Engineered matrices reveal stiffness-mediated chemoresistance in patient-derived pancreatic cancer organoids.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its fibrotic and stiff extracellular matrix. However, how the altered cell/extracellular-matrix signalling contributes to the PDAC tumour phenotype has been difficult to dissect. Here we design and engineer matrices that recapitulate the key hallmarks of the PDAC tumour extracellular matrix to address this knowledge gap. We show that patient-derived PDAC organoids from three patients develop resistance to several clinically relevant chemotherapies when cultured within high-stiffness matrices mechanically matched to in vivo tumours. Using genetic barcoding, we find that while matrix-specific clonal selection occurs, cellular heterogeneity is not the main driver of chemoresistance. Instead, matrix-induced chemoresistance occurs within a stiff environment due to the increased expression of drug efflux transporters mediated by CD44 receptor interactions with hyaluronan. Moreover, PDAC chemoresistance is reversible following transfer from high- to low-stiffness matrices, suggesting that targeting the fibrotic extracellular matrix may sensitize chemoresistant tumours. Overall, our findings support the potential of engineered matrices and patient-derived organoids for elucidating extracellular matrix contributions to human disease pathophysiology.

Expert Consensus on Pediatric Urodynamics Reporting Using Modified Delphi Technique.

PURPOSE: Urodynamic testing (UDS) is an important tool in the management of pediatric lower urinary tract conditions. There have been notable efforts to standardize pediatric UDS nomenclature and technique, but no formal guidelines exist on essential elements to include in a clinical report. We sought to identify ideal structure and elements of a pediatric UDS assessment based on expert consensus. MATERIALS AND METHODS: Pediatric urologists regularly performing UDS were queried using a Delphi process. Participants were invited representing varied geographic, experience, and societal involvement. Participants underwent 3 rounds of questionnaires between November 2022 and August 2023 focusing on report organization, elements, definitions, and automated electronic health record clinical decision support. Professional billing requirements were also considered. Consensus was defined as 80% agreeing either in favor of or against a topic. Elements without consensus were discussed in subsequent rounds. RESULTS: A diverse sample of 30 providers, representing 27 institutions across 21 US states; Washington, District of Columbia; and Canada completed the study. Participants reported interpreting an average number of 5 UDS reports per week (range 1-22). The finalized consensus report identifies 93 elements that should be included in a pediatric UDS report based on applicable study conditions and findings. CONCLUSIONS: This consensus report details the key elements and structure agreed upon by an expert panel of pediatric urologists. Further standardization of documentation should aid collaboration and research for patients undergoing UDS. Based on this information, development of a standardized UDS report template using electronic health record implementation principles is underway, which will be openly available for pediatric urologists.

Implementation of Food is Medicine Programs in Healthcare Settings: A Narrative Review.

Food is Medicine (FIM) programs to improve the accessibility of fruits and vegetables (FVs) or other healthy foods among patients with low income and diet-related chronic diseases are promising to improve food and nutrition security in the United States (US). However, FIM programs are relatively new and implementation guidance for healthcare settings using an implementation science lens is lacking. We used a narrative review to describe the evidence base on barriers and facilitators to FIM program integration in US healthcare settings following the Exploration, Preparation, Implementation, and Sustainment (EPIS) Framework. Evidence surrounding the EPIS Inner Context was a focus, including constructs Leadership, Organizational Characteristics, Quality and Fidelity Monitoring and Support, Organizational Staffing Processes, and Individual Characteristics. Peer-reviewed and grey literature about barriers and facilitators to FIM programs were of interest, defined as programs that screen and refer eligible patients with diet-related chronic disease experiencing food insecurity to healthy, unprepared foods. Thirty-one sources were included in the narrative review, including 22 peer-reviewed articles, four reports, four toolkits, and one thesis. Twenty-eight sources (90%) described EPIS Inner Context facilitators and 26 sources (84%) described FIM program barriers. The most common barriers and facilitators to FIM programs were regarding Quality and Fidelity Monitoring and Support (e.g., use of electronic medical records for tracking and evaluation, strategies to support implementation) and Organizational Staffing Processes (e.g., clear delineation of staff roles and capacity); although, barriers and facilitators to FIM programs were identified among all EPIS Inner Context constructs. We synthesized barriers and facilitators to create an EPIS-informed implementation checklist for healthcare settings for use among healthcare organizations/providers, partner organizations, and technical assistance personnel. We discuss future directions to align FIM efforts with implementation science terminology and theories, models, and frameworks to improve the implementation evidence base and support FIM researchers and practitioners.

