Development of the UroARC Surgical Calculator: A Novel Risk Calculator for Older Adults Undergoing Surgery for Bladder Outlet Obstruction.

PURPOSE: Bladder outlet obstruction (BOO) is common in older adults. Many older adults who pursue surgery have additional vulnerabilities affecting surgical risk, including frailty. A clinical tool that builds on frailty to predict surgical outcomes for the spectrum of BOO procedures would be helpful to aid in surgical decision-making but does not currently exist. MATERIALS AND METHODS: Medicare beneficiaries undergoing BOO surgery from 2014 to 2016 were identified and analyzed using the Medicare MedPAR, Outpatient, and Carrier files. Eight different BOO surgery categories were created. Baseline frailty was calculated for each beneficiary using the Claims-Based Frailty Index (CFI). All 93 variables in the CFI and the 17 variables in the Charlson Comorbidity Index were individually entered into stepwise logistic regression models to determine variables most highly predictive of complications. Similar and duplicative variables were combined into categories. Calibration curves and tests of model fit, including C statistics, Brier scores, and Spiegelhalter P values, were calculated to ensure the prognostic accuracy for postoperative complications. RESULTS: In total, 212,543 beneficiaries were identified. Approximately 42.5% were prefrail (0.15 ≤ CFI < 0.25), 8.7% were mildly frail (0.25 ≤ CFI < 0.35), and 1.2% were moderately-to-severely frail (CFI ≥0.35). Using stepwise logistic regression, 13 distinct prognostic variable categories were identified as the most reliable predictors of postoperative outcomes. Most models demonstrated excellent model discrimination and calibration with high C statistic and Spiegelhalter P values, respectively, and high accuracy with low Brier scores. Calibration curves for each outcome demonstrated excellent model fit. CONCLUSIONS: This novel risk assessment tool may help guide surgical prognostication among this vulnerable population.

UroARC: A novel surgical risk calculator for older adults undergoing pelvic organ prolapse and stress urinary incontinence surgery.

INTRODUCTION: Surgeries for pelvic organ prolapse (POP) and stress urinary incontinence (SUI) are commonly performed in older adults, many of whom are also frail. A surgical risk calculator for older adults undergoing POP/SUI surgeries that incorporates frailty, a factor known to increase the risk of surgical complications, would be helpful for preoperative counseling but currently does not exist. MATERIALS AND METHODS: Medicare Carrier, Outpatient, and MedPAR files were examined for beneficiaries undergoing POP and SUI surgery between 2014 and 2016. A total of 15 POP/SUI categories were examined. The Claims-Based Frailty Index (CFI), a validated measure of frailty in Medicare data, and Charlson Comorbidity Index were deconstructed into their individual variables, and individual variables were entered into stepwise logistic regression models to determine which variables were most highly predictive of 30-day complications and 1-year mortality. To verify the prognostic accuracy for each model for surgical complications of interest, calibration curves and tests of model fit, including C-statistic, Brier scores, and Spiegelhalter p values, were determined. RESULTS: In total, 108 479 beneficiaries were included. Among these, 4.7% had CFI scores consistent with mild to severe frailty (CFI≥0.25). A total of 13 prognostic variable categories were found to be most highly predictive of postoperative complications. Calibration curves for each outcome of interest showed models were well-fit. Most models demonstrated high c-statistic values (≥0.7) and high Spiegelhalter p values (≥0.9), indicating good model calibration and excellent discrimination, and low Brier scores (<0.02), indicating high model accuracy. CONCLUSIONS: Urologic surgery for older Adults Risk Calculator serves as a novel surgical risk calculator that is readily accessible to both patients and clinicians that specifically factors in components of frailty. Furthermore, this calculator accounts for the heterogeneity of an aging population and can assist in individualized surgical decision-making for these common procedures.

Sacral neuromodulation in nursing home residents: Predictors of success and complications in a national cohort of older adults.

