Medicine and Health Sciences Commons^™

Determining The Prognostic Value Of Complete Blood Count Subgroup Parameters In Staphylococcus Aureus Bacteremia, Emily L. Matthews, Thomas J. Dilworth

Journal of Patient-Centered Research and Reviews

Purpose: Serum cytokine alterations are associated with increased Staphylococcus aureus bacteremia (SAB) mortality. Unfortunately, clinical use of these cytokines is uncommon due to limited availability and high cost. Complete blood count (CBC) with differential reflects the host immune response, and CBC subgroup parameters may have prognostic value in SAB. We sought to determine the association between CBC subgroup parameters on the day of index blood culture and 30-day all-cause mortality in SAB patients.

Methods: We conducted a retrospective study of adult SAB patients with infectious diseases consultation to evaluate the discriminatory capacity of CBC subgroup parameters in predicting SAB mortality. …

Factors Influencing Self-Wound Care Adoption In Singaporean Communities: A Cross-Sectional Survey, Ling Jia Goh, Xiaoli Zhu

Journal of Patient-Centered Research and Reviews

Purpose: Managing wounds often requires frequent clinic visits, posing a burden on both patients and the healthcare system. Shared wound care, which encourages patients to manage dressings at home, has emerged as a potential solution. This study investigates factors influencing self-wound care adoption in Singapore.

Methods: A cross-sectional survey involving 328 participants from six primary healthcare centers was conducted. The survey examined demographics, wound characteristics, and perceptions towards shared wound care using a locally validated questionnaire. Parametric tests and logistic regression were used to analyze the data.

Results: Unlike older participants, younger adults valued time saved through self-care and found …

Trends In Gaps Of Care For Patients With Congenital Heart Disease: Implications For Social Determinants Of Health And Child Opportunity Index, Abbas H. Zaidi, Adam Alberts, Devyani Chowdhury, Claude Beaty, Benjamin Brewer, Ming Hui Chen, Sarah D. De Ferranti

Department of Surgery Faculty Papers

BACKGROUND: Lifelong continuity of care is essential for patients with congenital heart disease (CHD) to maximize health outcomes; unfortunately, gaps in care (GIC) are common. Trends in GIC and of social determinants of health factors contributing to GIC are poorly understood.

METHODS AND RESULTS: This retrospective cohort study included patients with CHD, aged 0 to 34 years, who underwent surgery between January 2003 and May 2020, followed up at a pediatric subspeciality hospital. Patients were categorized as having simple, moderate, and complex CHD based on 2018 American Heart Association and American College of Cardiology guidelines. Social determinants of health, such …

Preventing The Next Fall: The Power Of A Simple Checklist In Reducing Patient Falls, Ryan P. Bialaszewski, Michael Sander, Maria Hincapie, Rita Garza, Aurora Cavazos

MEDI 9331 Scholarly Activities Clinical Years

Background:
Preventable medical errors and adverse events in US hospitals are far too common and contribute to an estimated $17 billion annually in healthcare expenditures. Falls comprise the majority of these preventable adverse events and are a significant cause of increased healthcare costs, prolonged hospital stays, and patient morbidity and mortality. The average cost per hospital fall is estimated at $62,521 ($35,365 direct costs). Despite numerous preventative measures, the complexity of managing multiple interventions can lead to inconsistent application. Inspired by the success of surgical "time-out" checklists in operating rooms, we hypothesized that a standardized checklist for fall prevention could …

Conference Proceedings: Select Abstracts Presented At The 2024 Advocate Aurora Scientific Day, Advocate Aurora Scientific Day

Journal of Patient-Centered Research and Reviews

This abstract supplement includes findings presented through oral or poster presentations at the 50th annual Scientific Day event held on May 22, 2024. Scientific Day provides both an in-person and virtual forum for sharing of research, quality improvement, and case studies conducted by faculty, fellows, residents, and other health professionals associated with Illinois-based Advocate Health Care and Wisconsin-based Aurora Health Care.

