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Full-Text Articles in Pathology

High Tumor Cd161 Expression Predicts A Survival Advantage And Marks A Th1-Skewed Microenvironment, Briana Amicarella Burns, Manasvi Chandra, Vanaja Konduri, William K Decker Jan 2025

High Tumor Cd161 Expression Predicts A Survival Advantage And Marks A Th1-Skewed Microenvironment, Briana Amicarella Burns, Manasvi Chandra, Vanaja Konduri, William K Decker

Faculty, Staff and Students Publications

CD8+CD161+ T-cells exhibit augmented memory and cytolytic properties, mediating enhanced immunity in murine tumor models and improved survival in human non-small cell lung cancer. This T-cell subset might serve as a biomarker of positive response to therapy or even be isolated to augment current immunotherapeutic approaches yet limited knowledge of CD161 expression in human cancers restricts practical application. Here we bioinformatically tested the hypothesis that CD161 expression may be associated with positive outcomes in human cancers and investigated mechanisms underlying any observed advantages. Using TCGA-PANCAN dataset, we analyzed expression of CD161 in over 10,000 human tumors, correlating expression levels with …


The Reprogramming Factor Klf4 In Normal And Malignant Blood Cells, H Daniel Lacorazza Jan 2025

The Reprogramming Factor Klf4 In Normal And Malignant Blood Cells, H Daniel Lacorazza

Faculty, Staff and Students Publications

The Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger transcription factor that regulates cellular processes in stem cells, epithelial cells, and immune blood cells by controlling gene expression through genetic, epigenetic, and chromatin remodeling. The landmark 2006 publication identified KLF4 as one of the factors involved in reprogramming differentiated cells into pluripotent stem cells, sparking increased interest in KLF4 research a decade after its discovery, particularly in the fields of stem cell research, epithelial cell biology, endothelial cell function, and tumorigenesis. Over the years, KLF4 has emerged as a key transcription factor in modulating innate and adaptive immunity, …


Thromboelastography Versus Thromboelastometry For Unfractionated Heparin Monitoring In Adult Patients On Extracorporeal Membrane Oxygenation, Ellen B Yin, Arthur W Bracey, Subhasis Chatterjee Jan 2025

Thromboelastography Versus Thromboelastometry For Unfractionated Heparin Monitoring In Adult Patients On Extracorporeal Membrane Oxygenation, Ellen B Yin, Arthur W Bracey, Subhasis Chatterjee

Faculty, Staff and Students Publications

Background: Monitoring the anticoagulant effect of unfractionated heparin (UFH) in extracorporeal membrane oxygenation (ECMO) patients is complex but critically important to balance the risks of treatment related bleeding and circuit thrombosis. While guidelines recommend using more than one method to monitor UFH activity, the use of thromboelastometry (ROTEM) to monitor UFH in ECMO patients has not been investigated in detail.

Methods: This is an observational, single-center retrospective study looking at adult ECMO patients on UFH that had ROTEM and thromboelastography (TEG) tests obtained concurrently. A total of 20 samples were obtained from nine patients during the study period, …


Diagnostic Delay In Type I Autoimmune Pancreatitis: Clinical, Imaging, Endoscopic And Histologic Predictors Of Timely Diagnosis, Andres Urias Rivera, Travis Josephs, Shilpa Jain, Wasseem Skef, Tara Keihanian, Salmaan Jawaid, Wasif Abidi, Kalpesh Patel, Mohamed O Othman, Fares Ayoub Jan 2025

Diagnostic Delay In Type I Autoimmune Pancreatitis: Clinical, Imaging, Endoscopic And Histologic Predictors Of Timely Diagnosis, Andres Urias Rivera, Travis Josephs, Shilpa Jain, Wasseem Skef, Tara Keihanian, Salmaan Jawaid, Wasif Abidi, Kalpesh Patel, Mohamed O Othman, Fares Ayoub

Faculty, Staff and Students Publications

Background: The diagnosis of autoimmune pancreatitis (AIP) can be challenging due to nonspecific symptoms, low sensitivity of serologic markers, and some overlap in presentation with pancreatic ductal adenocarcinoma (PDAC). We aimed to quantify delays in the diagnosis of AIP and identify factors associated with diagnostic delay.

Methods: This was a single-center retrospective study between 2013 and 2023 of adult patients diagnosed with type 1 AIP based on HISORt criteria. Patients were compared to a randomly selected group of controls with PDAC. Data on clinical presentation, lab results, imaging, procedures, and initial treatment regimen were collected. Timing to diagnosis and predictive …


The Role Of The Triglyceride-Glucose Index As A Biomarker Of Cardio-Metabolic Syndromes, Verena Gounden, Sridevi Devaraj, Ishwarlal Jialal Dec 2024

The Role Of The Triglyceride-Glucose Index As A Biomarker Of Cardio-Metabolic Syndromes, Verena Gounden, Sridevi Devaraj, Ishwarlal Jialal

Faculty, Staff and Students Publications

BACKGROUND: The Triglyceride-glucose (TyG) index represents a simple, cost-effective, and valid proxy for insulin resistance. This surrogate marker has also been proposed as a predictor of metabolic and cardiovascular disease (CVD). In this descriptive review, we aimed to assess the utility of the TyG index as a predictive biomarker of cardiometabolic diseases.

