Cell‐intrinsic metabolic reprogramming is a hallmark of cancer that provides anabolic support to cell proliferation. How reprogramming influences tumor heterogeneity or drug sensitivities is not well understood. Here, we report a self‐organizing spatial pattern of glycolysis in xenograft colon tumors where pyruvate dehydrogenase kinase (PDK1), a negative regulator of oxidative phosphorylation, is highly active in clusters of cells arranged in a spotted array. To understand this pattern, we developed a reaction–diffusion model that incorporates Wnt signaling, a pathway known to upregulate PDK1 and Warburg metabolism. Partial interference with Wnt alters the size and intensity of the spotted pattern in tumors and in the model. The model predicts that Wnt inhibition should trigger an increase in proteins that enhance the range of Wnt ligand diffusion. Not only was this prediction validated in xenograft tumors but similar patterns also emerge in radiochemotherapy‐treated colorectal cancer. The model also predicts that inhibitors that target glycolysis or Wnt signaling in combination should synergize and be more effective than each treatment individually. We validated this prediction in 3D colon tumor spheroids.

Electrocorticography has been widely explored as a long-term signal acquisition platform for brain-computer interface (BCI) control of upper extremity prostheses. However, a comprehensive study of elementary upper extremity movements and their relationship to electrocorticogram (ECoG) signals has yet to be performed. This study examines whether kinematic parameters of 6 elementary upper extremity movements can be decoded from ECoG signals in 3 subjects undergoing subdural electrode placement for epilepsy surgery evaluation. To this end, we propose a 2-stage decoding approach that consists of a state decoder to determine idle/move states, followed by a Kalman filter-based trajectory decoder. This proposed decoder successfully classified idle/move states with an average accuracy of 91%, and the correlation between decoded and measured trajectory averaged 0.70 for position and 0.68 for velocity. These performances represent an improvement over a simple regression-based approach.

Background Covert cerebrovascular disease (CCD) has been shown to be associated with dementia in population‐based studies with magnetic resonance imaging (MRI) screening, but dementia risk associated with incidentally discovered CCD is not known. Methods and Results Individuals aged ≥50 years enrolled in the Kaiser Permanente Southern California health system receiving head computed tomography (CT) or MRI for nonstroke indications from 2009 to 2019, without prior ischemic stroke/transient ischemic attack, dementia/Alzheimer disease, or visit reason/scan indication suggestive of cognitive decline or stroke were included. Natural language processing identified incidentally discovered covert brain infarction (id‐CBI) and white matter disease (id‐WMD) on the neuroimage report; white matter disease was characterized as mild, moderate, severe, or undetermined. We estimated risk of dementia associated with id‐CBI and id‐WMD. Among 241 050 qualified individuals, natural language processing identified 69 931 (29.0%) with id‐WMD and 11 328 (4.7%) with id‐CBI. Dementia incidence rates (per 1000 person‐years) were 23.5 (95% CI, 22.9–24.0) for patients with id‐WMD, 29.4 (95% CI, 27.9–31.0) with id‐CBI, and 6.0 (95% CI, 5.8–6.2) without id‐CCD. The association of id‐WMD with future dementia was stronger in younger (aged <70 years) versus older (aged ≥70 years) patients and for CT‐ versus MRI‐discovered lesions. For patients with versus without id‐WMD on CT, the adjusted HR was 2.87 (95% CI, 2.58–3.19) for older and 1.87 (95% CI, 1.79–1.95) for younger patients. For patients with versus without id‐WMD on MRI, the adjusted HR for dementia risk was 2.28 (95% CI, 1.99–2.62) for older and 1.48 (95% CI, 1.32–1.66) for younger patients. The adjusted HR for id‐CBI was 2.02 (95% CI, 1.70–2.41) for older and 1.22 (95% CI, 1.15–1.30) for younger patients for either modality. Dementia risk was strongly correlated with id‐WMD severity; adjusted HRs compared with patients who were negative for id‐WMD by MRI ranged from 1.41 (95% CI, 1.25–1.60) for those with mild disease on MRI to 4.11 (95% CI, 3.58–4.72) for those with severe disease on CT. Conclusions Incidentally discovered CCD is common and associated with a high risk of dementia, representing an opportunity for prevention. The association is strengthened when discovered at younger age, by increasing id‐WMD severity, and when id‐WMD is detected by CT scan rather than MRI.

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