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Abstract Objective . UNet-based deep-learning (DL) architectures are promising dose engines for traditional linear accelerator (Linac) models. Current UNet-based engines, however, were designed differently with various strategies, making it challenging to fairly compare the results from different studies. The objective of this study is to thoroughly evaluate the performance of UNet-based models on magnetic-resonance (MR)-Linac-based intensity-modulated radiation therapy (IMRT) dose calculations. Approach . The UNet-based models, including the standard-UNet, cascaded-UNet, dense-dilated-UNet, residual-UNet, HD-UNet, and attention-aware-UNet, were implemented. The model input is patient CT and IMRT field dose in water, and the output is patient dose calculated by DL model. The reference dose was calculated by the Monaco Monte Carlo module. Twenty training and ten test cases of prostate patients were included. The accuracy of the DL-calculated doses was measured using gamma analysis, and the calculation efficiency was evaluated by inference time. Results . All the studied models effectively corrected low-accuracy doses in water to high-accuracy patient doses in a magnetic field. The gamma passing rates between reference and DL-calculated doses were over 86% (1%/1 mm), 98% (2%/2 mm), and 99% (3%/3 mm) for all the models. The inference times ranged from 0.03 (graphics processing unit) to 7.5 (central processing unit) seconds. Each model demonstrated different strengths in calculation accuracy and efficiency; Res-UNet achieved the highest accuracy, HD-UNet offered high accuracy with the fewest parameters but the longest inference, dense-dilated-UNet was consistently accurate regardless of model levels, standard-UNet had the shortest inference but relatively lower accuracy, and the others showed average performance. Therefore, the best-performing model would depend on the specific clinical needs and available computational resources. Significance . The feasibility of using common UNet-based models for MR-Linac-based dose calculations has been explored in this study. By using the same model input type, patient training data, and computing environment, a fair assessment of the models’ performance was present.

BACKGROUND: Premature menopause is a risk factor for accelerated cardiovascular aging, but underlying mechanisms remain incompletely understood. This study investigated the role of leukocyte telomere length (LTL), a marker of cellular aging and genomic instability, in the association of premature menopause with cardiovascular disease. METHODS: Participants from the UK Biobank and Women’s Health Initiative with complete reproductive history and LTL measurements were included. Primary analyses tested the association between age at menopause and LTL using multivariable-adjusted linear regression. Secondary analyses stratified women by history of gynecologic surgery. Mendelian randomization was used to infer causal relationships between LTL and age at natural menopause. Multivariable-adjusted Cox regression and mediation analyses tested the joint associations of premature menopause and LTL with incident coronary artery disease. RESULTS: This study included 130 254 postmenopausal women (UK Biobank: n=122 224; Women’s Health Initiative: n=8030), of whom 4809 (3.7%) had experienced menopause before age 40. Earlier menopause was associated with shorter LTL (meta-analyzed ß=−0.02 SD/5 years of earlier menopause [95% CI, −0.02 to −0.01]; P =7.2×10 -12 ). This association was stronger and significant in both cohorts for women with natural/spontaneous menopause (meta-analyzed ß=−0.04 SD/5 years of earlier menopause [95% CI, −0.04 to −0.03]; P <2.2×10 -16 ) and was independent of hormone therapy use. Mendelian randomization supported a causal association of shorter genetically predicted LTL with earlier age at natural menopause. LTL and age at menopause were independently associated with incident coronary artery disease, and mediation analyses indicated small but significant mediation effects of LTL in the association of menopausal age with coronary artery disease. CONCLUSIONS: Earlier age at menopause is associated with shorter LTL, especially among women with natural menopause. Accelerated telomere shortening may contribute to the heightened cardiovascular risk associated with premature menopause.

