Future Goal Aspirations of Students With Extensive Support Needs: Findings From NLTS 2012.

This study used data from the National Longitudinal Transition Study 2012 (NLTS 2012) to explore the future goal aspirations of students with extensive support needs who participate in alternate assessments, compared to other students with extensive support needs and to students with other disabilities. We examined students' individualized education program (IEP)/transition planning meeting experiences and postschool goals in relation to their functional, communication, and self-advocacy skills, as well as their school/community support. Students with other disabilities held higher expectations than all students with extensive support needs for future participation in postsecondary education, employment, independent living, and financial independence. All students had higher postschool goal expectations than their parents. Implications for supporting students with extensive support needs and directions for future research and practice are discussed.

Combatting Antibiotic-Resistant Staphylococcus aureus: Discovery of TST1N-224, a Potent Inhibitor Targeting Response Regulator VraRC, through Pharmacophore-Based Screening and Molecular Characterizations.

Staphylococcus aureus (S. aureus) is a major global health concern, causing various infections and presenting challenges due to antibiotic resistance. In particular, methicillin-resistant S. aureus, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus pose significant obstacles in treating S. aureus infections. Therefore, the critical need for novel drugs to counter these resistant forms is pressing. Two-component systems (TCSs), integral to bacterial regulation, offer promising targets for disruption. In this study, a comprehensive approach, involving pharmacophore-based inhibitor screening, along with biochemical and biophysical analyses were conducted to identify, characterize, and validate potential inhibitors targeting the response regulator VraRC of S. aureus. The constructed pharmacophore model, Phar-VRPR-N3, demonstrated effectiveness in identifying a potent inhibitor, TST1N-224 (IC50 = 60.2 ± 4.0 µM), against the formation of the VraRC-DNA complex. Notably, TST1N-224 exhibited strong binding to VraRC (KD = 23.4 ± 1.2 µM) using a fast-on-fast-off binding mechanism. Additionally, NMR-based molecular modeling revealed that TST1N-224 predominantly interacts with the α9- and α10-helixes of the DNA-binding domain of VraR, where the interactive and functionally essential residues (N165, K180, S184, and R195) act as hotspots for structure-based inhibitor optimization. Furthermore, TST1N-224 evidently enhanced the susceptibility of VISA to both vancomycin and methicillin. Importantly, TST1N-224 distinguished by 1,2,5,6-tetrathiocane with the 3 and 8 positions modified with ethanesulfonates holds significant potential as a lead compound for the development of new antimicrobial agents.

A Web-Based Resilience-Enhancing Program to Improve Resilience, Physical Activity, and Well-being in Geriatric Population: Randomized Controlled Trial.

BACKGROUND: Resilience is a protective factor in healthy aging, helping to maintain and recover physical and mental functions. The Resilience in Illness Model has proven effective in fostering resilience and well-being. Physical activity is crucial for older adults' independence and well-being, even as aging causes a progressive decline. Additionally, older adults face challenges such as spousal loss and physical disability, making preventive intervention strategies necessary. OBJECTIVE: This study aims to develop and evaluate a web-based program to enhance resilience, physical activity, and well-being among community-dwelling older adults. Additionally, we aim to gather feedback on the program's strengths and limitations. METHODS: A 4-week resilience-enhancing program was created, incorporating role-play and talk-in-interaction and focusing on 3 key skills: coping, control belief, and manageability. The program included scenarios such as becoming widowed and suffering a stroke, designed to engage older adults. A pilot test preceded the intervention. As a result of the COVID-19 pandemic, the program shifted from in-person to web-based sessions. A single-blind, parallel-group, randomized controlled trial was conducted. Participants aged over 65 years were recruited offline and randomly assigned to either an intervention or control group. A certified resilience practitioner delivered the program. Outcomes in resilience, physical activity, and well-being were self-assessed at baseline (T0), 4 weeks (T1), and 12 weeks (T2) after the program. A mixed methods approach was used to evaluate feedback. RESULTS: A web-based participatory program enhancing 3 skills-coping, control belief, and manageability for resilience-was well developed. Among 96 participants, 63 were randomized into the intervention group (n=31) and the control group (n=32). The mean age in the intervention group was 69.27 (SD 3.08) years and 74.84 (SD 6.23) years in the control group. Significant between-group differences at baseline were found in age (t45.6=-4.53, P<.001) and physical activity at baseline (t61=2.92, P=.005). No statistically significant between-group differences over time were observed in resilience (SE 7.49, 95% CI -10.74 to 18.61, P=.60), physical activity (SE 15.18, 95% CI -24.74 to 34.74, P=.74), and well-being (SE 3.74, 95% CI -2.68 to 11.98, P=.21) after controlling for baseline differences. The dropout rate was lower in the intervention group (2/31, 6%) compared with the control group (5/32, 16%). Moreover, 77% (24/31) of participants in the intervention group completed the entire program. Program feedback from the participants indicated high satisfaction with the web-based format and mentorship support. CONCLUSIONS: This study demonstrated that a web-based resilience-enhancing program is appropriate, acceptable, feasible, and engaging for community-dwelling older adults. The program garnered enthusiasm for its potential to optimize resilience, physical activity, and well-being, with mentorship playing a crucial role in its success. Future studies should aim to refine program content, engagement, and delivery methods to effectively promote healthy aging in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05808491; https://clinicaltrials.gov/ct2/show/NCT05808491.

