Medical Specialties Commons^™

Wnt7a, Naomi M Calhoun, Richard R Behringer

Faculty, Staff and Student Publications

WNT7A regulates numerous developmental processes. It can activate canonical and non-canonical signaling depending on context. It is expressed in the developing central nervous system, limb buds, reproductive organs, and other tissues. Spontaneous and targeted Wnt7a mutations in mouse models resulted in abnormal limbs, defects in male and female reproductive tract organs, infertility, and defects in cerebellar axon remodeling. In zebrafish, wnt7aa mutants exhibited neurogenesis and angiogenesis defects in the central nervous system. In humans, recessive WNT7A missense and nonsense mutations resulted in severe limb and pelvic bone defects. Alterations in WNT7A expression correlated with multiple types of cancer.

Bismuth-Infused Perivascular Wrap Facilitates Delivery Of Mesenchymal Stem Cells And Attenuation Of Neointimal Hyperplasia In Rat Arteriovenous Fistulas, Allan John R Barcena, Joy Vanessa D Perez, Marvin R Bernardino, Jossana A Damasco, Erin Marie D San Valentin, Carleigh Klusman, Benjamin Martin, Gino Martin Canlas, Francisco M Heralde, Natalie Fowlkes, Richard R Bouchard, Jizhong Cheng, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

BACKGROUND: Mesenchymal stem cells (MSCs) have emerged as novel therapies for supporting arteriovenous fistula (AVF) maturation, and bioresorbable polymeric scaffolds have enabled sustained MSC delivery into maturing AVFs. However, the radiolucency of biopolymeric wraps prevents in vivo monitoring of their integrity and location, hindering long-term preclinical investigations.

METHODS: We infused bismuth nanoparticles (BiNPs) into polycaprolactone (PCL) to fabricate an electrospun perivascular wrap capable of MSC delivery and conducive to longitudinal monitoring using conventional imaging. We tested the wraps' effects on the attenuation of markers of neointimal hyperplasia (i.e., endothelial dysfunction, hypoxia, and inflammation), the leading cause of AVF failure, in …

Disparities In Breast Cancer Detection Modalities And Outcomes Among Geriatric Female Cancer Patients, Zhaoli Liu, Mathilda Nicot-Cartsonis, Biai D E Digbeu, Daoqi Gao, Sharon H Giordano, Yong-Fang Kuo

Faculty, Staff and Student Publications

This study examined racial and geographic disparities in breast cancer detection modalities (screening-, diagnostic-, or non-mammography) with cancer stage and mortality. A retrospective cohort study was conducted using Texas Cancer Registry-Medicare linkage data for geriatric women. Cancers detected through screening and diagnostic mammography had 43 % (95 % CI, 39 %-46 %, p < .0001) and 31 % (95 % CI, 27 %-35 %, p < .0001) lower all-cause mortality, and 49 % (95 % CI, 41 %-54 %, p < .0001) and 37 % (95 % CI, 32 %-43 %, p < .0001) lower cancer-specific mortality, respectively, compared to non-mammography-detected breast cancers. Patients from rural areas were 17 % (95 % CI, 1.06 - 1.29) more likely to be diagnosed with mid- (p = .0023) and advanced stage (p = .003) cancers compared to their urban counterparts. Racial or geographic disparities in cancer detection modalities with associated mortality no longer exist after adjusting for covariates. Healthcare professionals can leverage these findings to promote rural cancer health equity.

