During cancer progression, malignant cells in the tumour invade surrounding tissues. This transformation of adherent cells to a motile phenotype has been associated with the epithelial mesenchymal transition (EMT). Here, we show that EMT-activated cells migrate through micropillar arrays as a collectively advancing front that scatters individual cells. Individual cells with few neighbours dispersed with fast, straight trajectories, whereas cells that encountered many neighbours migrated collectively with epithelial biomarkers. We modelled these emergent dynamics using a physical analogy to solidification phase transitions in binary mixtures, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity. Our measurements also indicate a degree of phenotypic plasticity as cells interconvert between individual and collective migration. The study of multicellular behaviours with single-cell resolution should enable further quantitative insights into heterogeneous tumour invasion.

Study Objective To determine the association between Anticholinergic Cognitive Burden (ACB) score and both cognitive impairment and health care utilization among a diverse ambulatory older adult population. Design Retrospective cohort study. Data Source Medication exposure and other clinical data were extracted from the Regenstrief Medical Record System (RMRS), and cognitive diagnosis was derived from a dementia screening and diagnosis study. Patients A total of 3344 community-dwelling older adults (age 65 yrs and older) who were enrolled in a previously published dementia screening and diagnosis study; of these, 3127 were determined to have no cognitive impairment, and 217 were determined to have cognitive impairment. Measurements and Main Results The study followed a two-phase screening and comprehensive neuropsychiatric examination to determine a cognitive diagnosis, which defined cognitive impairment as dementia or mild cognitive impairment. The ACB scale was used to identify anticholinergics dispensed in the 12 months prior to screening. A total daily ACB score was calculated by using pharmacy dispensing data from RMRS; each anticholinergic was multiplied by 1, 2, or 3 consistent with anticholinergic burden defined by the ACB scale. The sum of all ACB medications was divided by the number of days with any medication dispensed to achieve the total daily ACB score. Health care utilization included visits to inpatient, outpatient, and the emergency department, and it was determined by using visit data from the RMRS. The overall population had a mean age of 71.5 years, 71% were female, and 58% were African American. Each 1-point increase in mean total daily ACB score was associated with increasing risk of cognitive impairment (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.004–1.27, p=0.043). Each 1-point increase in mean total daily ACB score increased the likelihood of inpatient admission (OR 1.11, 95% CI 1.02–1.29, p=0.014) and number of outpatient visits after adjusting for demographic characteristics, number of chronic conditions, and prior visit history (estimate 0.382, standard error [SE] 0.113; p=0.001). The number of visits to the emergency department was also significantly different after similar adjustments (estimate 0.046, SE 0.023, p=0.043). Conclusion Increasing total ACB score was correlated with an increased risk for cognitive impairment and more frequent health care utilization. Future work should study interventions that safely reduce ACB and evaluate the impact on brain health and health care costs.

With over 110,000 patients waiting for organ transplantation, the current crisis in organ transplantation is based on a lack of donors after brain-death (DBD). A very large alternative pool of donor organs that remain untapped are the donors after cardiac death (DCD), recovered after cardiac activity has ceased and therefore sustained some ischemic injury. Machine perfusion has been proposed as a novel modality of organ preservation and treatment to render such cadaveric organs, and in particular livers, transplantable. Two key issues that remain unaddressed are how to assess whether a DCD liver is damaged beyond repair, and whether machine perfusion has rendered an injured organ sufficiently viable for transplantation. In this work, we present a metabolic analysis of the transient responses of cadaveric rat livers during normothermic machine perfusion (NMP), and develop an index of ischemia that enables evaluation of the organ ischemic injury level. Further, we perform a discriminant analysis to construct a classification algorithm with >0.98 specificity to identify whether a given perfused liver is ischemic or fresh, in effect a precursor for an index of transplantability and a basis for the use of statistical process control measures for automated feedback control of treatment of ischemic injury in DCD livers. The analyses yield an index based on squared prediction error (SPE) as log(SPE) >1.35 indicating ischemia. The differences between metabolic functions of fresh and ischemic livers during perfusion are outlined and the metabolites that varied significantly for ischemic livers are identified as ornithine, arginine, albumin and tyrosine.