Identification of potential biomarkers of leprosy: A study based on GEO datasets.

Leprosy has a high rate of cripplehood and lacks available early effective diagnosis methods for prevention and treatment, thus novel effective molecule markers are urgently required. In this study, we conducted bioinformatics analysis with leprosy and normal samples acquired from the GEO database(GSE84893, GSE74481, GSE17763, GSE16844 and GSE443). Through WGCNA analysis, 85 hub genes were screened(GS > 0.7 and MM > 0.8). Through DEG analysis, 82 up-regulated and 3 down-regulated genes were screened(|Log2FC| > 3 and FDR < 0.05). Then 49 intersection genes were considered as crucial and subjected to GO annotation, KEGG pathway and PPI analysis to determine the biological significance in the pathogenesis of leprosy. Finally, we identified a gene-pathway network, suggesting ITK, CD48, IL2RG, CCR5, FGR, JAK3, STAT1, LCK, PTPRC, CXCR4 can be used as biomarkers and these genes are active in 6 immune system pathways, including Chemokine signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, T cell receptor signaling pathway, Natural killer cell mediated cytotoxicity and Leukocyte transendothelial migration. We identified 10 crucial gene markers and related important pathways that acted as essential components in the etiology of leprosy. Our study provides potential targets for diagnostic biomarkers and therapy of leprosy.

Structure-guided identification and characterization of potent inhibitors targeting PhoP and MtrA to combat mycobacteria.

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. Drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors of TCSs can disrupt bacterial signaling, growth, and virulence, and can help combat drug-resistant TB. We conducted a comprehensive pharmacophore-based inhibitor screening and biochemical and biophysical examinations to identify, characterize, and validate potential inhibitors targeting the response regulators PhoP and MtrA of mycobacteria. The constructed pharmacophore model Phar-PR-n4 identified effective inhibitors of formation of the PhoP-DNA complex: ST132 (IC50 = 29 ± 1.6 µM) and ST166 (IC50 = 18 ± 1.3 µM). ST166 (KD = 18.4 ± 4.3 µM) and ST132 (KD = 14.5 ± 0.1 µM) strongly targeted PhoP in a slow-on, slow-off manner. The inhibitory potency and binding affinity of ST166 and ST132 for MtrAC were comparable to those of PhoP. Structural analyses and molecular dynamics simulations revealed that ST166 and ST132 mainly interact with the α8-helix and C-terminal ß-hairpin of PhoP, with functionally essential residue hotspots for structure-based inhibitor optimization. Moreover, ST166 has in vitro antibacterial activity against Macrobacterium marinum. Thus, ST166, with its characteristic 1,2,5,6-tetrathiocane and terminal sulphonic groups, has excellent potential as a candidate for the development of novel antimicrobial agents to combat pathogenic mycobacteria.

