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Objectives: Surgical site infections (SSIs) are the most common hospital-acquired infections in the United States, of which methicillin-resistant Staphylococcus aureus (MRSA) accounts for 43%. Preoperative povidone-iodine nasal swab (PNS) is considered an effective and cost-saving treatment for Staphylococcus aureus decolonization. We aim to assess the impact of preoperative PNS on SSI incidence. Materials and Methods: This retrospective observational study utilized elective surgical cases between January 1, 2018 and May 31, 2023, at a single academic medical center. The cohort was divided into PNS and no PNS groups. The cohort was propensity-matched, and Pearson χ2/Kruskal-Wallis tests were performed to compare group differences. Multivariable logistic regression was utilized to compare events between cohorts before and after matching. An alpha of <0.05 was considered significant. Results: A total of 45,998 (22,999 per group) matched participants were evaluated. On multivariate regression, the non-PNS treatment group was associated with an increase in hospital overall SSI occurrence (OR: 1.48, P = 0.02) but not specifically in-hospital methicillin-sensitive Staphylococcus aureus SSI, MRSA-SSI, or any 30-day SSI (P > 0.05). Compared with PNS treatment and prophylactic antibiotics, in-hospital SSI was higher in the absence of PNS treatment (OR: 1.83, P < 0.001), antibiotic (OR: 2.63, P < 0.001), or both (OR: 2.06, P < 0.01). Compared with PNS treatment plus prophylactic antibiotic, in-hospital MRSA-SSI was only higher in the absence of antibiotic (OR: 2.92, P < 0.01) treatment. Conclusions: Preoperative treatment with PNS may reduce overall in-hospital SSI but has no independent impact on MRSA SSI.

Abstract The establishment of guidelines and curriculum standards for medical physics residency training is a critical component of setting expectations and competencies for the profession. Since the last publication of these standards, residency training has become integrated into the eligibility criteria for most medical physics certification bodies. The rapid growth of medical physics requires periodic review of the curriculum to remove outdated approaches, update established knowledge, and add emerging technologies. The goal of this document is to provide a reference standard for residency training program directors, training mentors, and residents to guide creation and/or optimization of their program's curriculum. The document is intentionally forward‐looking to capture emerging technological advances including hybrid diagnostic and therapeutic delivery systems and applications of image processing. This document is an update of the current residency training curriculum. Version history of residency training guidelines Publication Title Date 2013 Essentials and Guidelines for Clinical Medical Physics Residency Training Programs—AAPM Report No. 249 2006 Essentials and Guidelines for Hospital‐Based Medical Physics Residency Training Programs—Report No. 90 1992 Essentials and Guidelines for Hospital‐Based Medical Physics Residency Training Programs—Report No. 36 The Work Group on Periodic Review of Medical Physics Residency Training (WGMPRT) would like to acknowledge the authors of past versions of this document as they form the basis for this update. It is the sincere hope of the WGMPRT that this report will continue to be used by the medical physics community to guide training in the profession.

Aims To determine the associations between measures of oestrogen exposure and Fuchs endothelial corneal dystrophy (FECD) severity. Methods Clinic-based cross-sectional study of 32 postmenopausal women and 11 men with mild or severe FECD, age>55 years. Participants completed questionnaires for data on demographics, anthropometric factors, medical history and potential risk factors for FECD. Women completed an additional reproductive history questionnaire used to calculate the months of lifetime oestrogen exposure. Slit-lamp biomicroscopy, specular microscopy, corneal Scheimpflug tomography and laboratory testing ( TCF4 repeat expansion quantification, total estradiol, free estradiol, sex hormone binding globulin (SHBG), calcaneal bone density) were performed. Logistic regression models were developed to predict FECD severity based on three-way interactions of each oestrogen exposure measure, sex and TCF4 genotype. Results 43 patients were enrolled in the study (mild FECD: 17 women, 3 men; severe FECD: 15 women, 8 men). Serum-free estradiol was higher in the severe compared with mild FECD group (0.21±0.2 vs 0.09±0.1 pg/mL; p=0.046). When stratified by sex, men showed no significant associations between oestrogen measures and FECD severity. However, in women, the odds of severe FECD were increased with more months of lifetime oestrogen exposure (all women; log OR (95% credible interval): 1.3 (0.14 to 4.3)), higher concentrations of free estradiol (all women; 2.1 (0.0049 to 10)), greater % free estradiol (only women without TCF4 repeat expansion; 1.3 (0.16 to 3.8)) and higher concentrations of SHBG (only women with TCF4 repeat expansion; 2.2 (0.45 to 9.1)). Conclusions While the application of these data is constrained by the limited number of participants, a clinic-based sample, small number of men compared with women and single-point measures of serum hormone measures, these data suggest that FECD severity is associated with higher oestrogen exposures in women but not men and may be dependent on TCF4 repeat expansion status.

