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Targeted protein degradation (TPD) facilitates the selective elimination of unwanted and pathological cellular cargoes via the proteasome or the lysosome, ranging from proteins to organelles and pathogens, both within and outside the cell. Currently, there are several in vitro and in vivo protocols that assess the degradative potency of a given degrader towards a myriad of targets, most notably soluble, monomeric oncoproteins. However, there is a clear deficiency of methodologies to assess the degradative potency of heterobifunctional chimeric degraders, especially those in the autophagy space, against pathological, mutant tau species, such as detergent-insoluble oligomers and high-molecular aggregates. The protocol below describes both in vitro and in vivo biochemical assays to induce tau aggregation, as well as to qualitatively and quantitatively measure the degradative potency of a given degrader towards said aggregates, with specific applications of the AUTOTAC (AUTOphagy-TArgeting Chimera) platform provided as an example. A well-defined set of methodologies to assess TPD-mediated degradation of pathological tau species will help expand the scope of the TPD technology to neurodegeneration and other proteinopathies, in both the lab and the clinic.Graphical abstractOverview of assays observing elimination of tauP301L aggregates with AUTOTAC. (A) Description of the biological working mechanism of heterobifunctional chimeric AUTOTAC degraders. (B) Schematic illustration of assays described in this paper.

Introduction: Cooperation among rehabilitation team members is essential in the home-based rehabilitation setting. Q-methodology that can quantitatively analyze the subjectivity of members of the rehabilitation team was used to explore the role of occupational therapists (OTs) in home-based rehabilitation. Methods: The Q-methodology process was implemented in five steps: Step 1 - Representative statements about the role of OTs were collected through in-depth interviews, open questionnaires, and literature reviews (Q-sample); Step 2 - A total of 34 rehabilitation team members (physical therapists, OTs, social workers, nutritionists) were recruited (P-sample); Step 3 - The statements were classified according to their subjective perspective (Q-sort); Step 4 - Factor analysis was performed based on the correlation among the responses from the participants (Q-factor analysis); Step 5 - The awareness factor for roles was interpreted (Interpretation of awareness factors). Results: The roles of OTs perceived by members of the home-based rehabilitation team were formed into five factors (A) Adaptation within home environments; (B) Professional development; (C) Reliable service execution; (D) Client needs resolution; and (E) Focus on activity participation. In all factors, perspectives on the role of OTs in helping clients participate in their roles and activities at home were included. These factors included issues and directions addressed in prior literature on the development of occupational therapy. Conclusions: In home-based rehabilitation, OTs must play a professional role in ensuring clients live fully at home, and cooperate with team members for an effective rehabilitation approach.

(1) Background: Stroke patients are exposed to various psychosocial factors, such as depression, anxiety, and stress, which can cause problems with respect to their quality of sleep and social participation. (2) Objectives: We analyzed the causal relationships between the factors affecting sleep quality and social participation in hospitalized and community-based stroke patients using a path analysis model. (3) Methods: A questionnaire survey was administered to stroke patients from June to November 2020 using the Pittsburgh Sleep Quality Index to assess sleep quality; the Beck Depression Inventory to assess depression; the Beck Anxiety Inventory to assess anxiety; the Stress Scale to assess stress; and the Reintegration to Normal Living Index to assess participation. The data thus obtained were subjected to descriptive statistics, frequency analysis, and Pearson correlation analysis. In addition, anxiety, stress, and spasticity were set as exogenous variables to perform path analysis of their causal effects on depression (parameter), sleep quality, and social participation (final endogenous variables). (4) Results: In total, 145 people participated in this study, and the data of 129 people, excluding 16 insincere respondents, were analyzed. The general characteristics of the subjects comprised 84 males (65.1%) and 45 females (34.9%). Poor sleep quality comprised 54.3%, and good sleep quality comprised 45.7%, where the average age was 58.29 ± 15.46 years and the duration from onset was 39.73 ± 51.49 months. This study confirmed correlations between social participation and sleep quality, spasticity, depression, anxiety, and stress. Path analysis also revealed that anxiety and stress led to depression and that depression is a risk factor for sleep quality and social participation. (5) Conclusions: Sleep quality and social participation in stroke patients play an important role in rehabilitation. By carrying out this study, direct and indirect factors that affect sleep quality and social participation were analyzed, and the quality level in rehabilitation treatment should be improved from a structural point of view when approaching psychosocial factors.

