) on gAB in multiple-baseline (MB) design. The performance of gAB was assessed by relative bias (RB), relative bias of variance (RBV), MSE, and coverage rate of 95% CIs (CR). Findings revealed that gAB was unbiased even under non-normal distributions. gAB's variance was generally overestimated, and its 95% CI was over-covered, especially when distributions were normal or nearly normal combined with small m and N. Large imprecision of gAB occurred when m was small and ρ was large. According to the ANOVA results, data distributions contributed to approximately 49% of variance in RB and 25% of variance in both RBV and CR. m and ρ each contributed to 34% of variance in MSE. We recommend gAB for MB studies and meta-analysis with N ≥ 16 and when either (1) data distributions are normal or nearly normal, m = 6, and ρ = 0.6 or 0.8, or (2) data distributions are mildly or moderately non-normal, m ≥ 4, and ρ = 0.2, 0.4, or 0.6. The paper concludes with a discussion of gAB's applicability and design-comparability, and sound reporting practices of ES indices.

Beyond the waves: Unraveling pandemic outcomes with genomic insights and immunity analysis - Evidence from 14 countries.

OBJECTIVE: Although the World Health Organization and many governments have recategorized COVID-19 as a generally mild to moderately severe disease, consecutive pandemic waves driven by immune escape variants have underscored the need for timely and accurate prediction of the next outbreak. Nevertheless, little attention has been paid to translating genomic data and infection- and vaccine-induced immunity into direct estimates. METHODS: We retrieved epidemiologic and genomic data shortly before pandemic waves across 14 developed countries from late 2021 to mid-2022 and examined associations between early-stage variant competition, infection- and vaccine-induced immunity, and the time intervals between wave peaks. We applied regression analysis and the generalized estimating equation method to construct an inferential model. RESULTS: Each per cent increase in the proportion of a new variant was associated with a 1.0% reduction in interpeak intervals on average. Curvilinear associations between vaccine-induced immunity and outcome variables were observed, suggesting that reaching a critical vaccine distribution rate may decrease the caseload of the upcoming wave. CONCLUSIONS: By leveraging readily accessible pre-outbreak genomic and epidemiologic data, our results not only substantiate the predictive potential of early variant fractions but also propose that immunity acquired through infection alone may not sufficiently mitigate transmission. Conversely, a rapid and widespread vaccination initiative appears to be correlated with a decrease in disease incidence.

A switch in N-terminal capping of ß-peptides creates novel self-assembled nanoparticles.

Small tripeptides composed entirely of ß3-amino acids have been shown to self-assemble into fibres following acylation of the N-terminus. Given the use of Fmoc as a strategy to initiate self-assembly in α-peptides, we hypothesized that the acyl cap can be replaced by an Fmoc without perturbation to the self-assembly and enable simpler synthetic protocols. We therefore replaced the N-acyl cap for an Fmoc group and herein we show that these Fmoc-protected ß3-peptides produce regular spherical particles, rather than fibrous structures, that are stable and capable of encapsulating cargo. We then demonstrated that these particles were able to deliver cargo to cells without any obvious signs of cytotoxicity. This is the first description of such regular nanoparticles derived from Fmoc-protected ß3-peptides.

Dysregulation of ribosome-associated quality control elicits cognitive disorders via overaccumulation of TTC3.

Ribosome-associated quality control (RQC) pathway is responsible for degradation of nascent polypeptides in aberrantly stalled ribosomes, and its defects may lead to neurological diseases. However, the underlying molecular mechanism of how RQC dysfunction elicits neurological disorders remains poorly understood. Here we revealed that neurons with knockout (KO) of ubiquitin ligase LTN1, a key gene in the RQC pathway, show developmental defects in neurons via upregulation of TTC3 and UFMylation signaling proteins. The abnormally enhanced TTC3 protein in Ltn1 KO neurons reduced further accumulation of translationally arrested products by preventing translation initiation of selective genes. However, the overaccumulated TTC3 protein in turn caused dendritic abnormalities and reduced surface-localized GABAA receptors during neuronal development. Ltn1 KO mice showed behavioral deficits associated with cognitive disorders, a subset of which were restored by TTC3 knockdown in medial prefrontal cortex. Together, the overactivated cellular compensatory mechanism against defective RQC through TTC3 overaccumulation induced synaptic and cognitive deficits. More broadly, these findings represent a novel cellular mechanism underlying neuronal dysfunctions triggered by exaggerated cellular stress response to accumulated abnormal translation products in neurons.