Effect of Return Electrode Placement at Apical Cochleostomy on Current Flow With a Cochlear Implant.

OBJECTIVES: A method for stimulating the cochlear apex using perimodiolar electrode arrays is described. This method involves implanting an electrode (ECE1) into the helioctrema in addition to standard cochlear implant placement. One objective is to verify a suitable approach for implanting ECE1 in the helicotrema. Another is to determine how placement of ECE1 reshapes electric fields. DESIGN: Two cadaveric half-heads were implanted, and electric voltage tomography was measured with ECE1 placed in many positions. RESULTS: An approach for placing ECE1 was identified. Changes in electric fields were only observed when ECE1 was placed into the fluid in the helicotrema. When inside the helicotrema, electric voltage tomography modeling suggests an increased current flow toward the apex. CONCLUSIONS: Placement of ECE1 into the cochlear apex is clinically feasible and has the potential to reshape electric fields to stimulate regions of the cochlea more apical than those represented by the electrode array.

Accuracy of intraoperative aberrometry versus modern preoperative methods in post-myopic laser vision correction eyes undergoing cataract surgery with capsular tension ring placement.

PURPOSE: To assess the accuracy of intraoperative wavefront aberrometry (IWA) versus modern intraocular lens formulas in post-myopic laser vision correction (LVC) patients undergoing cataract surgery with capsular tension ring placement. METHODS: This is a retrospective chart review conducted at an academic outpatient center. All post-myopic LVC eyes undergoing cataract surgery with IWA from a single surgeon from 05/2017 to 12/2019 were included. All patients received a capsular tension ring (CTR). Mean numerical error (MNE), median numerical error (MedNE), and percentages of prediction error within 0.50D, 0.75D, and 1.00D were calculated for the above formulas. RESULTS: Twenty-seven post-myopic LVC eyes from 18 patients were included. In post-myopic LVC, MNE with Optiwave Refractive Analysis (ORA), Barrett True K (BTK), Haigis, Haigis-L, Shammas, SRK/T, Hill-RBF v3.0, and W-K AL-adjusted Holladay 1 were + 0.224, - 0.094, + 0.193, - 0.231, - 0.372, + 1.013, + 0.860, and + 0.630 (F = 8.49, p < 0.001). MedNE were + 0.125, - 0.145, + 0.175, + 0.333, + 0.333, + 1.100, + 0.880, and + 0.765 (F = 7.89, p < 0.001), respectively. BTK provided improved accuracy in both MNE (p < 0.001) and MedNE (p = .033) when compared to ORA in pairwise analysis. If the ORA vs. BTK-suggested IOL power were routinely selected, 30% and 15% of eyes would have projected hyperopic outcomes, respectively (p = 0.09). CONCLUSIONS: Our study suggests that in post-myopic LVC eyes undergoing cataract surgery with CTRs, BTK performed more accurately than ORA with regard to accuracy and yielded a lower percentage of eyes with hyperopic outcomes. Haigis, Haigis-L, and Shammas yielded similar results to ORA with regard to accuracy and percentage of eyes with hyperopic outcomes. On average, Shammas and Haigis-L suggested IOLs that would yield outcomes more myopic than expected when compared to BTK.

Does Preoperative Testosterone Administration Decrease Complications in Distal Hypospadias Repair With Urethroplasty?