Background: Most strokes and cardiovascular diseases (CVDs) are potentially preventable if their risk factors are identified and well controlled. Digital platforms, such as the PreventS-MD web app (PreventS-MD) may aid health care professionals (HCPs) in assessing and managing risk factors and promoting lifestyle changes for their patients. Methods: This is a mixed-methods cross-sectional two-phase survey using a largely positivist (quantitative and qualitative) framework. During Phase 1, a prototype of PreventS-MD was tested internationally by 59 of 69 consenting HCPs of different backgrounds, age, sex, working experience, and specialties using hypothetical data. Collected comments/suggestions from the study HCPs in Phase 1 were reviewed and implemented. In Phase 2, a near-final version of PreventS-MD was developed and tested by 58 of 72 consenting HCPs using both hypothetical and real patient (n = 10) data. Qualitative semi-structured interviews with real patients (n = 10) were conducted, and 1 month adherence to the preventive recommendations was assessed by self-reporting. The four System Usability Scale (SUS) groups of scores (0–50 unacceptable; 51–68 poor; 68–80.3 good; >80.3 excellent) were used to determine usability of PreventS-MD. Findings: Ninety-nine HCPs from 27 countries (45% from low- to middle-income countries) participated in the study, and out of them, 10 HCPs were involved in the development of PreventS before the study, and therefore were not involved in the survey. Of the remaining 89 HCPs, 69 consented to the first phase of the survey, and 59 of them completed the first phase of the survey (response rate 86%), and 58 completed the second phase of the survey (response rate 84%). The SUS scores supported good usability of the prototype (mean score = 80.2; 95% CI [77.0–84.0]) and excellent usability of the final version of PreventS-MD (mean score = 81.7; 95% CI [79.1–84.3]) in the field. Scores were not affected by the age, sex, working experience, or specialty of the HCPs. One-month follow-up of the patients confirmed the high level of satisfaction/acceptability of PreventS-MD and (100%) adherence to the recommendations. Interpretation: The PreventS-MD web app has a high level of usability, feasibility, and satisfaction by HCPs and individuals at risk of stroke/CVD. Individuals at risk of stroke/CVD demonstrated a high level of confidence and motivation in following and adhering to preventive recommendations generated by PreventS-MD.

Background The 2021 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend following anti-phospholipase A2 receptor (PLA2R) antibody levels as a marker of treatment response in membranous nephropathy; however, the optimal timing to evaluate antibody levels and how to combine them with other clinical variables are currently unknown. Methods We used a cohort of 85 patients from the Membranous Nephropathy Trial Of Rituximab (MENTOR) with anti-PLA2R antibodies ≥14 RU/ml to identify risk factors for not experiencing proteinuria remission after 12 months of treatment with cyclosporine or rituximab. Three landmark times were considered: at baseline and after 3 and 6 months of treatment. Logistic regression model performance was evaluated using C-statistics and model fit (Akaike information criterion [AIC], R 2 ). Results The model at baseline that best predicted no remission included anti-PLA2R antibodies >323 RU/ml and creatinine clearance; the best model after 3 months included the change from baseline in both antibody and albumin levels; and the best model after 6 months included antibody levels >14 RU/ml, creatinine clearance, and the change from baseline in albumin. Compared with the model at baseline, the model at 3 months had better model fit (AIC 70.9 versus 96.4, R 2 51.8% versus 30.1%) and higher C-statistic (0.93 versus 0.83, P = 0.008). The model at 6 months had no difference in performance compared with the model at 3 months (AIC 68.6, R 2 53.0%, C-statistic 0.94, P = 0.67). Conclusions In patients with membranous nephropathy treated with cyclosporine or rituximab in the MENTOR trial, we found that the optimal method to evaluate risk factors for the probability of treatment response was to use anti-PLA2R antibody levels combined with albumin levels after 3 months of treatment, which was significantly better than using antibody levels alone or risk factor evaluation at baseline, with no added benefit of waiting until 6 months of treatment. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_10_09_CJN0000000000000237.mp3

Background: Upper facial third morphometrics are an important consideration in aesthetic facial surgery and facial gender-affirming surgery. Although there are generally accepted sexual dimorphic differences, an in-depth analysis of forehead morphometrics in attractive individuals is lacking. Methods: Thirty white female and 30 white male celebrities were included. Three full-face front-view photographs of each celebrity were evaluated by a facial analysis program, using Vision framework and MATLAB. After converting pixel distances to absolute distances, midline and lateral forehead heights were calculated and compared between men and women. Results: Forehead height was similar between attractive men and women, but forehead width was shorter in women. Analysis of forehead height at various points along the hairline demonstrated that forehead measurements above the lateral brow and brow peak were significantly greater in men. Mean forehead height above the lateral eyebrow was 3.51 cm in women and 4.16 cm in men (P = 0.017). Forehead height above the eyebrow peak was 4.34 cm in women and 5.55 cm in men (P < 0.001). Medial forehead height was similar between men and women, indicating that the greatest difference in attractive male and female foreheads is in the lateral forehead and forehead width. Conclusions: Analysis of attractive white celebrities demonstrated no significant differences in central forehead heights between men and women. Forehead width and lateral forehead height were significantly smaller in women, with an overall downward slanting contour. Male hairlines were more horizontal and slanting upward laterally. These results have implications in facial rejuvenation and facial gender-affirming surgery.