AIMS: There is limited evidence to support the efficacy of sacral neuromodulation (SNM) for older adults with overactive bladder (OAB). This study aims to report outcomes following SNM among nursing home (NH) residents, a vulnerable population with high rates of frailty and comorbidity. METHODS: This is a retrospective cohort study of long-stay NH residents who underwent a trial of percutaneous nerve evaluation (PNE) or Stage 1 permanent lead placement (Stage 1) between 2014 and 2016. Residents were identified using the Minimum Data Set linked to Medicare claims. The primary outcome of this study was successful progression from trial to implant. Rates of 1-year device explant/revisions were also investigated. RESULTS: Trial of SNM was observed in 1089 residents (mean age: 77.9 years). PNE was performed in 66.9% of residents and 33.2% underwent Stage 1. Of Stage 1 procedures, 23.8% were performed with simultaneous device implant (single-stage). Overall, 53.1% of PNEs and 72.4% of Stage 1 progressed to device implant, which was associated with Stage 1 procedure versus PNE (adjusted relative risk [aRR]: 1.34; 95% confidence interval [95% CI]: 1.21-1.49) and female versus male sex (aRR: 1.26; 95% CI: 1.09-1.46). One-year explant/revision was observed in 9.3% of residents (6.3% for PNE, 10.5% for Stage 1, 20.3% single-stage). Single stage procedure versus PNE was significantly associated with device explant/revision (aRR: 3.4; 95% CI: 1.9-6.2). CONCLUSIONS: In this large cohort of NH residents, outcomes following SNM were similar to previous reports of younger healthier cohorts. Surgeons managing older patients with OAB should use caution when selecting patients for single stage SNM procedures.

Quality of life among colorectal cancer survivors participating in a pilot randomized controlled trial of a web-based dietary intervention with text messages.

PURPOSE: We aimed to estimate the effect of a 12-week web-based dietary intervention with text messages on quality of life (QoL) among colorectal cancer (CRC) survivors. METHODS: Between 2017 and 2018, 50 CRC survivors were randomized (1:1) to receive a 12-week web-based dietary intervention with daily text messages or wait-list control. Health-related QoL was assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and colorectal quality of life module (QLQ-CR29) at baseline, 12, and 24 weeks. Within- and between-group mean changes in health-related QoL with 95% confidence intervals (CI) were calculated for both arms. RESULTS: Compared to the controls, participants receiving the intervention had an improvement in emotional functioning (mean change: 14.3; 95% CI: 3.0, 25.6) at 12 weeks and social functioning (mean change: 13.8; 95% CI: 2.1, 25.5) at 24 weeks. A decrease of fatigue from baseline was also observed in the intervention arm (mean change: - 9.1; 95% CI: - 17.1, - 1.1) at 24 weeks. No other changes in QoL scores were associated with the intervention. CONCLUSION: CRC survivors randomized to receive a web-based dietary intervention with text messages experienced higher emotional and social functioning. Further study with a larger population may be warranted. TRIAL REGISTRATION: clinicaltrials.gov, NCT02965521. Registered 16 November 2016, https://clinicaltrials.gov/ct2/keydates/NCT02965521.

An ultrasensitive system for measuring the USPs and OTULIN activity using Nanoluc as a reporter.

The deubiquitinating enzymes (DUBs) are a family of isopeptidases responsible for removing the ubiquitin from the ubiquitinated proteins. Identification of inhibitors for DUBs is emerging as an efficient way for discovering potential medicines for disease treatment. However, the high throughput screening (HTS) assay is still not available for all USPs, especially OTULIN. Here, we described a novel steadily quantifiable DUBs assay platform using Nanoluc (Nluc) as reporter. We further demonstrated that the Ub-Nluc assay could be used for HTS of DUBs inhibitors. Moreover, we generated a sensitive system for OTULIN inhibitors screening using Nluc as a reporter. In summary, our data indicate that Ub-Nluc and the improved Ub-Ub-GS-Nluc assay are efficient systems for measuring activities and screening inhibitors of USPs and OTULIN.

UroARC: A Novel Surgical Risk Calculator for Older Adults Undergoing Suprapubic Tube Placement.

