Diseases Commons^™

Encephaloceles: A Comprehensive Exploration Of Research, Causes, Prevention, And Innovative Approaches To Diagnosis And Treatment, Amanda N. Bautista

Mako: NSU Undergraduate Student Journal

Encephaloceles, a rare medical condition derived from Greek words meaning "brain hernia," involve the protrusion of brain tissue, cerebrospinal fluid, or membranes through a defect in the skull. These anomalies often present at birth and can occur in various locations on the skull. Recent research has shed light on the possible causes of encephaloceles, including genetic factors such as the Sonic Hedgehog pathway and inadequate folic acid intake during pregnancy. Folic acid is essential for proper neural tube closure during fetal development, making it a key preventive measure.

Emerging treatments for encephaloceles show promise, with a focus on mesenchymal stem …

Rapid Anti-Myeloma Activity By T Cells Expressing An Anti-Bcma Car With A Human Heavy-Chain-Only Antigen-Binding Domain, Lekha Mikkilineni, Danielle A Natrakul, Norris Lam, Elisabet E Manasanch, Jennifer Mann, Katherine A Weissler, Nathan Wong, Jennifer N Brudno, Stephanie L Goff, James C Yang, Micaela Ganaden, Rashmika Patel, Zhili Zheng, Jared J Gartner, Kathryn R Martin, Hao-Wei Wang, Constance M Yuan, Tyler Lowe, Irina Maric, Lipei Shao, Ping Jin, David F Stroncek, Steven L Highfill, Steven A Rosenberg, James N Kochenderfer

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA). We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ. We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater …

A Reliable Diabetic Retinopathy Grading Via Transfer Learning And Ensemble Learning With Quadratic Weighted Kappa Metric, Sai Venkatesh Chilukoti, Liqun Shan, Vijay Srinivas Tida, Anthony S. Maida, Xiali Hei

Computer Science Faculty Publications

The most common eye infection in people with diabetes is diabetic retinopathy (DR). It might cause blurred vision or even total blindness. Therefore, it is essential to promote early detection to prevent or alleviate the impact of DR. However, due to the possibility that symptoms may not be noticeable in the early stages of DR, it is difficult for doctors to identify them. Therefore, numerous predictive models based on machine learning (ML) and deep learning (DL) have been developed to determine all stages of DR. However, existing DR classification models cannot classify every DR stage or use a computationally heavy …

Tumor-Associated Antigen Targets For Novel Immune-Based Strategies In Prostate Cancer, Amman Bhasin, Patrick Mille, Aditya Eturi, Andrew Iskander, William Tester, Kevin Zarrabi

Kimmel Cancer Center Faculty Papers

Prostate cancer remains the most common malignancy among men in the United States. Advancements in androgen receptor signaling blockade have led to landmark approvals for its use in patients with locally advanced and metastatic disease. However, additional novel therapeutic strategies for both hormone-sensitive and castration-resistant diseases remain ongoing areas of study. Thus, we turn to the growth of immuno-oncology, which has led to improved treatment outcomes for a variety of hematologic and solid tumor malignancies. Prostate cancers have shown only modest results with immune checkpoint inhibition in published trials, and innovative strategies are now looking into enhancing cytotoxic T-cell activity …

Dynamic Prognosis Prediction For Patients On Dapt After Drug-Eluting Stent Implantation: Model Development And Validation, Fang Li, Laila Rasmy, Yang Xiang, Jingna Feng, Ahmed Abdelhameed, Xinyue Hu, Zenan Sun, David Aguilar, Abhijeet Dhoble, Jingcheng Du, Qing Wang, Shuteng Niu, Yifang Dang, Xinyuan Zhang, Ziqian Xie, Yi Nian, Jianping He, Yujia Zhou, Jianfu Li, Mattia Prosperi, Jiang Bian, Degui Zhi, Cui Tao

Faculty, Staff and Student Publications

BACKGROUND: The rapid evolution of artificial intelligence (AI) in conjunction with recent updates in dual antiplatelet therapy (DAPT) management guidelines emphasizes the necessity for innovative models to predict ischemic or bleeding events after drug-eluting stent implantation. Leveraging AI for dynamic prediction has the potential to revolutionize risk stratification and provide personalized decision support for DAPT management.