METHODS: A search was conducted in PubMed, and Web of Science to identify cross-sectional and more importantly prospective studies examining the use of the TyG index as a predictive biomarker. The following terms were utilized in addition to the TyG index: "insulin resistance", "metabolic syndrome", "diabetes"; "cardiovascular diseases". …


Quinoline-Based Compounds Can Inhibit Diverse Enzymes That Act On Dna, Jujun Zhou, Qin Chen, Ren Ren, Jie Yang, Bigang Liu, John R Horton, Caleb Chang, Chuxuan Li, Leora Maksoud, Yifei Yang, Dante Rotili, Abhinav K Jain, Xing Zhang, Robert M Blumenthal, Taiping Chen, Yang Gao, Sergio Valente, Antonello Mai, Xiaodong Cheng Dec 2024

Quinoline-Based Compounds Can Inhibit Diverse Enzymes That Act On Dna, Jujun Zhou, Qin Chen, Ren Ren, Jie Yang, Bigang Liu, John R Horton, Caleb Chang, Chuxuan Li, Leora Maksoud, Yifei Yang, Dante Rotili, Abhinav K Jain, Xing Zhang, Robert M Blumenthal, Taiping Chen, Yang Gao, Sergio Valente, Antonello Mai, Xiaodong Cheng

Faculty, Staff and Students Publications

DNA methylation, as exemplified by cytosine-C5 methylation in mammals and adenine-N6 methylation in bacteria, is a key epigenetic process. Developing non-nucleoside inhibitors to cause DNA hypomethylation is crucial for treating various conditions without the toxicities associated with existing cytidine-based hypomethylating agents. This study characterized fifteen quinoline-based analogs, particularly compounds with additions like a methylamine (9) or methylpiperazine (11), which demonstrate similar low micromolar inhibitory potency against human DNMT1 and Clostridioides difficile CamA. These compounds (9 and 11) intercalate into CamA-bound DNA via the minor groove, causing a conformational shift that moves the catalytic domain away from the DNA. This study …


Prenatal Identification Of Intracardiac Mass Expedites Surgical Management Of Capillary-Venous Malformation, Derek M Norton, Mounica Y Rao, Jianhong Zhang, M John Hicks, Anitha Parthiban, S Kristen Sexson Tejtel Dec 2024

Prenatal Identification Of Intracardiac Mass Expedites Surgical Management Of Capillary-Venous Malformation, Derek M Norton, Mounica Y Rao, Jianhong Zhang, M John Hicks, Anitha Parthiban, S Kristen Sexson Tejtel

Faculty, Staff and Students Publications

Fetal and neonatal cardiac tumors are rare and often benign. Clinical presentation is primarily related to mass effect, pericardial effusion or arrhythmia. Prenatal detection can assist with risk assessment and inform optimal delivery plan and postnatal management. We report a fetus with a right atrial mass discovered in the third trimester. After successful surgical resection, pathology confirmed the mass to be a capillary-venous malformation, which are rare and challenging to diagnose. The true incidence of these vascular malformations within cardiac spaces is difficult to discern given the historic classification of numerous different vascular malformations under the umbrella term hemangioma.


Ire1Α Silences Dsrna To Prevent Taxane-Induced Pyroptosis In Triple-Negative Breast Cancer, Longyong Xu, Fanglue Peng, Qin Luo, Yao Ding, Fei Yuan, Liting Zheng, Wei He, Sophie S Zhang, Xin Fu, Jin Liu, Ayse Sena Mutlu, Shuyue Wang, Ralf Bernd Nehring, Xingyu Li, Qianzi Tang, Catherine Li, Xiangdong Lv, Lacey E Dobrolecki, Weijie Zhang, Dong Han, Na Zhao, Eric Jaehnig, Jingyi Wang, Weiche Wu, Davis A Graham, Yumei Li, Rui Chen, Weiyi Peng, Yiwen Chen, Andre Catic, Zhibin Zhang, Bing Zhang, Anthony M Mustoe, Albert C Koong, George Miles, Michael T Lewis, Meng C Wang, Susan M Rosenberg, Bert W O'Malley, Thomas F Westbrook, Han Xu, Xiang H-F Zhang, C Kent Osborne, Jin Billy Li, Matthew J Ellis, Mothaffar F Rimawi, Jeffrey M Rosen, Xi Chen Dec 2024