PURPOSE: Testosterone administration prior to hypospadias repair is common practice among pediatric urologists; however, its impact on surgical outcomes remains controversial. We hypothesize that testosterone administration prior to distal hypospadias repair with urethroplasty significantly decreases postoperative complications. MATERIALS AND METHODS: We queried our hypospadias database for primary distal hypospadias repairs with urethroplasty from 2015 to 2021. Patients undergoing repair without urethroplasty were excluded. We collected information on patient age, procedure type, testosterone administration status, initial visit and intraoperative glans width, urethroplasty length, and postoperative complications. To determine the role of testosterone administration on incidence of complications, a logistic regression adjusting for initial visit glans width, urethroplasty length, and age was performed. RESULTS: A total of 368 patients underwent distal hypospadias repair with urethroplasty. One hundred thirty-three patients received testosterone and 235 did not. Initial visit glans width was significantly larger in the no-testosterone vs testosterone group (14.5 mm vs 13.1 mm, P = .001). Testosterone patients had significantly larger glans width at the time of surgery (17.1 mm vs 14.6 mm [no-testosterone group], P = .001). On multivariable logistic regression analysis after controlling for age at surgery, preoperative glans width, testosterone status, and urethroplasty length, testosterone administration did show significant association with reduced odds of postoperative complications (OR 0.4, P = .039). CONCLUSIONS: This retrospective review of patients shows that on multivariable analysis there is significant association between testosterone administration and decreased incidence of complications in patients undergoing distal hypospadias repair with urethroplasty. Future studies on testosterone administration should focus on specific cohorts of patients with hypospadias as benefits of testosterone may be more evident in some subgroups than others.

Deep Learning of Videourodynamics to Classify Bladder Dysfunction Severity in Patients With Spina Bifida.

PURPOSE: Urologists rely heavily on videourodynamics to identify patients with neurogenic bladders who are at risk of upper tract injury, but their interpretation has high interobserver variability. Our objective was to develop deep learning models of videourodynamics studies to categorize severity of bladder dysfunction. MATERIALS AND METHODS: We performed a cross-sectional study of patients aged 2 months to 28 years with spina bifida who underwent videourodynamics at a single institution between 2019 and 2021. The outcome was degree of bladder dysfunction, defined as none/mild, moderate, and severe, defined by a panel of 5 expert reviewers. Reviewers considered factors that increase the risk of upper tract injury, such as poor compliance, elevated detrusor leak point pressure, and detrusor sphincter dyssynergia, in determining bladder dysfunction severity. We built 4 models to predict severity of bladder dysfunction: (1) a random forest clinical model using prospectively collected clinical data from videourodynamics studies, (2) a deep learning convolutional neural network of raw data from the volume-pressure recordings, (3) a deep learning imaging model of fluoroscopic images, (4) an ensemble model averaging the risk probabilities of the volume-pressure and fluoroscopic models. RESULTS: Among 306 videourodynamics studies, the accuracy and weighted kappa of the ensemble model classification of bladder dysfunction when at least 75% expected bladder capacity was reached were 70% (95% CI 66%,76%) and 0.54 (moderate agreement), respectively. The performance of the clinical model built from data extracted by pediatric urologists was the poorest with an accuracy of 61% (55%, 66%) and a weighted kappa of 0.37. CONCLUSIONS: Our models built from urodynamic pressure-volume tracings and fluoroscopic images were able to automatically classify bladder dysfunction with moderately high accuracy.

Validation of the Prognostic Usefulness of the Gene Expression Profiling Test in Patients with Uveal Melanoma.