“It Is What It Is” – The Lived Experience Of Women With Breast Cancer Undergoing Axillary Lymph Node Dissection, Eva Vikhe Patil, Anna Forsberg, Carina Wennerholm, Jenny Drott

Journal of Patient-Centered Research and Reviews

Purpose: The lived experience of women undergoing axillary procedures as part of their breast cancer (BC) treatment remains unexplored. This lack of in-depth understanding could hamper implementation of person-centred care, which is concerning because BC is the most common form of cancer in women. The aim of this study was therefore to explore the lived experiences of women undergoing axillary lymph node dissection (ALND) due to BC.

Methods: Twelve women with a mean age of 59 years were interviewed about their lived experiences of axillary procedures as part of their BC treatment. The interviews were recorded, transcribed verbatim, and analysed …

Assessing The Climate Readiness Of Physician Education Leaders In Graduate Medical Education, Deborah Simpson, Anne Getzin, Aaron A. Levy, Victoria Gillet

Journal of Patient-Centered Research and Reviews

Climate change affects patient health through an array of exposures, including increasing heatwaves, extreme weather events, poor air quality, and expanding vector-borne illnesses. Physicians are at the forefront of addressing the health consequences of these exposures with patients, and environmental sustainability has become a priority for health care organizations. Accordingly, climate change and health is becoming a critical area for graduate medical education (GME). As GME leaders design and drive education in residency and fellowship programs, understanding those leaders’ baseline knowledge on this topic and its alignment with their organizations’ priorities is an essential step in the development of climate …

Social Isolation And Loneliness Prevention Among Rural Older Adults Aging-In-Place: A Needs Assessment, Jodi L. Southerland, Shimin Zheng, Kayla Dodson, Erin Mauck, Juanita-Dawne R. Bacsu, Monique J. Brown Ph.D., Mph, Jeremy Holloway, Steffi M. Kim, Ayse Malatyali, Matthew Lee Smith

Faculty Publications

Introduction: The adverse effects of social isolation and loneliness (SI/L) have been documented among older adults in rural communities and contribute to poor health outcomes, premature disability and mortality, and increased burden on the healthcare system. The identification of factors contributing to SI/L among older adults can build the foundation for rural policymakers and leaders to allocate resources and develop tailored strategies more efficiently. The purpose of this article is to describe findings from a needs assessment designed to understand local factors that contribute to SI/L among rural older adults in a county in Northeast Tennessee. Findings from the needs …

Reproduction Has Immediate Effects On Female Mortality, But No Discernible Lasting Physiological Impacts: A Test Of The Disposable Soma Theory, Sharon E Mitchell, Megan Simpson, Lena Coulet, Solenn Gouedard, Catherine Hambly, Juliano Morimoto, David B Allison, John R Speakman

Children’s Nutrition Research Center Staff Publications

The disposable soma theory (DST) posits that organisms age and die because of a direct trade-off in resource allocation between reproduction and somatic maintenance. DST predicts that investments in reproduction accentuate somatic damage which increase senescence and shortens lifespan. Here, we directly tested DST predictions in breeding and nonbreeding female C57BL/6J mice. We measured reproductive outputs, body composition, daily energy expenditure, and oxidative stress at peak lactation and over lifetime. We found that reproduction had an immediate and negative effect on survival due to problems encountered during parturition for some females. However, there was no statistically significant residual effect on …

Hell On Earth In Garth Nix’S Old Kingdom: Dark Jouissance And The Dead Mother, John Rosegrant

Mythlore: A Journal of J.R.R. Tolkien, C.S. Lewis, Charles Williams, and Mythopoeic Literature

