Digital Commons Network^™

Synergistic Activity Of Combined Flt3-Itd And Mdm2 Inhibition With Quizartinib And Milademetan In Flt3-Itd Mutant/Tp53 Wild-Type Acute Myeloid Leukemias, Weiguo Zhang, Li Li, Muharrem Muftuoglu, Mahesh Basyal, Noriko Togashi, Koichi Iwanaga, Fumie Tanzawa, Masashi Numata, Dale L Bixby, Harry P Erba, Nikolai Podoltsev, Gary J Schiller, Prasanna Kumar, Arnaud Lesegretain, Takeshi Isoyama, Takahiko Seki, Naval Daver, Michael Andreeff

Faculty, Staff and Student Publications

Purpose: Acute myeloid leukemia (AML) is characterized by frequent mutations in FMS-like tyrosine kinase 3 (FLT3), overexpression of murine double minute 2 (MDM2), and TP53 wild-type (WT). Monotherapies targeting FLT3 frequently result in the development of resistant disease. In this study, we investigated the antileukemic efficacy of co-targeting FLT3 and MDM2 with quizartinib and milademetan (Q/M) in FLT3 internal tandem duplication (FLT3-ITD) AML cell lines, xenograft and patient-derived xenograft (PDX) models, and a phase I clinical trial.

Experimental design: Preclinical studies used human and murine cell lines carrying FLT3-ITD and/or tyrosine kinase domain mutations, TP53 WT/knockdown, leukemia cell xenograft models, …

Targeting The Cd40 Costimulatory Receptor To Improve Virotherapy Efficacy In Diffuse Midline Gliomas, Sara Labiano, Javier Marco-Sanz, Iker Ausejo-Mauleon, Virginia Laspidea, Reyes Hernández-Osuna, Marc Garcia-Moure, Daniel De La Nava, Sara Nuin, Marisol Gonzalez-Huarriz, Timothy N Phoenix, Ibon Tamayo, Marta Zalacain, Andrea Lacalle, Lucía Marrodan, Montserrat Puigdelloses, Irati Hervás-Corpión, Maria C Ochoa, Noelia Casares, Oren J Becher, Candelaria Gomez-Manzano, Juan Fueyo, Jaime Gallego Perez-Larraya, Ana Patiño-Garcia, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse midline glioma (DMG) is a devastating pediatric brain tumor. The oncolytic adenovirus Delta-24-RGD has shown promising efficacy and safety in DMG patients but is not yet curative. Thus, we hypothesized that activating dendritic cells (DCs) through the CD40 costimulatory receptor could increase antigen presentation and enhance the anti-tumor effect of the virus, resulting in long-term responses. This study shows that the intratumoral co-administration of Delta-24-RGD and a CD40 agonistic antibody is well tolerated and induces long-term anti-tumor immunity, including complete responses (up to 40%) in DMG preclinical models. Mechanistic studies revealed that this therapy increased tumor-proliferating T lymphocytes and …

Antitumor Efficacy Of Intermittent Low-Dose Erlotinib Plus Sulindac Via Mhc Upregulation And Remodeling Of The Immune Cell Niche, Chakrapani Tripathi, Jorge E Tovar Perez, Sabeeta Kapoor, Ahmed Muhsin, Wan Mohaiza Dashwood, Yunus Demirhan, Melek Demirhan, Alessandro Shapiro, Altaf Mohammed, Shizuko Sei, Jacklyn Thompson, Mahira Zaheer, Krishna M Sinha, Powel H Brown, Michelle I Savage, Eduardo Vilar, Praveen Rajendran, Roderick H Dashwood