Ire1Α Silences Dsrna To Prevent Taxane-Induced Pyroptosis In Triple-Negative Breast Cancer, Longyong Xu, Fanglue Peng, Qin Luo, Yao Ding, Fei Yuan, Liting Zheng, Wei He, Sophie S Zhang, Xin Fu, Jin Liu, Ayse Sena Mutlu, Shuyue Wang, Ralf Bernd Nehring, Xingyu Li, Qianzi Tang, Catherine Li, Xiangdong Lv, Lacey E Dobrolecki, Weijie Zhang, Dong Han, Na Zhao, Eric Jaehnig, Jingyi Wang, Weiche Wu, Davis A Graham, Yumei Li, Rui Chen, Weiyi Peng, Yiwen Chen, Andre Catic, Zhibin Zhang, Bing Zhang, Anthony M Mustoe, Albert C Koong, George Miles, Michael T Lewis, Meng C Wang, Susan M Rosenberg, Bert W O'Malley, Thomas F Westbrook, Han Xu, Xiang H-F Zhang, C Kent Osborne, Jin Billy Li, Matthew J Ellis, Mothaffar F Rimawi, Jeffrey M Rosen, Xi Chen

Faculty, Staff and Students Publications

Chemotherapy is often combined with immune checkpoint inhibitor (ICI) to enhance immunotherapy responses. Despite the approval of chemo-immunotherapy in multiple human cancers, many immunologically cold tumors remain unresponsive. The mechanisms determining the immunogenicity of chemotherapy are elusive. Here, we identify the ER stress sensor IRE1α as a critical checkpoint that restricts the immunostimulatory effects of taxane-chemotherapy and prevents the innate immune recognition of immunologically cold triple-negative breast cancer (TNBC). IRE1α RNase silences taxane-induced dsRNA through RIDD (Regulated IRE1-Dependent Decay) to prevent NLRP3 inflammasome–dependent pyroptosis. Inhibition of IRE1α in Trp53−/− TNBC allows taxane to induce extensive dsRNAs that are sensed …


Diabetter Together: Clinical Trial Protocol For A Strengths-Based Peer Mentor Intervention For Young Adults With Type 1 Diabetes Transitioning To Adult Care, Samantha A Carreon, Charles G Minard, Sarah K Lyons, Wendy Levy, Stephanie Camey, Kishan Desai, Brenda Duran, Randi Streisand, Barbara J Anderson, Siripoom V Mckay, Tricia S Tang, Sridevi Devaraj, Ryan Ramphul, Marisa E Hilliard Dec 2024

Diabetter Together: Clinical Trial Protocol For A Strengths-Based Peer Mentor Intervention For Young Adults With Type 1 Diabetes Transitioning To Adult Care, Samantha A Carreon, Charles G Minard, Sarah K Lyons, Wendy Levy, Stephanie Camey, Kishan Desai, Brenda Duran, Randi Streisand, Barbara J Anderson, Siripoom V Mckay, Tricia S Tang, Sridevi Devaraj, Ryan Ramphul, Marisa E Hilliard

Faculty, Staff and Students Publications

Background: Type 1 diabetes (T1D) management is challenging for young adults, who are expected to transfer from the pediatric to adult T1D healthcare system while also managing typical developmental demands (e.g., social, financial, work/school, residential). Many young adults have extended gaps in care before following up in adult care, increasing risk for poor health outcomes. There are few evidence-based programs to support young adults with T1D to promote a timelier transition during this period. This paper reports on the design of DiaBetter Together, a randomized controlled trial to evaluate a 12-month Peer Mentor-delivered intervention compared to usual care among young …


The Long Road Of Drug Development For Endometriosis – Pains, Gains, And Hopes, Zian Liao, Diana Monsivais, Martin M Matzuk Dec 2024

The Long Road Of Drug Development For Endometriosis – Pains, Gains, And Hopes, Zian Liao, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Endometriosis, defined by the growth of endometrial tissues outside of the uterine cavity, is a global health burden for ∼200 million women. Patients with endometriosis usually present with chronic pain and are often diagnosed with infertility. The pathogenesis of endometriosis is still an open question; however, tissue stemness and immunological and genetic factors have been extensively discussed in the establishment of endometriotic lesions. Current treatments for endometriosis can be categorized into pharmacological management of hormone levels and surgical removal of the lesions. Both approaches have limited efficacy, with recurrences often encountered; thus, there is no complete cure for the disease …


Current Therapeutic Opportunities For Estrogen Receptor Mutant Breast Cancer, Murugesan Palaniappan Nov 2024

Current Therapeutic Opportunities For Estrogen Receptor Mutant Breast Cancer, Murugesan Palaniappan

Faculty, Staff and Students Publications

Estrogen receptor α (ERα) drives two out of three breast cancers and therefore ERα is a major therapeutic target for ER-positive breast cancer patients. Drugs that inhibit ERα activity or block estrogen synthesis in the body are currently being used in the clinic to treat ER-positive breast cancer and have been quite successful in controlling breast cancer progression for the majority of patients. However, ER-positive breast cancer often becomes resistant to these endocrine therapies, leading to endocrine-resistant metastatic breast cancer, a very aggressive cancer that leads to death. Recent large-scale genomic studies have revealed a series of activating somatic mutations …