The Old Kingdom’s River of Death is a hell impinging on life: The Dead take hideous Boschian forms, and helped by necromancers wielding “Free Magic” they often emerge from Death. Necromancers, Free Magic, and the Dead are battled by Abhorsens wielding “Charter magic,” Free Magic that has been transformed by symbols. Immersion in the Charter gives a joyous experience of connection to all life. Symbolization must unite with Free Magic to create this experience; symbolization alone is inadequate, as we see in the example of mundanely rational people who dwell in a neighboring land. But the source of joyous access …

Essays On Information Technology In Healthcare, Gleb Zavadskiy

USF Tampa Graduate Theses and Dissertations

Information technologies (IT) and information systems (IS) have profound significance across various sectors of society, including healthcare, business, education, government, and beyond. First, IT facilitates instant communication globally through email, messaging apps, video conferencing, and social media, revolutionizing how individuals and organizations interact, collaborate, and share information (Hacker et al. 2020; Tang and Hew 2020).

Secondly, the Internet and digital libraries provide worldwide access to vast amounts of information, what makes knowledge and education available to everyone, empowering individuals to learn and stay informed on diverse topics (Haleem et al. 2022). Another aspect of IT systems in various industries is …

“Ups And Downs, Joys And Sorrows” – Assessment And Clinical Relevance Of Patient Priorities In An Interdisciplinary Parkinson’S Disease Clinic, Esme D. Trahair, Allison M. Allen, Sneha Mantri

Journal of Patient-Centered Research and Reviews

Purpose: Barriers to communication and inaccurate provider assumptions about patient priorities limit the delivery of comprehensive, high-quality, patient-centered care (PCC) to people with Parkinson’s (PWP). This study aimed to analyze priorities of PWP using a qualitative, unstructured single-question survey and to test associations with validated quality of life (QOL) measures.

Methods: During appointments at a subspecialty, interdisciplinary clinic, PWP (n = 139) provided written responses to the prompt: “What is important for your care team to know about you?” Patient Health Questionnaire, Montreal Cognitive Assessment, and Hoehn and Yahr scales were obtained through retrospective chart review. Key qualitative themes were …

Molecular Tumor Testing On Colorectal Adenocarcinoma Specimens In A Large Community-Based Healthcare System, David H. Kruchko, Sareena Ali, Mahbubul Hasan, Madeline Sesselmann, Imad Almanaseer, Eli D. Ehrenpreis

Journal of Patient-Centered Research and Reviews

Purpose: This study aimed to describe the adherence of National Comprehensive Cancer Network guidelines to perform genetic screening for all colorectal cancer (CRC) specimens with molecular tumor testing, eg, immunohistochemical (IHC) testing, in a large community-based healthcare setting. The study also identified trends involving characteristics of CRC, individual reporting physician, and physician location and examined the potential impact of these trends on the performance of molecular tumor testing.

Methods: This was a retrospective, multi-center study using a centralized pathology database to assess molecular testing on CRC specimens. The primary endpoint was whether tumor testing of a CRC specimen was performed. …

Antiplatelet Strategy For Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Systematic Review And Network Meta-Analysis, Waqas Ullah, Harigopal Sandhyavenu, Amro Taha, Smitha Narayana Gowda, Maryam Mukhtar, Aravind Reddy Polam, Salman Zahid, David L. Fischman, Michael P. Savage, Sunil V. Rao, Mohamad Alkhouli

Division of Cardiology Faculty Papers

BACKGROUND: Optimal duration and choice of antiplatelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention remain controversial.

METHODS AND RESULTS: Digital databases (PubMed, Cochrane, and Embase) were queried to select all randomized controlled trials on a post-percutaneous coronary intervention population with acute coronary syndrome. Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel for 12 months was compared with 4 major strategies: high-potency, high- to low-potency, low-dose, and short-duration DAPT. A network meta-analysis was performed to compare the safety and efficacy of different antiplatelet strategies. This study was the second updated manuscript under the International Prospective Register of Systematic …