Abstract RATIONALE: Alveolar Type 2 (AT2) cells play a critical role in maintaining alveolar function and facilitating repair processes in the lung. Despite recent advancement on transcriptomic mapping of cell identities and AT fate selection, the mechanisms governing AT2 fate plasticity remain elusive. Notably, in AT2-derived pulmonary diseases such as COPD and IPF, disruptions in AT2 differentiation are observed, suggesting alterations may exist in the regulation of fate plasticity. Therefore, a refined model describing the regulation of AT2 fate plasticity is needed, along with an assessment of the model's conservation across murine and human AT2s. METHODS: We performed scRNA-sequencing, ATAC-seq, and bioinformatic analysis on samples across murine lung development and validating findings by immunostaining of embryonic lungs. We conducted organotypic cultures as well as genetically engineered mouse model experiments to assess changes in AT2 fate plasticity in. Further, we established a Mayo Clinic patient lung cell biorepository from patient tissue derived AT2s. In parallel, we performed long read scRNA-sequencing for isoform discovery, organotypic culture and immunostaining in human AT2 organoids, to characterize the presence of similar regulatory mechanisms. RESULTS: Throughout the late embryonic and early perinatal period, we found a window of fate plasticity exists in AT2s whereby they retain the capacity to give rise to AT1s, and that its being closed over time by the bZIP transcription factor C/EBPα, as its genetic deletion in AT2s results in regaining fate plasticity. By ATAC-seq and ChIP-seq, we found C/EBPα binds closely to the Dlk1 locus, a Notch signaling regulator implicated in AT2-to-AT1 conversion that is upregulated following Cebpa deletion. Following adult lung injury, we found C/EBPα downregulation is required for re-accessing AT2 fate plasticity and is likely mediated by the dominant negative C/EBP family member CHOP. Finally, we observe Cebpa loss also activates a “defender” AT2 state enriched in interferon stimulated antipathogenic gene expression that is distinct from its reparative state and propose AT2s can toggle between these states following infection to robustly protect and repair alveoli.Further, we validated the presence of C/EBPα and absence of Dlk1 in human AT2s isolated from healthy adult patients, which persists following in vitro expansion. We conclude that AT2 cells window of fate plasticity is dictated by a molecular circuit involving C/EBPα suppressing and Dlk1. Future works aim to remove C/EBPα in human AT2s to reopen their fate plasticity for cell therapy.

Abstract RATIONALE: Alveoli form late in development and, for first breath, alveolar type 1 (AT1) as well as AT2 epithelial cell types must be functional. While prior studies have mapped the cellular and transcriptional programs underlying this process and identified AT fate inductive cues, questions remain as to the timing and regulation of their emergence. Thus, we sought to identify when, where, and how AT2 cells first arise and motivated by recent work in embryonic stem cells, we investigated whether the biophysical parameter cell membrane tension (CMT) plays a role. METHODS: Single-cell RNA-sequencing (scRNAseq) datasets sampling mouse lung development were processed using cluster correlation, velocity, and gene ontology analysis. Marker expression and AT2 morphology was assessed by immunostaining, and their migration confirmed by time-lapse confocal microscopy on embryonic precision-cut lung slices (PCLS). CMT was measured via optical tweezers (OT) on isolated cells as well as fluorescence lifetime (FLIM) on organoids and PCLS. Progenitors (E15.5) and AT2s (E16.5- &gt;PN50) were isolated from distal region of the mouse lung, as well as human AT2s recently isolated, expanded, and banked in Mayo Clinic's recently established patient lung cell biorepository. CMT was raised using methyl-β-cyclodextran (MBCD) or polyethylene glycol (PEG). Small molecules CHIR and ICG-001 were used in culture to raise and lower β-catenin levels, respectively. Fluorescently labeled mesenchymal cells were isolated, expanded, and added to organoids in suspension for co-association experiments. RESULTS: No evidence of distal progenitors selecting either AT fate was found until E16.5, at which time we identified a distinct nascent AT2 (nAT2) state that ontology analysis detects upregulation of single-cell migration genes. Resistin-like molecule alpha (RELM-α), a type 2 inflammation regulator, labels nAT2s – which first individually emerged around E16.5 (although instances exist at E15.5) at intermediate zones between the branch tips and stalks of the distal epithelium. Following molecular emergence, we observed nAT2s extruded basally and can subsequently interact with nearby but anatomically distinct lumens, a behavior we provisionally name interlumenal junctioning and whose dynamics we validated by timelapse microscopy. Regarding CMT, we found its reduction in distal progenitors occurs prior to, and is required for, differentiation. We observed CMT reduction is sensitive to the manner of organoid culture, with on top culture resulting in more reduction and differentiation. Finally, we observed CMT is regulated cell-intrinsically via the adaptor protein β-catenin, as well as -extrinsically through osmotic (via PEG) or mesenchymal cell interactions, both of which reduce membrane fluidity.

