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05). CONCLUSION LAG-3 is expressed in NSCLC tumor cells. Furthermore, LAG-3 not only is expressed in tumor-infiltrating lymphocytes in NSCLC patients but also is ectopically expressed in tumor cells and associated with TNM stage. © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.Finding causative genetic mutations is important in the diagnosis and treatment of hereditary peripheral neuropathies. This study was conducted to find new genes involved in the pathophysiology of hereditary peripheral neuropathy. We identified a new mutation in the EBP50 gene, which is co-segregated with neuropathic phenotypes, including motor and sensory deficit in a family with Charcot-Marie-Tooth disease. EBP50 is known to be important for the formation of microvilli in epithelial cells, and the discovery of this gene mutation allowed us to study the function of EBP50 in the nervous system. EBP50 was strongly expressed in the nodal and paranodal regions of sciatic nerve fibers, where Schwann cell microvilli contact the axolemma, and at the growth tips of primary Schwann cells. In addition, EBP50 expression was decreased in mouse models of peripheral neuropathy. Knockout mice were used to study EBP50 function in the peripheral nervous system. Interestingly motor function deficit and abnormal histology of nerve fibers were observed in EBP50+/- heterozygous mice at 12 months of age, but not 3 months. in vitro studies using Schwann cells showed that NRG1-induced AKT activation and migration were significantly reduced in cells overexpressing the I325V mutant of EBP50 or cells with knocked-down EBP50 expression. In conclusion, we show for the first time that loss of function due to EBP50 gene deficiency or mutation can cause peripheral neuropathy. © 2020 Wiley Periodicals, Inc.BACKGROUND A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). DNA Damage inhibitor We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario. METHODS We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG ≥ 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, ly significant PCa. Facing men with elevated PSA and/or suspicious DRE, it could be a useful tool to help avoid excess initial Bx and to identify patients most likely to benefit from Bx. © 2020 Wiley Periodicals, Inc.AIM Identification of patients with heart failure and a poor prognosis is paramount to ensure timely and adequate treatment. We investigated the relationship between the new measures of noninvasive pressure-strain analysis, such as the global work index (GWI), and established prognostic parameters of echocardiography, cardiopulmonary exercise test (CPX), and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP). METHODS AND RESULTS We retrospectively analyzed data of 51 patients with heart failure. Echocardiography and CPX were performed, and NT-pro-BNP was determined. Patients with a GWI 1000 mm Hg% (NT-pro-BNP median 253 pg/mL [IQR 150, 549]; peak VO2 15.6 ± 4.2 mL/min/kg). CONCLUSION GWI correlates with known prognostic markers of heart failure. A GWI of less then 500 mm Hg% was a predictor of severely impaired ejection fraction, very low exercise capacity, and strongly elevated NT-pro-BNP, indicating a poor prognosis. © 2020 Wiley Periodicals, Inc.PURPOSE Dynamic contrast-enhanced MRI can be used in pharmacokinetic models to quantify functional parameters such as perfusion and permeability. However, precise quantification in preclinical models is challenged by the difficulties to dynamically measure the true arterial blood contrast agent concentration. We propose a novel approach toward a precise and experimentally feasible method to derive the arterial input function from DCE-MRI in mice. METHODS Arterial blood was surgically shunted from the femoral artery to the tail vein and led through an extracorporeal circulation that resided on the head of brain tumor-bearing mice inside the FOV of a 9.4T MRI scanner. Dynamic 3D-FLASH scanning was performed after injection of gadobutrol with an effective resolution of 0.175 × 0.175 × 1 mm and a temporal resolution of 4 seconds. Pharmacokinetic modeling was performed using the extended Tofts and two-compartment exchange model. RESULTS Arterial input functions measured inside the extracorporeal circulation showed little noise, small interindividual variance, and typical curve shapes. Ex vivo and mass spectrometry validation measurements documented the influence of shunt flow velocity and hematocrit on estimation of contrast agent concentrations. Modeling of tumors and muscles allowed fitting of the recorded dynamic concentrations, resulting in quantitative plausible parameters. CONCLUSION The extracorporeal circulation allows deriving the contrast agent dynamics in arterial blood with high robustness and at acceptable experimental effort from DCE-MRI, previously not achievable in mice. It sets the basis for quantitative precise pharmacokinetic modeling in small animals to enhance the translatability of preclinical DCE-MRI measurements to patients. © 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.Due to advances in captive nonhuman primate (NHP) medical care, the number of geriatric chimpanzees (≥35-years old) is growing. With old age comes a variety of physical conditions, including arthritis, stroke, and mobility impairments. Programs aimed at enhancing the welfare of geriatric chimpanzees are now quite common, but there are few published empirical evaluations of the efficacy of such programs. The current study aimed to create, implement, and evaluate the effects of participation in a physical therapy (PT) program on physical health, mobility, welfare, and behavior. Nine chimpanzees with mobility impairments participated in personalized PT routines (using positive reinforcement training) twice per week for 5 months. Additionally, nine control chimpanzees (non-mobility-impaired, matched with PT chimpanzees on age and gender) participated in body exam behavior sessions (also using positive reinforcement training) twice per week. All chimpanzees were rated on 14 health, well-being, and behavior items, as well as level of mobility throughout the PT program.