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Table S1. 15 Image Analysis Features Utilized by the Risk Classifier Table S2. Performance of Risk Classes Predicted by Test vs. Pathologic Diagnosis in Stratifying BE Patients with Prevalent HGD/EAC from Non-Progressor BE Patients. Figure S1. Representative Whole Slide Scan and Image Analysis Masks.

Table S1. Summary of Progression Endpoints in Incident Progressor Patients. Table S2. Correlation Among Quantitative Image Analysis Features Derived from the Same Candidate Biomarkers. Table S3. Comparison of Predictive Performance of Risk Classes Predicted by Test vs. Clinical Variables in Training Set of BE Patients. Table S4. Comparison of Predictive Performance of Risk Score as a Continuous Variable vs. Clinical Variables in Training Set. Table S5. Comparison of Predictive Performance of Risk Score as a Continuous Variable vs. Clinical Variables in Validation Set. Figure S1. Flowchart of Steps to Train and Validate 3-Tier 15-Feature/Measure Classifier for Risk Prediction in Barrett's Esophagus Biopsies. Figure S2. Multiplexed Biomarker Labeling and Imaging in Incident Progressor BE Cases. Supplementary Methods.

Background: There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC.Methods: We performed a multi-institutional case–control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days).Results: The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P < 0.0001]. The classifier also provided independent prognostic information that outperformed the subspecialist and generalist diagnosis.Conclusions: A tissue systems pathology test better predicts prevalent HGD/EAC in Barrett's esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test.Impact: A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240–8. ©2016 AACR.

Background: Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia.Methods: We performed a nested case–control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in ≥1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set.Results: A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6–19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression.Conclusion: We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables.Impact: The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958–68. ©2016 AACR.

Context Positron emission tomography imaging with 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) is used clinically for initial staging, restaging, and assessing therapy response in breast cancer. Tumor FDG uptake in steroid hormone receptor–positive breast cancer and physiologic FDG uptake in normal breast tissue can be affected by hormonal factors such as menstrual cycle phase, menopausal status, and hormone replacement therapy. Objective The purpose of this study was to determine the role of the progesterone receptor (PR) in regulating glucose and FDG uptake in breast cancer cells. Methods and Results PR-positive T47D breast cancer cells treated with PR agonists had increased FDG uptake compared with ethanol control. There was no significant change in FDG uptake in response to PR agonists in PR-negative MDA-MB-231 cells, MDA-MB-468 cells, or T47D PR knockout cells. Treatment of T47D cells with PR antagonists inhibited the effect of R5020 on FDG uptake. Using T47D cell lines that only express either the PR-A or the PR-B isoform, PR agonists increased FDG uptake in both cell types. Experiments using actinomycin D and cycloheximide demonstrated the requirement for both transcription and translation in PR regulation of FDG uptake. GLUT1 and PFKFB3 mRNA expression and the enzymatic activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were increased after progestin treatment of T47D cells. Conclusion Thus, progesterone and progestins increase FDG uptake in T47D breast cancer cells through the classical action of PR as a ligand-activated transcription factor. Ligand-activated PR ultimately increases expression and activity of proteins involved in glucose uptake, glycolysis, and the pentose phosphate pathway.

Full-coverage pedestrian survey to record cultural features on unexplored archaeological landscapes is costly in terms of time, money, and personnel. Over the past two decades, researchers have implemented remote sensing and landscape data collection techniques using unmanned aerial vehicles (UAVs) to combat some of these burdens, but the initial cost of equipment, software, and processing power has hindered the ubiquitous implementation of UAV technology as an accessible companion tool to traditional archaeological survey. This article presents a free and open-source, technology-independent analytical framework for the collection and processing of UAV images to produce high-resolution digital terrain models limited only by the equipment available to the researcher. Results from the free and open-source protocol are directly compared to those produced using proprietary software to illustrate the capabilities of freely available data processing tools for UAV-collected images. By replicating the methods outlined here, researchers should be able to identify and target areas of interest to increase fieldwork efficiency, decrease costs of implementing this technology, and produce high-resolution digital terrain models to conduct spatial analyses that pursue a deeper understanding of cultural landscapes.