Discovery of a potent inhibitor, D-132, targeting AsfvPolX, via protein-DNA complex-guided pharmacophore screening and in vitro molecular characterizations.

The heightened transmissibility and capacity of African swine fever virus (ASFV) induce fatal diseases in domestic pigs and wild boars, posing significant economic repercussions and global threats. Despite extensive research efforts, the development of potent vaccines or treatments for ASFV remains a persistent challenge. Recently, inhibiting the AsfvPolX, a key DNA repair enzyme, emerges as a feasible strategy to disrupt viral replication and control ASFV infections. In this study, a comprehensive approach involving pharmacophore-based inhibitor screening, coupled with biochemical and biophysical analyses, were implemented to identify, characterize, and validate potential inhibitors targeting AsfvPolX. The constructed pharmacophore model, Phar-PolX-S, demonstrated efficacy in identifying a potent inhibitor, D-132 (IC50 = 2.8 ± 0.2 µM), disrupting the formation of the AsfvPolX-DNA complex. Notably, D-132 exhibited strong binding to AsfvPolX (KD = 6.9 ± 2.2 µM) through a slow-on-fast-off binding mechanism. Employing molecular modeling, it was elucidated that D-132 predominantly binds in-between the palm and finger domains of AsfvPolX, with crucial residues (R42, N48, Q98, E100, F102, and F116) identified as hotspots for structure-based inhibitor optimization. Distinctively characterized by a 1,2,5,6-tetrathiocane with modifications at the 3 and 8 positions involving ethanesulfonates, D-132 holds considerable promise as a lead compound for the development of innovative agents to combat ASFV infections.

Postschool Goal Expectations for Youth With Intellectual and Developmental Disabilities.

Using National Longitudinal Transition Study 2012 data, this study explored parent and youth expectations in the areas of postsecondary education, employment, independent living, and financial independence. Compared to youth with other disabilities, youth with intellectual and developmental disabilities and their parents had much lower expectations for the four postschool goals, and parent expectations were much lower than youth's own expectations. Also, youth's race, along with their daily living skills and functional abilities, were positively associated with parent and youth expectations in several future goal areas. Our discussion highlights implications for improving the transition experiences of youth with intellectual and developmental disabilities.

Effects of coach extraversion and educational environment on transformational leadership and athlete outcomes: A moderated mediation model.

The importance of coach leadership to athlete development and performance has been identified in the literature. We respond to the call to investigate antecedents of coach transformational leadership and their indirect effects on athlete outcomes. We propose that coach extraversion as an antecedent of coach transformational leadership can indirectly impact follower cohesion and satisfaction. Building on this mediation model, we assert that educational environment (i.e., high school and university) may serve as a first-stage moderator between coach extraversion and transformational leadership. We used 48 coaches and their 570 athletes from competitive high school and university basketball teams to test this moderated mediation model. Our results indicate that coach extraversion indirectly impacts athlete cohesion and satisfaction via transformational leadership. Moreover, the indirect effects of coach extraversion on athlete outcomes via coach transformational leadership is conditionally significant only when coaches and athletes are in universities but not in high schools. Our findings highlight the importance of educational environment in determining the association between coach personality and leadership perception. Implications for research and practice are discussed.

Physical Therapy for Adults with Heart Failure.

Heart failure (HF) is a complex clinical syndrome caused by structural and/or functional abnormalities that results in significant disease burdens not only to the patients and their families but also to the society. Common symptoms/signs of HF include dyspnea, fatigue, and exercise intolerance, which significantly reduce the quality of life of individuals. Since the coronavirus disease 2019 (COVID-19) pandemic in 2019, it has been found that individuals with cardiovascular disease are more vulnerable to COVID-19-related cardiac sequelae including HF. In this article, we review the updated diagnosis, classifications, and interventional guidelines of HF. We also discuss the link between COVID-19 and HF. The latest evidence about physical therapy for patients with HF in both the stable chronic phase and acute cardiac decompensation phase is reviewed. Physical therapy for HF patients with circulatory support devices is also described.