PURPOSE: To validate the prognostic usefulness of gene expression profile (GEP) testing in patients with uveal melanoma. To determine whether combining tumor size with the GEP classification provides additional prognostic value. DESIGN: Retrospective analysis. PARTICIPANTS: Patients with a diagnosis of choroidal melanoma examined at Yale New Haven Hospital; University of California, San Diego; and Memorial Sloan Kettering Cancer Center. METHODS: Patients' demographic and clinical data and tumor characteristics were collected. Univariate and multivariate Cox hazard regression analysis were used to assess the association between tumor characteristics and GEP classification with metastasis as an outcome. MAIN OUTCOME MEASURES: Metastasis-free survival (MFS). RESULTS: Of the 337 individuals included in the study, 87 demonstrated metastases. The mean follow-up time was 37.2 (standard deviation [SD], 40.2) months for patients with metastases and 55.0 (SD, 49.3) months for those without metastases. Tumors of larger thickness and GEP class 2 (vs. class 1) were associated significantly with increased risk of metastasis. Tumor thickness showed better prognostic usefulness than GEP classification (Wald statistic, 40.7 and 24.2, respectively). Class 2 tumors with a thickness of 7.0 mm or more were associated with increased risk of metastasis than tumors with a thickness of < 7.0 mm (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.61-6.51), whereas class 1 tumors with a thickness of 9.0 mm or more were associated with increased risk of metastasis than tumors with a thickness of < 9.0 mm (HR, 2.07; 95% CI, 0.86-4.99). No difference in MFS was found between patients with class 1A tumors compared with those with class 1B tumors (P = 0.8). Patients with class 2 tumors showed an observed 5-year MFS of 47.5% (95% CI, 36.0%-62.8%). CONCLUSIONS: Tumor size was the most significant predictor of metastasis and provided additional prognostic value independent of GEP classification. In addition, rates of metastasis for class 2 tumors were lower than estimates reported by Castle Bioscience, and no difference in rates of metastasis were found between class 1A and 1B tumors. This indicates that tumor size should be accounted for when relying on GEP for prognostication and that patients with GEP class 1A or 1B tumors may benefit from the same metastatic surveillance protocols. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Deep learning imaging features derived from kidney ultrasounds predict chronic kidney disease progression in children with posterior urethral valves.

BACKGROUND: We sought to use deep learning to extract anatomic features from postnatal kidney ultrasounds and evaluate their performance in predicting the risk and timing of chronic kidney disease (CKD) progression for boys with posterior urethral valves (PUV). We hypothesized that these features would predict CKD progression better than clinical characteristics such as nadir creatinine alone. METHODS: We performed a retrospective cohort study of boys with PUV treated at two pediatric health systems from 1990 to 2021. Features of kidneys were extracted from initial postnatal kidney ultrasound images using a deep learning model. Three time-to-event prediction models were built using random survival forests. The Imaging Model included deep learning imaging features, the Clinical Model included clinical data, and the Ensemble Model combined imaging features and clinical data. Separate models were built to include time-dependent clinical data that were available at 6 months, 1 year, 3 years, and 5 years. RESULTS: Two-hundred and twenty-five patients were included in the analysis. All models performed well with C-indices of 0.7 or greater. The Clinical Model outperformed the Imaging Model at all time points with nadir creatinine driving the performance of the Clinical Model. Combining the 6-month Imaging Model (C-index 0.7; 95% confidence interval [CI] 0.6, 0.79) with the 6-month Clinical Model (C-index 0.79; 95% CI 0.71, 0.86) resulted in a 6-month Ensemble Model that performed better (C-index 0.82; 95% CI 0.77, 0.88) than either model alone. CONCLUSIONS: Deep learning imaging features extracted from initial postnatal kidney ultrasounds may improve early prediction of CKD progression among children with PUV. A higher resolution version of the Graphical abstract is available as Supplementary information.

Prevalence and associations between food insecurity and overweight/obesity among native Hawaiian and Pacific Islander adolescents.

OBJECTIVE: This study estimates the prevalence of, and associations between, family food insecurity and overweight/obesity among Native Hawaiian and Pacific Islander (NHPI) adolescents and explores socio-demographic factors which might have a moderation effect on the association. DESIGN: Cross-sectional study using 2014 NHPI-National Health Interview Survey data reported by a parent or guardian. Family-level food security was assessed by the US Department of Agriculture 10-item questionnaire. BMI for age and sex ≥ 85th and 95th percentiles defined overweight and obesity, respectively, according to US Centers for Disease Control and Prevention criteria. SETTING: The USA, including all 50 states and the District of Columbia. PARTICIPANTS: 383 NHPI adolescents aged 12-17 in the USA. RESULTS: A third (33·5 %) of NHPI adolescents aged 12-17 were overweight (19·1 %) or obese (14·4 %); 8·1 % had low food security; and 8·5 % had very low food security. Mean family food security score was 1·06, which corresponds to marginal food security. We found no association between family food insecurity and adolescent overweight/obesity or between any other covariates and overweight/obesity, except for family Supplemental Nutrition Assistance Program (SNAP) participation. Odds of being overweight/obese were 77 % lower for adolescents in families participating in SNAP (OR: 0·23, 95 % CI: 0·08, 0·64, P = 0·007). The association between SNAP participation and lower odds of overweight/obesity was particularly pronounced for adolescent girls in food-insecure families. CONCLUSIONS: The association between SNAP participation and lower odds of overweight/obesity suggests potential benefit of research to determine whether interventions to increase SNAP enrollment would improve NHPI adolescents' health outcomes.

