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This study utilised the Early Growth and Development Study (N = 561 adoptive children; 57.2% male, 55.3% White), a study of children adopted at birth, to examine heritable (birth parent psychopathology) and prenatal risk (prenatal maternal distress and smoking during pregnancy), infant negative affectivity, adoptive parent over‐reactivity and warmth as independent predictors of childhood externalising symptoms. The current study evaluated if: (1) infant negative affectivity and over‐reactive parenting are candidate mediators for the effects of heritable and prenatal risk on externalising symptoms and (2) parental warmth weakens the influence of heritable risk, prenatal risk, negative affectivity and over‐reactive parenting on externalising symptoms. There were main effects of heritable risk, infant negative affectivity and over‐reactive parenting on child externalising symptoms. The study found no support for the hypothesised mediation and moderation effects, suggesting that targeting parental over‐reactivity rather than warmth would be more effective in reducing the risk for childhood externalising symptoms. [ABSTRACT FROM AUTHOR]

Neurodevelopmental disorders (NDD) in offspring are associated with a complex combination of pre-and postnatal factors. This study uses machine learning and population data to evaluate the association between prepregnancy or perinatal risk factors and the NDD of offspring. Population-based retrospective cohort data were obtained from Korea National Health Insurance Service claims data for 209,424 singleton offspring and their mothers who gave birth for the first time in 2007. The dependent variables were motor development disorder (MDD), cognitive development disorder (CDD) and combined overall neurodevelopmental disorder (NDD) from offspring. Seventeen independent variables from 2002 to 2007 were included. Random forest variable importance and Shapley Additive Explanation (SHAP) values were calculated to analyze the directions of its associations with the predictors. The random forest with oversampling registered much higher areas under the receiver-operating-characteristic curves than the logistic regression of interaction and non-linearity terms, 79% versus 50% (MDD), 82% versus 52% (CDD) and 74% versus 50% (NDD). Based on random forest variable importance, low socioeconomic status and age at birth were highly ranked. In SHAP values, there was a positive association between NDD and pre- or perinatal outcomes, especially, fetal male sex with growth restriction associated the development of NDD in offspring. [ABSTRACT FROM AUTHOR]

Leucine‐rich repeat kinase 2 (LRRK2) is considered a promising therapeutic target for Parkinson's disease, Crohn's disease, and cancer. Despite considerable research, none of these inhibitors are available for clinical application. Herein, we designed and synthesized novel thienopyrimidine derivatives by a bioisosteric replacement and investigated their structure–activity relationships. Thieno[3,2‐d]pyrimidine derivative 22 showed the most potent inhibitory activity and inhibited both wild‐type and G2019S mutant LRRK2 with IC50 values of 30 and 14 nM, respectively. [ABSTRACT FROM AUTHOR]

Objective Background Method Results Conclusion Implications This community‐engaged codesign project identified the changes needed to tailor a family resilience‐building program, the Families Tackling Tough Times Together (FT), into a community setting.There is a need for low‐burden resources to help families mitigate stressful times and build resilience. Guided by Walsh's family resilience framework, FT aims to improve families' ability to cope, recover, and build resilience. Due to the success of FT during the COVID‐19 pandemic, the program is now being modified to help families in the state of Indiana.Three codesign workshops were held with community service providers (CSP) and families. Participants engaged with the FT materials and discussions related to program usability and feasibility. Data were analyzed using a rapid analysis approach.CSPs stated that FT program materials fit with their goals and workload. Families felt the FT program aligned with their personal needs and day‐to‐day lives. Challenges and concerns with the FT materials included activities that required additional resources or that may be intimidating for families to complete. Both CSPs and families provided helpful suggestions on how to modify the materials.The FT program was well received by participants and was viewed as a valuable addition to the services CSPs offer. Modifications will be made to the FT materials based on knowledge gained from the workshops.This work highlights the collaborative nature of the codesign process as well as the insights gained from participants regarding the use of the FT materials by CSPs as part of their routine service delivery with families in the community. [ABSTRACT FROM AUTHOR]

This study introduces a thermally responsive smart hydrogel with enhanced electrical properties achieved through volume switching. This advancement was realized by incorporating multiscale liquid metal particles (LMPs) into the PNIPAM hydrogel during polymerization, using their inherent elasticity and conductivity when deswelled. Unlike traditional conductive additives, LMPs endow the PNIPAM hydrogel with a remarkably consistent volume switching ratio, significantly enhancing electrical switching. This is attributed to the minimal nucleation effect of LMPs during polymerization and their liquid-like behavior, like vacancies in the polymeric hydrogel under compression. The PNIPAM/LMP hydrogel exhibits the highest electrical switching, with an unprecedented switch of 6.1 orders of magnitude. Even after repeated swelling/deswelling cycles that merge some LMPs and increase the conductivity when swelled, the hydrogel consistently maintains an electrical switch exceeding 4.5 orders of magnitude, which is still the highest record to date. Comprehensive measurements reveal that the hydrogel possesses robust mechanical properties, a tissue-like compression modulus, biocompatibility, and self-healing capabilities. These features make the PNIPAM/LMP hydrogel an ideal candidate for long-term implantable bioelectronics, offering a solution to the mechanical mismatch with dynamic human tissues.