Analysis of a Yp11.2 region deletion in a Chinese female with Turner syndrome: A case report.

In recent years, an increasing number of abnormal DNA genotypes caused by chromosomal abnormalities have been revealed in cases of individual identification and sex-typing analysis, especially analyses of the amelogenin and short tandem repeat (STR) loci on the sex chromosomes. Here, we report a 17-year-old female with Turner syndrome typed as male due to the presence of the amelogenin Y allele. The Y-STR haplotype showed allele dropout of three Y-STR loci (DYS549, DYS392 and DYS448). Further examination showed that the proband's karyotype was 45,X/46,X,del(Y) (q11.23), and the deletion of the Yp11.2 region was confirmed to encompass the observed microdeletion of the azoospermia factor (AZF)b + c region. One challenge in forensics is inaccurate sex typing of individuals at the molecular level, particularly for individuals with chromosomal abnormalities. This case suggests that various medical evaluations, including the examination of sex-related manifestations, karyotypes, and clinical phenotypes of individuals, along with the detection of sex-typing gene markers will be beneficial to overcome the issues caused by cytogenetic disorders of the sex chromosomes.

Immunogenicity of a spike protein subunit-based COVID-19 vaccine with broad protection against various SARS-CoV-2 variants in animal studies.

SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need. In this study, we developed a protein-based vaccine BCVax that is consisted of antigen delta strain spike protein and QS21-based adjuvant AB801 in nanoparticle immune stimulation complex format (AB801-ISCOM). Results from animal studies showed that high level of anti-S protein IgG was induced after two doses of BCVax and the IgG was capable of neutralizing multiple variants of pseudovirus including omicron BA.1 or BA.2 strains. In addition, strong Th1 response was stimulated after BCVax immunization. Furthermore, BCvax with AB801-ISCOM as the adjuvant showed significant stronger immunity compared with the vaccine using aluminum hydroxide plus CpG 1018 as the adjuvant. BCVax was also evaluated as a booster after two prior vaccinations, the IgG titers and pseudovirus neutralization activities against BA.2 or BA.4/BA.5 were further enhanced suggesting BCVax is a promising candidate as booster. Taken together, the pre-clinical data warrant BCVax for further development in clinic.

Hydrogen Bond-Enabled High-ICE Anode for Lithium-Ion Battery Using Carbonized Citric Acid-Coated Silicon Flake in PAA Binder.

A silicon-based lithium-ion battery (LIB) anode is extensively studied because of silicon's abundance, high theoretical specific capacity (4200 mAh/g), and low operating potential versus lithium. Technical barriers to large-scale commercial applications include the low electrical conductivity and up to about 400% volume changes of silicon due to alloying with lithium. Maintaining the physical integrity of individual silicon particles and the anode structure is the top priority. We use strong hydrogen bonds between citric acid (CA) and silicon to firmly coat CA on silicon. Carbonized CA (CCA) enhances electrical conductivity of silicon. Polyacrylic acid (PAA) binder encapsulates silicon flakes by strong bonds formed by abundant COOH functional groups in PAA and on CCA. It results in excellent physical integrity of individual silicon particles and the whole anode. The silicon-based anode shows high initial coulombic efficiency, around 90%, and the capacity retention of 1479 mAh/g after 200 discharge-charge cycles at 1 A/g current. At 4 A/g, the capacity retention of 1053 mAh/g was achieved. A durable high-ICE silicon-based LIB anode capable of high discharge-charge current has been reported.

The effectiveness of mind-body approaches for enhancing resilience in older adults: A systematic review and network meta-analysis.