Abstract RATIONALE. Significant sex-differences exist in asthma across the lifespan. Asthma prevalence and severity are greater in pre-pubescent boys compared to girls but greater in women after puberty. In women, asthma may improve after menopause when sex hormones wane. To address potential mechanisms underlying these changes, we compared the airway transcriptomics signatures of post-menopausal vs. premenopausal women. METHODS. We used bulk RNA seq data from bronchial epithelial cells from three different cohorts (SARP III, GEO-GSE85567, GEO-GSE201955) to perform a comprehensive analysis of differential gene expression and regulation. Data were combined into a meta-analysis, to compare pre-menopausal (n=114 cases with asthma, 48 controls) to post-menopausal women (n=52 cases with asthma, 13 controls). Differential gene expression between pre- and postmenopausal women was analyzed separately for asthma (Figure 1A) and control groups (not shown). Significant differentially expressed genes (DEGs) were identified by contrasting effect sizes (log fold-changes) between asthma and control groups using a Z-score interaction test. Accordingly, a scatter plot (Figure 1B) was created to represent whether differential gene expression between pre- and post-menopausal conditions is modified by disease status (asthma vs. control). The scatter plot also highlights that these findings are related to asthma per. se. and not to normal aging and menopausal transition. Pathway enrichment analysis was conducted using the differential expression data, followed by differential regulation analysis of the identified pathways. Statistical significance was assessed using a false discovery rate (FDR) threshold of 5%. RESULTS. Out of 15,468 genes that passed quality control, 19 genes were differentially expressed in bronchial epithelial cells from pre- and post-menopausal women with asthma (as compared to controls) (Figure 1A). Of these, 5 genes were down-regulated (ITLN1, POSTN, FCRL3, CCL22, PCSK6), and 14 genes were up-regulated (SPP1, S100A9, A2ML1, TNFRSF10C, CSF3R, OLFM1, C1QL2, NLRP3, HAL, PI3, RNASE1, TMEM178B, TNNI3, RNF175) when comparing pre- and post-menopausal women with asthma (Figure 1A). Of these 19 DEGs, 14 were differentially expressed in pre- as compared to post-menopausal women with asthma, but not in controls (Figure 1B). Comparing pre- to post-menopausal women with asthma, biologic pathways related to the innate and adaptive immune system activation and mitochondrial function (Electron transport Chain oxidative phosphorylation and ATP production) were both differentially regulated and expressed. CONCLUSIONS. This analysis highlights several DEGs and pathways that characterize asthma pathogenesis when comparing pre- and post-menopausal women, and emphasize the role of female sex hormones on the immune system response and mitochondrial function in asthma pathogenesis.

Abstract Rationale: Volatile organic compounds (VOCs) in exhaled breath change significantly after ultramarathons and could help monitor athletes’ physiological status to optimize training. While VOCs can reflect metabolic changes, the connection between VOCs and clinical blood and respiratory data remains unknown. In this study, we investigated how breath VOCs are linked to clinical variables that reflect the cardiovascular and respiratory system. Methods: Correlation analysis was performed between respiratory data collected in pre- and post-race samples from 24 runners who participated in the 2019 Ultra-Trail du Mont Blanc (UTMB®) ultra-marathon. Correlation analysis was then performed between these clinical data and previously published breath VOC data collected from the same individuals. Results: Clinical data indicated a slight decrease in runner's lung function post-race. Interestingly, in post-race samples, respiratory parameters vital capacity (VC) and forced expiratory volume in one second (FEV1) formed a moderate positive correlation with 2,3-butanediol (r = 0.53, r = 0.63, respectively), a compound produced by bacterial metabolism. We hypothesize that production of 2,3-butanediol results from the effect of exhaustive exercise on the gut microbiome, which may provide protection to ameliorate lung injury. Additionally, a strengthened correlation from moderate (r = 0.5 – 0.7) to strong (r &gt; 0.7) between VC and FEV1 (r = 0.67 to r = 0.84), forced vital capacity (FVC) and maximal expiratory pressure (MEP) (r = 0.57 to r = 0.75), was observed from pre-race to post-race samples. Finally, FEV1 and MEP shifted from no correlation (r &lt; 0.5) in pre-race to a strong correlation (r = 0.73) in post-race. Conclusion: The strengthened correlation between respiratory data in post-race samples suggests that the gut microbiome, under the effect of exercise, may have an indirect impact on both lung function and respiratory muscle function changes. Our findings support the notion that there is an intricate relationship between exhaustive exercise, altered gut microbiome activity, and lung function, and together they can influence athlete performance.