Organ Of Corti Macrophages: A Distinct Group Of Cochlear Macrophages With Potential Roles In Supporting Cell Degeneration And Survival, Mengxiao Ye, Celia Zhang, Dalian Ding, Guang-Di Chen, Henry J Adler, Rania Sharaf, Bo Hua Hu

Faculty, Staff and Student Publications

Macrophages are the primary immune cells in the cochlea, essential for maintaining cochlear homeostasis and orchestrating inflammatory responses to pathological events. Although these cells have been found in various parts of the cochlea, their presence in the organ of Corti, a critical structure for acoustic sensing, remains poorly understood. The present study was designed to examine macrophage responses to ototoxic drug-induced cochlear damage and age-related cochlear degeneration, with a particular focus on the pathological conditions that trigger macrophage recruitment into the organ of Corti. We used a model of ototoxicity induced by cyclodextrin, a cyclic oligosaccharide known for its ability …

A Cytotoxic Peptide-Drug Conjugate For Tumor-Specific Delivery Of Co-Injected Molecules, Norio Miyamura, Chisato M Yamazaki, Yasuaki Anami, Kyoji Tsuchikama, Kazuki N Sugahara

Faculty, Staff and Student Publications

An ideal cancer therapy enhances anti-tumor effects while minimizing side effects. iRGD, a non-cytotoxic peptide that activates a tumor-specific molecular transport machinery, promotes the penetration of co-injected drugs into tumor tissues. Clinical trials have demonstrated its potential as a tumor-specific delivery scaffold and potentiator of anti-cancer agents. In this study, we synthesized an iRGD conjugate containing monomethyl auristatin F (MMAF), a highly toxic antimitotic agent, and characterized its dual function as a tumor-specific cytotoxic agent and co-injected drug delivery scaffold. The iRGD-MMAF conjugate internalized and killed cultured tumor cells in an αv integrin-dependent manner. When injected systemically, iRGD-MMAF homed selectively …

Integrating Multi-Omics Data To Uncover Prostate Tissue Dna Methylation Biomarkers And Target Genes For Prostate Cancer Risk, Shuai Liu, Jingjing Zhu, Dylan Green, Hua Zhong, Quan Long, Chong Wu, Liang Wang, Youping Deng, Lang Wu

Faculty, Staff and Student Publications

Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk-associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (N = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. …

The Human Spinothalamic Tract: Lessons From Cordotomy, Anthony K Allam, Michael Benjamin Larkin, Ishan A Patel, Mohammed Hasen, David Mears, Patrick Dougherty, Ashwin Viswanathan

Faculty, Staff and Student Publications

The spinothalamic tract has long been known as a primary conductor of nociceptive information, with its anatomical and physiological understanding evolving over centuries of research. This comprehensive review traces the history of the spinothalamic tract beginning with Brown-Sequard’s 1860 report of contralateral analgesia following a hemisection of the spinal cord. As clinical and surgical interventions, such as cordotomies have advanced, so did our understanding of the spinothalamic tract’s function and anatomy. The spinothalamic tract’s role as a crossed pathway conducting pain and temperature sensations was solidified by the mid-20th century. However, intricate details of its somatotopic arrangement, anatomical distributions and …

Three-Dimensional Deep Learning Normal Tissue Complication Probability Model To Predict Late Xerostomia In Patients With Head And Neck Cancer, Hung Chu, Suzanne P M De Vette, Hendrike Neh, Nanna M Sijtsema, Roel J H M Steenbakkers, Amy Moreno, Johannes A Langendijk, Peter M A Van Ooijen, Clifton D Fuller, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Purpose: Conventional normal tissue complication probability (NTCP) models for patients with head and neck cancer are typically based on single-value variables, which, for radiation-induced xerostomia, are baseline xerostomia and mean salivary gland doses. This study aimed to improve the prediction of late xerostomia by using 3-dimensional information from radiation dose distributions, computed tomography imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL).