BACKGROUND: Resilience in older adults is associated with good well-being and resilience training has been shown to be beneficial. Mind-body approaches (MBAs) combine physical and psychological training in age-appropriate exercise programs.This study aims to evaluate the comparative effectiveness of different modes of MBAs in enhancing resilience in older adults. METHOD: Electronic databases and a manual search were searched to identify randomized controlled trials of different MBA modes. Data from the included studies were extracted for fixed-effect pairwise meta-analyses. Quality and risk were assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Cochrane's Risk of Bias tool, respectively. Pooled effect sizes with a standardized mean difference (SMD) and a 95% confidence interval (CI) were used to quantify the impact of MBAs in enhancing resilience in older adults. Network meta-analysis was employed to evaluate the comparative effectiveness of different interventions. The study was registered in PROSPERO (Registration No. CRD42022352269). RESULTS: Nine studies were included in our analysis. Pairwise comparisons indicated that MBAs, regardless of whether they were related to yoga, could significantly enhancing resilience in older adults (SMD: 0.26, 95% CI 0.09-0.44). With strong consistency, a network meta-analysis showed that physical and psychological programs and yoga-related programs were associated with resilience improvement (SMD: 0.44, 95% CI 0.01-0.88 and SMD: 0.42, 95% CI 0.06-0.79, respectively). CONCLUSION: High quality evidence demonstrates that two MBA modes-physical and psychological programs and yoga-related programs-enhance resilience in older adults. However, long-term clinical verification is required to confirm our results.

Auxin plays a role in the adaptation of rice to anaerobic germination and seedling establishment.

Auxin is well known to stimulate coleoptile elongation and rapid seedling growth in the air. However, its role in regulating rice germination and seedling establishment under submergence is largely unknown. Previous studies revealed that excessive levels of indole-3-acetic acid(IAA) frequently cause the inhibition of plant growth and development. In this study, the high-level accumulation of endogenous IAA is observed under dark submergence, stimulating rice coleoptile elongation but limiting the root and primary leaf growth during anaerobic germination (AG). We found that oxygen and light can reduce IAA levels, promote the seedling establishment and enhance rice AG tolerance. miRNA microarray profiling and RNA gel blot analysis results show that the expression of miR167 is negatively regulated by submergence; it subsequently modulates the accumulation of free IAA through the miR167-ARF-GH3 pathway. The OsGH3-8 encodes an IAA-amido synthetase that functions to prevent free IAA accumulation. Reduced miR167 levels or overexpressing OsGH3-8 increase auxin metabolism, reduce endogenous levels of free IAA and enhance rice AG tolerance. Our studies reveal that poor seed germination and seedling growth inhibition resulting from excessive IAA accumulation would cause intolerance to submergence in rice, suggesting that a certain threshold level of auxin is essential for rice AG tolerance.

kHz-frequency electrical stimulation selectively activates small, unmyelinated vagus afferents.

BACKGROUND: Vagal reflexes regulate homeostasis in visceral organs and systems through afferent and efferent neurons and nerve fibers. Small, unmyelinated, C-type afferents comprise over 80% of fibers in the vagus and form the sensory arc of autonomic reflexes of the gut, lungs, heart and vessels and the immune system. Selective bioelectronic activation of C-afferents could be used to mechanistically study and treat diseases of peripheral organs in which vagal reflexes are involved, but it has not been achieved. METHODS: We stimulated the vagus in rats and mice using trains of kHz-frequency stimuli. Stimulation effects were assessed using neuronal c-Fos expression, physiological and nerve fiber responses, optogenetic and computational methods. RESULTS: Intermittent kHz stimulation for 30 min activates specific motor and, preferentially, sensory vagus neurons in the brainstem. At sufficiently high frequencies (>5 kHz) and at intensities within a specific range (7-10 times activation threshold, T, in rats; 15-25 × T in mice), C-afferents are activated, whereas larger, A- and B-fibers, are blocked. This was determined by measuring fiber-specific acute physiological responses to kHz stimulus trains, and by assessing fiber excitability around kHz stimulus trains through compound action potentials evoked by probing pulses. Aspects of selective activation of C-afferents are explained in computational models of nerve fibers by how fiber size and myelin shape the response of sodium channels to kHz-frequency stimuli. CONCLUSION: kHz stimulation is a neuromodulation strategy to robustly and selectively activate vagal C-afferents implicated in physiological homeostasis and disease, over larger vagal fibers.

IoT-Based Fish Farm Water Quality Monitoring System.