Alternatively Spliced Map4 Isoforms Have Key Roles In Maintaining Microtubule Organization And Skeletal Muscle Function, Lathan Lucas, Larissa Nitschke, Brandon Nguyen, James A Loehr, George G Rodney, Thomas A Cooper Nov 2024

Alternatively Spliced Map4 Isoforms Have Key Roles In Maintaining Microtubule Organization And Skeletal Muscle Function, Lathan Lucas, Larissa Nitschke, Brandon Nguyen, James A Loehr, George G Rodney, Thomas A Cooper

Faculty, Staff and Students Publications

Skeletal muscle cells (myofibers) are elongated non-mitotic, multinucleated syncytia that have adapted a microtubule lattice. Microtubule-associated proteins (MAPs) play roles in regulating microtubule architecture. The most abundant MAP in skeletal muscle is MAP4. MAP4 consists of a ubiquitous MAP4 isoform (uMAP4), expressed in most tissues, and a striated-muscle-specific alternatively spliced isoform (mMAP4) that includes a 3,180-nucleotide exon (exon 8). To determine the role of mMAP4 in skeletal muscle, we generated mice that lack mMAP4 and express only uMAP4 due to genomic deletion of exon 8. We demonstrate that loss of mMAP4 leads to disorganized microtubule architecture and intrinsic loss of …


Perivascular Epithelioid Cell-Family Tumors In Children, Adolescents, And Young Adults: Clinicopathologic Features In 70 Cases, Phoebe M Hammer, Angus Toland, Muhammad Shaheen, Archana Shenoy, Ashwini Esnakula, M John Hicks, Mikako Warran, Alyaa Al-Ibraheemi, Jessica L Davis, Serena Y Tan Nov 2024

Perivascular Epithelioid Cell-Family Tumors In Children, Adolescents, And Young Adults: Clinicopathologic Features In 70 Cases, Phoebe M Hammer, Angus Toland, Muhammad Shaheen, Archana Shenoy, Ashwini Esnakula, M John Hicks, Mikako Warran, Alyaa Al-Ibraheemi, Jessica L Davis, Serena Y Tan

Faculty, Staff and Students Publications

Context.—: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors of uncertain histogenesis expressing smooth muscle and melanocytic markers. The clinicopathologic spectrum in young patients is not well documented.

Objective.—: To describe a multi-institutional series of PEComas in children, adolescents, and young adults.

Design.—: PEComas, not otherwise specified (NOS); angiomyolipomas (AMLs); lymphangioleiomyomatosis; and clear cell sugar tumors were retrospectively identified from 6 institutions and the authors' files.

Results.—: Seventy PEComas in 64 patients (median age, 15 years) were identified. They were more common in females (45 of 64 patients), occurring predominantly in the kidney (53 of 70), followed by the …


Diffuse Glioneuronal Tumor With Oligodendroglioma-Like Features And Nuclear Clusters Relapse In A Seven-Year-Old Boy: An Unusual Case Exhibiting Near-Tetraploidy And Chromosome 14 Diploidy, Francis M Torres, Thomas Denapoli, Ping-Sun Chen, Carrie Mohila, Kevin E Fisher, Kenneth Aldape, Mark R Lee, Timothy C Griffin Nov 2024

Diffuse Glioneuronal Tumor With Oligodendroglioma-Like Features And Nuclear Clusters Relapse In A Seven-Year-Old Boy: An Unusual Case Exhibiting Near-Tetraploidy And Chromosome 14 Diploidy, Francis M Torres, Thomas Denapoli, Ping-Sun Chen, Carrie Mohila, Kevin E Fisher, Kenneth Aldape, Mark R Lee, Timothy C Griffin

Faculty, Staff and Students Publications

Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) is a rare brain tumor of the central nervous system (CNS). Although only a few cases of DGONC have been reported following the initial description of the tumor, they have a distinct DNA methylation pattern and share a recurrent chromosomal finding of monosomy 14. We encountered a seven-year-old boy who presented with seizures and was found to have a left frontal and suprasellar mass. The tumor was grossly totally resected; histopathologic evaluation showed a cellular glioneuronal tumor with brisk mitotic activity. A near-tetraploid chromosome complement was detected, with associated diploidy …


Opioid Use In Thoracic Surgery: A Retrospective Study On Postoperative Complications, Jerry Xiao, Duc T Nguyen, Zoe K Lichtenberg, Elsie Rizk, Leonora M Meisenbach, Ray Chihara, Edward A Graviss, Min P Kim Oct 2024

Opioid Use In Thoracic Surgery: A Retrospective Study On Postoperative Complications, Jerry Xiao, Duc T Nguyen, Zoe K Lichtenberg, Elsie Rizk, Leonora M Meisenbach, Ray Chihara, Edward A Graviss, Min P Kim

Faculty, Staff and Students Publications

Background: Opioids are important medications that are used to control postoperative pain. The enhanced recovery after surgery (ERAS) program has reduced opioid use after surgery. In a surgical practice with a robust ERAS program, we wanted to determine if there was a relationship between in-hospital opioid use and postoperative complications.