Experiences of Farmers Market Vendors in a Healthy Food Incentive Program.

Healthy food incentive programs for Supplemental Nutrition Assistance Program participants, often implemented in farmers markets, have shown promise in improving the purchase and consumption of fruits and vegetables. However, variation in program context, program strategies, and participant populations has produced gaps in knowledge about which healthy food incentive program implementation strategies are most effective, and few studies have focused on farmers market vendors' experiences. This study evaluated experiences of farmers market vendors who participated in the Northwest Arkansas Double Your Dollars (NWA DYD) healthy food incentive program intended to increase access to healthy foods for local Hispanic/Latino and Marshallese community members with low incomes. Data were collected from a convenience sample of vendors participating in NWA DYD at the three largest participating markets on the last Saturday in October 2021. Program staff collected quantitative, categorical, and open-ended data through face-to-face surveys. Forty-one vendors completed the survey. Vendors believed NWA DYD was beneficial and easy to use, expanded their customer base, and increased participation of Hispanic/Latino and Marshallese shoppers. Vendors also identified challenges in participation related to administrative burdens and delayed reimbursements. Vendors did not identify NWA DYD as a driver for expanded production for the upcoming growing season. Vendors' experiences at NWA DYD provide implications for others interested in implementing effective healthy food incentive programs. Improving access to farmers markets through effective healthy food incentive programs is an important step toward increasing consumption of fresh, healthy foods among communities with low incomes facing elevated prevalence of chronic disease.

Step edge highlighters and illuminance changes influence stair descent in a real-world setting.

Studies investigating the effect of tread edge highlighters on descent speed differ, but collectively report the potential benefit of reduced fall risk. Here we examine the impact of adding high-contrast black vinyl striping to the front edge of each step's tread and its impact on descending gait speed (intervention), while controlling for illumination. Descending gait speed was estimated from 5,824 video observations using the stairway length and entry and exit times. A second stairway was unaltered (control) to compare to the intervention. Stair users were primarily 18-30 years old with a small percentage being middle-aged and older adults. Descending gait speed was significantly slower on the intervention stairway (Linear mixed effects model: standardised coefficient = -0.07, 95% CI = [-0.12, -0.02], p = .010) compared to the control and may be impacted by illuminance. We propose that the slowed gait speed could be due to changes in gait kinematics (e.g. foot clearance) and may reduce fall-risk. Practitioner summary: Tread-edge contrast enhancement could be a low-cost means to reduce fall-risk on stairways, but its impact on gait kinematics is not well understood. We found that contrast enhancement reduced descending gait speed, but descending gait speed's impact on fall risk reduction ultimately requires further investigation.

Quantifying Glans Width Changes in Response to Preoperative Androgen Stimulation in Patients Undergoing Hypospadias Repair.

PURPOSE: Testosterone (T) administration prior to hypospadias surgery to increase glans size remains controversial. Understanding T's effect on glans width (GW) is essential to understanding its potential impact on surgical outcomes. We hypothesized that preoperative T in prepubertal boys significantly increases GW at the time of hypospadias surgery. MATERIALS AND METHODS: Our single institutional database was queried to identify patients who underwent hypospadias surgery from 2016 to 2020, in which data for T administration and GW were available. Descriptive, nonparametric and categorical statistics were performed as indicated. RESULTS: A total of 579 patients were eligible for analysis. Median age at surgery was 0.9 years (IQR 0.6-1.6). A total of 247/579 patients (42.7%) received T. The median GW at surgery was 15 mm (IQR 13-17). When comparing patients who had T administered to those who did not, we found a significant difference in GW at surgery (16 mm vs 14 mm, p <0.001). The median change in GW from the office to surgery was 4 mm for those receiving T vs 0 mm for those not receiving T (p <0.001). We identified a greater change in GW from preoperative to intraoperative measurements in patients who received 2 doses of T vs 1 dose (4 mm vs 2 mm, p <0.001). A histogram plot revealed the distribution of GW change at surgery. CONCLUSIONS: In our prospectively collected cohort of patients undergoing hypospadias surgery, we were able to quantitate the change in GW from preoperative T. Two doses of T resulted in a significant increase in GW vs 1 dose.