Educational values and challenges of i-STEM project-based learning: A mixed-methods study with data-transformation design.

Integrated science, technology, engineering, and mathematics (STEM) embedding project-based learning (i-STEM PjBL) is still faced with challenges, and its educational values have not been revealed, which is what the study aimed to explore. Participants consisted of 48 freshmen from a senior high school, including 27 male students and 21 female students. The open-ended questionnaire and the interview for the students were administrated after the i-STEM PjBL. The qualitative data were converted into quantitative data counted by the occurrence frequencies of the codes. The results based on the integration and comparison of the open-ended questionnaire and interview outcomes showed that i-STEM PjBL provided students with positive educational values (including learning acquisition, performance, and perception), but there were also learning challenges in the process. Learning acquisition focused on the basic structure and components of a robot, principles of robot motion, hull structure, principles of sailboat navigation, and skills of designing and assembling sailboats. Learning performance referred that students were satisfied with their hands-on performances and confident of their abilities to perform better in similar disciplines, but did not learn well on programming. Learning perception indicated that students felt interested in i-STEM PjBL materials could acquire knowledge and skills from various fields, PjBL could be helpful to complete works, and principles could be helpful in practice, while programming design learning materials were not enough. Learning challenges indicated that students were unfamiliar with the usage of tools and hands-on operation, and they also felt challenged by programming. Students' feedback can be taken as references to modify and improve i-STEM PjBL and the materials in the future.

The impact of teacher feedback on students' decisions to stay on or change course after math failure in a Confucian cultural context.

Previous research indicated that instructors holding entity belief tended to judge students to have low ability and provided ability-comforting feedback following math failure. Students receiving such feedback tended to quit and change course, creating a potential decrease in the pool of students pursuing math related fields. In Confucian heritage cultures (CHCs), the ideal society is primarily based on fulfillment of duties. Thus, the ability-based findings, derived from WEIRD samples, may not apply to duty-based CHCs. We hypothesized that CHC's teachers holding obligation belief tend to attribute students' failure to lack of duty fulfillment and provide duty-based feedback, including duty-comforting and duty-advising feedback, which motivates students to stay on rather than change course. To validate our hypothesis, we conducted three scenario experiments with 160 college students with teaching experiences, 273 high school students, and 369 pre-service teachers in Taiwan. Results showed that while ability-based paradigm may be culture-free, duty-based paradigm seems to be culture-bound. Consistent with previous research, teachers with entity belief tended to give ability-comforting feedback, pushing students to pursue non-math related fields. In contrast, teachers with obligation belief were likely to offer duty-comforting and duty-advising feedback, contributing to students' persistent pursuit in math. Furthermore, three fifths of teachers were inclined to provide ability-comforting, duty-comforting and duty-advising feedback concurrently, thus putting students in an unpleasant predicament that might be detrimental to their psychological well-being. Theoretical and practical implications are discussed.

To mask or not to mask: Debunking the myths of mask-wearing during COVID-19 across cultures.

Mask-wearing is the simplest yet most effective preventive behavior during COVID-19. However, it has sparked great controversy, particularly in America. Little is known about what psychosocial factors predict people's decision to mask. This research challenges three myths about mask-wearing. First, does mask-wearing provide a false sense of security? Second, is knowledge of COVID-19 a more robust predictor than political ideology of mask-wearing behavior? Third, does resistance to masks reflect anti-authoritarianism or a lack of trust in government? With nationally representative samples across two cultures (N = 1,121), findings reveal a significant positive correlation between mask-wearing and other preventive behaviors. Moreover, knowledge of COVID-19 and trust in government significantly predicted mask-wearing. Implications of the results are also discussed in the cross-cultural context. Critically, findings could provide practical implications for public education and policymaking by uncovering how to more effectively promote compliance with recommended preventive behaviors during our ongoing struggle with COVID-19.

Controlling Chemoselectivity of Catalytic Hydroboration with Light.

The ability to selectively react one functional group in the presence of another underpins efficient reaction sequences. Despite many designer catalytic systems being reported for hydroboration reactions, which allow introduction of a functional handle for cross-coupling or act as mild method for reducing polar functionality, these platforms rarely deal with more complex systems where multiple potentially reactive sites exist. Here we demonstrate, for the first time, the ability to use light to distinguish between ketones and carboxylic acids in more complex molecules. By taking advantage of different activation modes, a single catalytic system can be used for hydroboration, with the chemoselectivity dictated only by the presence or absence of visible light.