Faculty, Staff and Student Publications

A previously reported clinical trial in familial adenomatous polyposis (FAP) patients treated with erlotinib plus sulindac (ERL + SUL) highlighted immune response/interferon-γ signaling as a key pathway. In this study, we combine intermittent low-dose ERL ± SUL treatment in the polyposis in rat colon (Pirc) model with mechanistic studies on tumor-associated immune modulation. At clinically relevant doses, short-term (16 weeks) and long-term (46 weeks) ERL ± SUL administration results in near-complete tumor suppression in Pirc colon and duodenum (p < 0.0001). We identify a low-dose threshold for significant antitumor activity in Pirc rats given SUL at 125 ppm in the diet plus ERL at 5 mg/kg body weight via twice-weekly oral gavage (SUL125 + ERL5 × 2). Longitudinal analyses show diminished expression of MHC class I and II genes in polyps larger than Grade 5, a novel finding in the Pirc model. Treatment with ERL ± SUL upregulates the corresponding MHC and immune-associated factors in a subset of Pirc colon polyps, Pirc tumor cell lines, murine colon carcinoma cells, and FAP patient-derived organoids, with Nlrc5 playing a critical role in this effect. Imaging mass cytometry reveals that SUL125 + ERL5 × 2 increases tumor-associated Cd4+ T cells by ~2.6-fold (p < 0.05), with no apparent effect on Cd8+ T cells. The treatment also increases tumor-associated Cd68+ cells (p < 0.05) and decreases Foxp3+ (p < 0.01) and Arg1+ (p < 0.05) cells. Thus, intermittent low-dose ERL + SUL treatment enhances tumor-associated MHC expression and remodels the immune cell niche toward a more permissive "helper" immune microenvironment. We conclude that early immune-interception strategies targeting interferon-γ signaling may benefit FAP patients at drug doses below the clinical standard of care.

Sensory Neuron-Expressed Fgf13 Controls Nociceptive Signaling In Diabetic Neuropathy Models, Aditya K Singh, Matteo Bernabucci, Nolan M Dvorak, Zahra Haghighijoo, Jessica Di Re, Nana A Goode, Feni K Kadakia, Laura A Maile, Olumarotimi O Folorunso, Paul A Wadsworth, Cynthia M Tapia, Pingyuan Wang, Jigong Wang, Haiying Chen, Yu Xue, Jully Singh, Kali Hankerd, Isaac J Gamez, Makenna Kager, Vincent Truong, Patrick Walsh, Stephanie I Shiers, Nishka Kuttanna, Hanyue Liao, Margherita Marchi, Erika Salvi, Ilaria D'Amato, Daniela D'Amico, Parsa Arman, Catharina G Faber, Rayaz A Malik, Marina De Tommaso, Dan Ziegler, Krishna Rajarathnam, Thomas A Green, Peter M Grace, Matthew R Sapio, Michael J Iadarola, Gregory D Cuny, Diana S Chow, Giuseppe Lauria Pinter, Steve Davidson, Dustin P Green, Jun-Ho La, Jin Mo Chung, Jia Zhou, Theodore J Price, Elizabeth Salisbury, Subo Yuan, Fernanda Laezza

Faculty, Staff and Student Publications

Nociception involves complex signaling, yet intrinsic mechanisms bidirectionally regulating this process remain unexplored. Here, we show that the fibroblast growth factor 13 (FGF13)/Nav1.7 protein-protein interaction (PPI) complex bidirectionally modulates nociception, and that the FGF13/Nav1.7 ratio is upregulated in type 2 diabetic neuropathy (T2DN). PW164, an FGF13/Nav1.7 channel C-terminal tail domain (CTD) PPI interface inhibitor, which reduces complex assembly, selectively suppressed Na+ currents sensitized by capsaicin-induced activation of TRPV1 channels in human induced pluripotent stem cell-derived (hIPSC-derived) sensory neurons and inhibited mechanical and thermal hyperalgesia in mice. FGF13 silencing mimics PW164 activity in culture and in vivo. Conversely, ZL192, an FGF13 …

Fgfr3-Induced Y158 Parp1 Phosphorylation Promotes Parp Inhibitor Resistance Via Brg1/Mre11-Mediated Dna Repair In Breast Cancer Models, Mei-Kuang Chen, Hirohito Yamaguchi, Yuan Gao, Weiya Xia, Jeffrey T Chang, Yu-Chun Hsiao, Tewodros W Shegute, Zong-Shin Lin, Chen-Shiou Wu, Yu-Han Wang, Jennifer K Litton, Qingqing Ding, Yongkun Wei, Yu-Yi Chu, Funda Meric-Bernstam, Helen Piwnica-Worms, Banu Arun, Jordi Rodon Ahnert, Jinsong Liu, Jun Yao, Wei-Chao Chang, Hung-Ling Wang, Coya Tapia, Constance T Albarracin, Khandan Keyomarsi, Shao-Chun Wang, Ying-Nai Wang, Gabriel N Hortobagyi, Chunru Lin, Liuqing Yang, Dihua Yu, Mien-Chie Hung