Methods and materials: An international cohort of 1208 patients with head and neck cancer from 2 institutes was used to train and twice validate DL models (deep convolutional neural network, EfficientNet-v2, and ResNet) with 3-dimensional dose distribution, …

Bronchoalveolar Lavage Cell Percentages As Diagnostic Markers Of Immune Checkpoint Inhibitor Pneumonitis, Mahnoor Mir, Felipe Soto, Pedro Antonio Amezcua Gomez, Rodrigo Del Rio Arroyo, Adarsh Suresh, Amber Su, Qiong Gan, John Stewart, Roberto Adachi, Diwakar D Balachandran, Lara Bashoura, Roberto F Casal, Burton F Dickey, George A Eapen, Scott E Evans, Horiana Grosu, Carlos A Jimenez, Julie Lin, David E Ost, Bruce F Sabath, Vickie R Shannon, Aung Naing, Jianjun Gao, Jia Wu, Karthik Suresh, Saadia A Faiz, Mehmet Altan, Ajay Sheshadri

Faculty, Staff and Student Publications

Introduction: Diagnostic biomarkers for immune checkpoint inhibitor pneumonitis (ICIP) are lacking. Bronchoalveolar lavage (BAL) lymphocytosis has been associated with ICIP, but studies have not evaluated BAL lymphocytosis as a diagnostic biomarker for ICIP.

Purpose: This study aimed to measure the association of BAL immune cell percentage with ICIP and test its performance as a diagnostic biomarker.

Methods: We performed a retrospective chart review of 476 patients treated with ICIs for solid organ or hematologic malignancies who underwent BAL between 2016 and 2022. Two independent reviewers, blinded to the results of BAL cell percentage, confirmed the diagnosis of ICIP or other …

Deep Dive Into Targeted Therapies: Understanding Idh1-Mutant Aml Treatments [Podcast], Amer M Zeidan, Courtney Dinardo

Faculty, Staff and Student Publications

This podcast episode reviews recent advances in the treatment of IDH1-mutant acute myeloid leukemia (AML), focusing on the mechanisms, efficacy, and safety profiles of approved IDH1 inhibitors. The purpose is to present expert insights and clinical data from key trials that underscore the clinical benefits of these targeted therapies. Through discussion of key findings from pivotal clinical trial studies, including data supporting the use of these agents in both newly diagnosed and relapsed or refractory (R/R) settings, the episode highlights significant outcomes such as increased overall response and prolonged duration of remission in patients treated with IDH1 inhibitors. The analysis …

Defining Spine Cancer Pain Syndromes: A Systematic Review And Proposed Terminology, Markian Pahuta, Ilya Laufer, Sheng-Fu Larry Lo, Stefano Boriani, Charles Fisher, Nicolas Dea, Michael H Weber, Dean Chou, Arjun Sahgal, Laurence Rhines, Jeremy Reynolds, Aron Lazary, Alessandro Gasbarrinni, Jorrit-Jan Verlaan, Ziya Gokaslan, Chetan Bettegowda, Mohamed Sarraj, Ori Barzilai, Ao Spine Knowledge Forum Tumor

Faculty, Staff and Student Publications

STUDY DESIGN: Systematic Review.

OBJECTIVES: Formalized terminology for pain experienced by spine cancer patients is lacking. The common descriptors of spine cancer pain as mechanical or non-mechanical is not exhaustive. Misdiagnosed spinal pain may lead to ineffective treatment recommendations for cancer patients.

METHODS: We conducted a systematic review of pain terminology that may be relevant to spinal oncology patients. We provide a comprehensive and unbiased summary of the existing evidence, not limited to the spine surgery literature, and subsequently consolidate these data into a practical, clinically relevant nomenclature for spine oncologists.

RESULTS: Our literature search identified 3515 unique citations. Through …

The Influence Of The Microbiome On Radiotherapy And Dna Damage Responses, Aadil Sheikh, Michael A Curran

Faculty, Staff and Student Publications

Colorectal cancer (CRC) is one of the most prevalent cancers in terms of diagnosis and mortality. Radiotherapy (RT) remains a mainstay of CRC therapy. As RT relies on DNA damage to promote tumor cell death, the activity of cellular DNA damage repair pathways can modulate cancer sensitivity to therapy. The gut microbiome has been shown to influence intestinal health and is independently associated with CRC development, treatment responses and outcomes. The microbiome can also modulate responses to CRC RT through various mechanisms such as community structure, toxins and metabolites. In this review we explore the use of RT in the …

