The chemotherapeutic use of cisplatin is limited by its severe side effects. In this study, by conducting different omics data analyses, we demonstrated that cisplatin induces cell death in a proximal tubular cell line by suppressing glycolysis- and tricarboxylic acid (TCA)/mitochondria-related genes. Furthermore, analysis of the urine from cisplatin-treated rats revealed the lower expression levels of enzymes involved in glycolysis, TCA cycle, and genes related to mitochondrial stability and confirmed the cisplatin-related metabolic abnormalities. Additionally, an increase in the level of p53, which directly inhibits glycolysis, has been observed. Inhibition of p53 restored glycolysis and significantly reduced the rate of cell death at 24 h and 48 h due to p53 inhibition. The foremost reason of cisplatin-related cytotoxicity has been correlated to the generation of mitochondrial reactive oxygen species (ROS) that influence multiple pathways. Abnormalities in these pathways resulted in the collapse of mitochondrial energy production, which in turn sensitized the cells to death. The quenching of ROS led to the amelioration of the affected pathways. Considering these observations, it can be concluded that there is a significant correlation between cisplatin and metabolic dysfunctions involving mROS as the major player.

Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1 years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4 minutes 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4x/week for 8 weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001) respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance.

Aortic pulse wave velocity (AoPWV) and augmentation index (AIx) are commonly used measures of large elastic artery stiffness and wave reflection, respectively. Recently, a new cuff-based SphygmoCor device (Xcel) has been developed to measure both AoPWV and AIx. We sought to examine the following: (1) the validity of Xcel compared with the well-validated tonometry-based SphygmoCor device (MM3); (2) the intratest and day-to-day reliability of Xcel; (3) the influence of body side (right or left) on Xcel measurements; and (4) the relation of Xcel measurements to carotid artery compliance, distensibility and β-stiffness index. We found that measurements of AoPWV and AIx between Xcel and MM3 were not different (P=0.26 and P=0.43, N=22 and 26, respectively) and were strongly related (r=0.85 and 0.75, P<0.0001), and based on Bland-Altman plots there was good agreement between them. Intra-test (intraclass correlation=0.996 and 0.983, P<0.0001; AoPWV and AIx, N=24 and 26, respectively) and day-to-day reliability (intraclass correlation=0.979 and 0.939, P<0.0001) were high. Xcel AoPWV and AIx on the left versus right body side were not different (P=0.19 and P=0.58, N=14 and 15, respectively) and were highly correlated (r=0.99 and 0.94, P<0.0001). AoPWV and AIx measured with Xcel were positively related with β-stiffness index (r=0.62 and 0.51, P< or = 0.005, N=23 and 24, respectively) and negatively related with distensibility (r = -0.58 and -0.44, P < or = 0.02, N=23 and 24, respectively). In conclusion, Xcel measures of AIx and AoPWV are valid, highly reliable and not affected by body side. Xcel is a useful tool for use in research and the clinic.

Two document representation methods are mainly used in solving text mining problems. Known for its intuitive and simple interpretability, the bag-ofwords method represents a document vector by its word frequencies. However, this method suffers from the curse of dimensionality, and fails to preserve accurate proximity information when the number of unique words increases. Furthermore, this method assumes every word to be independent, disregarding the impact of semantically similar words on preserving document proximity. On the other hand, doc2vec, a basic neural network model, creates low dimensional vectors that successfully preserve the proximity information. However, it loses the interpretability as meanings behind each feature is indescribable. This paper proposes the bag-of-concepts method as an alternative document representation method that overcomes the weaknesses of these two methods. This proposed method creates concepts through clustering word vectors generated from word2vec, and uses the frequencies of these concept clusters to represent document vectors. Through these data-driven concepts, the proposed method incorporates the impact of semantically similar ii words on preserving document proximity effectively. With appropriate weighting scheme such as concept frequency-inverse document frequency, the proposed method provides better document representation than previously suggested methods, and also offers intuitive interpretability behind the generated document vectors. Based on the proposed method, subsequently constructed text mining models, such as decision tree, can also provide interpretable and intuitive reasons on why certain collections of documents are different from others.

Large elastic arteries stiffen with age which predisposes older adults to increased risk for cardiovascular disease. Aerobic exercise training is known to reduce the risk for cardiovascular disease, but the optimal exercise prescription for attenuating large elastic arterial stiffening in older adults is not known. Purpose The purpose of this randomized controlled trial was to compare the effect of all-extremity high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on aortic pulse wave velocity (PWV) and carotid artery compliance in older adults. Methods Forty-nine sedentary older adults (age: 64±1 years), free of overt major clinical disease, were randomized to HIIT (n=17), MICT (n=18) or non-exercise controls (CONT; n=14). HIIT (4x4 minutes at 90% of peak heart rate interspersed with 3x3 minutes active recovery at 70% of peak heart rate) and isocaloric MICT (70% of peak heart rate) were performed on an all-extremity non-weight-bearing ergometer, 4 days/week, for 8 weeks under supervision. Aortic (carotid to femoral; cfPWV) and common carotid artery compliance were assessed at pre- and post-intervention. Results cfPWV improved by 0.5 m/sec in MICT (P=0.04), but did not significantly change in HIIT and CONT (P>0.05). Carotid artery compliance improved by 0.03 mm2/mmHg in MICT (P=0.001), while it remained unchanged in HIIT and CONT (P>0.05). Improvements in arterial stiffness in response to MICT were not confounded by changes in aortic or brachial blood pressure, heart rate, body weight, total and abdominal adiposity, blood lipids or aerobic fitness. Conclusion All-extremity MICT, but not HIIT, improved central arterial stiffness in previously sedentary older adults free of major clinical disease. Our findings have important implications for aerobic exercise prescription in older adults.