AbstractThe liver is a common site of cancer metastases. Systemic therapy is widely accepted as the standard treatment for liver metastases (LM), although select patients with liver oligometastases may be candidates for potentially curative liver resection. Recent data support the role of nonsurgical local therapies such as ablation, external beam radiotherapy, embolization, and hepatic artery infusion therapy for management of LM. Additionally, for patients with advanced, symptomatic LM, local therapies may provide palliative benefit. The American Radium Society gastrointestinal expert panel, including members representing radiation oncology, interventional radiology, surgical oncology, and medical oncology, performed a systemic review and developed Appropriate Use Criteria for the use of nonsurgical local therapies for LM. Preferred Reporting Items for Systematic reviews and Meta‐Analyses methodology was used. These studies were used to inform the expert panel, which then rated the appropriateness of various treatments in seven representative clinical scenarios through a well‐established consensus methodology (modified Delphi). A summary of recommendations is outlined to guide practitioners on the use of nonsurgical local therapies for patients with LM.

The diversity of patients pursuing facial aesthetic and facial gender-affirming surgery (FGAS) is increasing, yet there is a paucity of objective guidelines to facilitate surgical decision-making in patients of color. We conducted a quantitative analysis of black celebrities using standardized frontal photos of 21 female and 21 male celebrities. Celebrities were chosen from popular entertainment magazines and websites, including People Magazine, the Internet Movie Database (IMDb), Cosmopolitan, and Essence. For each celebrity, 100 facial landmarks were detected through a facial analysis artificial intelligence (AI) program. Black males had greater facial height, bizygomatic width, lower facial height, and bigonial width than females. However, the facial height to bigonial width ratio was similar between genders and approximated the golden ratio (1.618). Female faces demonstrated a greater mid-face height to total facial height proportion, and males had a greater lower facial height proportion. Females exhibited an upward-slanted medial brow and shorter total eyebrow length, nose height, and alar width. Forehead height above the lateral brow was greater in males, while central forehead height was similar to females. This is the first study that has utilized AI to provide ethnicity-specific facial morphometrics relevant to facial rejuvenation and FGAS in the black population.

Abstract Mesenchymal stem/stromal cells (MSCs), a class of cells with proliferative, immunomodulatory, and reparative functions, have shown therapeutic potential in a variety of systemic diseases, including metabolic syndrome (MetS). The cluster of morbidities that constitute MetS might be particularly amenable for the application of MSCs, which employ an arsenal of reparative actions to target multiple pathogenic pathways simultaneously. Preclinical studies have shown that MSCs can reverse pathological changes in MetS mainly by inhibiting inflammation, improving insulin resistance, regulating glycolipid metabolism, and protecting organ function. However, several challenges remain to overcome before MSCs can be applied for treating MetS. For example, the merits of autologous versus allogeneic MSCs sources remain unclear, particularly with autologous MSCs obtained from the noxious MetS milieu. The distinct characteristics and relative efficacy of MSCs harvested from different tissue sources also require clarification. Moreover, to improve the therapeutic efficacy of MSCs, investigators have explored several approaches that improved therapeutic efficacy but may involve potential safety concerns. This review summarized the potentially useful MSCs strategy for treating MetS, as well as some hurdles that remain to be overcome. In particular, larger-scale studies are needed to determine the therapeutic efficacy and safety of MSCs for clinical application.

AbstractObjectivesAlthough hemispheric surgeries are among the most effective procedures for drug‐resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1‐, 2‐, and 5‐years post‐hemispherectomy.MethodsRetrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time‐to‐seizure recurrence. A multivariate Cox proportional‐hazards regression model was developed to predict the likelihood of post‐hemispheric surgery seizure freedom at three time points (1‐, 2‐ and 5‐ years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops‐calculator.com/).ResultsThe selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non‐hemispheric resective surgery, and contralateral fluorodeoxyglucose–positron emission tomography [FDG‐PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time‐to‐seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG‐PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non‐lesional MRI, non‐stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%.SignificanceOnline calculators are useful, cost‐free tools that can assist physicians in risk estimation and inform joint decision‐making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.