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Species Sensitivity Distribution (SSD) is a key metric for understanding the potential ecotoxicological impacts of chemicals. However, SSDs have been developed to estimate for only handful of chemicals due to the scarcity of experimental toxicity data. Here we present a novel approach to expand the chemical coverage of SSDs using Artificial Neural Network (ANN). We collected over 2000 experimental toxicity data in Lethal Concentration 50 (LC50) for 8 aquatic species and trained an ANN model for each of the 8 aquatic species based on molecular structure. The R2 values of resulting ANN models range from 0.54 to 0.75 (median R2 = 0.69). We applied the predicted LC50 values to fit SSD curves using bootstrapping method, generating SSDs for 8424 chemicals in the ToX21 database. The dataset is expected to serve as a screening-level reference SSD database for understanding potential ecotoxicological impacts of chemicals.

Significant cellular senescence has been observed in cartilage harvested from patients with osteoarthritis (OA). In this study, we aim to develop a senescence-relevant OA-like cartilage model for developing disease-modifying OA drugs (DMOADs). Specifically, human bone marrow-derived mesenchymal stromal cells (MSCs) were expanded in vitro up to passage 10 (P10-MSCs). Following their senescent phenotype formation, P10-MSCs were subjected to pellet culture in chondrogenic medium. Results from qRT-PCR, histology, and immunostaining indicated that cartilage generated from P10-MSCs displayed both senescent and OA-like phenotypes without using other OA-inducing agents, when compared to that from normal passage 4 (P4)-MSCs. Interestingly, the same gene expression differences observed between P4-MSCs and P10-MSC-derived cartilage tissues were also observed between the preserved and damaged OA cartilage regions taken from human samples, as demonstrated by RNA Sequencing data and other analysis methods. Lastly, the utility of this senescence-initiated OA-like cartilage model in drug development was assessed by testing several potential DMOADs and senolytics. The results suggest that pre-existing cellular senescence can induce the generation of OA-like changes in cartilage. The P4- and P10-MSCs derived cartilage models also represent a novel platform for predicting the efficacy and toxicity of potential DMOADs on both preserved and damaged cartilage in humans.

Although the depression and anxiety subscales (DASS-D and DASS-A) of the 21-item Depression, Anxiety, and Stress Scales are commonly used in adolescents, few studies have investigated the convergent validity of/potential cutoff scores for these subscales in U.S. adolescents. To address these gaps, 306 U.S. adolescents completed the DASS-21, Generalized Anxiety Disorder-7 scale (GAD7), and Center for Epidemiological Studies-Depression Scale (CESD). The DASS-D and CESD were strongly correlated, while the DASS-A and GAD7 were strongly correlated in males and more moderately correlated in females. Using the CESD as reference, DASS-D cutoff scores of four for males and five for females provided the best balance of sensitivity and specificity. When using the GAD7 as reference, DASS-A cutoffs of six for females and five for males appeared best. These findings suggest the DASS-A and DASS-D demonstrate good convergent validity and may be suitable for identifying adolescents who are significantly anxious and/or depressed.

While the 21-item version of the Depression, Anxiety, and Stress Scales (DASS-21) is commonly used to measure depression, anxiety, and stress, there is emerging evidence that the DASS-21 total score can be used as a measure of distress in adolescents as well. However, little research has investigated the convergent validity of the DASS-21 as a measure of distress, and no studies have examined potential cutoffs for the DASS-21total score in adolescents. To address these gaps, the present study investigated the convergent validity of the DASS-21’s total score and determined preliminary cutoff scores that could be used to identify adolescents that are clinically distressed. After 306 high school students (mean age = 15.35) from midwestern USA high schools completed the DASS-21 and Langner Symptom Survey (LSS), a MANOVA revealed significant sex differences. In light of these differences, analyses were carried out separately for male and female adolescents. These analyses revealed that the DASS-21 total score was significantly correlated with the LSS for males (r = .80) and females (r = .76). When using adolescents’ classification on the LSS as a reference point, a cutoff score of 14 appeared to be best suited for female adolescents (sensitivity = .78; specificity = .74; AUC = .84), while a cutoff score of 17 appeared best for male adolescents (sensitivity = .72; specificity = .95, AUC = .99). These findings suggest that the DASS-21 total score demonstrates good convergent validity as a measure of distress and may be suitable for identifying adolescents that are clinically distressed. However, further validation of the present preliminary cutoff points is needed.