To approach or to avoid: The quadripolar model of achievement motivation revisited in a Confucian-heritage context.

Academic challenges and failure are inevitable in pursuit of higher education. According to the self-worth theory, trying hard but failing implies low ability that would be a threat to personal worth, thus preventing students from approaching academic challenges. Nevertheless, previous studies have shown that students in the Confucian-heritage contexts (CHCs) tend to persist rather than quit in the face of academic failure. According to the role obligation theory of self-cultivation (ROT), the CHC learners would perceive academic failure from personal and interpersonal perspectives. The former refers to personal obligations to exert oneself toward the ultimate good, and the latter refers to fulfilling filial obligations to parents by achieving academic excellence. Given the fundamental differences in learners' perceptions of academic failure between the CHCs and the Western, Educated, Industrialized, Rich, and Democratic (WEIRD) contexts, this study examined the applicability of the quadripolar model of achievement motivation based on the self-worth theory in a CHC higher education institution. Results of confirmatory factor analysis (CFA) supported a two-factor model of fear of failure, including a personal and an interpersonal subfactor. Latent class analysis (LCA) showed that apart from the four existing categories of the quadripolar model, two additional CHC categories emerged and constituted half of the sample. The two CHC categories demonstrated different learner characteristics compared with their corresponding quadripolar categories in terms of levels of emotional distress and academic risk-taking tendency. The results may help debunk the myth that learner characteristics in the CHCs are identical to those observed in the WEIRD contexts. The fundamental differences in fear of failure further indicated the inadequacy of the self-worth theory in explaining achievement motivation in the CHCs where relationalism and role obligations are significant parts of the cultural traditions.

Translation from the Ribosome to the Clinic: Implication in Neurological Disorders and New Perspectives from Recent Advances.

De novo protein synthesis by the ribosome and its multitude of co-factors must occur in a tightly regulated manner to ensure that the correct proteins are produced accurately at the right time and, in some cases, also in the proper location. With novel techniques such as ribosome profiling and cryogenic electron microscopy, our understanding of this basic biological process is better than ever and continues to grow. Concurrently, increasing attention is focused on how translational regulation in the brain may be disrupted during the progression of various neurological disorders. In fact, translational dysregulation is now recognized as the de facto pathogenic cause for some disorders. Novel mechanisms including ribosome stalling, ribosome-associated quality control, and liquid-liquid phase separation are closely linked to translational regulation, and may thus be involved in the pathogenic process. The relationships between translational dysregulation and neurological disorders, as well as the ways through which we may be able to reverse those detrimental effects, will be examined in this review.

Human Adipose-Derived Stem Cell Secreted Extracellular Matrix Incorporated into Electrospun Poly(Lactic-co-Glycolic Acid) Nanofibrous Dressing for Enhancing Wound Healing.

Wound dressing, which prevents dehydration and provides a physical barrier against infection to wound beds, can improve wound healing. The interactions between extracellular matrix (ECM) and growth factors is critical to the healing process. Electrospun nanofibers are promising templates for wound dressings due to the structure similarity to ECM of skin. Otherwise, the ECM secreted by human adipose-derived stem cells (hASCs) is rich in growth factors known to enhance wound healing. Accordingly, we propose that the PLGA nanofibrous template incorporated with hASCs-secreted ECM may enhance wound healing. In this study, PLGA nanofibrous matrixes with an aligned or a random structure were prepared by electrospinning. Human ASCs cultured on the aligned matrix had a better viability and produced a larger amount of ECM relative to that of random one. After 7 days' cultivation, the hASCs on aligned PLGA substrates underwent decellularization to fabricate cECM/PLGA dressings. By using immunohistochemical staining against F-actin and cell nucleus, the removal of cellular components was verified. However, the type I collagen and laminin were well preserved on the cECM/PLGA nanofibrous matrixes. In addition, this substrate was hydrophilic, with appropriate mechanical strength to act as a wound dressing. The L929 fibroblasts had good activity, survival and proliferation on the cECM/PLGA meshes. In addition, the cECM/PLGA nanofibrous dressings improved the wound healing of surgically created full-thickness skin excision in a mouse model. This hASCs-secreted ECM incorporated into electrospun PLGA nanofibrous could be a promising dressing for enhancing wound healing.