Patient-Reported Outcomes During Pelvic Radiation Therapy: A Secondary Analysis On Sexual Function From Nrg-Rtog 1203, Kelsey L Corrigan, Rebecca Paulus, Ann H Klopp, Lari B Wenzel, Anamaria R Yeung, J Spencer Thompson, Desiree E Doncals, Vijayananda Kundapur, Nancy H Wiggers, Dasarahally S Mohan, Sharad A Ghamande, Shannon N Westin, Kara L Schnarr, Michael L Haas, David K Gaffney, Steven E Waggoner, Pamela J Vanderwall, Noha T Jastaniyah, Stephanie L Pugh, Lisa A Kachnic

Faculty, Staff and Student Publications

Purpose: NRG-RTOG 1203 reported that intensity-modulated radiation therapy (IMRT) reduced patient-reported GI toxicities in patients with cervical/endometrial cancer receiving postoperative RT, compared with 3-dimensional conformal radiation therapy (3DRT). We conducted a secondary analysis of patient-reported sexual function (PR-SF) among treatment groups to identify factors associated with sexual dysfunction.

Methods and materials: Patients on NRG-RTOG 1203 were randomly assigned to 3DRT versus IMRT and completed Patient-Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) and FACT-Cx surveys at baseline, week 5 of RT, and at 4-6 weeks, 1 year, and 3 years after RT. Patient responses to FACT-Cx sexual function questions …

Reproducibility And Repeatability Of 18f-(2s, 4r)-4-Fluoroglutamine Pet Imaging In Preclinical Oncology Models, Gregory D Ayers, Allison S Cohen, Seong-Woo Bae, Xiaoxia Wen, Alyssa Pollard, Shilpa Sharma, Trey Claus, Adria Payne, Ling Geng, Ping Zhao, Mohammed Noor Tantawy, Seth T Gammon, H Charles Manning

Faculty, Staff and Student Publications

Introduction: Measurement of repeatability and reproducibility (R&R) is necessary to realize the full potential of positron emission tomography (PET). Several studies have evaluated the reproducibility of PET using 18F-FDG, the most common PET tracer used in oncology, but similar studies using other PET tracers are scarce. Even fewer assess agreement and R&R with statistical methods designed explicitly for the task. 18F-(2S, 4R)-4-fluoro-glutamine (18F-Gln) is a PET tracer designed for imaging glutamine uptake and metabolism. This study illustrates high reproducibility and repeatability with 18F-Gln for in vivo research.

Methods: Twenty mice bearing colorectal cancer cell line xenografts were injected with ~9 …

Patterns Of Loco-Regional Progression And Patient Outcomes After Definitive-Dose Radiation Therapy For Anaplastic Thyroid Cancer, Julianna K Bronk, Alexander Augustyn, Abdallah S R Mohamed, C David Fuller, Adam S Garden, Amy C Moreno, Anna Lee, William H Morrison, Jack Phan, Jay P Reddy, David I Rosenthal, Michael T Spiotto, Steven J Frank, Ramona Dadu, Naifa Busaidy, Mark Zafereo, Jennifer R Wang, Anastasios Maniakas, Renata Ferrarotto, Priyanka C Iyer, Maria E Cabanillas, G Brandon Gunn

Faculty, Staff and Student Publications

Background: The aim of this study is to characterize the patterns of loco-regional progression (LRP) and outcomes after definitive-dose intensity modulated radiation therapy (IMRT) for anaplastic thyroid cancer (ATC) with macroscopic neck disease at the time of IMRT.

Methods: Disease/treatment characteristics and outcomes for patients with unresected or incompletely resected ATC who received IMRT (≥45 Gy) were retrospectively reviewed. For those with LRP after IMRT, progressive/recurrent gross tumor volumes (rGTV) were contoured on diagnostic CTs and co-registered with initial planning CTs using deformable image registration. rGTVs were classified based on established spatial/dosimetric criteria.