OBJECTIVE: To develop a surgical risk calculator for older adults undergoing suprapubic tube (SPT) placement that specifically factors in frailty, a key predictor of surgical risk in this vulnerable and heterogenous population. METHODS: Medicare MedPAR, Outpatient, and Carrier files for beneficiaries undergoing SPT placement between 2014-2016 were examined. The Claims-Based Frailty Index (CFI), a validated measure of frailty, was used to calculate baseline frailty for each beneficiary. Stepwise regression models were used for each variable within the CFI and Charlson Comorbidity Index to determine the variables most highly predictive of postoperative complications. The most highly predictive variables were then combined into parsimonious categories. To ensure the prognostic accuracy for each outcome, calibration curves and tests of model fit, including C-statistics, Brier scores, and Spiegelhalter P-values were calculated. RESULTS: A total of 26,999 beneficiaries were included. Among these, 39.1% were pre-frail, 36.8% were mildly frail, and 12.3% were moderately to severely frail. Thirteen prognostic variable categories were deemed highly predictive of postoperative complications of interest. All models demonstrated low Brier scores, indicating high model accuracy, and high C-statistic and Spiegelhalter P-values, consistent with excellent model discrimination and calibration, respectively. Excellent model fit was seen on calibration curves for each outcome. CONCLUSION: UroARC is a novel surgical tool for older adults undergoing SPT placement that specifically factors in frailty. This risk calculator has high accuracy, calibration, and discrimination, and serves as a valuable resource to patients and clinicians for those undergoing consideration for SPT placement.

County-level racial disparities in prostate cancer specific mortality from 2005 to 2020.

BACKGROUND: Local conditions where people live continue to influence prostate cancer outcomes. By examining local characteristics associated with trends in Black-White differences in prostate cancer specific mortality (PCSM) over time, we aim to identify factors driving county-level PCSM disparities over a 15-year period. METHODS: We linked county-level data (Area Health Resource File) with clinicodemographic data of men with prostate cancer (Surveillance, Epidemiology, and End Results registry) from 2005 to 2020. Generalized linear mixed models evaluated associations between race and county-level age-standardized PCSM, adjusting for age, year of death, rurality, and county-level education, income, uninsured rates, and densities of urologists, radiologists, primary care providers, and hospital beds. RESULTS: 185,390 patients in 1085 counties were identified, of which 15.8% were non-Hispanic Black. Racial disparities in PCSM narrowed from 2005 to 2020 (25.4 per 100,000 to 19.2 per 100,000 overall; 57.9 per 100,000 to 38 per 100,000 for Non-Hispanic Black patients and 23.4 per 100,000 to 18.3 per 100,000 for Non-Hispanic White patients). For both Non-Hispanic Black and Non-Hispanic White patients, county PCSM changes varied greatly (-65% to + 77% and -61% to + 112%, respectively). From 2016 to 2020, Non-Hispanic Black harbored greater PCSM risk (RR 2.09, 95% CI 2.01-2.18); higher radiation oncologist density was significantly associated with lower mortality risk (RR 0.93, 95% CI 0.89-0.98) while other provider densities were not. CONCLUSION: Although overall rates improved, specific counties experienced worsening race-based disparities over time. Identifying locations of highest (and lowest) mortality disparities remains critical to development of location-specific solutions to racial disparities in prostate cancer outcomes.

Comparative network analysis reveals the regulatory mechanism of 1-methylcyclopropene on sugar and acid metabolisms in yellow peach stored at non-chilling temperatures.