Recruitment of skilled professionals for the infection preventionist (IP) role is an ongoing priority for organizations. The objective of this study was to understand differences in recruitment, hiring and training by facility setting and discuss targeted strategies for diverse organizations.A survey study investigated recruitment, hiring and training practices for IPs and stratified by facility location (multi-location health system (MLHS), urban, suburban and rural), specifically pertaining to job description requirements, background of candidates interviewed and hired and training programs.A Master's in Public Health degree was significantly more frequently listed on MLHS and urban facility job descriptions (37.3%, 43.7%, respectively) than suburban (27.4%) and rural facility job descriptions (17.2%)(P.01). Respondents from MLHS (41.3%), urban facilities (47.0%), suburban facilities (41.7%) were more likely to interview public health professionals than rural facilities (20.3%, P = .003). Respondents from MLHS, (73.3%), urban (68.4%), and suburban (62.2%) facilities were significantly more likely to use local Association for Professionals in Infection Control and Epidemiology chapter for training compared to rural facilities (32.4%)(P.001).Our results identified differences in facility setting with recruitment, hiring and training practices. Optimizing recruitment and training best practices will result in a large and well trained IP workforce and patient safety.

Phosphorylation of estrogen receptor α (ER) at serine 118 (pS118-ER) is induced by estrogen and is the most abundant posttranslational mark associated with a transcriptionally active receptor. Cistromic analysis of pS118-ER from our group revealed enrichment of the GRHL2 motif near pS118-ER binding sites. In this study, we used cistromic and transcriptomic analyses to interrogate the relationship between GRHL2 and pS118-ER. We found that GRHL2 is bound to chromatin at pS118-ER/GRHL2 co-occupancy sites prior to ligand treatment, and GRHL2 binding is required for maximal pS118-ER recruitment. pS118-ER/GRHL2 co-occupancy sites were enriched at active enhancers marked by H3K27ac and H3K4me1, along with FOXA1 and p300, compared to sites where each factor binds independently. Transcriptomic analysis yielded four subsets of ER/GRHL2-coregulated genes revealing that GRHL2 can both enhance and antagonize E2-mediated ER transcriptional activity. Gene ontology analysis indicated that coregulated genes are involved in cell migration. Accordingly, knockdown of GRHL2, combined with estrogen treatment, resulted in increased cell migration but no change in proliferation. These results support a model in which GRHL2 binds to selected enhancers and facilitates pS118-ER recruitment to chromatin, which then results in differential activation and repression of genes that control estrogen-regulated ER-positive breast cancer cell migration.

[Image: see text] Transient receptor potential ankyrin 1 (TRPA1) antagonists have generated broad interest in the pharmaceutical industry for the treatment of both pain and asthma. Over the past decade, multiple antagonist classes have been reported in the literature with a wide range of structural diversity. Our own work has focused on the development of proline sulfonamide and hypoxanthine-based antagonists, two antagonist classes with distinct physicochemical properties and pharmacokinetic (PK) trends. Late in our discovery program, cryogenic electron microscopy (cryoEM) studies revealed two different antagonist binding sites: a membrane-exposed proline sulfonamide transmembrane site and an intracellular hypoxanthine site near the membrane interface. A retrospective look at the discovery program reveals how the different binding sites, and their location relative to the cell membrane, influenced the optimization trajectories and overall drug profiles of each antagonist class.

Transient receptor potential ankyrin 1 (TRPA1) is a nonselective calcium-permeable ion channel highly expressed in the primary sensory neurons functioning as a polymodal sensor for exogenous and endogenous stimuli and has generated widespread interest as a target for inhibition due to its implication in neuropathic pain and respiratory disease. Herein, we describe the optimization of a series of potent, selective, and orally bioavailable TRPA1 small molecule antagonists, leading to the discovery of a novel tetrahydrofuran-based linker. Given the balance of physicochemical properties and strong in vivo target engagement in a rat AITC-induced pain assay, compound 20 was progressed into a guinea pig ovalbumin asthma model where it exhibited significant dose-dependent reduction of inflammatory response. Furthermore, the structure of the TRPA1 channel bound to compound 21 was determined via cryogenic electron microscopy to a resolution of 3 A, revealing the binding site and mechanism of action for this class of antagonists.