Results: Forty patients treated between 2010-2020 formed …

Selective Inhibition Of Canonical Stat3 Signaling Suppresses K-Ras Mutant Lung Tumorigenesis And Reinvigorates Anti-Tumor Immunity, Michael J Clowers, Zahraa Rahal, Sung-Nam Cho, Avantika Krishna, Bo Yuan, Leticia G Hamana Zorrilla, T Kris Eckols, Moses M Kasembeli, Samuel Liu, Stephen Peng, Marco Ramos-Castaneda, Annamarie L Thompson, Carlos Ignacio Rodriguez Reyna, Katherine E Larsen, Maria T Grimaldo, Shanshan Deng, Nastaran Karimi, Cody Chou, Walter V Velasco, Melody Zarghooni, Sayan Alekseev, Luisa M Solis Soto, Edwin J Ostrin, Humam Kadara, Suhendan Ekmekcioglu, David J Tweardy, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

Introduction: K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. One of the lynchpins of chronic inflammation in KM-LUAD is signal transducer and activator of transcription 3 (STAT3).

Methods: Here, we tested the anti-tumor and early immunotherapeutic efficacy of TTI-101, a selective small-molecule inhibitor of canonical STAT3 signaling, in a K-rasG12D mutant lung cancer mouse model (CC-LR).

Results: Treatment of CC-LR mice with TTI-101 resulted in reduced …

Dedifferentiated Liposarcomas Treated With Immune Checkpoint Blockade: The Md Anderson Experience, Madeline B Torres, Cheuk Hong Leung, Marianne Zoghbi, Rossana Lazcano, Davis Ingram, Khalida Wani, Emily Z Keung, M Alejandra Zarzour, Christopher P Scally, Kelly K Hunt, Anthony Conley, Andrew J Bishop, B Ashleigh Guadagnolo, Ahsan Farooqi, Devarati Mitra, Alison K Yoder, Michael S Nakazawa, Dejka Araujo, Andrew Livingston, Ravin Ratan, Shreyaskumar Patel, Vinod Ravi, Alexander J Lazar, Christina L Roland, Neeta Somaiah, Elise F Nassif Haddad

Faculty, Staff and Student Publications

Background: Dedifferentiated liposarcoma (DDLPS) is one of the most common types of soft tissue sarcoma (STS) characterized by liposarcomatous differentiation and a predilection for the retroperitoneum. Despite the growing number of histology-specific immune checkpoint blockade (ICB) trials in STS, it is still difficult to identify the radiographic objective response rate (ORR) for DDLPS in the real world setting. This study aimed to evaluate the ORR and survival of patients with DDLPS treated with ICB at a single center.

Methods: We conducted a retrospective study of 31 patients with pathologically confirmed DDLPS treated with ICB at MD Anderson Cancer Center between …

A Plain Language Summary Of The Final Analysis Of The Griffin Study Of Daratumumab Plus Lenalidomide, Bortezomib, And Dexamethasone For People With Newly Diagnosed Multiple Myeloma, Peter M Voorhees, Douglas W Sborov, Jacob Laubach, Jonathan L Kaufman, Brandi Reeves, Cesar Rodriguez, Rebecca Silbermann, Luciano J Costa, Larry D Anderson, Nitya Nathwani, Nina Shah, Naresh Bumma, Yvonne A Efebera, Sarah A Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M Wildes, Robert Z Orlowski, Kenneth H Shain, Andrew J Cowan, Shira Dinner, Katharine S Gries, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Saad Z Usmani, Paul G Richardson

Faculty, Staff and Student Publications

No abstract provided.