Faculty, Staff and Student Publications

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are used to treat BRCA-mutated (BRCAm) cancer patients; however, resistance has been observed. Therefore, biomarkers to indicate PARPi resistance and combination therapy to overcome that are urgently needed. We identified a high prevalence of activated FGF receptor 3 (FGFR3) in BRCAm triple-negative breast cancer (TNBC) cells with intrinsic and acquired PARPi resistance. FGFR3 phosphorylated PARP1 at tyrosine 158 (Y158) to recruit BRG1 and prolong chromatin-loaded MRE11, thus promoting homologous recombination (HR) to enhance PARPi resistance. FGFR inhibition prolonged PARP trapping and synergized with PARPi in vitro and in vivo. High-level PARP1 Y158 phosphorylation (p-Y158) positively …

Cancer Vaccination And Immune-Based Approaches In Pancreatic Cancer, Matthew D. Bloom, Ali Raza Shaikh, Zhengyang Sun, Babar Bashir, Adam E. Snook

Department of Medical Oncology Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high recurrence rates even after curative resection and adjuvant chemotherapy. Although immunotherapeutic approaches, such as immune checkpoint blockade (ICB), have revolutionized the treatment of some solid tumor malignancies, this has not been the case for PDAC. Several characteristics of PDAC, including its distinctive desmoplastic tumor microenvironment (TME), intratumor heterogeneity, and poor antigenicity and immune cell infiltration, contribute to its dismal immunotherapeutic landscape. Cancer vaccines offer one approach to overcoming these barriers, particularly in the resectable or borderline resectable settings, where tumor burden is low and immunosuppression is less pronounced. Various vaccination …

Serum Metabolomic Profiling Of Incident Type 2 Diabetes Mellitus In The Multi-Ethnic Study Of Atherosclerosis And Rotterdam Study, Xuanwei Jiang, Fang Zhu, Gonçalo Graça, Xihao Du, Jinjun Ran, Fariba Ahmadizar, Alexis C Wood, Yanqiu Zhou, Denise M Scholtens, Ali Farzaneh, M Arfan Ikram, Alan Kuang, Carel W Le Roux, Meghana D Gadgil, Marilyn C Cornelis, Kent D Taylor, Xiuqing Guo, Mohsen Ghanbari, Laura J Rasmussen-Torvik, Russell P Tracy, Alain G Bertoni, Jerome I Rotter, David M Herrington, Philip Greenland, Maryam Kavousi, Victor W Zhong

Children’s Nutrition Research Center Staff Publications

Objective: This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.

Methods: Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 3460; discovery cohort) and The Rotterdam Study (RS; n = 1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23 571 serum metabolomic spectral variables and incident T2DM. Replicated metabolites required an false discovery rate-adjusted P < .01 in MESA, P < .05 in RS, and consistent direction of association. Pathway and network analyses were conducted to elucidate biological mechanisms underlying T2DM development. The utility of the replicated metabolites in improving T2DM risk prediction was assessed based on the Framingham Diabetes Risk Score. A 2-sample Mendelian randomization was conducted to assess causal associations.

Results: Nineteen metabolites were significantly associated with incident T2DM. Pathway analyses …

Non-Invasive Telemonitoring In Heart Failure: A Systematic Review, Patrick A. Kwaah, Emmanuel Olumuyide, Kassem Farhat, Barbara Malaga-Espinoza, Ahmed Abdullah, Michael H. Beasley, Novi Y. Sari, Lily K. Stern, Julio A. Lamprea-Montealegre, Adrian Dasilva-Deabreu, Jiun-Ruey Hu

School of Medicine Publications

Background and Objectives: Heart failure (HF) represents a major public health challenge worldwide, with rising prevalence, high morbidity and mortality rates, and substantial healthcare costs. Non-invasive telemonitoring has emerged as a promising adjunct in HF management, yet its clinical effectiveness remains unclear. Materials and Methods: In this systematic review, we summarize randomized controlled trials (RCTs) between 2004 and 2024 examining the efficacy of non-invasive telemonitoring on mortality, readmission, and quality of life (QoL) in HF. In addition, we characterize the heterogeneity of features of different telemonitoring interventions. Results: In total, 32 RCTs were included, comprising 13,294 participants. While some individual …

Epha4 Signaling Dysregulation Links Abnormal Locomotion And The Development Of Idiopathic Scoliosis, Lianlei Wang, Xinyu Yang, Sen Zhao, Pengfei Zheng, Wen Wen, Kexin Xu, Xi Cheng, Qing Li, Anas M Khanshour, Yoshinao Koike, Junjun Liu, Xin Fan, Nao Otomo, Zefu Chen, Yaqi Li, Lulu Li, Haibo Xie, Panpan Zhu, Xiaoxin Li, Yuchen Niu, Shengru Wang, Sen Liu, Suomao Yuan, Chikashi Terao, Ziquan Li, Shaoke Chen, Xiuli Zhao, Pengfei Liu, Jennifer E Posey, Zhihong Wu, Guixing Qiu, Disco Study Group (Deciphering Disorders Involving Scoliosis & Comorbidities), Shiro Ikegawa, James R Lupski, Jonathan J Rios, Carol A Wise, Jianguo T Zhang, Chengtian Zhao, Nan Wu