METHODS AND RESULTS: We developed and validated a new AI-based pipeline using retrospective data of drug-eluting stent-treated patients, sourced from the Cerner Health Facts data set (n=98 236) and Optum's de-identified Clinformatics Data Mart Database (n=9978). The 36 months following drug-eluting stent implantation were …

Unraveling The Genetic Architecture Of Congenital Vertebral Malformation With Reference To The Developing Spine, Sen Zhao, Hengqiang Zhao, Lina Zhao, Xi Cheng, Zhifa Zheng, Mengfan Wu, Wen Wen, Shengru Wang, Zixiang Zhou, Haibo Xie, Dengfeng Ruan, Qing Li, Xinquan Liu, Chengzhu Ou, Guozhuang Li, Zhengye Zhao, Guilin Chen, Yuchen Niu, Xiangjie Yin, Yuhong Hu, Xiaochen Zhang, Deciphering Disorders Involving Scoliosis And Comorbidities (Disco) Study, Pengfei Liu, Guixing Qiu, Wanlu Liu, Chengtian Zhao, Zhihong Wu, Jianguo Zhang, Nan Wu

Faculty, Staff and Students Publications

Congenital vertebral malformation, affecting 0.13-0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord …

Harmonious Healing: A Review Of Music Therapy, A Humanities-Based Approach To Alzheimer’S Disease Treatment, Rohan K. Desai

Kentucky Undergraduate Journal for the Health Humanities

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease often characterized by memory loss, confusion, and overall cognitive decline. The aging global population has, in recent years, highlighted the fundamental lack of pharmacological treatments for individuals facing an AD diagnosis. In response, a growing body of research has shifted focus to non-pharmacological humanities-based interventions. One such intervention has been music therapy (MT). Music-focused measures have shown great promise as a method of slowing cognitive decline, but mixed results in the literature warrant the need for further investigation. Often, socioeconomic barriers can limit an individual’s access to drug-related treatments, but the affordable …

Health Economic Consequences Associated With Covid-19-Related Delay In Melanoma Diagnosis In Europe, Lara V Maul, Dagmar Jamiolkowski, Rebecca A Lapides, Alina M Mueller, Axel Hauschild, Claus Garbe, Paul Lorigan, Jeffrey E Gershenwald, Paolo Antonio Ascierto, Georgina V Long, Michael Wang-Evers, Richard A Scolyer, Babak Saravi, Matthias Augustin, Alexander A Navarini, Stefan Legge, István B Németh, Ágnes J Jánosi, Simone Mocellin, Anita Feller, Dieter Manstein, Alexander Zink, Julia-Tatjana Maul, Alessandra Buja, Kaustubh Adhikari, Elisabeth Roider

Faculty, Staff and Student Publications

IMPORTANCE: The COVID-19 pandemic resulted in delayed access to medical care. Restrictions to health care specialists, staff shortages, and fear of SARS-CoV-2 infection led to interruptions in routine care, such as early melanoma detection; however, premature mortality and economic burden associated with this postponement have not been studied yet.

OBJECTIVE: To determine the premature mortality and economic costs associated with suspended melanoma screenings during COVID-19 pandemic lockdowns by estimating the total burden of delayed melanoma diagnoses for Europe.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter economic evaluation used population-based data from patients aged at least 18 years with invasive primary cutaneous …

Impact Of Kras Mutations And Co-Mutations On Clinical Outcomes In Pancreatic Ductal Adenocarcinoma, Abdelrahman Yousef, Mahmoud Yousef, Saikat Chowdhury, Kawther Abdilleh, Mark Knafl, Paul Edelkamp, Kristin Alfaro-Munoz, Ray Chacko, Jennifer Peterson, Brandon G Smaglo, Robert A Wolff, Shubham Pant, Michael S Lee, Jason Willis, Michael Overman, Sudheer Doss, Lynn Matrisian, Mark W Hurd, Rebecca Snyder, Matthew H G Katz, Huamin Wang, Anirban Maitra, John Paul Shen, Dan Zhao

Faculty, Staff and Student Publications

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p < 0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p = 0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n = 408).