Abstract Background. Sarcopenia (i.e. skeletal muscle loss) and physical frailty are significant contributors to adverse clinical outcomes in lung cancer patients. Nutritional intake and physical activity influence skeletal muscle mass and strength. We determined the impact of lung cancer on clinical outcomes in hospitalized patients with sarcopenia, frailty, or sarcopenia+frailty. Design. The Nationwide Inpatient Sample (NIS) (years 2018-2020) from the United States was analyzed to study adult hospitalized patients with a diagnosis of lung cancer. Sarcopenia and frailty were defined by ICD10 codes that have been previously validated. Multivariate regression models were generated to determine the clinical impact of sarcopenia, frailty, or sarcopenia+frailty in patients with a diagnosis of lung cancer as compared to a general medical population (GMP) without lung cancer. Age was restricted to &gt;40 years old for both cohorts because lung cancer is rare in those less than 40 years old. Models were adjusted for age, race, sex, and comorbidities (cardiovascular disease, anemia, coagulopathy, HIV, depression, diabetes mellitus, and COPD). Results. Compared to the GMP (n=126,099), patients with lung cancer (n=241,913) were older (mean+SD age: 69.6+10.0 vs. 67.6+13.3 years, p&lt;0.001), and had a higher prevalence of sarcopenia (22.5% vs 9.0%, p&lt;0.001), frailty (53.4% versus 49.8%, p&lt;0.001), and sarcopenia+frailty (15.3% versus 6.8%, p&lt;0.001). COPD was common and found in 52.3% of lung cancer patients and 20.2% of the GMP. In lung cancer patients, the most common medical reasons for admission were sepsis, pneumonia, and COPD exacerbation. In GMP patients, the most common medical reasons for admission were sepsis, congestive heart failure, and acute kidney injury. In lung cancer patients, frailty had the greatest association with mortality (unadj OR 3.12, 95% CI: 3.02-3.23; adj OR 3.04, 95% CI: 2.91-3.17). Sarcopenia+frailty was most associated with greater healthcare utilization including greater healthcare cost (unadj OR 1.31, 95% CI: 1.29-1.32; adj OR 1.28, 95% CI: 1.26-1.30) and length of stay (unadj OR 1.57, 95% CI: 1.55-1.58; adj OR 1.50, 95% CI: 1.48-1.52). Sarcopenia+frailty were more likely to require additional healthcare facilities upon discharge and were the least likely to be discharged to home (unadj OR 0.32, 95% CI: 0.32-0.33; adj OR 0.35, 95% CI: 0.33-0.36). (see Table 1). Conclusion. While frailty was most associated with in-hospital mortality in lung cancer patients, sarcopenia+frailty was most associated with greater healthcare utilization. Our findings highlight the need to develop targeted interventions to improve clinical outcomes in lung cancer patients with sarcopenia and/or frailty.