Robot-Assisted Laparoscopic Ureterocalicostomy in the Setting of Ureteropelvic Junction Obstruction: A Multi-Institutional Cohort.

PURPOSE: Recurrent ureteropelvic junction obstruction (UPJO) after failed pyeloplasty is a complex surgical dilemma. The robot-assisted laparoscopic ureterocalicostomy (RALUC) is a potential surgical approach, but widespread adoption is limited due to the perceived technical challenge of the procedure. We present a multi-institutional pediatric cohort undergoing RALUC for recurrent or complex UPJO, and hypothesize that the procedure is reproducible, safe and efficacious. MATERIALS AND METHODS: A 3-center multi-institutional collaboration was initiated and medical records of children undergoing RALUC between 2012 and 2020 were retrospectively reviewed. The details on baseline demographics, perioperative characteristics and postoperative outcomes were aggregated. RESULTS: During the study period 24 patients, 7 (29%) females and 17 (71%) males, were identified. Of the patients 21 (86%) had a history of previous pyeloplasty prior to RALUC, of whom 5 (24%) had 2 prior failed ipsilateral pyeloplasties. The reason for performing RALUC was short ureter in 3 (13%), intrarenal pelvis in 5 (21%) and extensive scarring at the ureteropelvic junction locus in 16 (67%) patients. The median age of patients at time of surgery was 5.1 years (IQR: 1.9, 14.7). Of the patients 9 (38%) had percutaneous nephrostomy prior to surgery; if percutaneous nephrostomy tubes were placed for relief of obstruction, an antegrade contrast study was done postoperatively to confirm resolution of obstruction. No 30-day Clavien-Dindo Grade III-V complications were noted. During the median followup of 16.1 months (IQR: 6, 47.5), 22 (92%) had improved symptoms and hydronephrosis with no further intervention; 2 (8%) patients underwent endoscopic interventions after RALUC and both ultimately underwent nephrectomy. CONCLUSIONS: This multi-institutional cohort demonstrates that RALUC is a safe and efficacious salvage option for failed pyeloplasty or complex anatomy with an acceptable success profile, especially in cases of extensive scarring at the UPJO or an intrarenal pelvis.

Expanding the Use of Nephron-Sparing Surgery for Wilms Tumor.

Radical nephrectomy combined with contemporary chemotherapeutic and radiation therapy protocols has drastically improved outcomes for children with Wilms tumor. Patients with bilateral disease and a syndrome predisposing to tumor development have necessitated the use of nephron-sparing surgery in select cases. Success in managing these patients has increased the indication for partial nephrectomy, although current guidelines for unilateral Wilms tumor are limited. Given that children are being cured with increasing success, recent focus has shifted to long-term health outcomes in addition to tumor treatment. Specifically, renal function has an impact on long-term cardiovascular health and events. Adult outcomes with partial nephrectomy provide a guideline for a paradigm shift in the management of children with Wilms tumor, particularly with advances in imaging and adjuvant therapy. The data are limited for children undergoing partial nephrectomy for unilateral Wilms tumor and outcomes for larger tumors will need to be studied closely in future trials. Increased utilization of neoadjuvant chemotherapy could further expand the number of patients eligible for partial nephrectomy.

Posterior Urethral Valves Outcomes Prediction (PUVOP): a machine learning tool to predict clinically relevant outcomes in boys with posterior urethral valves.