From Science To Society: Exploring The Nexus Between Obesity Research And Public Awareness In Brazil, Sofia Lafetá Pinto Santos, Renata Miyabara, Rym Ghimouz, Mirela Dobre, Andrei Brateanu, Luciana Aparecida Campos, Ovidiu Constantin Baltatu

All Works

Raising public awareness about the medical aspects of obesity is crucial in Brazil, given its escalating prevalence. This study investigated the correlation between scientific research on obesity in the country and public awareness by scrutinizing scientific publications and online search trends. Scientific data were sourced from Dimensions, while online engagement data were extracted from Google Trends. Key metrics were analyzed, including scientific publication trends, Altmetrics, news image trends, YouTube trends, and web search trends. Linear regression and the Mann-Kendall test assessed trends, and Principal Component Analysis (PCA) explored dataset variations. Scientific publications on obesity in Brazil consistently increased from 2004 …

Yap1 Status Defines Two Intrinsic Subtypes Of Lcnec With Distinct Molecular Features And Therapeutic Vulnerabilities, C Allison Stewart, Lixia Diao, Yuanxin Xi, Runsheng Wang, Kavya Ramkumar, Alejandra G Serrano, Azusa Tanimoto, B Leticia Rodriguez, Benjamin B Morris, Li Shen, Bingnan Zhang, Yan Yang, Samera H Hamad, Robert J Cardnell, Alberto Duarte, Moushumi Sahu, Veronica Y Novegil, Bernard E Weissman, Michael Frumovitz, Neda Kalhor, Luisa Solis Soto, Pedro Da Rocha, Natalie Vokes, Don L Gibbons, Jing Wang, John V Heymach, Bonnie Glisson, Lauren Averett Byers, Carl M Gay

Faculty, Staff and Student Publications

Purpose: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine malignancy that, like small cell lung cancer (SCLC), is associated with the absence of druggable oncogenic drivers and dismal prognosis. In contrast to SCLC, however, there is little evidence to guide optimal treatment strategies, which are often adapted from SCLC and non-small cell lung cancer approaches.

Experimental design: To better define the biology of LCNEC, we analyzed cell line and patient genomic data and performed IHC and single-cell RNA sequencing of core needle biopsies from patients with LCNEC and preclinical models.

Results: In this study, we demonstrate that the presence …

Accurate Identification Of Locally Aneuploid Cells By Incorporating Cytogenetic Information In Single Cell Data Analysis, Ziyi Li, Ruoxing Li, Irene Ganan-Gomez, Hussein A Abbas, Guillermo Garcia-Manero, Wei Sun

Faculty, Staff and Student Publications

Single-cell RNA sequencing is a powerful tool to investigate the cellular makeup of tumor samples. However, due to the sparse data and the complex tumor microenvironment, it can be challenging to identify neoplastic cells that play important roles in tumor growth and disease progression. This is especially relevant for blood cancers, where neoplastic cells may be highly similar to normal cells. To address this challenge, we have developed partCNV and partCNVH, two methods for rapid and accurate detection of aneuploid cells with local copy number deletion or amplification. PartCNV uses an expectation-maximization (EM) algorithm with mixtures of Poisson distributions and …

Npm1-Mutated Myeloid Neoplasms Are A Unique Entity Not Defined By Bone Marrow Blast Percentage, Georgina Gener-Ricos, Alex Bataller, Juan Jose Rodriguez-Sevilla, Kelly S Chien, Andres E Quesada, Emmanuel Almanza-Huante, Danielle Hammond, Koji Sasaki, Courtney Dinardo, Tapan Kadia, Naval Daver, Gautam Borthakur, Ghayas C Issa, Nicholas J Short, Rashmi Kanagal-Shamanna, Hagop M Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo

Faculty, Staff and Student Publications

Introduction: NPM1-mutated (NPM1mut) myeloid neoplasms (MNs) with < 20% bone marrow (BM) blasts (NPM1mut MNs< 20) are uncommon, and their classification remains inconsistent.