Methods: We performed a retrospective nested case-control study of patients who underwent thoracic surgical intervention at the Houston Methodist Hospital (HMH) between 11/2020 and 11/2021 from the thoracic surgery database with hospital morphine milligram equivalent (MME) information, comparing patients who did and did not experience postoperative complications. We determined the …


Novel Genes Of The Male Reproductive System: Potential Roles In Male Reproduction And As Non-Hormonal Male Contraceptive Targets, Thomas X Garcia, Martin M Matzuk Oct 2024

Novel Genes Of The Male Reproductive System: Potential Roles In Male Reproduction And As Non-Hormonal Male Contraceptive Targets, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

The development of novel non-hormonal male contraceptives represents a pivotal frontier in reproductive health, driven by the need for safe, effective, and reversible contraceptive methods. This comprehensive review explores the genetic underpinnings of male fertility, emphasizing the crucial roles of specific genes and structural variants (SVs) identified through advanced sequencing technologies such as long-read sequencing (LRS). LRS has revolutionized the detection of structural variants and complex genomic regions, offering unprecedented precision and resolution over traditional next-generation sequencing (NGS). Key genetic targets, including those implicated in spermatogenesis and sperm motility, are highlighted, showcasing their potential as non-hormonal contraceptive targets. The review …


Addressing Platelet Insecurity – A National Call To Action, Eric A Gehrie, Pampee P Young, Sridhar V Basavaraju, Arthur W Bracey, Andrew P Cap, Liz Culler, Nancy M Dunbar, Mary Homer, Iris Isufi, Rob Macedo, Tanya Petraszko, Glenn Ramsey, Christopher A Tormey, Richard M Kaufman, Edward L Snyder Oct 2024

Addressing Platelet Insecurity – A National Call To Action, Eric A Gehrie, Pampee P Young, Sridhar V Basavaraju, Arthur W Bracey, Andrew P Cap, Liz Culler, Nancy M Dunbar, Mary Homer, Iris Isufi, Rob Macedo, Tanya Petraszko, Glenn Ramsey, Christopher A Tormey, Richard M Kaufman, Edward L Snyder

Faculty, Staff and Students Publications

No abstract provided.


Synthesis And Optimization Of Small Molecule Inhibitors Of Prostate Specific Antigen, Jeffery A Erickson, Ravikumar Jimmidi, Prashanth Anamthathmakula, Xuan Qin, Jian Wang, Leyi Gong, Jaehyeon Park, Gary Koolpe, Caitlin Tan, Martin M Matzuk, Feng Li, Srinivas Chamakuri, Wipawee Winuthayanon Sep 2024

Synthesis And Optimization Of Small Molecule Inhibitors Of Prostate Specific Antigen, Jeffery A Erickson, Ravikumar Jimmidi, Prashanth Anamthathmakula, Xuan Qin, Jian Wang, Leyi Gong, Jaehyeon Park, Gary Koolpe, Caitlin Tan, Martin M Matzuk, Feng Li, Srinivas Chamakuri, Wipawee Winuthayanon

Faculty, Staff and Students Publications

Semen liquefaction is a postejaculation process that transforms semen from a gel-like (coagulated) form to a water-like consistency (liquefied). This process is primarily regulated by serine proteases from the prostate gland, most prominently, prostate-specific antigen (PSA; KLK3). Inhibiting PSA activity has the potential to impede liquefaction of human semen, presenting a promising target for nonhormonal contraception in the female reproductive tract. This study employed triazole B1 as a starting compound. Through systematic design, synthesis, and optimization, we identified compound 20 (CDD-3290) as a 216 nM inhibitor of PSA with better stability in media than triazole B1. Further, we also evaluated …


Sensory Dysfunction, Microbial Infections, And Host Responses In Alzheimer's Disease, Praveen Bathini, Emanuele Brai, Brian J Balin, Lynn Bimler, David B Corry, Davangere P Devanand, Richard L Doty, Garth D Ehrlich, William A Eimer, Tamas Fulop, David L Hahn, Christine J Hammond, Joseph Infanti, Ruth Itzhaki, Richard Lathe, Christopher Scott Little, Rima Mcleod, Shima T Moein, Amy R Nelson, George Perry, Or A Shemesh, Rudolph E Tanzi, Wilmore C Webley, Nikki M Schultek, Lavinia Alberi Auber Sep 2024

Sensory Dysfunction, Microbial Infections, And Host Responses In Alzheimer's Disease, Praveen Bathini, Emanuele Brai, Brian J Balin, Lynn Bimler, David B Corry, Davangere P Devanand, Richard L Doty, Garth D Ehrlich, William A Eimer, Tamas Fulop, David L Hahn, Christine J Hammond, Joseph Infanti, Ruth Itzhaki, Richard Lathe, Christopher Scott Little, Rima Mcleod, Shima T Moein, Amy R Nelson, George Perry, Or A Shemesh, Rudolph E Tanzi, Wilmore C Webley, Nikki M Schultek, Lavinia Alberi Auber