Faculty, Staff and Students Publications

Idiopathic scoliosis (IS) is the most common form of spinal deformity with unclear pathogenesis. In this study, we first reanalyzed the loci associated with IS, drawing upon previous studies. Subsequently, we mapped these loci to candidate genes using either location-based or function-based strategies. To further substantiate our findings, we verified the enrichment of variants within these candidate genes across several large IS cohorts encompassing Chinese, East Asian, and European populations. Consequently, we identified variants in the EPHA4 gene as compelling candidates for IS. To confirm their pathogenicity, we generated zebrafish mutants of epha4a. Remarkably, the zebrafish epha4a mutants exhibited …

Neonatal Seizures: Advances In Diagnosis And Management, Elissa G Yozawitz, Ronit M Pressler, Eli M Mizrahi

Faculty, Staff and Students Publications

The International League Against Epilepsy (ILAE) created the ILAE Neonatal Task Force that classified neonatal seizures, defined neonatal epilepsy syndromes, and specified treatment guidelines. These frameworks, in addition to improved access to genetic testing and other recent advances, have revolutionized the diagnosis and management of neonatal seizures. PLAIN LANGUAGE SUMMARY: Neonatal seizures, occurring within the first 4 weeks of life, present unique challenges due to the immature neonatal brain. The International League Against Epilepsy (ILAE) Neonatal Task Force revolutionized diagnosis and management through classification, syndrome definition, and treatment guidelines. Despite advancements, challenges persist, including accurate diagnosis and limited evidence-based treatment …

Parietal Cortex Is Recruited By Frontal And Cingulate Areas To Support Action Monitoring And Updating During Stopping, Jung Uk Kang, Layth Mattar, José Vergara, Victoria E Gobo, Hernan G Rey, Sarah R Heilbronner, Andrew J Watrous, Benjamin Y Hayden, Sameer A Sheth, Eleonora Bartoli

Faculty, Staff and Students Publications

Recent evidence indicates that the intraparietal sulcus (IPS) may play a causal role in action stopping, potentially representing a novel neuromodulation target for inhibitory control dysfunctions. Here, we leverage intracranial recordings in human subjects to establish the timing and directionality of information flow between IPS and prefrontal and cingulate regions during action stopping. Prior to successful inhibition, information flows primarily from the inferior frontal gyrus (IFG), a critical inhibitory control node, to IPS. In contrast, during stopping errors the communication between IPS and IFG is lacking, and IPS is engaged by posterior cingulate cortex, an area outside of the classical …

Role Of Lipoprotein(A) In Atherosclerotic Cardiovascular Disease In South Asian Individuals, Darshan Patel, Marlys L Koschinsky, Anandita Agarwala, Pradeep Natarajan, Harpreet S Bhatia, Anurag Mehta, Jaideep Patel, Matthew Peters, Shreya Pandya, Usman Sagheer, Raman Puri, Salim S Virani, Dinesh K Kalra

Faculty, Staff and Students Publications

South Asian individuals (SA), representing approximately one quarter of the global population, experience a disproportionately high burden of cardiovascular disease. Some of this increased susceptibility is accounted for by traditional risk factors such as diabetes, hypertension, carbohydrate-rich diets, and rising rates of obesity and metabolic syndrome. However, other previously underappreciated risk factors may also play a crucial role. These include environmental pollution, genetic factors, and Lp(a) (lipoprotein(a)). Various epidemiological and genetic studies support the role of Lp(a) as a causal and independent risk factor for atherosclerotic cardiovascular disease. SA have a higher prevalence of elevated Lp(a) levels (25% have levels …

Depressive Disorders, Bad Mental Health Days, And Diabetes Management Behaviors Among Non-Hispanic American Indian/Alaska Native Adults: Findings From The Behavioral Risk Factor Surveillance System, Kaipeng Wang, Luohua Jiang, Jie Zhu, Spero M. Manson

Graduate School of Social Work: Faculty Scholarship

Objective

This study examined the association between diagnosis of depressive disorder, the number of bad mental health days per month, and diabetes management behaviors among American Indian/Alaska Native (AI/AN) adults with diabetes.