Grape-Pi: Graph-Based Neural Networks For Enhanced Protein Identification In Proteomics Pipelines, Chunhui Gu, Seyyed Mahmood Ghasemi, Yining Cai, Johannes F Fahrmann, James P Long, Hiroyuki Katayama, Chong Wu, Jody Vykoukal, Jennifer B Dennison, Samir Hanash, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

Motivation: Protein identification via mass spectrometry (MS) is the primary method for untargeted protein detection. However, the identification process is challenging due to data complexity and the need to control false discovery rates (FDR) of protein identification. To address these challenges, we developed a graph neural network (GNN)-based model, Graph Neural Network using Protein-Protein Interaction for Enhancing Protein Identification (Grape-Pi), which is applicable to all proteomics pipelines. This model leverages protein-protein interaction (PPI) data and employs two types of message-passing layers to integrate evidence from both the target protein and its interactors, thereby improving identification accuracy.

Results: Grape-Pi achieved significant …

A Critical Assessment Of Artificial Intelligence In Magnetic Resonance Imaging Of Cancer, Chengyue Wu, Meryem Abbad Andaloussi, David A Hormuth, Ernesto A B F Lima, Guillermo Lorenzo, Casey E Stowers, Sriram Ravula, Brett Levac, Alexandros G Dimakis, Jonathan I Tamir, Kristy K Brock, Caroline Chung, Thomas E Yankeelov

Faculty, Staff and Student Publications

Given the enormous output and pace of development of artificial intelligence (AI) methods in medical imaging, it can be challenging to identify the true success stories to determine the state-of-the-art of the field. This report seeks to provide the magnetic resonance imaging (MRI) community with an initial guide into the major areas in which the methods of AI are contributing to MRI in oncology. After a general introduction to artificial intelligence, we proceed to discuss the successes and current limitations of AI in MRI when used for image acquisition, reconstruction, registration, and segmentation, as well as its utility for assisting …

Inhibition Of Nitric Oxide Synthase Transforms Carotid Occlusion-Mediated Benign Oligemia Into De Novo Large Cerebral Infarction, Ha Kim, Jinyong Chung, Jeong Wook Kang, Dawid Schellingerhout, Soo Ji Lee, Hee Jeong Jang, Inyeong Park, Taesu Kim, Dong-Seok Gwak, Ji Sung Lee, Sung-Ha Hong, Kang-Hoon Je, Hee-Joon Bae, Joohon Sung, Eng H Lo, James Faber, Cenk Ayata, Dong-Eog Kim

Faculty, Staff and Student Publications

No abstract provided.

Small Molecule-Based Regulation Of Gene Expression In Human Astrocytes Switching On And Off The G-Quadruplex Control Systems, Vijay Kumar M J, Jérémie Mitteaux, Zi Wang, Ellery Wheeler, Nitin Tandon, Sung Yun Jung, Robert H E Hudson, David Monchaud, Andrey S Tsvetkov

Faculty, Staff and Student Publications

A great deal of attention is being paid to strategies seeking to uncover the biology of the four-stranded nucleic acid structure G-quadruplex (G4) via their stabilization in cells with G4-specific ligands. The conventional definition of chemical biology implies that a complete assessment of G4 biology can only be achieved by implementing a complementary approach involving the destabilization of cellular G4s by ad hoc molecular effectors. We report here on an unprecedented comparison of the cellular consequences of G4 chemical stabilization by pyridostatin (PDS) and destabilization by phenylpyrrolocytosine (PhpC) at both transcriptome- and proteome-wide scales in patient-derived primary human astrocytes. Our …

Overview Of The Head And Neck Tumor Segmentation For Magnetic Resonance Guided Applications (Hnts-Mrg) 2024 Challenge, Kareem A Wahid, Cem Dede, Dina M El-Habashy, Serageldin Kamel, Michael K Rooney, Yomna Khamis, Moamen R A Abdelaal, Sara Ahmed, Kelsey L Corrigan, Enoch Chang, Stephanie O Dudzinski, Travis C Salzillo, Brigid A Mcdonald, Samuel L Mulder, Lucas Mccullum, Qusai Alakayleh, Carlos Sjogreen, Renjie He, Abdallah S R Mohamed, Stephen Y Lai, John P Christodouleas, Andrew J Schaefer, Mohamed A Naser, Clifton D Fuller