BACKGROUND: Early kidney and anatomic features may be predictive of future progression and need for additional procedures in patients with posterior urethral valve (PUV). The objective of this study was to use machine learning (ML) to predict clinically relevant outcomes in these patients. METHODS: Patients diagnosed with PUV with kidney function measurements at our institution between 2000 and 2020 were included. Pertinent clinical measures were abstracted, including estimated glomerular filtration rate (eGFR) at each visit, initial vesicoureteral reflux grade, and renal dysplasia at presentation. ML models were developed to predict clinically relevant outcomes: progression in CKD stage, initiation of kidney replacement therapy (KRT), and need for clean-intermittent catheterization (CIC). Model performance was assessed by concordance index (c-index) and the model was externally validated. RESULTS: A total of 103 patients were included with a median follow-up of 5.7 years. Of these patients, 26 (25%) had CKD progression, 18 (17%) required KRT, and 32 (31%) were prescribed CIC. Additionally, 22 patients were included for external validation. The ML model predicted CKD progression (c-index = 0.77; external C-index = 0.78), KRT (c-index = 0.95; external C-index = 0.89) and indicated CIC (c-index = 0.70; external C-index = 0.64), and all performed better than Cox proportional-hazards regression. The models have been packaged into a simple easy-to-use tool, available at https://share.streamlit.io/jcckwong/puvop/main/app.py CONCLUSION: ML-based approaches for predicting clinically relevant outcomes in PUV are feasible. Further validation is warranted, but this implementable model can act as a decision-making aid. A higher resolution version of the Graphical abstract is available as Supplementary information.

A review and analysis of personal and ambient PM2.5 measurements: Implications for epidemiology studies.

BACKGROUND: In epidemiology studies, ambient measurements of PM2.5 are often used as surrogates for personal exposures. However, it is unclear the degree to which ambient PM2.5 reflects personal exposures. OBJECTIVE: In order to examine potential sources of bias in epidemiology studies, we conducted a review and meta-analysis of studies to determine the extent to which short-term measurements of ambient PM2.5 levels are related to short-term measurements of personal PM2.5 levels. METHODS: We conducted a literature search of studies reporting both personal and ambient measurements of PM2.5 published in the last 10 years (2009-2019) and incorporated studies published prior to 2009 from reviews. RESULTS: Seventy-one studies were identified. Based on 17 studies reporting slopes, a meta-analysis revealed an overall slope of 0.56 µg/m3 (95% CI: [0.39, 0.73]) personal PM2.5 per µg/m3 increase in ambient PM2.5. Slopes for summer months were higher (slope = 0.73, 95% CI: [0.64, 0.81]) than for winter (slope = 0.46, 95% CI: [0.36, 0.57]). Based on 44 studies reporting correlations, we calculated an overall personal-ambient PM2.5 correlation of 0.63 (95% CI: [0.55, 0.71]). Correlations were stronger in studies conducted in Canada (r = 0.86, 95% CI: [0.67, 0.94]) compared to the USA (r = 0.60, 95% CI: [0.49, 0.70]) and China (r = 0.60, 95% CI: [0.46, 0.71]). Correlations also were stronger in urban areas (r = 0.53, 95% CI: [0.43, 0.62]) vs. suburban areas (r = 0.36, 95% CI: [0.21, 0.49]). SIGNIFICANCE: Our results suggest a large degree of variability in the personal-ambient PM2.5 association and the potential for exposure misclassification and measurement error in PM2.5 epidemiology studies.

Reducing Sodium Content of Foods Served in Arkansas's Largest School District: Evaluation of the Sodium Reduction in Communities Program.

PURPOSE AND OBJECTIVES: The Centers for Disease Control and Prevention's Sodium Reduction in Communities Program aims to reduce dietary sodium intake through policy, systems, and environmental approaches. The objective of our study was to evaluate changes in sodium levels over 5 years (2016-2021) in food served in school lunches as an outcome of a Sodium Reduction in Communities program in Arkansas's largest school district. INTERVENTION APPROACH: We collaborated with Springdale Public Schools (SPS) to reduce dietary sodium intake in school lunches through increased implementation of 1) food service guidelines, 2) procurement practices, 3) food preparation practices, and 4) environmental strategies. These activities were maintained from year 1 through year 5. Implementation priorities were informed each year by evaluation findings from the preceding year. EVALUATION METHODS: We collected lunch service records and information on nutritional content of menu items for the 30 schools under the direction of SPS's Child Nutrition Department. We used a pretest-posttest quantitative evaluation design to analyze annual changes in the sodium content of meals, from baseline through year 5. RESULTS: From baseline through year 1, SPS reduced sodium served per diner, per entrée offered, and per entrée served. These reductions were maintained from baseline through 5 years of follow-up. Mean sodium per 1,000 kcal per diner served was 1,740 mg at baseline and was lower in each of the 5 follow-up years: 1,488 mg (14% decrease) in year 1; 1,495 mg (14% decrease) in year 2; 1,612 mg (7% decrease) in year 3; 1,560 mg (10% decrease) in year 4; and 1,532 mg (12% decrease) in year 5. Energy served per diner remained stable. IMPLICATIONS FOR PUBLIC HEALTH: Our study provides evidence for sustained sodium reduction strategies in a large ethnically and socioeconomically diverse school district, pointing to the potential benefit of implementing similar strategies in other school districts. The study also shows how program evaluation can be used to support sustainability.