Keratin scaffolds with human adipose stem cells: Physical and biological effects toward wound healing.

Keratin, a natural biomaterial derived from wool or human hair, has the intrinsic ability to interact with different types of cells and the potential to serve as a controllable extracellular matrix that can be used a scaffold for tissue engineering. In this study, we demonstrated a simple and fast technique to construct 3D keratin scaffolds for accelerated wound healing using a lyophilization method based on extraction of keratin from human hair. The physical properties of the keratin scaffolds such as water uptake, pore size, and porosity can be adjusted by changing the protein concentrations during the fabrication process. The keratin scaffolds supported human adipose stem cells (hASCs) adhesion, proliferation, and differentiation. In vivo study performed on ICR mice showed that keratin scaffolds with hASCs shortened skin wound healing time, accelerated epithelialization, and promoted wound remodeling. Therefore, keratin scaffolds alone or together with hASCs may serve as therapeutic agents for repairing wounded tissue.

Surface modification: activation and deactivation of osteogenic differentiation based on detachable growth factor protein.

An advanced material interface is modified by using a substrate-independent coating of detachable poly-para-xylylene, enabling dynamical control of the immobilization and detachment of biomolecules, and a previously installed biological function is deactivated or tuned with reduced activity. The induction of osteogenesis activity, and subsequent deactivation of such osteogenesis activity, is demonstrated.

Photo-Crosslinked Keratin/Chitosan Membranes as Potential Wound Dressing Materials.

In this study, we combined two kinds of natural polymers, chitosan and keratin, to develop a portable composite membrane via UV irradiation. UV-crosslinking without an additional chemical agent makes the fabrication more ideal by reducing reactants and avoiding residual toxic chemicals. This novel composite could perform synergistic functions benefitting from chitosan and keratin; including a strong mechanical strength, biodegradability, biocompatibility, better cell adhesion, and proliferation characteristics. Furthermore, compared with our previous research, this keratin-chitosan composite membrane was improved in that it was made to be portable, enabling it to be versatile and have various applications in vitro and in vivo. Based on these facts, this innovative composite membrane has high potential for serving as an outstanding candidate for wound healing or other biomedical applications.

Cortactin-binding protein 2 increases microtubule stability and regulates dendritic arborization.

Neurons are characterized by subcellular compartments, such as axons, dendrites and synapses, that have highly specialized morphologies and biochemical specificities. Cortactin-binding protein 2 (CTTNBP2), a neuron-specific F-actin regulator, has been shown to play a role in the regulation of dendritic spine formation and their maintenance. Here, we show that, in addition to F-actin, CTTNBP2 also associates with microtubules before mature dendritic spines form. This association of CTTNBP2 and microtubules induced the formation of microtubule bundles. Although the middle (Mid) region of CTTNBP2 was sufficient for its association with microtubules, for microtubule bundling, the N-terminal region containing the coiled-coil motifs (NCC), which mediates the dimerization or oligomerization of CTTNBP2, was also required. Our study indicates that CTTNBP2 proteins form a dimer or oligomer and brings multiple microtubule filaments together to form bundles. In cultured hippocampal neurons, knockdown of CTTNBP2 or expression of the Mid or NCC domain alone reduced the acetylation levels of microtubules and impaired dendritic arborization. This study suggests that CTTNBP2 influences both the F-actin and microtubule cytoskeletons and regulates dendritic spine formation and dendritic arborization.

CTTNBP2, but not CTTNBP2NL, regulates dendritic spinogenesis and synaptic distribution of the striatin-PP2A complex.