Faculty, Staff and Student Publications

Magnetic resonance (MR)-guided radiation therapy (RT) is enhancing head and neck cancer (HNC) treatment through superior soft tissue contrast and longitudinal imaging capabilities. However, manual tumor segmentation remains a significant challenge, spurring interest in artificial intelligence (AI)-driven automation. To accelerate innovation in this field, we present the Head and Neck Tumor Segmentation for MR-Guided Applications (HNTS-MRG) 2024 Challenge, a satellite event of the 27th International Conference on Medical Image Computing and Computer Assisted Intervention. This challenge addresses the scarcity of large, publicly available AI-ready adaptive RT datasets in HNC and explores the potential of incorporating multi-timepoint data to enhance RT …

Transcriptomic Profile Analysis Of Brain Tissue In The Absence Of Functional Trpm8 Calcium Channel, Erick B Saldes, Alexandra Erdmier, Jai Velpula, Timothy E Koeltzow, Michael X Zhu, Swapna Asuthkar

Faculty, Staff and Student Publications

Background/Objectives: Transient Receptor Potential Melastatin 8 (TRPM8) is a non-selective, Ca2+-permeable cation channel involved in thermoregulation and other physiological processes, such as basal tear secretion, cell differentiation, and insulin homeostasis. The activation and deactivation of TRPM8 occur through genetic modifications, channel interactions, and signaling cascades. Recent evidence suggests a significant role of TRPM8 in the hypothalamus and amygdala related to pain sensation and sexual behavior. Notably, TRPM8 has been implicated in neuropathic pain, migraines, and neurodegenerative diseases such as Parkinson's disease. Our laboratory has identified testosterone as a high-affinity ligand of TRPM8. TRPM8 deficiency appears to influence behavioral traits in …

Disruption Of Distal Appendage Protein Cep164 Causes Skeletal Malformation In Mice, Hiroyuki Yamaguchi, Megumi Kitami, Margaret Li, Sowmya Swaminathan, Radbod Darabi, Ken-Ichi Takemaru, Yoshihiro Komatsu

Faculty, Staff and Student Publications

The primary cilium is a cellular antenna to orchestrate cell growth and differentiation. Deficient or dysfunctional cilia are frequently linked to skeletal abnormalities. Previous research demonstrated that ciliary proteins regulating axoneme elongation are essential for skeletogenesis. However, the role of the ciliary proteins responsible for initiating cilium assembly in skeletal development remains unknown. Here, we investigate the function of centrosomal protein of 164 kDa (CEP164), a key ciliogenesis regulator that localizes at the distal appendages of the mother centriole, during skeletal development in mice. Interestingly, the mesodermal cell-specific Cep164 deletion resulted in severe bone defects and osteoblast-specific deletion of Cep164 …

A Bayesian Pharmacokinetics Integrated Phase I-Ii Design To Optimize Dose-Schedule Regimes, Mengyi Lu, Ying Yuan, Suyu Liu

Faculty, Staff and Student Publications

The schedule of administering a drug has profound impact on the toxicity and efficacy profiles of the drug through changing its pharmacokinetics (PK). PK is an innate and indispensable component of the dose-schedule optimization. Motivated by this, we propose a Bayesian PK integrated dose-schedule finding (PKIDS) design to identify the optimal dose-schedule regime by integrating PK, toxicity, and efficacy data. Based on the causal pathway that dose and schedule affect PK, which in turn affects efficacy and toxicity, we jointly model the three endpoints by first specifying a Bayesian hierarchical model for the marginal distribution of the longitudinal dose-concentration process. …

Neurofilament Light Chain In Serum Of Cancer Patients With Acute Neurological Complications, Amulya Gottiparthy, Keng Lam, Suprateek Kundu, Zixi Yang, Ivo Tremont-Lukats, Sudhakar Tummala

Faculty, Staff and Student Publications

Aim: Neurofilament light chain (NfL) is a nonspecific sensitive biomarker of axonal damage.