Associations among Self-Reported Mental Health, Physical Activity, and Diet during the COVID-19 Pandemic.

Background: Understanding the relationship between physical activity, diet, and mental health during the COVID-19 pandemic may help inform resources encouraging healthy lifestyle choices during the time of an increased threat to health and wellbeing. Aim: Our objective was to examine how self-rated mental health was associated with engagement in physical activity and consumption of fruits and vegetables during the COVID-19 pandemic. Methods: The study utilized cross-sectional survey data from adults (≥18 years of age) living, working, and/or receiving healthcare in Arkansas (n = 754). Multivariable regression models were used to examine the associations between self-rated mental health and the number of days respondents engaged in 30 min of physical activity and the number of days respondents consumed five or more servings of fruits and vegetables. Results: Respondents who reported somewhat poor/poor mental health reported engaging in at least 30 min of physical activity fewer days per week (ß = -.77, p = .018) compared with those reporting excellent mental health, after controlling for sociodemographic factors and self-rated health. The significant association observed in the first two models between mental health and number of days consuming five or more servings of fruits and vegetables became non-significant after inclusion of self-rated health. Conclusion: The relationship between mental health and physical activity and diet reaffirms a need for healthcare providers to promote the importance of maintaining both a healthy physical activity level and a nutrient-rich diet in the face of challenging circumstances, such as a global pandemic.

Total Motile Sperm Count in Adolescent Boys with Varicocele is Associated with Hormone Levels and Total Testicular Volume.

PURPOSE: The risk factors for future infertility in adolescents with varicocele are controversial, and little is known about the association between hormone levels and semen parameters. Semen analysis is likely the closest marker of fertility but may be difficult to obtain in some boys secondary to personal, familial or religious reasons. Identifying other clinical surrogates for abnormal semen parameters may offer an alternative for assessing varicocele severity in these boys. We hypothesized that hormone levels and total testicular volume are predictive of abnormal total motile sperm count. MATERIALS AND METHODS: We retrospectively reviewed Tanner 5 boys with palpable left varicoceles who underwent a semen analysis and had serum hormone levels tested (luteinizing hormone, follicle-stimulating hormone, inhibin B, anti-müllerian hormone and/or total testosterone) within a 6-month period. Total testicular volume was also calculated. Abnormal total motile sperm count was defined as <9 million sperm per ejaculate. RESULTS: A total of 78 boys (median age 17.2 years, IQR 16.5-18.0) were included. Luteinizing hormone, anti-müllerian hormone and total testosterone were not correlated with any semen analysis parameter. There was a negative correlation between follicle-stimulating hormone and total motile sperm count (ρ -0.35, p=0.004) and positive correlation between inhibin B and total motile sperm count (ρ 0.50, p <0.001). Total testicular volume was significantly positively correlated with total motile sperm count (ρ 0.35, p=0.01). ROC analyses revealed an optimal follicle-stimulating hormone cutoff of 2.9, an optimal inhibin B cutoff of 204 and an optimal total testicular volume cutoff of 34.4 cc to predict abnormal total motile sperm count. CONCLUSIONS: Total motile sperm count is inversely associated with follicle-stimulating hormone levels, and directly associated with inhibin B levels and total testicular volume. Optimized cutoffs for serum follicle-stimulating hormone, inhibin B and total testicular volume may prove to be reasonable surrogates for total motile sperm count in boys who defer semen analysis for personal or religious/cultural reasons.