This study investigates pronoun interpretation by second language (L2) learners of English, focusing on whether first language (L1) transfer and/or processing difficulty affect L2 learners' pronoun resolution. It is hypothesized that L2 learners' non-target performance in L2-pronoun interpretation is attributable to two sources. The first is the computational complexity required for pronoun resolution, as argued in L1 acquisition by Grodzinsky and Reinhart and L2 acquisition by Slabakova et al. The second is how pronoun interpretation operates in L1. The hypothesis is tested by comparing Korean and Spanish L2-English learners' interpretation of English pronouns using a Truth Value Judgment Task. Both groups had difficulty rejecting pronouns with local-referential antecedents when their proficiency levels were low. Additionally, Korean speakers showed more non-target responses than Spanish speakers due to their knowledge of pronoun interpretation in Korean. These results indicate that both L1 transfer and processing difficulty may be sources of L2 learners' non-target pronoun interpretation, supporting the hypothesis of the study.

Rapid review methodology aims to facilitate faster conduct of systematic reviews to meet the needs of the decision-maker, while also maintaining quality and credibility. This systematic review aimed to determine the impact of different methodological shortcuts for undertaking rapid reviews on the risk of bias (RoB) of the results of the review. Review stages for which reviews and primary studies were sought included the preparation of a protocol, question formulation, inclusion criteria, searching, selection, data extraction, RoB assessment, synthesis, and reporting. We searched 11 electronic databases in April 2022, and conducted some supplementary searching. Reviewers worked in pairs to screen, select, extract data, and assess the RoB of included reviews and studies. We included 15 systematic reviews, 7 scoping reviews, and 65 primary studies. We found that several commonly used shortcuts in rapid reviews are likely to increase the RoB in the results. These include restrictions based on publication date, use of a single electronic database as a source of studies, and use of a single reviewer for screening titles and abstracts, selecting studies based on the full-text, and for extracting data. Authors of rapid reviews should be transparent in reporting their use of these shortcuts and acknowledge the possibility of them causing bias in the results. This review also highlights shortcuts that can save time without increasing the risk of bias. Further research is needed for both systematic and rapid reviews on faster methods for accurate data extraction and RoB assessment, and on development of more precise search strategies.

African swine fever is a devastating and lethal swine disease that poses a major threat to wild boars and domestic pigs (1). The causative agent, African swine fever virus (ASFV), [...]

Estrogen is beneficial to patients with Alzheimer's disease (AD) but has a limited clinical use due to its proliferative and oncogenic effects on non-neuronal cells responsive to estrogen. In an attempt to find an estrogen substitute that retains the beneficial effects of estrogen with minimal side effects, we compared the neuroprotective and proliferative effects of genistein, a selective estrogen receptor (ER) β-agonist, with those of estrogen. Genistein and 17β-estradiol showed comparable levels of protection against Aβ-induced deaths of cultured SH-SY5Y human neuroblastoma cells, which were blocked by an estrogen receptor antagonist, ICI 182,780. On the other hand, 17β-estradiol, but not genistein, induced proliferation of uterine endometrial cells. Our results suggest that genistein is a potential alternative to estrogen in the treatment of Alzheimer's disease.

Studies on human papillomavirus (HPV) prevention education and its educational effects for elementary school students are necessary. This study aimed to examine the effects of human papillomavirus (HPV) prevention education on knowledge about cervical cancer, HPV, immunization, and attitude about immunization among girls in the sixth grade elementary school of South Korea. A quasi-experimental pretest-posttest control group design is used. The sample included 131 girls (Intervention: n = 65, Control: n = 66) in the sixth grade elementary school of South Korea. Human papillomavirus (HPV) prevention education included the contents of the definition of human papillomavirus, types of human papillomavirus, human-papillomavirus-related diseases, cervical cancer, human papillomavirus prevention methods, types of vaccines, vaccination effects, vaccination costs, vaccination frequency for 12-year-old girls, and recommended vaccination age. Human papillomavirus (HPV) prevention education was applied on the intervention group in a total of one 40-minute class in the classroom. There were statistically significant differences in knowledge about cervical cancer (t = 9.712, p < 0.001), knowledge about HPV (t = 9.638, p < 0.001), knowledge about immunization (t = 5.178, p < 0.001), and attitude about immunization (t = 3.113, p= 0.002) between the groups. This study suggests that human papillomavirus (HPV) prevention education was an effective intervention for improving knowledge about cervical cancer, knowledge about HPV, knowledge about immunization, and attitude about immunization. In public health education, human papillomavirus (HPV) prevention education can be implied for Korean girls in sixth grade elementary school.