Faculty, Staff and Students Publications

Sensory functions of organs of the head and neck allow humans to interact with the environment and establish social bonds. With aging, smell, taste, vision, and hearing decline. Evidence suggests that accelerated impairment in sensory abilities can reflect a shift from healthy to pathological aging, including the development of Alzheimer's disease (AD) and other neurological disorders. While the drivers of early sensory alteration in AD are not elucidated, insults such as trauma and infections can affect sensory function. Herein, we review the involvement of the major head and neck sensory systems in AD, with emphasis on microbes exploiting sensory pathways …


Cyp3a-Mediated Carbon-Carbon Bond Cleavages In Drug Metabolism, Junhui Zhou, Xuan Qin, Shenzhi Zhou, Kevin R Mackenzie, Feng Li Sep 2024

Cyp3a-Mediated Carbon-Carbon Bond Cleavages In Drug Metabolism, Junhui Zhou, Xuan Qin, Shenzhi Zhou, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Cytochrome P450 enzymes (P450s) play a critical role in drug metabolism, with the CYP3A subfamily being responsible for the biotransformation of over 50% of marked drugs. While CYP3A enzymes are known for their extensive catalytic versatility, one intriguing and less understood function is the ability to mediate carbon-carbon (C-C) bond cleavage. These uncommon reactions can lead to unusual metabolites and potentially influence drug safety and efficacy. This review focuses on examining examples of C-C bond cleavage catalyzed by CYP3A, exploring the mechanisms, physiological significance, and implications for drug metabolism. Additionally, examples of CYP3A-mediated ring expansion via C-C bond cleavages are …


Initiation Of Metformin In Early Pregnancy Results In Fetal Bioaccumulation, Growth Restriction, And Renal Dysmorphology In A Primate Model, Erin Bolte, Tyler Dean, Brandon Garcia, Maxim D Seferovic, Kristin Sauter, Gwendolynn Hummel, Matthew Bucher, Feng Li, John Hicks, Xuan Qin, Melissa A Suter, Enrico R Barrozo, Michael Jochum, Cynthia Shope, Jacob E Friedman, Maureen Gannon, Stephanie R Wesolowski, Carrie E Mccurdy, Paul Kievit, Kjersti M Aagaard Sep 2024

Initiation Of Metformin In Early Pregnancy Results In Fetal Bioaccumulation, Growth Restriction, And Renal Dysmorphology In A Primate Model, Erin Bolte, Tyler Dean, Brandon Garcia, Maxim D Seferovic, Kristin Sauter, Gwendolynn Hummel, Matthew Bucher, Feng Li, John Hicks, Xuan Qin, Melissa A Suter, Enrico R Barrozo, Michael Jochum, Cynthia Shope, Jacob E Friedman, Maureen Gannon, Stephanie R Wesolowski, Carrie E Mccurdy, Paul Kievit, Kjersti M Aagaard

Faculty, Staff and Students Publications

Background: In recent years, pragmatic metformin use in pregnancy has stretched to include prediabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and (most recently) preeclampsia. However, with its expanded use, concerns of unintended harm have been raised.

Objective: This study developed an experimental primate model and applied ultrahigh performance liquid chromatography coupled to triple-quadrupole mass spectrometry for direct quantitation of maternal and fetal tissue metformin levels with detailed fetal biometry and histopathology.

Study design: Within 30 days of confirmed conception (defined as early pregnancy), 13 time-bred (timed-mated breeding) Rhesus dams with pregnancies designated for fetal necropsy were initiated on …


Determining Predictors Of Actual Living Kidney Donation Based On Potential Donor Characteristics, Andrea M Meinders, Edward A Graviss, Duc T Nguyen, Jonathan Daw, Krista L Lentine, John Devin Peipert, Ahmed Osama Gaber, David A Axelrod, Francis L Weng, Amy D Waterman Sep 2024

Determining Predictors Of Actual Living Kidney Donation Based On Potential Donor Characteristics, Andrea M Meinders, Edward A Graviss, Duc T Nguyen, Jonathan Daw, Krista L Lentine, John Devin Peipert, Ahmed Osama Gaber, David A Axelrod, Francis L Weng, Amy D Waterman

Faculty, Staff and Students Publications

Background: Living donor kidney transplantation is the optimal treatment for end-stage kidney disease; however, few living donor candidates (LDCs) who begin evaluation actually donate. While some LDCs are deemed medically ineligible, others discontinue for potentially modifiable reasons.

Methods: At five transplant centers, we conducted a prospective cohort study measuring LDCs' clinical and psychosocial characteristics, educational preparation, readiness to donate, and social determinants of health. We followed LDCs for 12 months after evaluation to determine whether they donated a kidney, opted to discontinue, had modifiable reasons for discontinuing, were medically ineligible, or had other recipient-related reasons for discontinuing.