Abstract RATIONALE: Significant sex differences exist in the prevalence and severity of asthma across the lifespan. Asthma is more prevalent and severe in pubescent boys compared to girls but worse in girls and women after puberty. The transition to menopause brings significant reductions in estrogen and progesterone levels. In this study, we test the hypothesis that the effect of menopause on asthma prevalence and outcomes is modified by the use of female sex hormones. METHODS: We used data from nine two-year cycles (1999-2000 to 2015-2016) from NHANES to determine the association between menopause and asthma outcomes. We defined severe asthma based on GINA treatment classes 4&5. We used analytic sample weights to compute national estimates according to NHANES guidelines. Adult (age &gt;18 years) women were considered to be menopaused if (1) they reported to be menopaused during the NHANES survey, (2) they had bilateral oophorectomy, or (3) they were ≥52 years. Weighted logistic regression analyses were used to adjust for age, race, body mass index (BMI), smoking, blood eosinophil count, female hormone therapy, and oral contraceptives. Analyses were performed using the SURVEY package in R. RESULTS: The cohorts’ clinical characteristics are listed in table 1. Compared to pre-menopause (weighted n=60,394,897), menopause (weighted n=52,364,594) was associated with higher rates of active asthma (9.2 vs. 8.9%, p=0.004) and severe asthma (5% vs. 1.8%, p&lt;0.001), but not lifetime asthma (15.1 vs. 16.3%, p=0.063). Notably, postmenopausal women had higher BMIs (weighted median [IQR]: 28.1 [24.2-33.1] vs. 26.1 [22.6-32.1], p&lt;0.001), longer asthma durations (weighted median [IQR]: 20.0 [7.0-41.0] vs. 15.0 [8.0-24.0], p&lt;0.001), and lower lung functions (p&lt;0.001) (table 1). Adjusted analysis did not show significant associations between menopause and lifetime asthma (adjusted OR, 1.074; 95% CI, 0.901-1.280), active asthma (adjusted OR, 1.072; 95% CI, 0.865-1.328), or severe asthma (adjusted OR, 1.369; 95% CI, 0.958-1.954). Interestingly, a history of female hormone therapy and oral contraceptives use was associated with a higher risk of lifetime asthma (adjusted OR, 1.191; 95% CI, 1.031-1.375 and adjusted OR, 1.287; 95% CI, 1.169-1.417 respectively). Among women with active asthma, menopause was not associated with non-severe exacerbations (adjusted OR, 1.335; 95% CI, 0.883-2.021) or with severe exacerbations requiring ER visits (adjusted OR, 1.416; 95% CI, 0.818-2.451). Conclusion: The increased prevalence of active asthma and severe asthma among menopausal women can largely be attributed to age-related changes, comorbidities, and hormone therapy use rather than menopause alone.

Abstract Background. Sarcopenia (i.e. skeletal muscle loss) is a significant contributor to adverse clinical outcomes in patients with COPD. Nutritional intake and physical activity influence sarcopenia and frailty. There is increasing recognition that social determinants of health (SDOH) play critical roles in nutritional status. We evaluated the impact of SDOH on clinical outcomes in hospitalized patients with COPD and sarcopenia and/or frailty. Design. The Nationwide Inpatient Sample (NIS) (years 2018-2020) was analyzed to study adult hospitalized patients with a primary diagnosis of COPD (J43, J44). SDOH was defined by ICD-10 Z-codes as a composite sum of problems related to housing and economic status, unemployment, occupation, psychosocial, family, and healthcare access. Sarcopenia and frailty were defined by a composite of ICD10 codes that have been previously validated in the literature. Multivariate regression models were generated to determine the impact of sarcopenia, frailty, and sarcopenia+frailty on clinical outcomes in COPD patients, which were adjusted for age, race, sex, SDOH, and comorbidities (cardiovascular disease, anemia, coagulopathy, HIV, depression, diabetes mellitus). Results. Of the 282,164 COPD patients that were analyzed, 7254 (2.6%) had codes related to SDOH, 21,035 (7.5%) had sarcopenia, 106,995 (37.9%) had frailty, and 11,293 (4%) had both sarcopenia and frailty. The predominant SDOH code was related to housing (70.9%) followed by social environment (11.5%). SDOH codes were more prevalent in patients with sarcopenia alone (3.6%), compared with frailty (2.5%) or sarcopenia+frailty (2.6%) (p&lt;0.001). When adjusted for demographics including age, race, and sex, SDOH was associated with greater odds of sarcopenia (adj OR 1.64, 95% CI: 1.51-1.79), frailty (adj OR 1.17, 95% CI: 1.11-1.24), and sarcopenia+frailty (adj OR 1.72; 95% CI: 1.54-1.90). COPD patients with sarcopenia+frailty had the greatest association with adverse clinical outcomes (i.e. in-hospital mortality, higher healthcare cost, and higher length of stay), followed by frailty alone, and sarcopenia alone (Table 1). Conclusion. In COPD patients, SDOH increased the odds for a diagnosis of sarcopenia, frailty, and sarcopenia+frailty. Sarcopenia+frailty had the greatest association with adverse outcomes in COPD patients, followed by frailty alone, and sarcopenia alone.