Soluble carbohydrates and organic acids are critical determinants of fruit flavor and consumer preference, both of which are susceptible to postharvest treatments and storage conditions. While the individual effectiveness of 1-methylcyclopropene (1-MCP) and non-chilling temperature storage in delaying fruit ripening and influencing flavor development has been established, their combined effects on peach storage traits remain unexplored. This study investigated the impact of 1-MCP combined with non-chilling temperature storage on the quality and flavor attributes of yellow peach. Our results revealed that 1-MCP treatment reduced ethylene production during storage and delayed ripening and softening by down-regulating ethylene biosynthesis and signaling genes. Transcriptomic analysis indicated that 1-MCP maintained higher levels of soluble carbohydrates by up-regulating sucrose phosphate synthase (PpSPS1/2) and sorbitol dehydrogenase (PpSDH1) while down-regulating hexokinase (PpHXK1). Concurrently, 1-MCP preserved citric and malic acid levels by suppressing aconitate hydratase (PpACO1) and inducing malate dehydrogenase (PpMDH1), thereby delaying flavor degradation. Co-expression network analysis implicated ethylene response factors (PpERFs) as major regulators of sugar and acid metabolisms genes, with PpERF19 potentially functioning as a key transcriptional controller. Overall, this study verified the efficacy of combined 1-MCP and non-chilling storage for yellow peach preservation, identified key 1-MCP-modulated genes involved in sugar and acid metabolisms, and provided insights into regulating peach flavor development via postharvest approaches.

Determining Long-term Prostate Cancer Outcomes for Active Surveillance Patients Without Early Disease Progression: Implications for Slowing or Stopping Surveillance.

BACKGROUND AND OBJECTIVE: Active surveillance (AS) of prostate cancer (PCa) is the standard of care for low-grade disease, but there is limited guidance on tailoring protocols for stable patients. We investigated long-term outcomes for patients without initial progression and risk factors for upgrade. METHODS: Men on AS with Gleason grade group (GG) 1 PCa on three serial biopsies, ≥5 yr without progression, and ≥10 yr of follow-up were included. Outcomes were upgrade (GG ≥2), major upgrade (GG ≥3), progression to treatment, metastasis, PCa-specific survival, and overall survival. Cox proportional hazards regression models were used to estimate the associations between patient characteristics and risk of upgrade. KEY FINDINGS AND LIMITATIONS: A total of 774 men met the inclusion criteria. At 10, 12, and 15 yr, upgrade-free survival rates were 56%, 45%, and 21%; major upgrade-free survival rates were 88%, 83%, and 61%; treatment-free survival rates were 86%, 83%, and 73%; metastasis-free survival rates were 99%, 99%, and 98%; and overall survival rates were 98%, 96%, and 95%, respectively. PCa-specific survival was 100% at 15 yr. On a multivariable analysis, year of diagnosis, age, body mass index (BMI), and biopsy core positivity were associated with upgrade (all p < 0.01), whereas age and prostate-specific antigen (PSA) density were associated with major upgrade. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients without progression for 5 yr on AS had modest rates of upgrade and low rates of metastasis, and mortality at 15 yr of follow-up. Year of diagnosis, older age, increased BMI, and increased biopsy core positivity were associated with upgrade, whereas older age and greater PSA density were associated with an increased risk of major upgrade. A subset of these patients may benefit from deintensification of AS protocols. PATIENT SUMMARY: There are little reported data or clinical guidelines for patients with PCa who are stable for many years on active surveillance (AS). We show, in a large cohort, that PCa patients without progression for 5 yr on AS have modest rates of upgrade and very low rates of metastasis, and mortality rates at 15 yr of follow-up, and that older age, increased body mass index, and increased PCa volume are associated with an increased likelihood of future upgrade. This study supports continued AS in this patient population and deintensification in select patients.

Transcriptome Co-Expression Network Analysis of Peach Fruit with Different Sugar Concentrations Reveals Key Regulators in Sugar Metabolism Involved in Cold Tolerance.