Results: Among 2184 …


A Machine Learning Model For Risk Stratification Of Postdiagnosis Diabetic Ketoacidosis Hospitalization In Pediatric Type 1 Diabetes: Retrospective Study, Devika Subramanian, Rona Sonabend, Ila Singh Aug 2024

A Machine Learning Model For Risk Stratification Of Postdiagnosis Diabetic Ketoacidosis Hospitalization In Pediatric Type 1 Diabetes: Retrospective Study, Devika Subramanian, Rona Sonabend, Ila Singh

Faculty, Staff and Students Publications

BACKGROUND: Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in pediatric type 1 diabetes (T1D), occurring in approximately 20% of patients, with an economic cost of $5.1 billion/year in the United States. Despite multiple risk factors for postdiagnosis DKA, there is still a need for explainable, clinic-ready models that accurately predict DKA hospitalization in established patients with pediatric T1D.

OBJECTIVE: We aimed to develop an interpretable machine learning model to predict the risk of postdiagnosis DKA hospitalization in children with T1D using routinely collected time-series of electronic health record (EHR) data.

METHODS: We conducted a retrospective case-control …


Promoting Resilience In Stress Management For Adolescents With Type 1 Diabetes: A Randomized Clinical Trial, Joyce P Yi-Frazier, Marisa E Hilliard, Maeve B O'Donnell, Chuan Zhou, Britney M Ellisor, Samantha Garcia Perez, Brenda Duran, Yuliana Rojas, Faisal S Malik, Daniel J Desalvo, Catherine Pihoker, Miranda C Bradford, Samantha Scott, Sridevi Devaraj, Abby R Rosenberg Aug 2024

Promoting Resilience In Stress Management For Adolescents With Type 1 Diabetes: A Randomized Clinical Trial, Joyce P Yi-Frazier, Marisa E Hilliard, Maeve B O'Donnell, Chuan Zhou, Britney M Ellisor, Samantha Garcia Perez, Brenda Duran, Yuliana Rojas, Faisal S Malik, Daniel J Desalvo, Catherine Pihoker, Miranda C Bradford, Samantha Scott, Sridevi Devaraj, Abby R Rosenberg

Faculty, Staff and Students Publications

IMPORTANCE: Type 1 diabetes (T1D) requires demanding self-management health behaviors, and adolescents with T1D are at risk for poor psychosocial and medical outcomes. Developing resilience skills may help adolescents with T1D and elevated distress navigate common stressors and achieve positive outcomes.

OBJECTIVE: To test the efficacy of the Promoting Resilience in Stress Management (PRISM) intervention on levels of hemoglobin A1c (HbA1c), diabetes distress, self-management behaviors, resilience, and quality of life among adolescents.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, parallel, 1:1 randomized clinical trial that followed up 172 participants for 12 months was conducted from January 1, 2020, to November …


Crohn's Disease-Associated Granulomatous Pancreatitis With Exocrine Pancreatic Insufficiency, Anthony A Xu, Sara Vincent, Samuel Ma, Vanessa Catania, Neda Zarrin-Khameh Aug 2024

Crohn's Disease-Associated Granulomatous Pancreatitis With Exocrine Pancreatic Insufficiency, Anthony A Xu, Sara Vincent, Samuel Ma, Vanessa Catania, Neda Zarrin-Khameh

Faculty, Staff and Students Publications

Extraintestinal manifestations of inflammatory bowel disease occur commonly and can lead to considerable morbidity. Pancreatic manifestations of inflammatory bowel disease have been reported to be more common in Crohn's disease (CD) than ulcerative colitis. We report a case of granulomatous inflammation in the body of the pancreas with exocrine pancreatic insufficiency, which prompted a diagnosis switch from ulcerative colitis to CD. This is of interest to readers to remind them that pancreatic manifestations can occur and are more common in CD.


Challenges Of Insulin-Like Growth Factor-1 Testing, Rongrong Huang, Junyan Shi, Ruhan Wei, Jieli Li Aug 2024

Challenges Of Insulin-Like Growth Factor-1 Testing, Rongrong Huang, Junyan Shi, Ruhan Wei, Jieli Li

Faculty, Staff and Students Publications

Insulin-like growth factor 1 (IGF-1), primarily synthesized in the liver, was initially discovered due to its capacity to replicate the metabolic effects of insulin. Subsequently, it emerged as a key regulator of the actions of growth hormone (GH), managing critical processes like cell proliferation, differentiation, and apoptosis. Notably, IGF-1 displays a longer half-life compared to GH, making it less susceptible to factors that may affect GH concentrations. Consequently, the measurement of IGF-1 proves to be more specific and sensitive when diagnosing conditions such as acromegaly or GH deficiency. The recognition of the existence of IGFBPs and their potential to interfere …


