Browsing by Author "Wang, Hao"
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Item Association Between Empathy and Burnout Among Emergency Medicine Physicians(Elmer Press, 2019-07) Wolfshohl, Jon A.; Bradley, Keegan; Bell, Charles; Bell, Sarah; Hodges, Caleb; Knowles, Heidi; Chaudhari, Bharti R.; Kirby, Ryan; Kline, Jeffrey A.; Wang, Hao; Emergency Medicine, School of MedicineBackground: The association between physician self-reported empathy and burnout has been studied in the past with diverse findings. We aimed to determine the association between empathy and burnout among United States emergency medicine (EM) physicians using a novel combination of tools for validation. Methods: This was a prospective single-center observational study. Data were collected from EM physicians. From December 1, 2018 to January 31, 2019, we used the Jefferson scale of empathy (JSE) to assess physician empathy and the Copenhagen burnout inventory (CBI) to assess burnout. We divided EM physicians into different groups (residents in each year of training, junior/senior attendings). Empathy, burnout scores and their association were analyzed and compared among these groups. Results: A total of 33 attending physicians and 35 EM residents participated in this study. Median self-reported empathy scores were 113 (interquartile range (IQR): 105 - 117) in post-graduate year (PGY)-1, 112 (90 - 115) in PGY-2, 106 (93 - 118) in PGY-3 EM residents, 112 (105 - 116) in junior and 114 (101 - 125) in senior attending physicians. Overall burnout scores were 43 (33 - 50) in PGY-1, 51 (29 - 56) in PGY-2, 43 (42 - 53) in PGY-3 EM residents, 33 (24 - 47) in junior attending and 25 (22 - 53) in senior attending physicians separately. The Spearman correlation (ρ) was -0.11 and β-weight was -0.23 between empathy and patient-related burnout scores. Conclusion: Self-reported empathy declines over the course of EM residency training and improves after graduation. Overall high burnout occurs among EM residents and improves after graduation. Our analysis showed a weak negative correlation between self-reported empathy and patient-related burnout among EM physicians.Item Bacterial-Driven Inflammation and Mutant BRAF Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy(American Association for Cancer Research, 2021) DeStefano Shields, Christina E.; White, James R.; Chung, Liam; Wenzel, Alyssa; Hicks, Jessica L.; Tam, Ada J.; Chan, June L.; Dejea, Christine M.; Fan, Hongni; Michel, John; Maiuri, Ashley R.; Sriramkumar, Shruthi; Podicheti, Ram; Rusch, Douglas B.; Wang, Hao; De Marzo, Angelo M.; Besharati, Sepideh; Anders, Robert A.; Baylin, Stephen B.; O’Hagan, Heather M.; Housseau, Franck; Sears, Cynthia L.; Medical and Molecular Genetics, School of MedicineColorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced by inflammation, mutagens, and/or microbiota. Colorectal cancers with activating mutations in BRAF are associated with distinct clinical characteristics, although the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (MinApcΔ716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model is characterized by IL17-dependent, distal colon adenomas. Herein, we report that the addition of the BRAF V600E mutation to this model results in the emergence of a distinct locus of midcolon tumors. In ETBF-colonized BRAF V600E Lgr5 CreMin (BLM) mice, tumors have similarities to human BRAF V600E tumors, including histology, CpG island DNA hypermethylation, and immune signatures. In comparison to Min ETBF tumors, BLM ETBF tumors are infiltrated by CD8+ T cells, express IFNγ signatures, and are sensitive to anti-PD-L1 treatment. These results provide direct evidence for critical roles of host genetic and microbiota interactions in colorectal cancer pathogenesis and sensitivity to immunotherapy. SIGNIFICANCE: Colorectal cancers with BRAF mutations have distinct characteristics. We present evidence of specific colorectal cancer gene-microbial interactions in which colonization with toxigenic bacteria drives tumorigenesis in BRAF V600E Lgr5 CreMin mice, wherein tumors phenocopy aspects of human BRAF-mutated tumors and have a distinct IFNγ-dominant immune microenvironment uniquely responsive to immune checkpoint blockade.Item Colon Tumors in Enterotoxigenic Bacteroides fragilis (ETBF)-Colonized Mice Do Not Display a Unique Mutational Signature but Instead Possess Host-Dependent Alterations in the APC Gene(American Society for Microbiology, 2022) Allen, Jawara; Huber, Axel Rosendahl; Pleguezuelos-Manzano, Cayetano; Puschhof, Jens; Wu, Shaoguang; Wu, Xinqun; Boot, Charelle; Saftien, Aurelia; O’Hagan, Heather M.; Wang, Hao; van Boxtel, Ruben; Clevers, Hans; Sears, Cynthia L.; Medical and Molecular Genetics, School of MedicineEnterotoxigenic Bacteroides fragilis (ETBF) is consistently found at higher frequency in individuals with sporadic and hereditary colorectal cancer (CRC) and induces tumorigenesis in several mouse models of CRC. However, whether specific mutations induced by ETBF lead to colon tumor formation has not been investigated. To determine if ETBF-induced mutations impact the Apc gene, and other tumor suppressors or proto-oncogenes, we performed whole-exome sequencing and whole-genome sequencing