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Item A Cross-Sectional Analysis of Testicular Cancer Symptom Recognition and Stage of Diagnosis(Sage, 2022) Rovito, Michael J.; Craycraft, Mike; Adams, Wesley B.; Maresca, Michael; Saab, Mohamad M.; Cary, Clint; Gooljar, Chayna; Martinez, Sydney; Zanet, Rama Abu; Urology, School of MedicineThere is a need to further explore the relationship between atypical symptom reporting and stage diagnosis to help develop a clearer defined list of possible testicular cancer (TC) symptoms that could assist physicians diagnose the disease earlier. A cross-sectional study was employed to explore possible associations between TC symptom presentation and stage of diagnosis. An original 40-item survey was distributed among 698 TC survivors to determine the potential impact of several risk factors, experiences, and behaviors upon diagnosis. This analysis aimed to explore how certain patient-driven experiences (e.g., symptoms, perceptions, and behaviors) could serve as catalysts for seeking medical care for testicular health concerns. Experiencing hot flashes or having no symptoms had a positive association with later-stage diagnosis while change in shape had a significant negative association with later-stage diagnosis. While the logistic regression model explained relatively low variance in the data (R2 = .1415), it was statistically significant (χ2p < .001). Pain (odds ratio [OR] = 1.6524, p < .05), hot flashes (OR = 5.7893, p < .01), and no symptoms experienced (OR = 12.4836, p < .01) were all significant predictors of a more advanced stage diagnosis. The concern around uncommon/atypical symptoms are that they are indistinct and do not serve as clear signs that TC is present. However, perhaps in tandem with other more overt symptoms, their discovery can serve in a more confirmatory role for a suspect case. If observed with other uncommonly reported symptoms, these uncommon symptoms could provide another pathway in the TC diagnostic process. Clinical and patient education is warranted to increase awareness of uncommon TC symptoms.Item An mHealth App to Support Caregivers in the Medical Management of Their Child With Cancer: Beta Stage Usability Study(JMIR, 2024-10-17) Mueller, Emily L.; Cochrane, Anneli R.; Campbell, Madison E.; Nikkhah, Sarah; Holden, Richard J.; Miller, Andrew D.; Pediatrics, School of MedicineBackground: Previous research demonstrated that caregivers of children with cancer desired a mobile health (mHealth) tool to aid them in the medical management of their child. Prototyping and alpha testing of the Cope 360 app (Commissioning Agents, Inc) resulted in improvements in the ability to track symptoms, manage medications, and prepare for urgent medical needs. Objective: This study aims to engage caregivers of children with cancer in beta testing of a smartphone app for the medical management of children with cancer, assess acceptance, identify caregivers' perceptions and areas for improvement, and validate the app's design concepts and use cases. Methods: In this pilot, study caregivers of children with cancer used the Cope 360 mHealth app for 1 week, with the goal of daily logging. Demographics and a technology acceptance survey were obtained from each participant. Recorded semistructured interviews were transcribed and analyzed iteratively using NVivo (version 12, QSR International) and analyzed for information on usage, perceptions, and suggestions for improvement. Results: A total of 10 caregivers participated in beta testing, primarily women (n=8, 80%), married, with some college education, and non-Hispanic White (n=10, 100%). The majority of participants (n=7, 70%) had children with acute lymphocytic leukemia who were being treated with chemotherapy only (n=8, 80%). Overall, participants had a favorable opinion of Cope 360. Almost all participants (n=9, 90%) believed that using the app would improve their ability to manage their child's medical needs at home. All participants reported that Cope 360 was easy to use, and most would use the app if given the opportunity (n=8, 80%). These values indicate that the app had a high perceived ease of use with well-perceived usefulness and behavioral intention to use. Key topics for improvement were identified including items that were within the scope of change and others that were added to a future wish list. Changes that were made based on caregiver feedback included tracking or editing all oral and subcutaneous medications and the ability to change the time of a symptom tracked or medication administered if unable to do so immediately. Wish list items included adding a notes section, monitoring skin changes, weight and nutrition tracking, and mental health tracking. Conclusions: The Cope 360 app was well received by caregivers of children with cancer. Our validation testing suggests that the Cope 360 app is ready for testing in a randomized controlled trial to assess outcome improvements.Item An mHealth App to Support Caregivers in the Medical Management of Their Child With Cancer: Co-design and User Testing Study(JMIR, 2022-03-16) Mueller, Emily L.; Cochrane, Anneli R.; Campbell, Madison E.; Nikkhah, Sarah; Miller, Andrew D.; Pediatrics, School of MedicineBackground: Caregivers face new challenges and tasks when their child is diagnosed with cancer, which can be overwhelming. Mobile technology has the capacity to provide immediate support at their fingertips to aid in tracking symptoms, managing medication, and planning for emergencies. Objective: The objective of this study is to engage directly with end users and proxies to co-design and create a mobile technology app to support caregivers in the medical management of their child with cancer. Methods: We engaged directly with caregivers of children with cancer and pediatric oncology nurse coordinators (proxy end users) to co-design and create the prototype of the Cope 360 mobile health app. Alpha testing was accomplished by walking the users through a series of predetermined tasks that encompassed all aspects of the app including tracking symptoms, managing medications, and planning or practicing for a medical emergency that required seeking care in the emergency department. Evaluation was accomplished through recorded semistructured interviews and quantitative surveys to capture demographic information and measure the system usability score. Interviews were transcribed and analyzed iteratively using NVivo (version 12; QSR International). Results: This study included 8 caregivers (aged 33-50 years) of children with cancer, with most children receiving chemotherapy, and 6 nurse coordinators, with 3 (50%) of them having 11 to 20 years of nursing experience. The mean system usability score given by caregivers was 89.4 (95% CI 80-98.8). Results were grouped by app function assessed with focus on specific attributes that were well received and those that required refinement. The major issues requiring refinement included clarity in the medical information and terminology, improvement in design of tasks, tracking of symptoms including adjusting the look and feel of certain buttons, and changing the visual graph used to monitor symptoms to include date anchors. Conclusions: The Cope 360 app was well received by caregivers of children with cancer but requires further refinement for clarity and visual representation. After refinement, testing among caregivers in a real-world environment is needed to finalize the Cope 360 app before its implementation in a randomized controlled trial.Item Anticachectic regulator analysis reveals Perp-dependent antitumorigenic properties of 3-methyladenine in pancreatic cancer(American Society for Clinical Investigation, 2022-01-25) Dasgupta, Aneesha; Arneson-Wissink, Paige C.; Schmitt, Rebecca E.; Cho, Dong Seong; Ducharme, Alexandra M.; Hogenson, Tara L.; Krueger, Eugene W.; Bamlet, William R.; Zhang, Lizhi; Razidlo, Gina L.; Fernandez-Zapico, Martin E.; Doles, Jason D.; Anatomy, Cell Biology and Physiology, School of MedicineApproximately 80% of pancreatic cancer patients suffer from cachexia, and one-third die due to cachexia-related complications such as respiratory failure and cardiac arrest. Although there has been considerable research into cachexia mechanisms and interventions, there are, to date, no FDA-approved therapies. A major contributing factor for the lack of therapy options could be the failure of animal models to accurately recapitulate the human condition. In this study, we generated an aged model of pancreatic cancer cachexia to compare cachexia progression in young versus aged tumor-bearing mice. Comparative skeletal muscle transcriptome analyses identified 3-methyladenine (3-MA) as a candidate antiwasting compound. In vitro analyses confirmed antiwasting capacity, while in vivo analysis revealed potent antitumor effects. Transcriptome analyses of 3-MA-treated tumor cells implicated Perp as a 3-MA target gene. We subsequently (a) observed significantly higher expression of Perp in cancer cell lines compared with control cells, (b) noted a survival disadvantage associated with elevated Perp, and (c) found that 3-MA-associated Perp reduction inhibited tumor cell growth. Finally, we have provided in vivo evidence that survival benefits conferred by 3-MA administration are independent of its effect on tumor progression. Taken together, we report a mechanism linking 3-MA to Perp inhibition, and we further implicate Perp as a tumor-promoting factor in pancreatic cancer.Item Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation(The American Society for Clinical Investigation, 2021-05-17) Xu, Hanchen; Van der Jeught, Kevin; Zhou, Zhuolong; Zhang, Lu; Yu, Tao; Sun, Yifan; Li, Yujing; Wan, Changlin; So, Ka Man; Liu, Degang; Frieden, Michael; Fang, Yuanzhang; Mosley, Amber L.; He, Xiaoming; Zhang, Xinna; Sandusky, George E.; Liu, Yunlong; Meroueh, Samy O.; Zhang, Chi; Wijeratne, Aruna B.; Huang, Cheng; Ji, Guang; Lu, Xiongbin; Medical and Molecular Genetics, School of MedicineOne of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell–mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non–ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I–mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient–derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy.Item Author Correction: A pyramidal deep learning pipeline for kidney whole-slide histology images classification(Springer Nature, 2021-11-02) Abdeltawab, Hisham; Khalifa, Fahmi; Ghazal, Mohammed; Cheng, Liang; Gondim, Dibson; El‑Baz, Ayman; Pathology and Laboratory Medicine, School of MedicineThis corrects the article "A pyramidal deep learning pipeline for kidney whole-slide histology images classification" in volume 11, 20189.Item Barriers to and facilitators of effective management of fever episodes in hospitalised Kenyan children with cancer: protocol for convergent mixed methods study(BMJ Publishing, 2023-11-02) Nessle, Charles Nathaniel; Njuguna, Festus; Dettinger, Julia; Koima, Raphael; Nyamusi, Lenah; Kisembe, Evelynn; Kinja, Sarah; Ndung’u, Mercy; Njenga, Dennis; Langat, Sandra; Olbara, Gilbert; Moyer, Cheryl; Vik, Terry; Pediatrics, School of MedicineIntroduction: Febrile neutropenia is an oncological emergency in children with cancer, associated with serious infections and complications. In low-resourced settings, death from infections in children with cancer is 20 times higher than in high-resourced treatment settings, thought to be related to delays in antibiotic administration and management. The barriers to effective management of fever episodes in children with cancer have not previously been described. This convergent mixed-methods study will provide the evidence to develop fever treatment guidelines and to inform their effective implementation in children with cancer at Moi Teaching and Referral Hospital (MTRH), a level 6 referral hospital in western Kenya. Methods and analysis: Prospective data collection of paediatric patients with cancer with new fever episodes admitted to MTRH will be performed during routine treatment. Clinical variables will be collected from 50 fever episodes, including cancer diagnosis and infectious characteristics of the fever episode, and elapsed time from fever onset to various milestones in the management workflow. Semistructured qualitative interviews with healthcare providers (estimated 20 to reach saturation) will explore the barriers to and facilitators of appropriate management of fever episodes in children with cancer. The interview guide was informed by a theoretical framework and Consolidated Framework for Implementation Research. A mixed-methods analysis use of joint display tables and process mapping will link and integrate the two types of data with meta-inferences. Ethics and dissemination: Institutional review board approval was obtained from the MTRH (0004273) and the University of Michigan (HUM0225674), and the study was registered with National Commission for Science Technology and Innovation (P/23/22885). Written consent will be obtained from all participants. Results will be formally shared with local and national policy leadership and local end users, presented at relevant national academic conferences and submitted for publication in a peer-reviewed journal.Item Barriers to mental health service use and preferences for addressing emotional concerns among lung cancer patients(Wiley, 2014-07) Mosher, Catherine E.; Winger, Joseph G.; Hanna, Nasser; Jalal, Shadia I.; Fakiris, Achilles J.; Einhorn, Lawrence H.; Birdas, Thomas J.; Kesler, Kenneth A.; Champion, Victoria L.; Psychology, School of ScienceOBJECTIVE: This study examined barriers to mental health service use and preferences for addressing emotional concerns among lung cancer patients (N=165) at two medical centers in the Midwestern United States. METHODS: Lung cancer patients completed an assessment of anxiety and depressive symptoms, mental health service use, barriers to using these services, and preferences for addressing emotional concerns. RESULTS: Only 45% of distressed patients received mental health care since their lung cancer diagnosis. The most prevalent patient-reported barriers to mental health service use among non-users of these services (n=110) included the desire to independently manage emotional concerns (58%) and inadequate knowledge of services (19%). In addition, 57% of distressed patients who did not access mental health services did not perceive the need for help. Seventy-five percent of respondents (123/164) preferred to talk to a primary care physician if they were to have an emotional concern. Preferences for counseling, psychiatric medication, peer support, spiritual care, or independently managing emotional concerns also were endorsed by many patients (range=40-50%). Older age was associated with a lower likelihood of preferring to see a counselor. CONCLUSIONS: Findings suggest that many distressed lung cancer patients underuse mental health services and do not perceive the need for such services. Efforts to increase appropriate use of services should address patients' desire for autonomy and lack of awareness of services.Item The Cancer Loneliness Scale and Cancer-related Negative Social Expectations Scale: development and validation(SpringerLink, 2017-07) Adams, Rebecca N.; Mosher, Catherine E.; Rand, Kevin L.; Hirsh, Adam T.; Monahan, Patrick O.; Abonour, Rafat; Kroenke, Kurt; Psychology, School of SciencePURPOSE: Loneliness is a known risk factor for poor mental and physical health outcomes and quality of life in the general population, and preliminary research suggests that loneliness is linked to poorer health outcomes in cancer patients as well. Various aspects of the cancer experience contribute to patients feeling alone and misunderstood. Furthermore, loneliness theory suggests that negative social expectations, which may specifically relate to the cancer experience, precipitate and sustain loneliness. Cancer-specific tools are needed to assess key constructs of this theory. In the current study, we developed and tested measures of (1) loneliness attributed to cancer (i.e., cancer-related loneliness) and (2) negative social expectations related to cancer. METHODS: First, we developed the items for the measures based on theory, prior research, and expert feedback. Next, we assessed the measures' psychometric properties (i.e., internal consistency and construct validity) in a diverse sample of cancer patients. RESULTS: The final products included a 7-item unidimensional Cancer Loneliness Scale and a 5-item unidimensional Cancer-related Negative Social Expectations Scale. Evidence of excellent reliability and validity was found for both measures. CONCLUSIONS: The resulting measures have both clinical and research utility.Item Caregiver Perspectives on Patient Participation in Biological Pediatric Cancer Research(MDPI, 2022-06-16) Kendel, Nicole E.; Belsky, Jennifer A.; Stanek, Joseph R.; Streby, Keri A.; Shah, Nilay; Pediatrics, School of MedicineAdolescent cancer patients and their caregivers have demonstrated willingness to participate in invasive biological sampling, either for their own potential benefit or for research purposes. However, many malignancies occur primarily in prepubescent patients and there are no similar studies in this population. Our study objective was to assess the willingness of caregivers to consent to research studies involving invasive biological sampling in children ≤ 13 years of age. Participants completed a survey assessing their willingness to allow various procedures both with and without clinical benefit to their children. Most respondents were willing to allow additional blood draws regardless of potential benefit to their children (95.6% were willing when there would be benefits and 95.6% were willing when there would not). Although the overall willingness was lower with other hypothetical procedures, the majority of respondents were still willing to allow additional biopsies for research purposes. Caregivers of young children with cancer will allow their children to undergo additional invasive procedures for research purposes. This willingness decreased with more invasive procedures without potential direct benefit, but interest remained in more than half of participants. Caregivers for young patients with cancer should be approached for participation in future biological/correlative studies.