A computationally engineered RAS rheostat reveals RAS-ERK signaling dynamics.

Synthetic protein switches controlled with user-defined inputs are powerful tools for studying and controlling dynamic cellular processes. To date, these approaches have relied primarily on intermolecular regulation. Here we report a computationally guided framework for engineering intramolecular regulation of protein function. We utilize this framework to develop chemically inducible activator of RAS (CIAR), a single-component RAS rheostat that directly activates endogenous RAS in response to a small molecule. Using CIAR, we show that direct RAS activation elicits markedly different RAS-ERK signaling dynamics from growth factor stimulation, and that these dynamics differ among cell types. We also found that the clinically approved RAF inhibitor vemurafenib potently primes cells to respond to direct wild-type RAS activation. These results demonstrate the utility of CIAR for quantitatively interrogating RAS signaling. Finally, we demonstrate the general utility of our approach in design of intramolecularly regulated protein tools by applying it to the Rho family of guanine nucleotide exchange factors

Validation of the Chinese version 10-item Perceived Efficacy in Patient-Physician Interactions scale in patients with osteoarthritis

OBJECTIVES: This study aimed to assess the reliability and validity of the Chinese version of the 10-item Perceived Efficacy in Patient–Physician Interaction (PEPPI-10) scale in hospitalized patients with severe knee osteoarthritis in the People’s Republic of China. METHODS: Between January and March 2015, the Chinese versions of PEPPI, self-efficacy for exercise scale, osteoporosis self-efficacy scale, and modified fall efficacy scale were applied to assess 110 severe knee osteoarthritis patients who were hospitalized in the second ward of the department of arthroplasty surgery of Tianjin Hospital. RESULTS: The Chinese version of the PEPPI-10 scale had a high coefficient of internal consistency (Cronbach’s α coefficient, 0.907). The score of the Chinese version of PEPPI was weakly correlated with the scores of the Chinese versions of self-efficacy for exercise scale, osteoporosis self-efficacy scale, and modified fall efficacy scale. CONCLUSION: The Chinese version of the PEPPI-10 scale exhibits sufficient internal consistency and convergent validity in hospitalized patients with severe knee osteoarthritis in the People’s Republic of China

Disparities in the survivorship experience among Latina survivors of breast cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144236/1/cncr31342_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144236/2/cncr31342.pd

Adjuvant chemotherapy dosing in low-income women: the impact of Hispanic ethnicity and patient self-efficacy

Unwarranted breast cancer adjuvant chemotherapy dose reductions have been documented in black women, women of lower socioeconomic status, and those who are obese. No information on the quality of chemotherapy is available in Hispanic women. The purpose of this study was to characterize factors associated with first cycle chemotherapy dose selection in a multi-ethnic sample of low-income women receiving chemotherapy through the Breast and Cervical Cancer Prevention Treatment Program (BCCPT) and to investigate the impact of Hispanic ethnicity and patient self-efficacy on adjuvant chemotherapy dose selection. Survey and chemotherapy information were obtained from consenting participants enrolled in the California BCCPT. Analyses identified clinical and non-clinical factors associated with first cycle chemotherapy doses less than 90 % of expected doses. Of 552 patients who received chemotherapy, 397 (72 %) were eligible for inclusion. First cycle dose reductions were given to 14 % of the sample. In multivariate analyses, increasing body mass index and non-academic treatment site were associated with doses below 90 % of the expected doses. No other clinical or non-clinical factors, including ethnicity, were associated with first cycle doses selection. In this universally low-income sample, we identified no association between Hispanic ethnicity and other non-clinical patient factors, including patient self-efficacy, in chemotherapy dose selection. As seen in other studies, obesity was associated with systematic dose limits. The guidelines on chemotherapy dose selection in the obese may help address such dose reductions. A greater understanding of the association between type of treatment site and dose selection is warranted. Overall, access to adequate health care allows the vast majority of low-income women with breast cancer to receive high-quality breast cancer chemotherapy

Quality of life over 5 years after a breast cancer diagnosis among low‐income women: Effects of race/ethnicity and patient‐physician communication