Clinical Features And Outcomes Of Pediatric And Adult Patients Hospitalized For Coronavirus Disease 2019: A Comparison Across Age Strata, Grace X Li, Komal Gopchandani, Noah Brazer, Ashley Tippett, Chris Choi, Hui-Mien Hsiao, Miriam Oseguera, Abiodun Foresythe, Sanchita Bhattacharya, Venice Servellita, Alicia Sotomayor Gonzalez, Jennifer K Spinler, Mark D Gonzalez, Dalia Gulick, Colleen Kraft, Vyjayanti Kasinathan, Yun F Wayne Wang, Jennifer Dien Bard, Pei Ying Chen, Jessica Flores-Vazquez, Audrey R Odom John, Paul J Planet, Sridevi Devaraj, Ananth V Annapragada, Ruth Ann Luna, Charles Y Chiu, Christina A Rostad Aug 2024

Clinical Features And Outcomes Of Pediatric And Adult Patients Hospitalized For Coronavirus Disease 2019: A Comparison Across Age Strata, Grace X Li, Komal Gopchandani, Noah Brazer, Ashley Tippett, Chris Choi, Hui-Mien Hsiao, Miriam Oseguera, Abiodun Foresythe, Sanchita Bhattacharya, Venice Servellita, Alicia Sotomayor Gonzalez, Jennifer K Spinler, Mark D Gonzalez, Dalia Gulick, Colleen Kraft, Vyjayanti Kasinathan, Yun F Wayne Wang, Jennifer Dien Bard, Pei Ying Chen, Jessica Flores-Vazquez, Audrey R Odom John, Paul J Planet, Sridevi Devaraj, Ananth V Annapragada, Ruth Ann Luna, Charles Y Chiu, Christina A Rostad

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to cause hospitalizations and severe disease in children and adults.

METHODS: This study compared the risk factors, symptoms, and outcomes of children and adults hospitalized for COVID-19 from March 2020 to May 2023 across age strata at 5 US sites participating in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence consortium. Eligible patients had an upper respiratory swab that tested positive for severe acute respiratory syndrome coronavirus 2 by nucleic acid amplification. Adjusted odds ratios (aOR) of clinical outcomes were determined for children versus adults, for pediatric age …


If At First We Don't Succeed, Should We Try, Try Again?, Kriti Puri, Susan W Denfield Jul 2024

If At First We Don't Succeed, Should We Try, Try Again?, Kriti Puri, Susan W Denfield

Faculty, Staff and Students Publications

No abstract provided.


Developing The Openflexure Microscope Towards Medical Use: Technical And Social Challenges Of Developing Globally Accessible Hardware For Healthcare, Joe Knapper, Freya Whiteford, Daniel Rosen, William Wadsworth, Julian Stirling, Catherine Mkindi, Joram Mduda, Valerian L Sanga, Paul T Nyakyi, Thomas Hervé Mboa Nkoudou, Elisée Jafsia, Stephane Fadanka, Kelsey Hummel, Sharmila Anandasabapathy, Richard Bowman Jul 2024

Developing The Openflexure Microscope Towards Medical Use: Technical And Social Challenges Of Developing Globally Accessible Hardware For Healthcare, Joe Knapper, Freya Whiteford, Daniel Rosen, William Wadsworth, Julian Stirling, Catherine Mkindi, Joram Mduda, Valerian L Sanga, Paul T Nyakyi, Thomas Hervé Mboa Nkoudou, Elisée Jafsia, Stephane Fadanka, Kelsey Hummel, Sharmila Anandasabapathy, Richard Bowman

Faculty, Staff and Students Publications

The OpenFlexure Microscope is an accessible, three-dimensional-printed robotic microscope, with sufficient image quality to resolve diagnostic features including parasites and cancerous cells. As access to lab-grade microscopes is a major challenge in global healthcare, the OpenFlexure Microscope has been developed to be manufactured, maintained and used in remote environments, supporting point-of-care diagnosis. The steps taken in transforming the hardware and software from an academic prototype towards an accepted medical device include addressing technical and social challenges, and are key for any innovation targeting improved effectiveness in low-resource healthcare. This article is part of the Theo Murphy meeting issue 'Open, reproducible …


Utility Of Cystatin C-Based Equation For The Estimation Of Glomerular Filtration Rate In A Pediatric Population, Ridwan B Ibrahim, Poyyapakkam Srivaths, Estella Tam, Sridevi Devaraj Jul 2024

Utility Of Cystatin C-Based Equation For The Estimation Of Glomerular Filtration Rate In A Pediatric Population, Ridwan B Ibrahim, Poyyapakkam Srivaths, Estella Tam, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: The accurate assessment of kidney function is vital for the early detection of kidney damage. The estimated glomerular filtration rate GFR (eGFR) from serum cystatin C (CysC) and creatinine-based equations are commonly used in clinical practice as an alternative to the invasive measured glomerular filtration rate (mGFR), which is the usually accepted overall best index of kidney function in health and disease. Recently the CKiD under 25 (CkiD U25) equations have been shown to perform well in children and young adults with chronic kidney disease (CKD). In this focused report, we evaluated the performance of the CkiD U25 equations …