We show that the algorithm’s ability to reduce unexplained disparities is rooted in the racial and socioeconomic diversity of the training set. Because algorithmic severity measures better capture underserved patients’ pain, and severity measures influence treatment decisions, algorithmic predictions could potentially redress disparities in access to treatments like arthroplasty.Despite recent therapeutic advances in cancer treatment, metastasis remains the principal cause of cancer death. Recent work has uncovered the unique biology of metastasis-initiating cells that results in tumor growth in distant organs, evasion of immune surveillance and co-option of metastatic microenvironments. Here we review recent progress that is enabling therapeutic advances in treating both micro- and macrometastases. Such insights were gained from cancer sequencing, mechanistic studies and clinical trials, including of immunotherapy. These studies reveal both the origins and nature of metastases and identify new opportunities for developing more effective strategies to target metastatic relapse and improve patient outcomes.Shadow enhancers are seemingly redundant transcriptional cis-regulatory elements that regulate the same gene and drive overlapping expression patterns. Recent studies have shown that shadow enhancers are remarkably abundant and control most developmental gene expression in both invertebrates and vertebrates, including mammals. Shadow enhancers might provide an important mechanism for buffering gene expression against mutations in non-coding regulatory regions of genes implicated in human disease. Technological advances in genome editing and live imaging have shed light on how shadow enhancers establish precise gene expression patterns and confer phenotypic robustness. Shadow enhancers can interact in complex ways and may also help to drive the formation of transcriptional hubs within the nucleus. Despite their apparent redundancy, the prevalence and evolutionary conservation of shadow enhancers underscore their key role in emerging metazoan gene regulatory networks.Rheumatoid arthritis (RA) is characterized by joint leukocyte infiltration, synovial inflammation and bone damage result from osteoclastogenesis. Bruton’s tyrosine kinase (BTK) is a key regulator of B cell receptor (BCR) and Fc gamma receptor (FcγR) signaling involved in the pathobiology of RA and other autoimmune disorders. SOMCL-17-016 is a potent and selective tricyclic BTK inhibitor, structurally distinct from other known BTK inhibitors. In present study we investigated the therapeutic efficacy of SOMCL-17-016 in a mouse collagen-induced arthritis (CIA) model and underlying mechanisms. CIA mice were administered SOMCL-17-016 (6.25, 12.5, 25 mg·kg-1·d-1, ig), or ibrutinib (25 mg·kg-1·d-1, ig) or acalabrutinib (25 mg·kg-1·d-1, ig) for 15 days. We showed that oral administration of SOMCL-17-016 dose-dependently ameliorated arthritis severity and bone damage in CIA mice; it displayed a higher in vivo efficacy than ibrutinib and acalabrutinib at the corresponding dosage. We found that SOMCL-17-016 administration dose-dependently inhibited anti-IgM-induced proliferation and activation of B cells from CIA mice, and significantly decreased anti-IgM/anti-CD40-stimulated RANKL expression in memory B cells from RA patients. In RANKL/M-CSF-stimulated RAW264.7 cells, SOMCL-17-016 prevented osteoclast differentiation and abolished RANK-BTK-PLCγ2-NFATc1 signaling. In summary, this study demonstrates that SOMCL-17-016 presents distinguished therapeutic effects in the CIA model. SOMCL-17-016 exerts a dual inhibition of B cell function and osteoclastogenesis, suggesting that it to be a promising drug candidate for RA treatment.Several viruses of the corona family interact, via their spike (S) proteins, with human cellular receptors. Spike proteins of SARS-CoV-1 and SARS-CoV-2 virions, being structurally related but not identical, mediate attachment to the human angiotensin-converting enzyme 2 (hACE2) receptor in similar but non-identical ways. Molecular-level understanding of interactions between spike proteins and hACE2 can aid strategies for blocking attachment of SARS-CoV-1, a potentially reemerging health threat, to human cells. We have identified dominant molecular-level interactions, some attractive and some repulsive, between the receptor binding domain of SARS-CoV-1 spike proteins (S-RBD) and hACE2. We performed fragment-based quantum-biochemical calculations which directly relate biomolecular structure to the hACE2…S-RBD interaction energy. Consistent with X-ray crystallography and cryo-EM, the interaction energy between hACE2 and S-RBD ([Formula see text]26 kcal/mol) corresponds to a net intermolecular attraction which is significantly enhanced by inclusion of dispersion van der Waals forces. Protein fragments at the hACE2…S-RBD interface, that dominate host-virus attraction, have been identified together with their constituent amino acid residues. Two hACE2 fragments which include residues (GLU37, ASP38, TYR41, GLN42) and (GLU329, LYS353, GLY354), respectively, as well as three S-RBD fragments which include residues (TYR436), (ARG426) and (THR487, GLY488, TYR491), respectively, have been identified as primary attractors at the hACE2…S-RBD interface.We introduce a novel visual-stimuli four-arm maze (ViS4M) equipped with spectrally- and intensity-controlled LED emitters and dynamic grayscale objects that relies on innate exploratory behavior to assess color and contrast vision in mice. Its application to detect visual impairments during normal aging and over the course of Alzheimer’s disease (AD) is evaluated in wild-type (WT) and transgenic APPSWE/PS1∆E9 murine models of AD (AD+) across an array of irradiance, chromaticity, and contrast conditions. Substantial color and contrast-mode alternation deficits appear in AD+ mice at an age when hippocampal-based memory and learning is still intact. Profiling of timespan, entries and transition patterns between the different arms uncovers variable AD-associated impairments in contrast sensitivity and color discrimination, reminiscent of tritanomalous defects documented in AD patients. Transition deficits are found in aged WT mice in the absence of alternation decline. MEK inhibitor drugs Overall, ViS4M is a versatile, controlled device to measure color and contrast-related vision in aged and diseased mice.