BackgroundThe current study was performed to identify risk factors for a lower quality of life (QOL) among low-income women with breast cancer (BC), with an emphasis on the impact of patient-physician communication. In addition, ethnic/racial group differences in QOL changes over time were examined.MethodsA longitudinal study was conducted among 921 low-income women with BC. Patients were interviewed at 6 months, 18 months, 36 months, and 60 months after their diagnosis of BC. Mixed-effect regression models were performed to investigate predictors for and time effects on QOL. The main outcomes included the Medical Outcomes Study Health Survey Short Form-36 Mental Component Summary scale (SF-36 MCS), Medical Outcomes Study Health Survey Short Form-36 Physical Component Summary scale (SF-36 PCS), and the Ladder of Life scale. Chief independent variables included physician information-giving and patient self-efficacy in interacting with physicians.ResultsThere were no significant changes noted over time in QOL except with regard to physical functioning, with survivors reporting a significant decrease over time (P<.0001). Mean SF-36 MCS and SF-36 PCS scores were lower than national general population norms at all time points. Both patient self-efficacy in interacting with physicians and physician information-giving were found to be positively associated with the SF-36 MCS (P = .03 and P = .02, respectively) and Ladder of Life (P = .01 and P = .03, respectively) scales. Latinas who were less acculturated reported higher SF-36 MCS and SF-36 PCS scores (P<.0001 and P = .01, respectively) and better global QOL (P<.0001) than white women.ConclusionsLow-income women with BC experienced poor physical and mental health. The results of the current study suggest that QOL among low-income women with BC would be enhanced by interventions aimed at empowering patients in communicating with physicians and increasing the amount of information provided by physicians

Validation of the Chinese version 10-item Perceived Efficacy in Patient-Physician Interactions scale in patients with osteoarthritis.

ObjectivesThis study aimed to assess the reliability and validity of the Chinese version of the 10-item Perceived Efficacy in Patient-Physician Interaction (PEPPI-10) scale in hospitalized patients with severe knee osteoarthritis in the People's Republic of China.MethodsBetween January and March 2015, the Chinese versions of PEPPI, self-efficacy for exercise scale, osteoporosis self-efficacy scale, and modified fall efficacy scale were applied to assess 110 severe knee osteoarthritis patients who were hospitalized in the second ward of the department of arthroplasty surgery of Tianjin Hospital.ResultsThe Chinese version of the PEPPI-10 scale had a high coefficient of internal consistency (Cronbach's α coefficient, 0.907). The score of the Chinese version of PEPPI was weakly correlated with the scores of the Chinese versions of self-efficacy for exercise scale, osteoporosis self-efficacy scale, and modified fall efficacy scale.ConclusionThe Chinese version of the PEPPI-10 scale exhibits sufficient internal consistency and convergent validity in hospitalized patients with severe knee osteoarthritis in the People's Republic of China

Adjuvant chemotherapy dosing in low-income women: the impact of Hispanic ethnicity and patient self-efficacy

Unwarranted breast cancer adjuvant chemotherapy dose reductions have been documented in black women, women of lower socioeconomic status, and those who are obese. No information on the quality of chemotherapy is available in Hispanic women. The purpose of this study was to characterize factors associated with first cycle chemotherapy dose selection in a multi-ethnic sample of low-income women receiving chemotherapy through the Breast and Cervical Cancer Prevention Treatment Program (BCCPT) and to investigate the impact of Hispanic ethnicity and patient self-efficacy on adjuvant chemotherapy dose selection. Survey and chemotherapy information were obtained from consenting participants enrolled in the California BCCPT. Analyses identified clinical and non-clinical factors associated with first cycle chemotherapy doses less than 90 % of expected doses. Of 552 patients who received chemotherapy, 397 (72 %) were eligible for inclusion. First cycle dose reductions were given to 14 % of the sample. In multivariate analyses, increasing body mass index and non-academic treatment site were associated with doses below 90 % of the expected doses. No other clinical or non-clinical factors, including ethnicity, were associated with first cycle doses selection. In this universally low-income sample, we identified no association between Hispanic ethnicity and other non-clinical patient factors, including patient self-efficacy, in chemotherapy dose selection. As seen in other studies, obesity was associated with systematic dose limits. The guidelines on chemotherapy dose selection in the obese may help address such dose reductions. A greater understanding of the association between type of treatment site and dose selection is warranted. Overall, access to adequate health care allows the vast majority of low-income women with breast cancer to receive high-quality breast cancer chemotherapy