Research design and methods

Data were drawn from the Behavioral Risk Factor Surveillance System (2018–2021), including 2,272 self-identified non-Hispanic AI/AN adults diagnosed with non-gestational diabetes. Key variables included a self-reported prior diagnosis of depressive disorder and the number of bad mental health days in the past month. Outcome variables were seven diabetes management behaviors, such as taking a diabetes management class and performing daily foot checks. Statistical analyses …

Spatial Proximity Of Immune Cell Pairs To Cancer Cells In The Tumor Microenvironment As Biomarkers For Patient Stratification, Jian-Rong Li, Xingxin Pan, Yupei Lin, Yanding Zhao, Yanhong Liu, Yong Li, Christopher I Amos, Chao Cheng

Faculty, Staff and Students Publications

Background/objectives: The tumor microenvironment (TME) plays a critical role in cancer progression by shaping immune responses and influencing patient outcomes. We hypothesized that the relative proximity of specific immune cell pairs to cancer cells within the TME could help predict their pro- or anti-tumor functions and reflect clinically relevant immune dynamics.

Methods: We analyzed imaging mass cytometry (IMC) data from lung adenocarcinoma (LUAD) and triple-negative breast cancer (TNBC) cohorts. For each immune cell pair, we calculated a relative distance (RD) score, which quantifies the spatial difference in proximity to cancer cells. We assessed the prognostic and predictive significance of these …

Mitral Valve Repair During Cabg Surgery: Navigating The Gray Area Of Moderate Ischemic Mitral Regurgitation, Husam Shadid, Ismael A. Salas De Armas, Marwan F. Jumean

Journal of Shock and Hemodynamics

Ischemic mitral regurgitation is a consequence of prior myocardial infarction, resulting in regional wall motion abnormalities, leaflet tethering, papillary muscle displacement, and annular dilatation. In patients with multivessel coronary artery disease, approximately 30-50% develop moderate to severe ischemic mitral regurgitation, associated with a threefold increase in the incidence of congestive heart failure and cardiac death. We present a case involving a 66-year-old male with multivessel coronary artery disease, heart failure with reduced ejection fraction (30-35%), and diabetes who was found to have moderate ischemic mitral regurgitation at the time of coronary artery bypass graft surgery. The decision to pursue mitral …

The Overlooked Impact Of Background Diet And Adherence In Nutrition Trials, Javier I Ottaviani, Hagen Schroeter, Dennis M Bier, John W Erdman, Howard D Sesso, Joann E Manson, Gunter G C Kuhnle

Children’s Nutrition Research Center Staff Publications

Randomised controlled trials in nutrition (RCTN) face unique challenges, including the considerable influence of the background diet and the challenge of assuring intervention adherence by participants. The impact of these factors on the outcome of RCTNs has been difficult to quantify, but nutritional biomarkers represent a valuable tool to address these challenges. Using flavanols as a model dietary intervention and a set of recently validated flavanol biomarkers, we here investigated the impact of background diet and adherence on the outcomes of a subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS, NCT 02422745). We found that 20% of participants …

Large B Cell Lymphoma Microenvironment Archetype Profiles, Xubin Li, Kartik Singhal, Qing Deng, Dai Chihara, David Russler-Germain, R Andrew Harkins, Jared Henderson, Kotaro Arita, Atish Kizhakeyil, Ryan Sun, Priya Lakra, Usama Hussein, Jennifer A Foltz, Ashley Wilson, Evelyn Schmidt, Imran Nizamuddin, Tommy Dinh, Akhil Kesaraju, Mark P Hamilton, Carl Allen, Maher K Gandhi, Joshua Tobin, Aixiang Jiang, Laura Hilton, David W Scott, Francisco Vega, Christopher R Flowers, Jason R Westin, Obi L Griffith, Todd A Fehniger, Malachi Griffith, Michael R Green

Faculty, Staff and Student Publications

Large B cell lymphomas (LBCL) are clinically and biologically heterogeneous lymphoid malignancies with complex microenvironments that are central to disease etiology. Here we have employed single-nucleus multiome profiling of 232 tumor and control biopsies to characterize diverse cell types and subsets that are present in LBCL tumors, effectively capturing the lymphoid, myeloid, and non-hematopoietic cell compartments. Cell subsets co-occurred in stereotypical Lymphoma Microenvironment Archetype Profiles (LymphoMAPs) defined by; (i) a sparsity of T cells and high frequencies of cancer-associated fibroblasts and tumor-associated macrophages [FMAC]; (ii) lymph node architectural cell types with naïve and memory T cells [LN]; or (iii) activated …