Methods: This case series identified cancer patients with neurological complications who had serum NfL measurements and paired these results to outcomes.

Results: NfL serum levels were available in 15 patients with hematological malignancies or solid tumors. The neurological complications studied were immune effector cell-associated neurotoxicity syndrome, immune checkpoint inhibitor-related encephalopathy, anoxic brain injury, Guillain-Barre syndrome, hemophagocytic lymphohistiocytosis, transverse myelitis, paraneoplastic syndrome, central nervous system demyelinating disorder and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. All patients but one with serum NfL >900 pg/ml died …

Predicting Kidney Graft Function And Failure Among Kidney Transplant Recipients, Yi Yao, Brad C Astor, Wei Yang, Tom Greene, Liang Li

Faculty, Staff and Student Publications

Background: Graft loss is a major health concern for kidney transplant (KTx) recipients. It is of clinical interest to develop a prognostic model for both graft function, quantified by estimated glomerular filtration rate (eGFR), and the risk of graft failure. Additionally, the model should be dynamic in the sense that it adapts to accumulating longitudinal information, including time-varying at-risk population, predictor-outcome association, and clinical history. Finally, the model should also properly account for the competing risk by death with a functioning graft. A model with the features above is not yet available in the literature and is the focus of …

Implications Of Myocardial Strain In Primary Mitral Regurgitation-A Cardiovascular Magnetic Resonance Study, Simone Romano, Danai Kitkungvan, Duc T Nguyen, Carlos El-Tallawi, Edward A Graviss, Afshin Farzaneh-Far, Dipan J Shah

Faculty, Staff and Student Publications

Aims: Chronic primary mitral regurgitation (MR) results in progressive left ventricular (LV) remodelling. Abnormal myocardial deformation (strain) can be present despite preserved ejection fraction (EF). Cardiovascular magnetic resonance (CMR) feature-tracking techniques allow assessment of global longitudinal strain (GLS) from routine cine images. The aim of this study is to evaluate the prognostic value of CMR feature tracking-derived GLS in patients with primary MR.

Methods and results: Consecutive patients undergoing CMR for chronic MR from January 2012 to June 2018 were enrolled. Patients with LVEF < 50% were excluded. The composite primary outcome aiming to detect decompensation related to MR comprised (i) referral for mitral surgery owing to symptoms or LV systolic dysfunction or (ii) cardiovascular death. The secondary outcome was all-cause death. A total of 422 patients were followed for a median of 2.7 years, and the primary endpoint was met in 93 patients (34 patients reported symptoms at baseline). At multivariable analysis, GLS≥ -16.6% was associated with primary outcome [hazard ratio (HR) 1.90, P = 0.01]. In moderate MR cohort, patients with GLS≥ -16.6% had worse event-free survival, whereas there was no significant difference in mild or severe MR groups. GLS≥ -16.0% remained associated with all-cause death after adjusting for other covariates including the MR severity (HR 2.24, P = 0.02).

Conclusion: In patients with primary MR with preserved systolic function, GLS was associated with our composite …

The Win Ratio Approach In Bayesian Monitoring For Two-Arm Phase Ii Clinical Trial Designs With Multiple Time-To-Event Endpoints, Xinran Huang, Jian Wang, Jing Ning

Faculty, Staff and Student Publications

To assess the preliminary therapeutic impact of a novel treatment, futility monitoring is commonly employed in Phase II clinical trials to facilitate informed decisions regarding the early termination of trials. Given the rapid evolution in cancer treatment development, particularly with new agents like immunotherapeutic agents, the focus has often shifted from objective response to time-to-event endpoints. In trials involving multiple time-to-event endpoints, existing monitoring designs typically select one as the primary endpoint or employ a composite endpoint as the time to the first occurrence of any event. However, relying on a single efficacy endpoint may not adequately evaluate an experimental …