on tumors isolated after ETBF and sham colonization of Apcmin/+ and Apcmin/+Msh2fl/flVC mice, as well as whole-genome sequencing of organoids cocultured with ETBF. Our results indicate that ETBF-induced tumor formation results from loss of heterozygosity (LOH) of Apc, unless the mismatch repair system is disrupted, in which case, tumor formation results from new acquisition of protein-truncating mutations in Apc. In contrast to polyketide synthase-positive Escherichia coli (pks+ E. coli), ETBF does not produce a unique mutational signature; instead, ETBF-induced tumors arise from errors in DNA mismatch repair and homologous recombination DNA damage repair, established pathways of tumor formation in the colon, and the same genetic mechanism accounting for sham tumors in these mouse models. Our analysis informs how this procarcinogenic bacterium may promote tumor formation in individuals with inherited predispositions to CRC, such as Lynch syndrome or familial adenomatous polyposis (FAP). IMPORTANCE: Many studies have shown that microbiome composition in both the mucosa and the stool differs in individuals with sporadic and hereditary colorectal cancer (CRC). Both human and mouse models have established a strong association between particular microbes and colon tumor induction. However, the genetic mechanisms underlying putative microbe-induced colon tumor formation are not well established. In this paper, we applied whole-exome sequencing and whole-genome sequencing to investigate the impact of ETBF-induced genetic changes on tumor formation. Additionally, we performed whole-genome sequencing of human colon organoids exposed to ETBF to validate the mutational patterns seen in our mouse models and begin to understand their relevance in human colon epithelial cells. The results of this study highlight the importance of ETBF colonization in the development of sporadic CRC and in individuals with hereditary tumor conditions, such as Lynch syndrome and familial adenomatous polyposis (FAP).Item Coming in Warm: Qualitative Study and Concept Map to Cultivate Patient‐Centered Empathy in Emergency Care(Wiley, 2019) Pettit, Katie E.; Rattray, Nicholas A.; Wang, Hao; Stuckey, Shanna; Courtney, D. Mark; Messman, Anne M.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineBackground Increased empathy may improve patient perceptions and outcomes. No training tool has been derived to teach empathy to emergency care providers. Accordingly, we engaged patients to assist in creating a concept map to teach empathy to emergency care providers. Methods We recruited patients, patient caretakers and patient advocates with emergency department experience to participate in three separate focus groups (n = 18 participants). Facilitators guided discussion about behaviors that physicians should demonstrate in order to rapidly create trust, enhance patient perception that the physician understood the patient's point of view, needs, concerns, fears, and optimize patient/caregiver understanding of their experience. Verbatim transcripts from the three focus groups were read by the authors and by consensus, 5 major themes with 10 minor themes were identified. After creating a codebook with thematic definitions, one author reviewed all transcripts to a library of verbatim excerpts coded by theme. To test for inter‐rater reliability, two other authors similarly coded a random sample of 40% of the transcripts. Authors independently chose excerpts that represented consensus and strong emotional responses from participants. Results Approximately 90% of opinions and preferences fell within 15 themes, with five central themes: Provider transparency, Acknowledgement of patient's emotions, Provider disposition, Trust in physician, and Listening. Participants also highlighted the need for authenticity, context and individuality to enhance empathic communication. For empathy map content, patients offered example behaviors that promote perceptions of physician warmth, respect, physical touch, knowledge of medical history, explanation of tests, transparency, and treating patients as partners. The resulting concept map was named the “Empathy Circle”. Conclusions Focus group participants emphasized themes and tangible behaviors to improve empathy in emergency care. These were incorporated into the “Empathy Circle”, a novel concept map that can serve as the framework to teach empathy to emergency care providers.Item Dew formation reduction in global warming experiments and the potential consequences(Elsevier, 2021-02) Feng, Tianjiao; Zhang, Lixu; Chen, Qian; Ma, Zhiyuan; Wang, Hao; Shangguan, Zijian; Wang, Lixin; He, Jin-Sheng; Earth Sciences, School of ScienceDew, as an important contribution of non-rainfall water (NRW), plays a vital role in ecosystem processes in arid and semi-arid regions and is expected to be affected by climate warming. Infrared heater warming systems have been widely used to simulate climate warming effects on ecosystems. However, how this warming system affects dew formation has been long ignored and rarely addressed. In a typical alpine grassland ecosystem on the northeast of the Tibetan Plateau, we measured dew amount and duration using three independent methods: artificial