Nav1.7 is an extensively investigated target for pain with a strong genetic link in humans, yet in spite of this effort, it remains challenging to identify efficacious, selective, and safe inhibitors. Here, we disclose the discovery and preclinical profile of GDC-0276 (1) and GDC-0310 (2), selective Nav1.7 inhibitors that have completed Phase 1 trials. Our initial search focused on close-in analogues to early compound 3. This resulted in the discovery of GDC-0276 (1), which possessed improved metabolic stability and an acceptable overall pharmacokinetics profile. To further derisk the predicted human pharmacokinetics and enable QD dosing, additional optimization of the scaffold was conducted, resulting in the discovery of a novel series of N-benzyl piperidine Nav1.7 inhibitors. Improvement of the metabolic stability by blocking the labile benzylic position led to the discovery of GDC-0310 (2), which possesses improved Nav selectivity and pharmacokinetic profile over 1.

Despite the stark decline in North Carolina's teen birth rates over the past three decades, rates remain disproportionately highest amongst Black, Latinx, and Native American teens in comparison to white teens. Numerous upstream factors continue to drive racial inequities, creating greater disparities in birth rates among teens of color.

While there is a growing body of scholarship on the experiences of LGBTQ+ youth in school and community settings, less is known about Latinx LGBTQ+ youth specifically. In response, this phenomenological study examined the experiences of eight Latinx LGBTQ+ youth relative to school and community belonging, with a specific focus on urban environments, using intersectionality and minority stress frameworks, and Lee and Robbins’ operational definition of belongingness. Three overarching themes emerged from the data: (a) navigating challenges, (b) the importance of an inclusive climate, and (c) thriving through adversity. Further, authenticity was identified as an additional indicator of belonging among Latinx LGBTQ+ youth. This article reviews the study’s findings, explores implications for Extension research and practice, and suggests strategies for educators and youth-serving professionals.

Phosphorylation of estrogen receptor α (ER) at serine 118 (pS118-ER) is induced by estrogen and is the most abundant post-translational mark associated with a transcriptionally active receptor. Cistromic analysis of pS118-ER from our group found enrichment of the GRHL2 motif near pS118-ER binding sites. In this report we use cistromic and transcriptomic analyses to interrogate the relationship between GRHL2 and pS118-ER. We found that GRHL2 is bound to chromatin at pS118-ER/GRHL2 co-occupancy sites prior to ligand treatment, and GRHL2 binding is required for maximal pS118-ER recruitment. pS118-ER/GRHL2 co-occupancy sites were enriched at active enhancers marked by H3K27ac and H3K4me1, along with FOXA1 and p300. Transcriptomic analysis yielded four subsets of ER/GRHL2 co-regulated genes revealing that GRHL2 can both enhance and antagonize E2-mediated ER transcriptional activity. Gene ontology analysis identified several coregulated genes involved in cell migration. Accordingly, knockdown of GRHL2 combined with estrogen treatment resulted in increased cell migration but no change in proliferation. These results support a model in which GRHL2 binds to select enhancers and facilitates pS118-ER recruitment to chromatin which then results in differential activation and repression of genes that control ER-positive breast cancer cell migration.

Liquid chromatography–electrospray ionization–tandem mass spectrometry (LC–ESI–MS-MS) with stable isotope-labeled internal standards (SIL-ISs) is the gold standard for quantitative analysis of drugs and metabolites in complex biological samples. Significant isotopic effects associated with deuterium labeling often cause the deuterated IS to elute at a different retention time from the target analyte, diminishing its capability to compensate for matrix effects. In this study, we systematically compared the analytical performance of deuterated (2H) SIL-IS to non-deuterated (13C and 15N) SIL-ISs for quantifying urinary 2-methylhippuric acid (2MHA) and 4-methylhippuric acid (4MHA), biomarkers of xylenes exposure, with an LC–ESI–MS-MS assay. Analytical method comparison between ISs demonstrated a quantitative bias for urinary 2MHA results, with concentrations generated with 2MHA-[2H7] on average 59.2% lower than concentrations generated with 2MHA-[13C6]. Spike accuracy, measured by quantifying the analyte-spiked urine matrix and comparing the result to the known spike concentration, determined that 2MHA-[2H7] generated negatively biased urinary results of −38.4%, whereas no significant bias was observed for 2MHA-[13C6]. Post-column infusion demonstrated that ion suppression experienced by 2MHA and 2MHA-[13C6] was not equally experienced by 2MHA-[2H7], explaining the negatively biased 2MHA results. The quantitation of urinary 4MHA results between ISs exhibited no significant quantitative bias. These results underscore the importance of the careful selection of ISs for targeted quantitative analysis in complex biological samples.