Selective Alanine Transporter Utilization Is A Therapeutic Vulnerability In Arid1a-Mutant Ovarian Cancer, Hao Nie, Liping Liao, Rafal J Zielinski, Javier A Gomez, Akshay V Basi, Erin H Seeley, Lin Tan, Agnes Julia Bilecz, Wei Zhou, Heng Liu, Chen Wang, Shuai Wu, Yuan Qi, Taito Miyamoto, Federica Severi, Aaron R Goldman, Shengqing Gu, Anil K Sood, Amir A Jazaeri, Ronny Drapkin, Daniel T Claiborne, Nan Zhang, Philip L Lorenzi, Jared K Burks, Ernst Lengyel, Eyal Gottlieb, Rugang Zhang

Faculty, Staff and Student Publications

Subunits of the SWI/SNF chromatin remodeling complex are altered in ~20% of human cancers. Exemplifying the alterations is the ARID1A mutation that occurs in ~50% ovarian clear cell carcinoma (OCCC), a disease with limited therapeutic options. Here, we showed that ARID1A mutations create a dependence on alanine by regulating alanine transporters to increase intracellular alanine levels. ARID1A directly repressed alanine importer SLC38A2 and simultaneously promoted alanine exporter SLC7A8. ARID1A inactivation increased alanine utilization predominantly in protein synthesis and passively through the tricarboxylic acid cycle. Indeed, ARID1A-mutant OCCCs were hyper-sensitive to inhibition of SLC38A2. In addition, SLC38A2 inhibition enhanced chimeric antigen …

Novel Piperidone And Bispidine Derivatives: A New Approach In Cancer Therapy, Lereen Khaled Youssry

Theses and Dissertations

Cancer remains the second leading cause of death worldwide. As a result, scientists have been trying to find novel therapeutic approaches that target specific metabolic pathways selective to tumor cells. In this study, two novel piperidone and bispidine derivatives, organic molecules that target polyamine metabolism, were synthesized, and their potential cytotoxic, antioxidant and anti-inflammatory effects were investigated. Polyamines are naturally occurring metabolites that were reported to be in excess at cancer cells and were accounted for tumor proliferation, invasion and metastasis. Accordingly, the novel piperidone and bispidine derivatives were expected to disrupt tumor growth and progression via up-regulation of key …

Early Wound Dressing (Soft Gauze/Tape Dressing) Removal After Cesarean Delivery: A Meta-Analysis Of Randomized Trials, Leshae Cenac, Serena Guerra, Alicia Huckaby, Gabriele Saccone, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To assess whether removing the wound dressing within 24 hours after a cesarean delivery leads to any negative effects on wound healing and to recommend the best time for dressing removal.

DATA SOURCES: Science Direct, PubMed, Cochrane Library, and Scopus as the electronic databases from their inception until December 2024.

CRITERIA FOR STUDY ELIGIBILITY: Randomized controlled trials (RCTs) were incorporated in the databases, irrespective of their publication language, sample size, publication date, use of blinding, or study setting/location.

STUDY APPRAISAL AND SYNTHESIS METHODS: A systematic review of RCTs was conducted to compare wound outcomes in cesarean delivery patients with …

The Feasibility Of Passively Tracking Children’S Tv Viewing And Mobile Device Use In Naturalistic Settings, Teresia M O'Connor, Tatyana Garza, Uzair Alam, Anil Kumar Vadathya, Jennette P Moreno, Alicia Beltran, Samah Haidar, Nimah Haidar, Sheryl O Hughes, Debbe Thompson, Salma M A Musaad, Tom Baranowski, Jason A Mendoza, Joseph Young, Akane Sano, Ashok Veeraraghavan

Faculty, Staff and Students Publications

Research on children's technology and digital media (TDM) is hampered by a lack of robust approaches for assessing TDM use. This study assessed the feasibility of passively measuring children's TV screens and mobile devices (TDM) in a naturalistic setting. In the three-day feasibility study, FLASH-TV was set up on one to two TVs the child (5-12 year olds) typically used in the home (n=20). Children's mobile device use was assessed with either the Chronicle App or ScreenTime screenshots. Parents completed three TDM diaries. An exit interview with the parent explored their perceptions of the assessments and the child's TDM use …

Gene Expression In Tumor And Adjacent Normal Tissues In Lung Adenocarcinoma Subtypes, Olga Y Gorlova, Ivan P Gorlov, R Taylor Ripley, Chao Cheng, Yafang Li, Bo Peng, Yanhong Liu, Hee-Jin Jang, Sung Wook Kang, Claire Lee, Priyanka Ranchod, Bryan M Burt, Hyun-Sung Lee, Christopher I Amos

Faculty, Staff and Students Publications

Background: Lung adenocarcinoma (LUAD) has several histologically distinct subtypes that differ by a number of clinical features including patient survival. Molecular mechanisms underlying histological and clinical differences between subtypes remain poorly understood.