Methods: The clinicopathologic features of 54 patients with NPM1mut MNs < 20 were evaluated and compared with wild-type NPM1 MNs < 20 and NPM1mut MNs≥20, respectively.

Results: NPM1mut MNs had similar features regardless of blast percentage, except for higher IDH2 (29% vs 7%, p = .023) and FLT3 (70% vs 11%, p < .001) frequency in patients with ≥20% BM blasts. Thirty-three (61%) patients with NPM1mut MNs < 20 received low-intensity chemotherapy (LIC) and 12 (22%) received intensive chemotherapy (IC). Higher complete remission rates (75% vs 27%, p = .006) and median overall survival (mOS) (not reached vs 30.4 months, p = .06) were observed with IC compared to LIC. Young patients (age < 60 years) did not reach mOS either when treated with LIC or IC. Stem cell transplant was associated with increased survival only in patients treated with LIC (HR, 0.24; p = .025). No differences in mOS were observed by BM blast strata (32.2 months, not reached and 46.9 months for < 10%, 10%-19%, and ≥20% blasts, p = .700) regardless of treatment modality (LIC: p = .900; IC: p = .360). Twenty-three patients (43%) with NPM1mut MNs < 20 had marrow blast progression to ≥20%.

Conclusions: Overall, NPM1mut MNs define a unique entity independent of BM blast percentage.

Biochemical And Structural Insights Into A 5′ To 3′ Rna Ligase Reveal A Potential Role In Trna Ligation, Yingjie Hu, Victor A Lopez, Hengyi Xu, James P Pfister, Bing Song, Kelly A Servage, Masahiro Sakurai, Benjamin T Jones, Joshua T Mendell, Tao Wang, Jun Wu, Alan M Lambowitz, Diana R Tomchick, Krzysztof Pawłowski, Vincent S Tagliabracci

Faculty, Staff and Student Publications

ATP-grasp superfamily enzymes contain a hand-like ATP-binding fold and catalyze a variety of reactions using a similar catalytic mechanism. More than 30 protein families are categorized in this superfamily, and they are involved in a plethora of cellular processes and human diseases. Here, we identify C12orf29 (RLIG1) as an atypical ATP-grasp enzyme that ligates RNA. Human RLIG1 and its homologs autoadenylate on an active site Lys residue as part of a reaction intermediate that specifically ligates RNA halves containing a 5’-phosphate and a 3’-hydroxyl. RLIG1 binds tRNA in cells and can ligate tRNA within the anticodon loop in vitro. Transcriptomic …

Transcranial Direct Current Stimulation For Improving Balance In Healthy Older Adults And Older Adults With Stroke: A Scoping Review, Shih-Chiao Tseng, Sharon Dunnivan-Mitchell, Dana Cherry, Shuo-Hsiu Chang

Faculty, Staff and Student Publications

Background/Objectives: Age-related decline in balance and postural control is common in healthy elders and is escalated in aging adults with stroke. Transcranial direct current stimulation (tDCS) has emerged as one of the promising brain stimulations adjoining therapeutic exercise to enhance the recovery of balance and motor functions in persons with and without neurological disorders. This review aims to summarize and compare the available evidence of the tDCS on improving balance in the older adults without neurological disorders and the older adults with stroke.

Methods: The Ovid (Medline) database was searched from its inception through to 06/15/2024 for randomized …

Proportional Hazards Violations In Phase Iii Cancer Clinical Trials: A Potential Source Of Trial Misinterpretation, Timothy A Lin, Zachary R Mccaw, Alex Koong, Christine Lin, Joseph Abi Jaoude, Roshal Patel, Ramez Kouzy, Molly B El Alam, Alexander D Sherry, Sonal S Noticewala, Clifton D Fuller, Charles R Thomas, Ryan Sun, J Jack Lee, Ruitao Lin, Ying Yuan, Yu Shyr, Tomer Meirson, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: Survival analyses of novel agents with long-term responders often exhibit differential hazard rates over time. Such proportional hazards violations (PHV) may reduce the power of the log-rank test and lead to misinterpretation of trial results. We aimed to characterize the incidence and study attributes associated with PHVs in phase III oncology trials and assess the utility of restricted mean survival time and maximum combination test as additional analyses.