Gestational Diabetes Augments Group B Streptococcus Infection By Disrupting Maternal Immunity And The Vaginal Microbiota, Vicki Mercado-Evans, Marlyd E Mejia, Jacob J Zulk, Samantha Ottinger, Zainab A Hameed, Camille Serchejian, Madelynn G Marunde, Clare M Robertson, Mallory B Ballard, Simone H Ruano, Natalia Korotkova, Anthony R Flores, Kathleen A Pennington, Kathryn A Patras

Faculty, Staff and Student Publications

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing reveals differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM immune disruptions include reduced uterine natural killer cell activation, impaired recruitment to placentae, …

Chronic Wasting Disease: State Of The Science, Jason C Bartz, Rebeca Benavente, Byron Caughey, Sonja Christensen, Allen Herbst, Edward A Hoover, Candace K Mathiason, Debbie Mckenzie, Rodrigo Morales, Marc D Schwabenlander, Daniel P Walsh, The Nc North American Interdisciplinary Chronic Wasting Disease Research Consortium Members

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting cervid species, both free-ranging and captive populations. As the geographic range continues to expand and disease prevalence continues to increase, CWD will have an impact on cervid populations, local economies, and ecosystem health. Mitigation of this "wicked" disease will require input from many different stakeholders including hunters, landowners, research biologists, wildlife managers, and others, working together. The NC1209 (North American interdisciplinary chronic wasting disease research consortium) is composed of scientists from different disciplines involved with investigating and managing CWD. Leveraging this broad breadth of expertise, the Consortium has created a state-of-the-science …

From Primary Myelofibrosis To Chronic Myeloid Leukemia, Bcr::Abl1+ B-Lymphoblastic Leukemia, And Back To Primary Myelofibrosis: An Illustration Of Dynamic Clonal Evolution, Devin Wang, Wataru Kamata, Fengxi Ye, M James You

Faculty, Staff and Student Publications

The simultaneous detection of BCR::ABL1 and JAK2 V617F was rarely reported and their clonal relationship and dynamic clonal shift were not characterized. Here, we described a unique case with the initial presentation as JAK2 V617F+ primary myelofibrosis, followed by the emergence of BCR::ABL1+ chronic myeloid leukemia. The patient then developed BCR::ABL1+ B-lymphoblastic leukemia. Treatment for B-lymphoblastic leukemia prompted a regression to the state of primary myelofibrosis. In light of these observations, we proposed a clonal evolution model for this case.

Metabolism, Fibrosis, And Apoptosis: The Effect Of Lipids And Their Derivatives On Keloid Formation, Chen-Yu Li, Ru-Xin Xie, Shi-Wei Zhang, Jiao Yun, Ai Zhong, Ying Cen, Jun-Jie Chen

Faculty, Staff and Student Publications

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA …

Nanoparticles For Applications In Specific Diagnostics And Precision Medicine, Naxhije Berisha

Dissertations, Theses, and Capstone Projects

Heterogeneity is common in the expression of cancer and treatment response. Precision medicine enables healthcare providers to tailor medical care to an individual's distinct genetic and environmental makeup. This customization has the potential to result in more efficient treatments while minimizing side effects. We believe that by studying the interface of nanotechnology and cancer medicine we can elucidate innovative solutions that address the challenges of disease heterogeneity. This includes advancements in drug delivery, formulations development, and diagnostic sensing. We highlight three studies that use nanotechnology for applications in precision medicine. In Chapter 2, we highlight design optimization of drug formulations …

Glucose Metabolism In Posterior Cingulate Cortex Has Supplementary Value To Predict The Progression Of Cognitively Unimpaired To Dementia Due To Alzheimer’S Disease: An Exploratory Study Of 18f-Fdg-Pet, Qi Zhang, Chunqiu Fan, Luyao Wang, Taoran Li, Min Wang, Ying Han, Jiehui Jiang, Alzheimer’S Disease Neuroimaging Initiative

Faculty, Staff and Student Publications

Amyloid-β (Aβ) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aβ positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in …

Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer

Faculty, Staff and Students Publications

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia …

Endothelial Cells Adopt A Pro-Reparative Immune Responsive Signature During Cardiac Injury, Hali Long, Jeffrey D Steimle, Francisco Jose Grisanti Canozo, Jong Hwan Kim, Xiao Li, Yuka Morikawa, Minjun Park, Diwakar Turaga, Iki Adachi, Joshua D Wythe, Md Abul Hassan Samee, James F Martin