Methods: We conducted a comparative analyses of gene expression in acinar, lepidic, papillary and solid subtypes, as well as mucinous adenocarcinoma. We used a novel, more efficient approach to identify subtype-specific genes. We compared the mean gene expression level separately for tumors and adjacent normal tissue with pure or a highly represented (≥ 75%) subtype of interest to the mean expression in tumors where the subtype of interest …

Exogenous Arginine Differentially Regulates Inflammatory Cytokine And Inducible Nitric Oxide Synthase Expression In Macrophages, Kelsey Stayer, Saliha Pathan, Aalekhya Biswas, Huiqiao Li, Yi Zhu, Fong Wilson Lam, Juan Marini, Sundararajah Thevananther

Faculty, Staff and Students Publications

Immune dysfunction and late mortality from multiorgan failure are hallmarks of severe sepsis. Arginine, a semi-essential amino acid important for protein synthesis, immune response, and circulatory regulation, is deficient in sepsis. However, arginine supplementation in sepsis remains controversial due to the potential to upregulate inducible nitric oxide synthase (iNOS)-mediated excessive nitric oxide (NO) generation in macrophages, leading to vasodilation and hemodynamic catastrophe. Citrulline supplementation has been considered an alternative to replenishing arginine via de novo synthesis, orchestrated by argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase (ASL). However, the functional relevance of the ASS1-ASL pathway in macrophages after endotoxin stimulation is …

Mbiochemical Identification And Clinical Description Of Edetomidine Exposure In People Who Use Fentanyl In Philadelphia, Pa, Phil Durney, Jennifer L. Kahoud, Tareva Warrick-Stone, Maeve Montesi, Meg Carter, Sabrina Butt, Alberto Martinez Mencia, Louisa Omoregie, Monali Shah, Mariah Bloomfield, Nicholas Tomasko, Rebecca C. Jaffe, Allison Herens, Warren R. Korn, Karen Alexander, Douglas F. Stickle, Dennis Goodstein, Lara Weinstein, Kory S. London

Department of Emergency Medicine Faculty Papers

Medetomidine, a veterinary α2-adrenergic agonist, has recently emerged as an adulterant in the non-medical opioid supply, yet human exposure has remained poorly characterized. We conducted a pragmatic retrospective cohort analysis utilizing chart review and liquid chromatography-tandem mass spectrometry (LC-MS/MS) toxicology testing on available urine samples from patients presenting to two hospitals in Philadelphia, PA, who fit two clinical phenotypes, intoxication or withdrawal. Samples also underwent glucuronidase pre-treatment to assess impact on the yield of medetomidine and xylazine metabolite detection. Testing identified universal exposure to medetomidine (58/58 samples) via the 3-hydroxy-medetomidine (3-OH-M) metabolite, post glucuronidase treatment and variable xylazine exposure (40/58 …

Digitally Fabricated Interocclusal Wafer Versus Wafer-Less Distal Segment Repositioning For Bilateral Sagittal Split Osteotomy (Bsso) In Skeletal Mandibular Deformities (Randomized Controlled Trial), Hesham Osama Morsi Ass.Lect., Mohammed Abdelsalam Omara Ass.Prof., Mostafa Ibrahim Shindy Prof, Galal Gamal El Behairy Prof.