Cortactin-binding protein 2 (CTTNBP2) interacts with cortactin to regulate cortactin mobility and control dendritic spine formation. CTTNBP2 has also been associated with autistic spectrum disorder. The regulation of dendritic spinogenesis could explain the association of CTTNBP2 with autism. Sequence comparison has indicated that CTTNBP2 N-terminal-like protein (CTTNBP2NL) is a CTTNBP2 homologue. To confirm the specific effect of CTTNBP2 on dendritic spinogenesis, here we investigate whether CTTNBP2NL has a similar function to CTTNBP2. Although both CTTNBP2 and CTTNBP2NL interact with cortactin, CTTNBP2NL is associated with stress fibers, whereas CTTNBP2 is distributed to the cortex and intracellular puncta. We also provide evidence that CTTNBP2, but not CTTNBP2NL, is predominantly expressed in the brain. CTTNBP2NL does not show any activity in the regulation of dendritic spinogenesis. In addition to spine morphology, CTTNBP2 is also found to regulate the synaptic distribution of striatin and zinedin (the regulatory B subunits of protein phosphatase 2A [PP2A]), which interact with CTTNBP2NL in HEK293 cells. The association between CTTNBP2 and striatin/zinedin suggests that CTTNBP2 targets the PP2A complex to dendritic spines. Thus we propose that the interactions of CTTNBP2 and cortactin and the PP2A complex regulate spine morphogenesis and synaptic signaling.

Cortactin-binding protein 2 modulates the mobility of cortactin and regulates dendritic spine formation and maintenance.

Dendritic spines, the actin-rich protrusions emerging from dendrites, are the locations of excitatory synapses in mammalian brains. Many molecules that regulate actin dynamics also influence the morphology and/or density of dendritic spines. Since dendritic spines are neuron-specific subcellular structures, neuron-specific proteins or signals are expected to control spinogenesis. In this report, we characterize the distribution and function of neuron-predominant cortactin-binding protein 2 (CTTNBP2) in rodents. An analysis of an Expressed Sequence Tag database revealed three splice variants of mouse CTTNBP2: short, long, and intron. Immunoblotting indicated that the short form is the dominant CTTNBP2 variant in the brain. CTTNBP2 proteins were highly concentrated at dendritic spines in cultured rat hippocampal neurons as well as in the mouse brain. Knockdown of CTTNBP2 in neurons reduced the density and size of dendritic spines. Consistent with these morphological changes, the frequencies of miniature EPSCs in CTTNBP2 knockdown neurons were lower than those in control neurons. Cortactin acts downstream of CTTNBP2 in spinogenesis, as the defects caused by CTTNBP2 knockdown were rescued by overexpression of cortactin but not expression of a CTTNBP2 mutant protein lacking the cortactin interaction. Finally, immunofluorescence staining demonstrated that, unlike cortactin, CTTNBP2 stably resided at dendritic spines even after glutamate stimulation. Fluorescence recovery after photobleaching further suggested that CTTNBP2 modulates the mobility of cortactin in neurons. CTTNBP2 may thus help to immobilize cortactin in dendritic spines and control the density of dendritic spines.

[Rapid genetic screening of Leber's hereditary optic neuropathy with mtDNA G11778A mutation by AS-PCR with whole blood].

OBJECTIVE: Rapid Genetic Screening of Leber's hereditary optic neuropathy (LHON) with mtDNA G11778A mutation by allele-specific polymerase chain reaction (AS-PCR) with whole blood. METHODS: Whole blood with anticoagulant was used as a template of AS-PCR for the analysis of LHON with mtDNA G11778A point mutation. The amplified DNA fragment was directly observed by electrophoretogram with ethidium bromide stained. RESULTS: The accuracy was 100% by using this method in 24 blood samples tested, and the specific of PCR of which used whole blood as template was better than one of the purified mtDNA. The reliability of the method for screening of LHON with mtDNA G11778A mutation was checked by double-blind test in 22 blood samples. CONCLUSION: This method does not need purified DNA from blood and only required one step of PCR. Thus, it is very simple, rapid and accurate for the clinical genetic screening of LHON with mtDNA G11778A point mutation.

Self-polymerization of archaeal RadA protein into long and fine helical filaments.

The Archaeal protein RadA, a RecA/Rad51 homolog, is able to promote pairing and exchange of DNA strands with homologous sequences. Here, we have expressed, purified, and crystallized the catalytically active RadA protein from Sulfolobus solfataricus (Sso). Preliminary X-ray analysis indicated that Sso RadA protein likely forms helical filament in protein crystals. Using atomic force microscopy with a carbon nanotube (CNT) tip for high-resolution imaging, we demonstrated that Sso RadA protein indeed forms fine helical filaments up to 1 microm in length ( approximately 10nm pitch) in the absence of DNA and nucleotide cofactor. We also observed that Sso RadA protein helical filament could dissemble upon incubation with ssDNA, and then the proteins associate with ssDNA to form nucleoprotein filament.