Nitric oxide (NO) is a self-regulating gaseous molecule as well as an interacting partner with different reactive oxygen species (ROS). Endogenous NO increased, but hydrogen peroxide (H2O2) and superoxide radical anion (${\rm O}_2^{\cdot -}$) decreased in Chinese cabbage leaves treated with sodium nitroprusside (SNP) (0.5 mM). Antioxidant enzyme genes BrCat1, BrCat2, BrAPX, BrGR1, and BrGST1 expressions were transiently induced by the SNP (0.5 mM). Pretreated SNP (0.5 mM) enhanced tolerance to subsequent challenges by phytotoxic SNP (5 mM) and methyl viologen (MV) (50 μM), but accelerated cellular damage by H2O2 (4 M) shown by electrolyte leakage and lipid peroxidation. The SNP (0.5 mM) differentially modulated endogenous NO and ROS levels as well as antioxidant enzyme gene expressions by excess SNP, MV, and H2O2 stresses. These results suggest that NO as a signal molecule differentially interacts with challenging stresses in Chinese cabbage leaves, followed by differential cellular damage and antioxidant responses.

Abstract Since a potential link between statins and the risk of adverse chronic periodontitis (CP) has been raised, we aimed to validate the association between statin use and the incidence of CP using nationwide cohort data. This longitudinal follow-up study included 169,381 patients prescribed statins who were matched with an equal number of controls using propensity scores from the Korean National Health Insurance Service-Health Screening Cohort database (2002–2015). A Cox proportional hazard model was used to assess the occurrence of CP following statin use after adjusting for multiple covariates. The occurrence of CP was significantly higher in patients who had long-term use (1–3 years, 3–5 years, or > 5 years) than with short-term use (≤ 1 year) of statins. After adjustment, statin users exhibited an occurrence of CP 1.32-fold higher (95% confidence interval 1.30–1.33) than that of the matched nonusers (incidence: 25.0 and 22.0 per 100 person-years, respectively). Subgroup analyses supported the adverse impact of statins on CP independent of age and gender. Statin user odds ratios for developing CP were higher compared to those of nonusers. This was consistent in individuals aged > 40 years in both genders, especially with long-term use.

Purpose To develop a denoising convolutional neural network-based image processing technique and investigate its efficacy in diagnosing breast cancer using low-dose mammography imaging. Materials and Methods A total of 6 breast radiologists were included in this prospective study. All radiologists independently evaluated low-dose images for lesion detection and rated them for diagnostic quality using a qualitative scale. After application of the denoising network, the same radiologists evaluated lesion detectability and image quality. For clinical application, a consensus on lesion type and localization on preoperative mammographic examinations of breast cancer patients was reached after discussion. Thereafter, coded low-dose, reconstructed full-dose, and full-dose images were presented and assessed in a random order. Results Lesions on 40% reconstructed full-dose images were better perceived when compared with low-dose images of mastectomy specimens as a reference. In clinical application, as compared to 40% reconstructed images, higher values were given on full-dose images for resolution (p < 0.001); diagnostic quality for calcifications (p < 0.001); and for masses, asymmetry, or architectural distortion (p = 0.037). The 40% reconstructed images showed comparable values to 100% full-dose images for overall quality (p = 0.547), lesion visibility (p = 0.120), and contrast (p = 0.083), without significant differences. Conclusion Effective denoising and image reconstruction processing techniques can enable breast cancer diagnosis with substantial radiation dose reduction.