Peach fruits are known to be highly susceptible to chilling injury (CI) during low-temperature storage, which has been linked to the level of sugar concentration in the fruit. In order to better understand the relationship between sugar metabolism and CI, we conducted a study examining the concentration of sucrose, fructose, and glucose in peach fruit with different sugar concentrations and examined their relationship with CI. Through transcriptome sequencing, we screened the functional genes and transcription factors (TFs) involved in the sugar metabolism pathway that may cause CI in peach fruit. Our results identified five key functional genes (PpSS, PpINV, PpMGAM, PpFRK, and PpHXK) and eight TFs (PpMYB1/3, PpMYB-related1, PpWRKY4, PpbZIP1/2/3, and PpbHLH2) that are associated with sugar metabolism and CI development. The analysis of co-expression network mapping and binding site prediction identified the most likely associations between these TFs and functional genes. This study provides insights into the metabolic and molecular mechanisms regulating sugar changes in peach fruit with different sugar concentrations and presents potential targets for breeding high-sugar and cold-tolerant peach varieties.

Enrichment of Residual Carbon in Coal Gasification Fine Slag via Wet Sieving Separation with Ultrasonic Pretreatment.

To overcome the environmental and economic challenges posed by the increasing amounts of the coal gasification slag, here, a simple and efficient method for enriching the residual carbon from the coal gasification fine slag was proposed. The residual carbon enrichment pattern in the particle size distribution of coal gasification fine slags after the ultrasonic pretreatment was mainly enriched toward the 500-250 µm and 250-125 µm particle size classes by analyzing the changes in the particle size distribution and apparent morphology. The pulp pretreatment at the ultrasonic output power of 270 W for 4 min was determined as the optimal experimental condition with respect to the yield, ash content, and ash rejection of the concentrates. Compared to the conventional wet sieving separation, the yield and ash content of the final concentrates were reduced by 7.99 and 14.96%, respectively. Moreover, the ash rejection of the final concentrates was as high as 88.51%, indicating an increment of 11.63% than the conventional wet sieving separation. Furthermore, thermogravimetric analysis confirmed that the final concentrates exhibited the lowest reactivity; however, these demonstrated had the highest carbon content (nearly 70%) with 27.27% ash content. The combustion characteristics analysis showed that the wet screening concentrate after ultrasonic pretreatment had the highest composite combustion characteristic index (S) of 3.17 × 10-8, as compared to the raw and conventional sieving concentrates.

mHealth Interventions to Promote a Healthy Diet and Physical Activity among Cancer Survivors: A Systematic Review of Randomized Controlled Trials.

Background: Technology-based interventions are increasingly used to improve physical activity (PA) and diet. Methods: We conducted a systematic review of randomized controlled trials (RCTs) published up to August 2021 that tested mobile health (mHealth) PA and/or dietary interventions among cancer survivors and reported on the feasibility, satisfaction, behavioral change, and/or quality of life (QOL) outcomes. Results: In total, 61 articles were identified on PubMed, and 23 of those met the inclusion criteria. The most common cancers were breast (n = 1000), prostate (n = 713), and colorectal (n = 650). Participants were predominantly White (median: 84%, interquartile range (IQR): 20%) and college-educated (58%). The interventions varied, but the most common combination of components (six studies) was a website/mobile app with an activity tracker and coaching. In terms of duration, 70% (n = 16) of the interventions lasted 12 weeks. The median total tracker wear was 87% of the study days (IQR: 6%) and the median text-message reply rate was 73% (IQR 4%). Most participants (median: 87%; IQR: 16%) were satisfied with at least one intervention component. Eleven out of 18 studies examining behavioral change reported significant between-group differences and six out of 11 studies examining QoL reported significant improvements. Conclusions: mHealth interventions are a promising approach to improving the PA and diets of cancer survivors. Research in racially/ethnically and socioeconomically diverse populations is needed.

p38 inhibition provides anti-DNA virus immunity by regulation of USP21 phosphorylation and STING activation.

Stimulator of IFN genes (STING) is a central adaptor protein that mediates the innate immune responses to DNA virus infection. Although ubiquitination is essential for STING function, how the ubiquitination/deubiquitination system is regulated by virus infection to control STING activity remains unknown. In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. Inhibition of p38 MAPK enhanced the production of IFNs in response to virus infection and protected mice from lethal HSV-1 infection. Thus, our study reveals a critical role of p38-mediated USP21 phosphorylation in regulating STING-mediated antiviral functions and identifies p38-USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses.