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Engineered GM-CSF polarizes protumorigenic tumor-associated macrophages to an antitumorigenic phenotype and potently synergizes with IL-12 immunotherapy
Kang, Seounghun; Mansurov, Aslan; Kurtanich, Trevin; Chun, Hye Rin; Slezak, Anna J; Volpatti, Lisa R; Chang, Kevin; Wang, Thomas; Alpar, Aaron T; Refvik, Kirsten C; Hansen, O Isabella; Borjas, Gustavo J; Berg, Brendan T K; Shim, Ha-Na; Hultgren, Kevin T; Gomes, Suzana; Wang, Yue; Solanki, Ani; Ishihara, Jun; Swartz, Melody A; Hubbell, Jeffrey A
BACKGROUND:The use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses. Therefore, the rational design of immune modulators that can control the immune suppressive properties of TAMs and polarize them, as well as dendritic cells (DCs), toward a more proinflammatory phenotype is a principal objective in cancer immunotherapy. METHODS:Here, using a protein engineering approach to enhance cytokine residence in the tumor microenvironment, we examined combined stimulation of the myeloid compartment via tumor stroma-binding granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance responses in both DCs and T cells via stroma-binding interleukin-12 (IL-12). We evaluated tumor responses at the levels of outcome, cellular responses, and cytokine responses in both the tumors and the tumor-draining lymph nodes. We further investigated the potentiation of DC response to IL-12 by GM-CSF stimulation ex vivo. RESULTS:T cell populations. Furthermore, engineered GM-CSF potentiated DC response to IL-12, upregulating DC expression of IL-12 receptor and enhancing their expression of proinflammatory cytokines and chemokines on IL-12 exposure. This resulted in remarkable synergistic efficacy in multiple solid tumor models treated with the dual cytokine combination. The combination therapy also improved the efficacy of CPI in a CPI-resistant genetically-engineered melanoma model and exhibited synergistic antitumor efficacy in a pulmonary metastasis model. CONCLUSION/CONCLUSIONS:Our strategy provides a rational design for combination immunotherapy targeting both myeloid and lymphoid compartments through complementary mechanisms.
PMCID:11667343
PMID: 39794939
ISSN: 2051-1426
CID: 5778592
Creating effective teams and valuing patient-centered care to change culture and improve equity on labor and delivery: a qualitative study
Vangompel, Emily White; Verma, Shelly; Wator, Caroline; Carlock, Francesca; Lyndon, Audrey; Borders, Ann; Holl, Jane
ISI:001382728600005
CID: 5779672
ARTHRITIS CARE & RESEARCH [Letter]
Gupta, Nishant; Carsons, Steven E.; Carteron, Nancy L.; Scofield, Robert Hal; Lee, Augustine S.; Thomas, Donald E.; Moua, Teng; Ussavarungsi, Kamonpun; St Clair, E. William; Meehan, Richard; Dunleavy, Kieron; Makara, Matt; Hammitt, Katherine Morland
ISI:001383081700001
ISSN: 2151-464x
CID: 5778782
Tips and Tricks for Image-Guided Breast Biopsies: Technical Factors for Success
Dodelzon, Katerina; Grimm, Lars; Coffey, Kristen; Reig, Beatriu; Mullen, Lisa; Dashevsky, Brittany Z; Bhole, Sonya; Parikh, Jay
Image-guided biopsy is an integral step in the diagnosis and management of suspicious image-detected breast or axillary lesions, allowing for accurate diagnosis and, if indicated, treatment planning. Tissue sampling can be performed under guidance of a full spectrum of breast imaging modalities, including stereotactic, tomosynthesis, sonographic, and MRI, each with its own set of advantages and limitations. Procedural planning, which includes consideration of technical, patient, and lesion factors, is vital for diagnostic accuracy and limitation of complications. The purpose of this paper is to review and provide guidance for breast imaging radiologists in selecting the best procedural approach for the individual patient to ensure accurate diagnosis and optimal patient outcomes. Common patient and lesion factors that may affect successful sampling and contribute to postbiopsy complications are reviewed and include obesity, limited patient mobility, patient motion, patients prone to vasovagal reactions, history of anticoagulation, and lesion location, such as proximity to vital structures or breast implant.
PMID: 39313444
ISSN: 2631-6129
CID: 5778172
Factors associated with retention in Quitline counseling for smoking cessation among HIV-positive smokers receiving care at HIV outpatient clinics in Vietnam
Nguyen, Nam Truong; Nguyen, Trang; Vu, Giap Van; Cleland, Charles M; Pham, Yen; Truong, Nga; Kapur, Reet; Alvarez, Gloria Guevara; Phan, Phuong Thu; Armstrong-Hough, Mari; Shelley, Donna
BACKGROUND:Quitline counseling is an effective method for supporting smoking cessation, offering personalized and accessible assistance. Tobacco use is a significant public health issue among people living with HIV. In Vietnam, over 50% of men living with HIV use tobacco. However, there is limited research on Quitline use and retention rates in this population and a lack of research on factors associated with retention in Quitline counseling. The study aims to evaluate the factors associated with retention in Quitline counseling for smoking cessation among HIV-positive smokers receiving care at HIV outpatient clinics in Vietnam. METHOD/METHODS:The study analyzed data from a randomized controlled trial (RCT) that compared the effectiveness of three smoking cessation interventions for smokers living with HIV at 13 Outpatient Clinics in Ha Noi. A total of 221 smokers aged 18 and above living with HIV participated in Arm 1 of the RCT, which included screening for tobacco use (Ask), health worker-delivered brief counseling (Assist), and proactive referral to Vietnam's national Quitline (AAR), in which the Quitline reached out to the patient to engage them in up to 10 sessions of smoking cessation counseling. Retention in Quitline counseling was defined as participating in more than five counseling calls. The study used bivariate and logistic regression analyses to explore the associations between retention and other factors. RESULTS:Fifty-one percent of HIV-positive smokers completed more than five counseling sessions. Smokers living with HIV aged 35 or older (OR = 5.53, 95% CI 1.42-21.52), who had a very low/low tobacco dependence level (OR = 2.26, 95% CI 1.14-4.51), had a lower score of perceived importance of quitting cigarettes (OR = 0.87, 95% CI 0.76-0.99), had a household ban or partial ban on cigarettes smoking (OR = 2.58, 95% CI 1.39-4.80), and had chosen a quit date during the Quitline counseling (OR = 3.0, 95% CI 1.63-5.53) were more likely to retain in the Quitline counseling than those smokers living with HIV whose ages were less than 35, who had a high/very high tobacco dependence level, had a higher score of perception of the importance of quitting cigarettes, did not have a household ban on cigarettes smoking, and did not choose a quit date during counseling. CONCLUSION/CONCLUSIONS:There is a high retention rate in Quitline counseling services among PLWHs receiving care at HIV outpatient clinics. Tailoring interventions to the associated factors such as age, tobacco dependence, perceived importance of quitting, household smoking bans, and setting a quit date during counseling may improve engagement and outcomes, aiding in the reduction of smoking prevalence among HIV-positive individuals.
PMCID:11687760
PMID: 39739725
ISSN: 1932-6203
CID: 5779232
Application of a Heuristic Framework for Multilevel Interventions to Eliminate the Impact of Unjust Social Processes and Other Harmful Social Determinants of Health
Guilamo-Ramos, Vincent; Thimm-Kaiser, Marco; Benzekri, Adam; Johnson, Celia; Williams, Desiree; Wilhelm-Hilkey, Nash; Goodman, Melody; Hagan, Holly
There is consensus about the importance of developing a strong cadre of effective multilevel interventions to eliminate the impacts of unjust social processes, such as structural racism and other harmful social determinants of health (SDOH), on health inequities in the USA. However, the available cadre of rigorously evaluated evidence-based interventions for SDOH mitigation remains underdeveloped relative to the magnitude of historic and current health inequities. The proposed manuscript addresses this gap in two ways: first, by introducing a heuristic framework to inform decisions in multilevel intervention development, study design, and selection of analytic methods and, second, by providing a roadmap for future applications of the framework in multilevel intervention research through an exemplar application using the ongoing NIH-funded evaluation study of the Nurse-Community-Family Partnership (NCFP) intervention. NCFP leverages individual, family, institutional, and system factors to shape COVID-19 mitigation outcomes at the individual and household levels. NCFP takes an approach informed by the heuristic framework to addressing and mitigating unjust social processes and other harmful SDOH. We discuss the application of a two-arm parallel explanatory group randomized trial to evaluate the efficacy of NCFP in improving the primary (COVID-19 testing uptake) and secondary (adoption of COVID-19 control measures, COVID-19 vaccine uptake, mutual aid capacity, etc.) outcomes at the individual and household levels. The analysis approach relies on random-intercept models, and we calculate the variance partitioning coefficient to estimate the extent to which household- and individual-level variables contribute to the outcome, allowing examination of NCFP effects at multiple levels.
PMCID:11239765
PMID: 38607535
ISSN: 1573-6695
CID: 5779512
Diversity-Related, Student-Led National Medical Organizations: Leadership Opportunities for Learners
Brutus, Nicholas N; Spencer, Dennis J; Huell, Derek; Astudillo, Yaritzy M; Ott, Austen; Lee, Joyce H; Calac, Alex; Sánchez, John P
INTRODUCTION/UNASSIGNED:In light of the lack of diversity in academic medicine leadership, diversity-related, student-led national medical organizations (NMOs) provide a space for solace and reprieve among common peers while providing an opportunity to develop leadership competencies in a supportive environment. Despite the impact NMOs have had on cultivating generations of leaders in medicine, trainees may not identify opportunities for leadership development that are transferable to future careers in academic medicine. METHODS/UNASSIGNED:We designed and implemented a dynamic 60-minute workshop with an interactive PowerPoint presentation, author-owned video testimonials (from past student leaders of NMOs), two case presentations, and reflection exercises. We assessed learner self-perceived confidence via workshop surveys. The target audience of this module was medical trainees, including medical students, residents, and fellows. RESULTS/UNASSIGNED:Forty-three workshop attendees across three sites submitted partial or complete survey evaluations. Respondents included medical students (77%), with the remainder self-identified as either postbaccalaureate students, residents/fellows, academic faculty, or physicians. A comparison of pre- and postresponses showed a statistically significant increase in confidence in addressing each of the four educational objectives. Participants felt the case presentations offered relevant applicable examples. DISCUSSION/UNASSIGNED:For many trainees, the role that diversity-related NMOs play in developing leadership competencies may be unclear and not articulated in traditional medical curricula. In this module, we provide examples of how NMOs facilitate leadership development and may encourage our diverse trainees to eventually become academic faculty.
PMCID:11671812
PMID: 39735709
ISSN: 2374-8265
CID: 5779202
Exploring the Molecular Link Between Diabetes and Erectile Dysfunction Through Single-Cell Transcriptome Analysis
Begum, Mahmuda; Choubey, Mayank; Tirumalasetty, Munichandra Babu; Arbee, Shahida; Sadik, Sibly; Mohib, Mohammad Mohabbulla; Srivastava, Shivani; Minhaz, Naofel; Alam, Riffat; Mohiuddin, Mohammad Sarif
Erectile dysfunction (ED) is a pathophysiological condition in which the patients cannot achieve an erection during sexual activity, and it is often overlooked yet prevalent among diabetic men, globally affecting approximately 35-75% of diabetic individuals. The precise mechanisms through which diabetes contributes to ED remain elusive, but the existing literature suggests the potential involvement of nerve and vascular damage that affects the penile supply. In the present review, we reanalyze the existing human single-cell transcriptomic data from patients having diabetes mellitus-associated ED with normal erections. The analysis validates the expression of genes associated with antioxidative pathways, growth factors, adipokines, angiogenesis, vascular functions, penile erection, sexual function, and inflammation in diverse cell types from healthy individuals and those with ED. Our transcriptomic analysis reveals alterations in the expression of adiponectin receptors in the pathogenesis of ED compared to their counterparts in healthy subjects. This comprehensive review sheds light on the molecular underpinnings of ED in the context of diabetes, providing an in-depth understanding of the biological and cellular alterations involved and paving the way for possible targeted therapeutic discoveries in the field of diabetes-associated male infertility.
PMCID:11675191
PMID: 39766863
ISSN: 2073-4425
CID: 5779312
The essential and evolving nature of oncology social work: Accomplishments and impact, 2010-present
Zebrack, Brad; Schapmire, Tara; Damaskos, Penny; Grignon, Michael; Smith, Sophia K
This paper demonstrates the essential nature of oncology social work and the critical role that oncology social workers (OSWs) play in the achievement of high-quality cancer care that improves patient outcomes, contains cost, advances population health, reduces provider burn-out among healthcare providers, and does it in a manner that addresses disparities and achieves equity. To this end, this paper's purpose is two-fold: (1) to review and demonstrate OSW contributions to the advancement of comprehensive cancer care over the last 15 years, and (2) to consider next steps for the Association of Oncology Social Work (AOSW) and the Oncology Social Work profession to achieve its mission and calling. To enhance the viability and security of OSWs and the professional organizations that support them, this report summarizes a breadth and depth of work and includes recommendations for the profession.
PMID: 39373332
ISSN: 1540-7586
CID: 5778192
An Eponymous History of Hemostatic, Tissue, and Reduction Clamps in Orthopedic Surgery [Historical Article]
Derry, Kendall H; Dayan, Isaac; Morgan, Allison M; Lehane, Kevin; Fisher, Nina D; Bi, Andrew S
Eponyms are widely used in the field of orthopedic surgery, including for surgical instruments. Although their use is at times controversial, an appreciation of the history behind eponymous terms allows one to both recognize the shortcomings of the past and simultaneously be inspired by ingenious inventors. The primary purpose of this review is to provide a historical perspective of clamps and forceps commonly used in orthopedic surgery, to better appreciate the evolution of their use over time, and to inspire innovation to constantly improve upon surgical instrumentation as the field of orthopedic surgery advances. [Orthopedics. 2024;47(6):e287-e291.].
PMID: 39509579
ISSN: 1938-2367
CID: 5779762