Experimental design: Clinicaltrials.gov and PubMed were searched to identify two-arm, randomized, phase III superiority-design cancer trials with time-to-event primary endpoints and published results through 2020. Patient-level data were reconstructed from published …

Evaluating Debio 1347 In Patients With Fgfr Fusion-Positive Advanced Solid Tumors From The Fuze Multicenter, Open-Label, Phase Ii Basket Trial, Petros Grivas, Elena Garralda, Funda Meric-Bernstam, Ingo K Mellinghoff, Lipika Goyal, James J Harding, E Claire Dees, Rastislav Bahleda, Nilofer S Azad, Asha Karippot, Razelle Kurzrock, Josep Tabernero, Juha Kononen, Matthew C H Ng, Rutika Mehta, Nataliya V Uboha, Frédéric Bigot, Valentina Boni, Samantha E Bowyer, Valeriy Breder, Andrés Cervantes, Nancy Chan, James M Cleary, Mallika Dhawan, Rikke L Eefsen, James Ewing, Donna M Graham, Tormod K Guren, Jin Won Kim, Krassimir Koynov, Do-Youn Oh, Rebecca Redman, Chia-Jui Yen, David Spetzler, Marie-Claude Roubaudi-Fraschini, Valerie Nicolas-Metral, Rafik Ait-Sarkouh, Claudio Zanna, Abdallah Ennaji, Anna Pokorska-Bocci, Keith T Flaherty

Faculty, Staff and Student Publications

Purpose: This multicenter phase II basket trial investigated the efficacy, safety, and pharmacokinetics of Debio 1347, an investigational, oral, highly selective, ATP-competitive, small molecule inhibitor of FGFR1-3, in patients with solid tumors harboring a functional FGFR1-3 fusion.

Patients and methods: Eligible adults had a previously treated locally advanced (unresectable) or metastatic biliary tract (cohort 1), urothelial (cohort 2), or another histologic cancer type (cohort 3). Debio 1347 was administered at 80 mg once daily, continuously, in 28-day cycles. The primary endpoint was the objective response rate. Secondary endpoints included duration of response, progression-free survival, overall survival, pharmacokinetics, and incidence of …

First-In-Human Clinical Outcomes With Ng-350a, An Anti-Cd40 Expressing Tumor-Selective Vector Designed To Remodel Immunosuppressive Tumor Microenvironments, Aung Naing, Danny Khalil, Oliver Rosen, D Ross Camidge, Tom Lillie, Rui-Ru Ji, Andrea Stacey, Matthew Thomas, Lee Rosen

Faculty, Staff and Student Publications

Background: Tumor-selective oncolytic viral vectors are promising anticancer therapeutics; however, challenges with dosing and potency in advanced/metastatic cancers have limited efficacy and usage. NG-350A is a next-generation blood-stable adenoviral vector engineered to express an agonist anti-cluster of differentiation (CD)40 antibody without affecting tumor-selectivity and oncolytic potency.

Methods: Intravenous and intratumoral (IT) administration of NG-350A was assessed in a phase Ia/Ib study in patients with metastatic/advanced epithelial tumors (NCT03852511). Dose-escalation was performed separately for intravenous (four dose levels available, each with infusions on Days 1, 3 and 5 of a 57-day treatment period) and IT (single injection on D1 …