Background Surgical site infection (SSI) prevention bundles have proven successful in decreasing infections. Surgeon and nurse engagement and endorsement are essential for success. The objective of this quality improvement project was to develop, implement and sustain a colon SSI prevention bundle and determine which bundle components are most strongly associated with prevention of SSI. Methods The bundle was developed and implemented in a 525 bed Level I trauma hospital and included pre-, intra- and postoperative components. Bundle adherence and SSI rate were continually tracked and communicated to surgeons and nursing staff throughout project. Univariate and multivariate analyses were performed to determine the components associated with lowest SSI rates. Results There were 280 elective and urgent/emergent colon surgeries between October 2015 and March 2018. Over 60% had preoperative components, 76.5% had intraoperative components and 55.6% had postoperative bundle components with a nonsignificant decreasing trend in SSI rate of −0.5 SSI/100 procedures per quarter. The multivariate analysis suggested that use of 2% chlorhexidine gluconate/70% alcohol skin prep, use of wound protector and change of gloves for fascial closure were associated with fewer SSI. Discussion The implementation of a colon SSI prevention bundle in a Level I trauma hospital with pre-, intra- and postoperative components was described. Future directions include focusing implementation efforts on bundle components that significantly prevent SSI to improve adherence.

Centering mambo sauce as both a cultural staple and a metaphor for struggles over ownership in Washington, D.C., this article explores mambo sauce’s role in constructing a D.C. identity. Drawing on data from ethnographic interviews and newspaper headlines, I argue that, against the background of intense and consistent gentrification that has left the city’s population younger, whiter, and wealthier, mambo sauce becomes a lens through which to examine larger tensions related to race, class, and power. Specifically, I examine mambo sauce as a form of Black cultural production to explore the dialectical relationship between how mambo travels well beyond the carryout restaurants in Black working-class neighborhoods and the displacement of Black residents in the gentrifying city.

A compressive strain applied to bilayer films (e.g. thin film adhered to a thick substrate) can lead to buckled or wrinkled morphologies, which has many important applications in stretchable electronics, anti-counterfeit technology, and high-precision micro and nano-metrology. A number of buckling-based metrology methods have been developed to quantify the residual stress and viscoelastic properties of polymer thin films. However, in some systems (e.g. solvent-induced swelling or thermal strain), the compressive strain is unknown or difficult to measure. We present a quantitative method of measuring the compressive strain of wrinkled polymer films and coatings with knowledge of the "skin" thickness, wrinkle wavelength, and wrinkle amplitude. The derived analytical expression is validated with a well-studied model system, e.g., stiff, thin film (PS) bonded to a thick, compliant substrate (PDMS). After validation, we use our expression to quantify the applied swelling strain of previously reported wrinkled poly(styrene-alt-maleic anhydride) brush surfaces. Finally, the applied strain is used to rationalize the observed persistence length of aligned wrinkles created during atomic force microscopy (AFM) lithography and subsequent solvent exposure.