condensing surfaces, leaf wetness sensors and in situ dew formation on plants from 2012 to 2017. We also measured plant traits related to dew conditions. The results showed that (1) warming reduced the dew amount by 41.6%-91.1% depending on the measurement method, and reduced dew duration by 32.1 days compared to the ambient condition. (2) Different plant functional groups differed in dew formation. (3) Under the infrared warming treatment, the dew amount decreased with plant height, while under the ambient conditions, the dew amount showed the opposite trend. We concluded that warming with an infrared heater system greatly reduces dew formation, and if ignored, it may lead to overestimation of the effects of climate warming on ecosystem processes in climate change simulation studies.Item Differential Activity of PARP Inhibitors in BRCA1- Versus BRCA2-Altered Metastatic Castration-Resistant Prostate Cancer(American Society of Clinical Oncology, 2021-07-22) Taza, Fadi; Holler, Albert E.; Fu, Wei; Wang, Hao; Adra, Nabil; Albany, Costantine; Ashkar, Ryan; Cheng, Heather H.; Sokolova, Alexandra O.; Agarwal, Neeraj; Kessel, Adam; Bryce, Alan; Nafissi, Nellie; Barata, Pedro; Sartor, A. Oliver; Bastos, Diogo; Smaletz, Oren; Berchuck, Jacob E.; Taplin, Mary-Ellen; Aggarwal, Rahul; Sternberg, Cora N.; Vlachostergios, Panagiotis J.; Alva, Ajjai S.; Su, Christopher; Marshall, Catherine H.; Antonarakis, Emmanuel S.; Medicine, School of MedicineTwo poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and rucaparib) are US Food and Drug Administration-approved for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 mutations, but the relative efficacy of PARP inhibition in BRCA1- versus BRCA2-altered mCRPC is understudied. Methods: We conducted a multicenter retrospective analysis involving 12 sites. We collected genomic and clinical data from 123 patients with BRCA1/2-altered mCRPC who were treated with PARP inhibitors. The primary efficacy end point was the prostate-specific antigen (PSA) response (≥ 50% PSA decline) rate. Secondary end points were PSA progression-free survival (PSA-PFS), clinical or radiographic PFS, and overall survival. We compared clinical outcomes, and other genomic characteristics, among BRCA1- versus BRCA2-altered mCRPC. Results: A total of 123 patients (13 BRCA1 and 110 BRCA2) were included. PARP inhibitors used were olaparib (n = 116), rucaparib (n = 3), talazoparib (n = 2), and veliparib (n = 2). At diagnosis, 72% of patients had Gleason 8-10 disease. BRCA1 patients were more likely to have metastatic disease at presentation (69% v 37%; P = .04). Age, baseline PSA, metastatic distribution, and types of previous systemic therapies were similar between groups. There were equal proportions of germline mutations (51% v 46%; P = .78) in both groups. BRCA1 patients had more monoallelic (56% v 41%; P = .49) and concurrent TP53 (55% v 36%; P = .32) mutations. PSA50 responses in BRCA1- versus BRCA2-altered patients were 23% versus 63%, respectively (P = .01). BRCA2 patients achieved longer PSA-PFS (HR, 1.94; 95% CI, 0.92 to 4.09; P = .08), PFS (HR, 2.08; 95% CI, 0.99 to 4.40; P = .05), and overall survival (HR, 3.01; 95% CI, 1.32 to 6.83; P = .008). Biallelic (compared with monoallelic) mutations, truncating (compared with missense) mutations, and absence of a concurrent TP53 mutation were associated with PARP inhibitor sensitivity. Conclusion: PARP inhibitor efficacy is diminished in BRCA1- versus BRCA2-altered mCRPC. This is not due to an imbalance in germline mutations but might be related to more monoallelic mutations and/or concurrent TP53 alterations in the BRCA1 group.Item Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism A Randomized Clinical Trial(AMA, 2017-01) Block, Geoffrey A.; Bushinsky, David A.; Cheng, Sunfa; Cunningham, John; Dehmel, Bastian; Drueke, Tilman B.; Ketteler, Markus; Kewalramani, Reshma; Martin, Kevin J.; Moe, Sharon M.; Patel, Uptal D.; Silver, Justin; Sun, Yan; Wang, Hao; Chertow, Glenn M.; Department of Medicine, School of MedicineImportance Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects. Objective To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet. Design, Setting, and Participants A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 to May 2014, with end of follow-up in January 2015. Interventions Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily. Main Outcomes and Measures The primary efficacy end point was noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting. Results The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2% were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was −10.5% (95% CI, −17.5% to −3.5%, P for noninferiority, <.001; P for superiority, .004). One hundred seventy-eight patients (52.4%) randomized to etelcalcetide achieved more than 50% reduction in PTH concentrations compared with 138 patients (40.2%) randomized to cinacalcet (P = .001; difference in proportions, 12.2%; 95% CI, 4.7% to 19.5%). The most common adverse effect was decreased blood calcium (68.9% vs 59.8%). Conclusions and Relevance Among patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism, the use of etelcalcetide was not inferior to cinacalcet in reducing serum PTH concentrations over 26 weeks; it also met superiority criteria. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety.Item Human Iris Image Analysis for the Classification of Fuchs’ Crypts and Peripupillary Rings(Springer, 2022-09-01) Wang, Hao; Fang, Shiaofen; Wilke, Frankie; Larsson, Mats; Walsh, Susan; Computer and Information Science, School of ScienceThe human iris is one of the most important identifiable features that contain many complex patterns. In this work, we attempted to automatically classify irises with machine learning models based on several different iris patterns in order to assist genetic research related to pigmentation and structural tissue differences within the human iris. Specifically, two main iris patterns that are commonly observed in the general population were analyzed: the Fuchs’ crypts and the peripupillary pigmented ring. A two-stage machine learning model was proposed to classify the iris crypt frequency, in which a Mask R-CNN model was first built to identify the number of crypts of each size level in the iris, followed by a SVM model to determine the final category. Another KNN model, which used the area-refined histogram features, was applied to classify the iris based on the peripupillary pigmented ring. The labels used in the images were generated independently by two trained expert raters. The performance of these models was evaluated on a test set with overall accuracies of the models estimated at 80.0% and 86.6% for crypts and pigmented ring, respectively. These optimized objective models were therefore concordant with the inter-rater reliability scores produced by expert human raters.Item An Interactive Approach to Bias Mitigation in Machine Learning(IEEE, 2021-10) Wang, Hao; Mukhopadhyay, Snehasis; Xiao, Yunyu; Fang, Shiaofen; Computer and Information Science, School of ScienceUnderrepresentation and misrepresentation of protected groups in the training data is a significant source of bias for Machine Learning (ML) algorithms, resulting in decreased confidence and trustworthiness of the generated ML models. Such bias can be mitigated by incorporating both objective as well as subjective (through human users) measures of bias, and compensating for them by means of a suitable selection algorithm over subgroups of training data. In this paper, we propose a methodology of integrating bias detection and mitigation strategies through interactive visualization of machine learning models in selected protected spaces. In this approach, a (partially generated) ML model performance is visualized and evaluated by a human user or a community of human users in terms of potential presence of bias using both objective and subjective criteria. Guided by such human feedback, the ML algorithm can implement a variety of remedial sampling strategies to mitigate the bias using an iterative human-in-the-loop approach. We also provide experimental results with a benchmark ML dataset to demonstrate that such an interactive ML approach holds considerable promise in detecting and mitigating bias in ML models.Item Perception of Physician Empathy Varies With Educational Level and Gender of Patients Undergoing Low-Yield Computerized Tomographic Imaging(SAGE, 2020-06-01) Kline, Jeffrey A.; Lin, Michelle P.; Hall, Cassandra L.; Puskarich, Michael A.; Dehon, Erin.; Kuehl, Damon R.; Wang, Ralph C.; Hess, Erik P.; Runyon, Michael S.; Wang, Hao; Courtney, D Mark.; Emergency Medicine, School of MedicineObjective: Lack of empathic communication between providers and patients may contribute to low value diagnostic testing in emergency care. Accordingly, we measured the perception of physician empathy and trust in patients undergoing low-value computed tomography (CT) in the emergency department (ED). Methods: Multicenter study of ED patients undergoing CT scanning, acknowledged by ordering physicians as unlikely to show an emergent condition. Near the end of their visit, patients completed the Jefferson Scale of Patient Perception of Physician Empathy (JSPPPE), Trust in Physicians Survey (TIPS), and the Group Based Medical Mistrust Scale (GBMMS). We stratified results by patient demographics including gender, race, and education. Results: We enrolled 305 participants across 9 sites with diverse geographic, racial, and ethnic representation. The median scores (interquartile ranges) for the JSPPPE, TIPS, and GBMMS for all patients were 29 (24-33.5), 55 (47-62), and 18 (12-29). Compared with white patients, nonwhite patients had similar JSPPPE and TIPS scores but had higher (worse) GBMMS scores. Females had significantly lower JSPPPE and TIPS scores than males, and scores were lower (worse) in females with college degrees. Patients in the lowest tier of educational status had the highest (better) JSPPPE and TIPS scores. Scores were invariant with physician characteristics. Conclusion: Among patients undergoing low-value CT scanning in the ED, the degree of patient perception of physician empathy and trust varied based on the patients’ level of education and gender. Given this variation, an intervention to increase patient perception of physician empathy should contain individualized strategies to address these subgroups, rather than a one-size-fits-all approach.