Cdk12 Loss Drives Prostate Cancer Progression, Transcription-Replication Conflicts, And Synthetic Lethality With Paralog Cdk13, Jean Ching-Yi Tien, Jie Luo, Yu Chang, Yuping Zhang, Yunhui Cheng, Xiaoju Wang, Jianzhang Yang, Rahul Mannan, Somnath Mahapatra, Palak Shah, Xiao-Ming Wang, Abigail J Todd, Sanjana Eyunni, Caleb Cheng, Ryan J Rebernick, Lanbo Xiao, Yi Bao, James Neiswender, Rachel Brough, Stephen J Pettitt, Xuhong Cao, Stephanie J Miner, Licheng Zhou, Yi-Mi Wu, Estefania Labanca, Yuzhuo Wang, Abhijit Parolia, Marcin Cieslik, Dan R Robinson, Zhen Wang, Felix Y Feng, Jonathan Chou, Christopher J Lord, Ke Ding, Arul M Chinnaiyan

Faculty, Staff and Student Publications

Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a metastatic castration-resistant prostate cancer (mCRPC) subtype. It remains unclear, however, whether CDK12 loss drives prostate cancer (PCa) development or uncovers pharmacologic vulnerabilities. Here, we show Cdk12 ablation in murine prostate epithelium is sufficient to induce preneoplastic lesions with lymphocytic infiltration. In allograft-based CRISPR screening, Cdk12 loss associates positively with Trp53 inactivation but negatively with Pten inactivation. Moreover, concurrent Cdk12/Trp53 ablation promotes proliferation of prostate-derived organoids, while Cdk12 knockout in Pten-null mice abrogates prostate tumor growth. In syngeneic systems, Cdk12/Trp53-null allografts exhibit luminal morphology and immune checkpoint blockade sensitivity. Mechanistically, Cdk12 inactivation …

A Phase Ib/Ii Randomized Clinical Trial Of Oleclumab With Or Without Durvalumab Plus Chemotherapy In Patients With Metastatic Pancreatic Ductal Adenocarcinoma, Andrew L Coveler, Matthew J Reilley, Mark Zalupski, Teresa Macarulla, Christos Fountzilas, Mariano Ponz-Sarvisé, Adnan Nagrial, Nataliya V Uboha, Sophia Frentzas, Michael Overman, Anne Noonan, Wells A Messersmith, Nick Pavlakis, Niharika B Mettu, Ina Bisha, Ying Wang, Paul Smith, Elina Murtomaki, Agata A Bielska, Veronique Bragulat, Zachary A Cooper, Rakesh Kumar, David R Spigel

Faculty, Staff and Student Publications

Purpose: Pancreatic ductal adenocarcinoma upregulates CD73, potentially contributing to immune surveillance evasion. Combining oleclumab (CD73 inhibitor) and durvalumab with chemotherapy may identify an effective treatment option.

Patients and methods: We describe a multicenter phase Ib/II randomized clinical trial in patients with metastatic pancreatic ductal adenocarcinoma, untreated (cohort A) or previously received gemcitabine-based chemotherapy (cohort B; NCT03611556). During escalation, patients received oleclumab 1,500 or 3,000 mg, durvalumab 1,500 mg, and gemcitabine plus nab-paclitaxel (GnP; cohort A; n = 14) or modified FOLFOX (cohort B; n = 11). During expansion, cohort A patients (n = 170) were randomized to GnP (arm …

Development And Validation Of A Machine Learning Model To Predict Myocardial Blood Flow And Clinical Outcomes From Patients’ Electrocardiogram, Fares Alahdab, Maliazurina Binti Saad, Ahmed Ibrahim Ahmed, Qasem Al Tashi, Muhammad Aminu, Yushui Han, Jonathan B Moody, Venkatesh L Murthy, Jia Wu, Mouaz H Al-Mallah

Faculty, Staff and Student Publications

We develop a machine learning (ML) model using electrocardiography (ECG) to predict myocardial blood flow reserve (MFR) and assess its prognostic value for major adverse cardiovascular events (MACEs). Using 3,639 ECG-positron emission tomography (PET) and 17,649 ECG-single-photon emission computed tomography (SPECT) data pairs, the ML model is trained with a swarm intelligence approach and support vector regression (SVR). The model achieves a receiver-operator curve (ROC) area under the curve (AUC) of 0.83, with a sensitivity and specificity of 0.75. An ECG-MFR value below 2 is significantly associated with MACE, with hazard ratios (HRs) of 3.85 and 3.70 in the discovery …