Faculty, Staff and Students Publications

Modulation of the heart’s immune microenvironment is crucial for recovery after ischemic events such as myocardial infarction (MI). Endothelial cells (ECs) can have immune regulatory functions; however, interactions between ECs and the immune environment in the heart after MI remain poorly understood. We identified an EC-specific IFN responsive and immune regulatory gene signature in adult and pediatric heart failure (HF) tissues. Single-cell transcriptomic analysis of murine hearts subjected to MI uncovered an EC population (IFN-ECs) with immunologic gene signatures similar to those in human HF. IFN-ECs were enriched in regenerative-stage mouse hearts and expressed genes encoding immune responsive transcription factors …

Anticoagulation With Osocimab In Patients With Kidney Failure Undergoing Hemodialysis: A Randomized Phase 2 Trial, Jeffrey I Weitz, László B Tankó, Jürgen Floege, Keith A A Fox, Deepak L Bhatt, Ravi Thadhani, James Hung, Ákos F Pap, Dagmar Kubitza, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Individuals with kidney failure undergoing hemodialysis are at elevated risk for thromboembolic events. Factor (F) XI, which is in the intrinsic pathway of coagulation, is emerging as an attractive target for new anticoagulants that may be safer than existing agents. Osocimab-an inhibitory FXIa antibody-is a potential treatment option for such patients. We conducted a phase 2b, double-blind, placebo-controlled trial, in which 704 participants (448 male, 256 female) with kidney failure undergoing hemodialysis were randomized to receive lower- or higher-dose osocimab or placebo. In total, 686 participants (436 male, 250 female) received treatment for ≤18 months (planned minimal treatment period of …

Left Main Coronary Artery Disease: A Contemporary Review Of Diagnosis And Management, Muzamil Khawaja, Michael Britt, Muhammad Asad Khan, Uzair Munaf, Hassaan Arshad, Rehma Siddiqui, Hafeez Ul Hassan Virk, Mahboob Alam, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Significant left main coronary artery disease is a very high-risk subgroup of coronary artery disease that is a crucial indicator of heightened morbidity and mortality rates. Despite its clinical significance, uncertainties persist regarding the optimal management strategy for patients, particularly given its phenotypic variations. Existing evidence-based guidelines offer insights into revascularization options, yet questions remain regarding long-term prognoses and clinical outcomes when comparing percutaneous coronary intervention to coronary artery bypass grafting. This comprehensive review aims to provide an in-depth analysis of contemporary strategies for the diagnosis, assessment, and treatment of left main coronary artery disease. By synthesizing current literature and …

Association Between Regulatory T Cells And Ischemic Heart Disease: A Mendelian Randomization Study, Yucheng Hou, Ke Si, Jingyue Yang, Tan Liu, Basel Abdelazeem, Nonthikorn Theerasuwipakorn, Jingwei Zhao, Zhenya Shen

Faculty, Staff and Student Publications

BACKGROUND: An imbalance of innate and acquired immune responses is significantly involved in the pathophysiology of coronary atherosclerosis and the occurrence of ischemic heart disease (IHD). Regulatory T cells (Tregs) play an essential regulatory role in atherosclerotic plaque formation and maintenance; therefore, dysfunction of Tregs triggers the formation of atherosclerotic plaques and accelerates their progression. However, due to the inherent limitations of observational research, clinical evidence is limited concerning the relationship between the variation in peripheral Tregs and the risk of IHD, and the cause-and-effect relationship between these factors is unclear. Mendelian randomization (MR) uses genetic variation as a proxy …

Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington’s disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly …

Reconstitution Of Human Pdac Using Primary Cells Reveals Oncogenic Transcriptomic Features At Tumor Onset, Yi Xu, Michael H Nipper, Angel A Dominguez, Zhenqing Ye, Naoki Akanuma, Kevin Lopez, Janice J Deng, Destiny Arenas, Ava Sanchez, Francis E Sharkey, Colin M Court, Aatur D Singhi, Huamin Wang, Martin E Fernandez-Zapico, Lu-Zhe Sun, Siyuan Zheng, Yidong Chen, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Animal studies have demonstrated the ability of pancreatic acinar cells to transform into pancreatic ductal adenocarcinoma (PDAC). However, the tumorigenic potential of human pancreatic acinar cells remains under debate. To address this gap in knowledge, we expand sorted human acinar cells as 3D organoids and genetically modify them through introduction of common PDAC mutations. The acinar organoids undergo dramatic transcriptional alterations but maintain a recognizable DNA methylation signature. The transcriptomes of acinar organoids are similar to those of disease-specific cell populations. Oncogenic KRAS alone do not transform acinar organoids. However, acinar organoids can form PDAC in vivo after acquiring the …

Prevention And Potential Treatment Strategies For Respiratory Syncytial Virus, Bo-Wen Sun, Peng-Peng Zhang, Zong-Hao Wang, Xia Yao, Meng-Lan He, Rui-Ting Bai, Hao Che, Jing Lin, Tian Xie, Zi Hui, Xiang-Yang Ye, Li-Wei Wang

Faculty, Staff and Student Publications

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and …

Non-Canonical Hedgehog Signaling Mediates Profibrotic Hematopoiesis-Stroma Crosstalk In Myeloproliferative Neoplasms, Jessica E Pritchard, Juliette E Pearce, Inge A M Snoeren, Stijn N R Fuchs, Katrin Götz, Fabian Peisker, Silke Wagner, Adam Benabid, Niklas Lutterbach, Vanessa Klöker, James S Nagai, Monica T Hannani, Anna K Galyga, Ellen Sistemich, Bella Banjanin, Niclas Flosdorf, Eric Bindels, Kathrin Olschok, Katharina Biaesch, Nicolas Chatain, Neha Bhagwat, Andrew Dunbar, Rita Sarkis, Olaia Naveiras, Marie-Luise Berres, Steffen Koschmieder, Ross L Levine, Ivan G Costa, Hélène F E Gleitz, Rafael Kramann, Rebekka K Schneider

Faculty, Staff and Student Publications

The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs. We show that Gli1 protein levels in patient peripheral blood mononuclear cells (PBMCs) mark fibrotic progression and that, in murine MPN models, absence of hematopoietic Gli1, but not Gli2 or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1 has a …

Role Of Polyunsaturated Fat In Modifying Cardiovascular Risk Associated With Family History Of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies, Federica Laguzzi, Agneta Åkesson, Matti Marklund, Frank Qian, Bruna Gigante, Traci M Bartz, Julie K Bassett, Anna Birukov, Hannia Campos, Yoichiro Hirakawa, Fumiaki Imamura, Susanne Jäger, Maria Lankinen, Rachel A Murphy, Mackenzie Senn, Toshiko Tanaka, Nathan Tintle, Jyrki K Virtanen, Kazumasa Yamagishi, Matthew Allison, Ingeborg A Brouwer, Ulf De Faire, Gudny Eiriksdottir, Luigi Ferrucci, Nita G Forouhi, Johanna M Geleijnse, Allison M Hodge, Hitomi Kimura, Markku Laakso, Ulf Risérus, Anniek C Van Westing, Stefania Bandinelli, Ana Baylin, Graham G Giles, Vilmundur Gudnason, Hiroyasu Iso, Rozenn N Lemaitre, Toshiharu Ninomiya, Wendy S Post, Bruce M Psaty, Jukka T Salonen, Matthias B Schulze, Michael Y Tsai, Matti Uusitupa, Nicholas J Wareham, Seung-Won Oh, Alexis C Wood, William S Harris, David Siscovick, Dariush Mozaffarian, Karin Leander, Fatty Acids And Outcomes Research Consortium (Force)

Faculty, Staff and Students Publications

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.

METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were …

Advancements In Revascularization Strategies For Acute Mesenteric Ischemia: A Comprehensive Review, Jacob J Gries, Hafeez Ul Hassan Virk, Bing Chen, Takashi Sakamoto, Mahboob Alam, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Even with modern advancements in the management of acute mesenteric ischemia over the past decade, morbidity and mortality remain high, and the best primary treatment modality is still debated amongst interventionalists. Traditionally, interventionalists have favored an open surgical approach but are now trending for endovascular interventions due to apparent reduced mortality and complications. Newer studies suggest hybrid approaches, and intestinal stroke centers may be superior to either strategy alone. This narrative review will explore the natural history of acute mesenteric ischemia with the aim of increasing interventionalist awareness of modern advancements in revascularization strategies for this devastating disease.

