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Abstract Suicide remains a leading cause of death and a significant public health concern in the United States. A majority (83%) of suicide decedents had a healthcare visit within the prior 365 days, presenting unique opportunities to utilize healthcare data for AI-based interventions. While previous works applied machine learning (ML) to analyze healthcare records for suicide attempt risk prediction (SARP), they lack external validation. Additionally, advantages of deep learning (DL) over ML for tabular SARP remains understudied. We performed external validation of a state-of-the-art SARP model from the Mental Health Research Network using over 750,000 UMass Memorial Health patient encounters. We further compared ML vs DL, assessing cross-setting healthcare generalizability. We found existing models did not generalize well, ML significantly outperformed DL on most metrics, and DL achieved higher sensitivity. These findings underscore the need for developing robust, generalizable SARP models for diverse healthcare contexts, improving identification of individuals at risk. 

Reconstruction of critical-size bone defects remains a persistent clinical challenge after trauma, tumour resection and degenerative disease. Nanoparticles (NPs) have emerged as versatile platforms that couple tunable material properties with targeted molecular delivery to direct regeneration. This review synthesizes advances from the past decade across inorganic (for example, nanostructured hydroxyapatite and bioactive glasses), polymeric, lipid, and bioinspired NPs, and links key design parameters—size, shape, mechanics, surface chemistry and degradability—to osteogenic outcomes. We examine how NPs steer stem-cell fate through mechanotransduction and canonical signaling (Wnt/β-catenin, BMP/Smad, MAPK), and highlight emerging mechanisms including controlled ion release, redox modulation, protein-corona dynamics and macrophage immune reprogramming toward pro-healing phenotypes. Three key modes of translational application are emphasized: NPs as carriers for proteins, nucleic acids and small molecules; as bioactive or reinforcing components within load-bearing scaffolds; and as injectable microenvironments that provide spatiotemporal control of cell signaling cues. Ongoing clinical applications in dental, orthopedic and spinal therapeutics show growing adoption, while also revealing gaps in long-term safety, Good Manufacturing Practices (GMP), and regulation. In future developments, stimuli-responsive and self-reporting nanomaterials, informed by AI-guided design and integrated with 3D bioprinting, offer routes to patient-specific grafts with predictable performance. By consolidating mechanisms into practical design rules, we chart a path from tunable nanoscale interfaces to reliable, clinically impactful bone regeneration. 

Organoids are self-organizing, three-dimensional structures that replicate the main features of an organ. It is a fast-evolving area of research in regenerative medicine and cell biology. While the primary or stem cells are adapted for most of the organoid systems, Human Embryonic Kidney (HEK) 293T cells have been used in specialized applications within organoid systems when genetic manipulation is necessary. Unfortunately, HEK293T cells often suffer from loose adherence, which limits their applications in organoid formation. To improve cellular adhesion and proliferation, and to provide insights into the pathways involved in adhesion, HEK293T cells were cultured on a glass substrate sputtered with indium tin oxide (ITO) that is covered with a self-assembled monolayer (SAM) of 3-(mercaptopropyl) trimethoxysilane (MPS) (hereafter known as ITO-MPS SAM-coated substrate), a SAM of 3-(aminopropyl) triethoxysilane (APTES), and a SAM of 1-octadecanethiol (ODT). The ITO-MPS SAM scaffold yielded the most promising results, based on cell proliferation using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays. Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyze the metabolomics present in the media with and without ITO-MPS-SAM coated substrates for a period of 120 h. The findings from the MTT assays demonstrate improved cell adhesion and proliferation on the ITO-MPS SAM-scaffold. The confocal microscopy images are consistent with these findings and provide a visual confirmation of the enhanced cellular environment. The metabolomic analysis yielded twenty-six metabolites, including sixteen adhesion promoters and modulators. These findings provide valuable insights into optimizing substrate conditions for improving cell adhesion and proliferation in HEK293T cells, potentially enhancing 3D cell culture and organoid research. The study also highlights novel metabolomic changes associated with improved cellular adhesion, contributing to the broader field of regenerative medicine and tissue engineering. 

ABSTRACT Ferroelectric domain variants that are energetically equivalent are expected to remain preserved during polarization reversal under a symmetry‐preserving electric field. However, recent experiments on relaxor–ferroelectric crystals have revealed irreversible elimination of inclined domain walls during AC poling, while the underlying mesoscale mechanism remains unclear. Here, we investigate domain‐wall motion during AC poling of rhombohedral Pb()– single crystals containing 71 and 109 domain walls within a quasi‐two‐dimensional laminated geometry using phase‐field simulations. Simulations reveal that domain‐wall behavior during polarization reversal depends on the spacing ratio between 71 and 109 domain walls. Closely spaced 71 domain walls undergo irreversible elimination, whereas widely separated walls are preserved. A threshold ratio for domain‐wall elimination is identified and found to depend on mechanical boundary conditions. By tracking domain‐wall trajectories, we attribute this behavior to unsynchronized motion of neighboring 71 domain walls arising from long‐range elastic interactions when walls become strongly coupled. This collective motion breaks the symmetry between domain variants and leads to irreversible domain‐wall elimination. These findings provide mechanistic insight into collective domain‐wall evolution during polarization reversal and suggest that proximity‐driven symmetry breaking may provide a mesoscale mechanism for domain engineering in ferroelectrics with high domain‐wall densities. 

Adolescent binge drinking in humans is associated with adverse outcomes, here we examined sex- and withdrawal-dependent changes in affective behaviors and metabolomic profiles in male and female mice following AIE exposure. Male and female C57BL/6 J mice were exposed to intermittent ethanol vapor inhalation from postnatal (PND) 28–42, a model of intermittent binge-like ethanol exposure during adolescence. Affective behavior was assessed using the open field test (OFT), light/dark test (LDT), and tail suspension test (TST) during short-term withdrawal (PND 49–53) and again during long-term withdrawal (PND 91–95). Serum samples were collected 24 h after the final exposure cycle (PND 43), fecal samples were collected during each OFT, and liver samples were collected at euthanasia (PND 119; ~80 days after exposure) for metabolomic analysis. Ethanol sensitivity in adulthood was additionally assessed using loss of righting reflex (LORR) on PND 116. Overall, AIE produced modest, sex- and withdrawal-dependent behavioral effects, whereas metabolomic differences were most pronounced in males shortly after exposure and diminished with longer withdrawal. These findings support future work testing whether early metabolomic shifts track later behavioral vulnerability.