First paragraphs: Landmark: 1. An object or feature of a landscape . . . that is easily seen and recognized from a distance, especially one that enables someone to establish their location. Synonyms: mark, indicator, guiding light, signal, beacon, lodestar. 2. An event or discovery marking an important stage or turning point in something. Synonyms: milestone, watershed . . . major achievement. (“Landmark,” n.d., para. 1 & 4) Dr. Monica White’s Freedom Farmers: Agricultural Resistance and the Black Freedom Movement stands literally as a landmark, ushering in a new era of community-based scholarship with and for agrarian justice. From here on out, scholars, activists, practitioners have a lodestar from which to research, practice, and advocate for food, farm, and racial justice: Dr. White’s framework of “collective agency and com­munity resilience” (CACR). Food studies scholars from across and beyond academic disciplines are in strong consensus as to the importance of this pivotal book—a manuscript that draws upon and advances rural sociology, history, agri-food studies, Black history, cooperative economics, and more. In this set of reflections on Freedom Farmers, McCutcheon lauds how the work is a “love letter” to past, present, and future Black farmers, and the powerful pedagogical potential of such celebration. Reese recounts how the book excavates the erased histories of Black women leaders and farmers, showing us how to “re/see the world” through this powerful lens. Babb calls the text a gift that “flips the script” to provide informative and inspirational narratives of food justice and food sovereignty in action. Hall commends how the book “pushes us to participate in the remaking of our communities with honesty, resilience, solidarity, and love.” Sarmiento notes how, even as the book critiques structural racism, it offers a generous, affirmative vision of resistance and agency. Wilson concurs that the book opens radical possibilities for hope, particularly in the classroom. I would also point readers to Cynthia Greenlee’s (2018) Civil Eats interview with Dr. White, which highlights how the book sheds light on the over­looked role of Black farmers in the Civil Rights movement, resurgence of Black agriculture and scholarship on it, and the ongoing necessity of affirming collective agency in the fight against racism at large. . . . - - - - - - - - - - - A note from the authors: Special thanks to West Virginia University's Food Justice Lab for first gathering us in 2018, and to WVU's Wilderness Geography Wild Food Lab. Thanks also to American University School of International Service for supporting the American Association of Geographer's 2019 Author-Meets-Colleagues Panel for Dr. White's book.

We describe a primer pair that amplifies a 203 base pair fragment containing 4 single nucleotide polymorphisms (SNPs) within the cytochrome b region of the mitochondrial DNA that, when sequenced, conclusively distinguishes Washington state gray wolves from domestic dogs. The method is more efficient and cost-effective than other established methods for genetically distinguishing domestic dogs from gray wolves when using potentially degraded scat samples. Further testing may find that the SNP panel is also applicable to studies in Oregon, Idaho, Montana, and Wyoming, as these wolves belong to the same distinct population segment as Washington state gray wolves.

Background: The U.S. Centers for Disease Control and Prevention recommend bathing prior to surgery, surgical skin antisepsis, peri-operative antibiotic administration, normothermia throughout the p...

Fifty years of evolution in infection prevention and control programs have involved significant accomplishments related to clinical practices, methodologies, and technology. However, regulatory mandates, and resource and research limitations, coupled with emerging infection threats such as the COVID-19 pandemic, present considerable challenges for infection preventionists. This article provides guidance and recommendations in 14 key areas. These interventions should be considered for implementation by United States health care facilities in the near future.

The objective of this study was to develop a pilot physician driven patient pyoderma gangrenosum (PG) registry to summarise patient baseline demographics, PG-related medical history, treatments, and outcomes for patients with pyoderma gangrenosum. Standardised patient information was collected prospectively during clinical encounters between December 2019 and July 2021 at a single academic institution. Eligibility criteria for the study was a diagnosis of pyoderma gangrenosum determined by a PARACELSUS score of at least 10 for ulcerative patients. Main outcome measures included demographic data, PG related history and comorbidities, past and current treatments, healing outcomes, hospitalisations and recurrences of PG. The Pyoderma Gangrenosum Study (PYGAS) Registry currently includes 52 patients with 56 target lesions of four distinct PG subtypes (41 ulcerative, 12 peristomal, 2 vegetative and 1 bullous). For the 38 patients with 41 total ulcerative PG lesions, referrals to our institution most commonly came from dermatologists (42.1%). The median follow-up time in our initial registry was 5.5 months (95% CI = 4.1-11.5 months), with average time between follow-up visits at 1.1 months. These ulcers were most commonly treated with first-line systemic immunosuppressants (70.6%), such as corticosteroids or cyclosporine. Additional use of systemic immunomodulators at baseline visit was statistically significantly associated with healing (P = 0.048). This pilot study suggests that use of systemic immunomodulators has an impact on healing of PG patients. Wound care regimens are variable, and assessing their impact on treatment outcomes could be challenging. Standardisation of both wound care regimens and data collection in prospective clinical studies is necessary to assess their impact in PG treatment outcomes.