Comparison Of Three Rapid Diagnostic Tests For Bloodstream Infections Using Benefit-Risk Evaluation Framework (Bed-Frame), Richard D Smith, Min Zhan, Shanshan Zhang, Surbhi Leekha, Anthony Harris, Yohei Doi, Scott Evans, J Kristie Johnson, Robert K Ernst

Faculty, Staff and Student Publications

Rapid diagnostic tests (RDTs) for bloodstream infections have the potential to reduce time to appropriate antimicrobial therapy and improve patient outcomes. Previously, an in-house, lipid-based, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) method, Fast Lipid Analysis Technique (FLAT MS), has shown promise as a rapid pathogen identification method. In this study, FLAT MS for direct from blood culture identification was evaluated and compared to FDA-cleared identification methods using the Benefit-risk Evaluation Framework (BED-FRAME) analysis. FLAT MS was evaluated and compared to Bruker Sepsityper and bioMérieux BioFire FilmArray BCID2 using results from a previous study. For this study, 301 …

Classification Of Colorectal Cancer Using Resnet And Efficientnet Models, Abhishek Ranjan, Priyanshu Srivastva, B Prabadevi, R Sivakumar, Rahul Soangra, Shamala K. Subramaniam

Physical Therapy Faculty Articles and Research

Introduction:

Cancer is one of the most prevalent diseases from children to elderly adults. This will be deadly if not detected at an earlier stage of the cancerous cell formation, thereby increasing the mortality rate. One such cancer is colorectal cancer, caused due to abnormal growth in the rectum or colon. Early screening of colorectal cancer helps to identify these abnormal growth and can exterminate them before they turn into cancerous cells.

Aim:

Therefore, this study aims to develop a robust and efficient classification system for colorectal cancer through Convolutional Neural Networks (CNNs) on histological images.

Methods:

Despite challenges in …

Development And Validation Of A Nomogram For Predicting Pulmonary Infection In Patients Receiving Immunosuppressive Drugs, Chuxuan Luo, Yue Zhang, Jiajie Zhang, Chen Jin, Xiaolan Ye, Yan Ren, Huajuan Shen, Maosheng Chen, Yiwen Li, Qiang He, Guangbiao Xu, Lina Shao

Faculty, Staff and Student Publications

Objective: Pulmonary infection (PI), a severe complication of immunosuppressive therapy, affects patients' prognosis. As part of this study, we aimed to construct a pulmonary infection prediction (PIP) model and validate it in patients receiving immunosuppressive drugs (ISDs). Methods: Totally, 7,977 patients being treated with ISDs were randomised 7:3 to the developing (n = 5,583) versus validation datasets (n = 2,394). Our predictive nomogram was established using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. With the use of the concordance index (C-index) and calibration curve, the prediction performance of the final model was …

Novel Pan-Err Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism And Mitochondrial Function, Weiyi Xu, Cyrielle Billon, Hui Li, Andrea Wilderman, Lei Qi, Andrea Graves, Jernie Rae Dela Cruz Rideb, Yuanbiao Zhao, Matthew Hayes, Keyang Yu, Mckenna Losby, Carissa S Hampton, Christiana M Adeyemi, Seok Jae Hong, Eleni Nasiotis, Chen Fu, Tae Gyu Oh, Weiwei Fan, Michael Downes, Ryan D Welch, Ronald M Evans, Aleksandar Milosavljevic, John K Walker, Brian C Jensen, Liming Pei, Thomas Burris, Lilei Zhang

Faculty, Staff and Students Publications

BACKGROUND: Cardiac metabolic dysfunction is a hallmark of heart failure (HF). Estrogen-related receptors ERRα and ERRγ are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for HF. However, in vivo studies demonstrating the potential usefulness of ERR agonist for HF treatment are lacking, because compounds with pharmacokinetics appropriate for in vivo use have not been available.

METHODS: Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915. We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo. We …