Typhoons in summer and cold snaps during winter in Taiwan often cause huge aquaculture losses. Simultaneously, the lack of human resources is a problem. Therefore, we used wireless transmission technology with various sensors to transmit the temperature, pH value, dissolved oxygen, water level, and life expectancy of the sensor in the fish farm to the server. The integrated data are transmitted to mobile devices through the Internet of Things, enabling administrators to monitor the water quality in a fish farm through mobile devices. Because the current pH sensors cannot be submerged in the liquid for a long time for measurements, human resources and time are required to take the instrument to each fish farm for testing at a fixed time. Therefore, a robotic arm was developed to complete automatic measurement and maintenance actions. We designed this arm with a programmable logic controller, a single chip combined with a wireless transmission module, and an embedded system. This system is divided into control, measurement, server, and mobility. The intelligent measurement equipment designed in this study can work 24 h per day, which effectively reduces the losses caused by personnel, material resources, and data errors.

LLPS of FXR1 drives spermiogenesis by activating translation of stored mRNAs.

Postmeiotic spermatids use a unique strategy to coordinate gene expression with morphological transformation, in which transcription and translation take place at separate developmental stages, but how mRNAs stored as translationally inert messenger ribonucleoproteins in developing spermatids become activated remains largely unknown. Here, we report that the RNA binding protein FXR1, a member of the fragile X-related (FXR) family, is highly expressed in late spermatids and undergoes liquid-liquid phase separation (LLPS) to merge messenger ribonucleoprotein granules with the translation machinery to convert stored mRNAs into a translationally activated state. Germline-specific Fxr1 ablation in mice impaired the translation of target mRNAs and caused defective spermatid development and male infertility, and a phase separation-deficient FXR1L351P mutation in Fxr1 knock-in mice produced the same developmental defect. These findings uncover a mechanism for translational reprogramming with LLPS as a key driver in spermiogenesis.

LMX1B Activated Circular RNA GFRA1 Modulates the Tumorigenic Properties and Immune Escape of Prostate Cancer.

Prostate cancer (PCa) is the most common cancer affecting men, with increasing global mortality and morbidity rates. Despite the progress in the diagnosis and treatment of PCa, patient outcomes remain poor, and novel therapeutic targets for PCa are urgently needed. Recently, circular RNAs (circRNAs) have been studied in-depth as potential biomarkers for many diseases. In this study, circRNA microarrays using four pairs of PCa tissues were utilized to show that circGFRA1 was upregulated in PCa tumor tissues. CircGFRA1 is suggested to play an oncogene role in PCa progression as the silencing of circGFRA1 inhibited the proliferation, migration, and immune escape activity of PCa cells. Furthermore, by utilizing bioinformatics analysis, RIP, RNA pull-down, and luciferase reporter assays, our results showed that LMX1B could bind to the GFRA1 promoter and regulate circGFRA1 expression in PCa cells and circGFRA1 upregulated HECTD1 expression through sponging miR-3064-5p. This novel LMX1B/circGFRA1/miR-3064-5p/HECTD1 axis identified in PCa provides new insights for developing novel therapeutic strategies for PCa.

Associations of Content Domain-Specific Possible Selves with Adolescent Drinking Behaviors.

Alcohol use ranks as one of the most prevalent health-risk behaviors among Taiwanese adolescents. Possible selves-personalized future-oriented cognitions about the self-are significant motivators of one's actions, which may potentially influence adolescent drinking behavior. This study aimed to estimate the content domain-specific possible selves and their associations with drinking behaviors among Taiwanese adolescents. A total of 225 Taiwanese seventh and eighth graders from a public junior high school were recruited. An anonymous self-reported questionnaire was used to collect data during two time-points at six-month intervals. Results showed that having a "physical appearance" related hoped-for possible self and a "friendship" related feared possible self was associated with adolescent alcohol use after six months. Whereas, having the "physical appearance" related hoped-for and feared possible selves were associated with alcohol problems, at both, baseline and six months later. Future studies could clarify the meaning behind "physical appearance" related possible selves.