Immuno-Scanning Electron Microscopy Of Islet Primary Cilia, Sanja Sviben, Alexander J Polino, Isabella L Melena, Jing W Hughes

2020-Current year OA Pubs

The definitive demonstration of protein localization on primary cilia has been a challenge for cilia biologists. Primary cilia are solitary thread-like projections that have a specialized protein composition, but as the ciliary structure overlays the cell membrane and other cell parts, the identity of ciliary proteins are difficult to ascertain by conventional imaging approaches like immunofluorescence microscopy. Surface scanning electron microscopy combined with immunolabeling (immuno-SEM) bypasses some of these indeterminacies by unambiguously showing protein expression in the context of the three-dimensional ultrastructure of the cilium. Here, we apply immuno-SEM to specifically identify proteins on the primary cilia of mouse and …

Interleukin-15 And High-Intensity Exercise: Relationship With Inflammation, Body Composition And Fitness In Cancer Survivors, Morgan J. Farley, Alexander N. Boytar, Kirsten N. Adlard, Chloe E. Salisbury, Nicolas H. Hart, Mia A. Schaumberg, David G. Jenkins, Tina L. Skinner

Research outputs 2022 to 2026

Pre-clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth. These anti-oncogenic effects of exercise were associated with the exercise-mediated release of myokines such as interleukin (IL)-15. However, no study has quantified the acute IL-15 response in human cancer survivors, and whether physiological adaptations to exercise training (i.e. body composition and cardiorespiratory fitness) influence this response. In the present study breast, prostate and colorectal cancer survivors (n = 14) completed a single bout of high-intensity interval exercise (HIIE) [4×4 min at 85–95% heart rate (HR) peak, 3 min at 50–70% HR peak] before and …

Intraindividual Discordance Between Remnant Cholesterol And Low-Density Lipoprotein Cholesterol Associated With Incident Stroke: Results From 2 National Cohorts, Cancan Cui, Pingan Li, Yitian Qi, Jiayin Song, Tianjiao Han, Xinyun Shang, Lois Balmer, Chen Sheng, Yining Zha, Zhonghang Xu, Xu Wang, Zhiyuan Wu

Research outputs 2022 to 2026

BACKGROUND: The atherogenic effect of remnant cholesterol is being increasingly acknowledged. This study aimed to explore the association of discordance between remnant cholesterol and low-density lipoprotein cholesterol with stroke onset using 2 Chinese national cohorts. METHODS AND RESULTS: We studied 11 139 participants from CHARLS (China Health and Retirement Longitudinal Study) and 5993 participants from CHNS (China Health and Nutrition Survey) aged 45 years or older. The discordance between remnant cholesterol and low-density lipoprotein cholesterol was defined using the difference in percentile units (>15 units). There were 988 (8.9%) and 128 (2.1%) stroke events reported during follow-up in the …

Exposure To Per- And Polyfluoroalkyl Substances And Alterations In Plasma Microrna Profiles In Children, Yijie Li, Brittney O Baumert, Nikos Stratakis, Jesse A Goodrich, Haotian Wu, Shelley H Liu, Hongxu Wang, Emily Beglarian, Scott M Bartell, Sandrah Proctor Eckel, Douglas Walker, Damaskini Valvi, Michele Andrea La Merrill, Thomas H Inge, Todd Jenkins, Justin R Ryder, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Marina Vafeiadi, Aikaterini Margetaki, Theano Roumeliotaki, Max Aung, Rob Mcconnell, Andrea Baccarelli, David Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans.

OBJECTIVE: To investigate associations between PFAS concentrations and miRNA levels in children.

METHODS: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and …