Dentistry

Objective: This study aimed to compare the accuracy of condylar positioning between 2 computer-guided orthognathic surgical protocols: a waferless screw hole plate locating (WSL CPD) technique versus an occlusal splint with distal extending arms (OWDA-CPD) approach. Materials and Methods: Twenty-four patients requiring mandibular orthognathic surgery (class II or III deformities) were randomly allocated into 2 groups (n=12 each). Group I underwent a waferless protocol utilizing 3D-printed osteotomy and screw hole locating guides, while group II received an occlusal splint with distal extensions for condylar positioning. Preoperative and postoperative cone-beam computed tomography (CBCT) scans were used to assess condylar displacement in …

The Healthcare Workforce In Nevada, 2024, Olivia K. Cheche, William E. Brown Jr., Caitlin J. Saladino

Health

This fact sheet presents data on the healthcare workforce in Nevada. The U.S. Bureau of Labor Statistics’ Occupational Employment and Wage Statistics Query System provides data on the amount of employment in all job sectors at the state and metropolitan statistical area (MSA) levels. This fact sheet focuses on employment and wage data for the State of Nevada, the Las Vegas-Henderson-Paradise, NV MSA, and the Reno, NV MSA as of May 2024.

Incidence And Clinical Profile Of Cardiovascular Abnormalities In Infants Of Diabetic Mother, Kailas Randad, Praveen Das, Akash Dnyandeo Sarkate, Qudsiya Ansari

Digital Journal of Clinical Medicine

Background: Maternal diabetes is associated with adverse pregnancy outcomes, notably congenital heart disease (CHD) in infants of diabetic mothers (IDMs). This study evaluated the prevalence and spectrum of CHDs in IDMs and the effect of maternal glycemic control.

Materials and Methods: A prospective observational study was conducted over 18 months at a tertiary care centre in Mumbai. A total of 112 IDMs were enrolled. Maternal glycemic status was assessed using HbA1c and random blood sugar. All infants underwent clinical examination, oxygen saturation measurement, and echocardiography.

Results: CHDs were identified in 26.7% of infants. The most frequent lesions …

Savings Associated With Bundled Payments For Outpatient Spine Surgery Among Medicare Beneficiaries, Austin S. Kilaru, Grace Y. Ng, Erkuan Wang, Erin Huang, Aidan P. Crowley, Jingsan Zhu, Joshua M. Liao, Said A. Ibrahim, Torrey Shirk, Deborah S. Cousins, Neil R. Malhotra, Amol S. Navathe

Department of Medicine Faculty Papers

IMPORTANCE: Few value-based payment programs have targeted outpatient surgery, although these procedures comprise most surgeries performed in hospitals. In 2018, the Centers for Medicare and Medicaid Services introduced Bundled Payments for Care Improvement Advanced (BPCI Advanced), the first episode-based payment model to include an outpatient surgical condition-spine surgery. It is not known whether bundled payments reduce spending or improve quality for outpatient surgery, despite plans to expand outpatient episodes in future models.

OBJECTIVE: To determine whether hospital participation in the first year of BPCI Advanced for outpatient and inpatient spine surgery (back and neck except spinal fusion procedures [BNESF]) was …

Impact Of Sanitation System Types On Residential And Environmental Presence Of Human Waste And Parasites In Alabama, Brandon Hunter, Catherine Coleman Flowers, Rojelio Mejia, Marc Arnold Deshusses

Faculty, Staff and Students Publications

Lowndes County is a predominantly Black rural county in Alabama, in the United States, which has a historical and current legacy of racial discrimination, creating inequitable infrastructure access and adverse health impacts. Over 80% rely on on-site sanitation infrastructure and most are failing. A community assessment of exposure to untreated sewage was conducted using samples from residential drinking water, surface swabs, and soil combined with environmental water and soil samples using culture-based and quantitative polymerase chain reaction (qPCR) methods. Testing varied slightly across samples, due to difficulty of access or availability. Of 43 households, 68% and 55% of houses had …

The Current And Future Burden Of Long Covid In The United States, Sarah M Bartsch, Kevin L Chin, Ulrich Strych, Danielle C John, Tej D Shah, Maria Elena Bottazzi, Kelly J O'Shea, Mckaylee Robertson, Colleen Weatherwax, Jessie Heneghan, Marie F Martinez, Allan Ciciriello, Sarah Kulkarni, Kavya Velmurugan, Alexis Dibbs, Sheryl A Scannell, Yanhan Shen, Denis Nash, Peter J Hotez, Bruce Y Lee

Faculty, Staff and Students Publications

Background: Long coronavirus disease (COVID), which affects an estimated 44.69-48.04 million people in the United States, is an ongoing public health concern that will persist as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread.

Methods: We developed a computational simulation model representing the clinical course, health effects, and associated costs of a person with long COVID.

Results: Simulations show that the average total cost of a long COVID case can range from $5084-$11 646 (assuming symptoms only last 1 year) with 92.5%-95.2% of these costs being productivity losses. Therefore, the current number of long COVID cases could cost …