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Articles 1 - 30 of 135
Full-Text Articles in Chemicals and Drugs
Spatially Distinct Cellular And Molecular Landscapes Define Prognosis In Triple-Negative Breast Cancer, Kavitha Mukund, Darya Veraksa, David Frankhouser, Lixin Yang, Jerneja Tomsic, Raju Pillai, Srijan Atti, Zahra Mesrizadeh, Daniel Schmolze, Jovanny Zabaleta, Xiao-Cheng Wu, Mary-Anne Leblanc, Lucio Miele, Augusto Ochoa, Victoria Seewaldt, Shankar Subramaniam
Spatially Distinct Cellular And Molecular Landscapes Define Prognosis In Triple-Negative Breast Cancer, Kavitha Mukund, Darya Veraksa, David Frankhouser, Lixin Yang, Jerneja Tomsic, Raju Pillai, Srijan Atti, Zahra Mesrizadeh, Daniel Schmolze, Jovanny Zabaleta, Xiao-Cheng Wu, Mary-Anne Leblanc, Lucio Miele, Augusto Ochoa, Victoria Seewaldt, Shankar Subramaniam
School of Medicine Faculty Publications
Triple-negative breast cancer (TNBC) is a prevalent breast cancer subtype with the lowest 5-year survival. Several factors influence outcomes, but their inherent molecular and cellular heterogeneity are increasingly acknowledged as crucial determinants. Here, we report on the spatio-molecular heterogeneity underlying TNBC tumors in a retrospective, treatment-naive cohort with differential prognoses (17 good prognoses [GPx] >15-year survival and 15 poor prognoses [PPx] < 3-year survival]) profiled using GeoMx Digital Spatial Profiler. Analyses reveal that epithelial and microenvironment (TME) states are transcriptionally distinct between groups. Invasive GPx epithelia show an increase in immune transcripts, with a more immune-rich TME (via IF). PPx epithelia, in contrast, are more metabolically and translationally active, with a mesenchymal/fibrotic TME. Pre-cancerous epithelia in PPx exhibit a presence of aggressiveness, marked by increased EMT signaling and complement activity. We identify distinct epithelial gene signatures for PPx and GPx that can accurately classify diagnostic samples and likely inform therapy.
Zoliflodacin Versus Ceftriaxone Plus Azithromycin For Treatment Of Uncomplicated Urogenital Gonorrhoea: An International, Randomised, Controlled, Open-Label, Phase 3, Non-Inferiority Clinical Trial, Alison Luckey, Manica Balasegaram, Lindley A. Barbee, Teresa A. Batteiger, Helen Broadhurst, Stephanie E. Cohen, Sinead Delany-Moretlwe, Henry J.C. De Vries, Jodie A. Dionne, Katherine Gill, Chris Kenyon, Rossaphorn Kittiyaowamarn, Drew Lewis, John P. Mueller, Vimla Naicker, Seamus O'Brien, John P. O'Donnell, Nittaya Phanuphak, Elizabeth Spooner, Subasree Srinivasan, Stephanie N. Taylor, Magnus Unemo, Zinhle Zwane, Edward W. Hook, Zoliflodacin Phase 3 Study Group
Zoliflodacin Versus Ceftriaxone Plus Azithromycin For Treatment Of Uncomplicated Urogenital Gonorrhoea: An International, Randomised, Controlled, Open-Label, Phase 3, Non-Inferiority Clinical Trial, Alison Luckey, Manica Balasegaram, Lindley A. Barbee, Teresa A. Batteiger, Helen Broadhurst, Stephanie E. Cohen, Sinead Delany-Moretlwe, Henry J.C. De Vries, Jodie A. Dionne, Katherine Gill, Chris Kenyon, Rossaphorn Kittiyaowamarn, Drew Lewis, John P. Mueller, Vimla Naicker, Seamus O'Brien, John P. O'Donnell, Nittaya Phanuphak, Elizabeth Spooner, Subasree Srinivasan, Stephanie N. Taylor, Magnus Unemo, Zinhle Zwane, Edward W. Hook, Zoliflodacin Phase 3 Study Group
School of Medicine Faculty Publications
Background Development of new treatments for gonorrhoea is a global public health priority. We aimed to evaluate the efficacy and safety of zoliflodacin versus ceftriaxone plus azithromycin in patients with uncomplicated urogenital gonorrhoea. Methods In this phase 3, multinational, randomised, controlled, open-label, non-inferiority clinical trial, participants aged 12 years and older with clinical suspicion of uncomplicated urogenital gonorrhoea were eligible for inclusion. The trial was done in 17 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA. Participating countries with high disease prevalence were identified for participation in the study. Sites selected for participation were led by …
The Vascular Density/Angiogenesis Marker Cd31/Pecam1 Does Not Correlate With Overall Survival In Neuroendocrine Tumors, Nicholas J. Skill, Kenneth Avanzino, Yvette Bren-Mattison, J. Philip Boudreaux, Ramcharan Thiagarajan, Mary Maluccio
The Vascular Density/Angiogenesis Marker Cd31/Pecam1 Does Not Correlate With Overall Survival In Neuroendocrine Tumors, Nicholas J. Skill, Kenneth Avanzino, Yvette Bren-Mattison, J. Philip Boudreaux, Ramcharan Thiagarajan, Mary Maluccio
School of Medicine Faculty Publications
Abstract: Neuroendocrine neoplasms (NENs) are rare cancers. CD31/PECAM1 is an adhesion molecule that modulates endothelial cell-to-cell contact. Increased CD31 expression is a marker for tumor growth, and cancer aggressiveness. The purpose of this study was to better understand the prognostic value of CD31 expression in primary and metastatic NEN tumors in terms of correlations with overall survival and pathological metrics, tumor grade, and tumor primary/metastatic location. As NENs are highly vascular tumors, the hypothesis is that CD31 staining is an important prognostic biomarker and target. This is based on prior correlations between CD31 staining and 3-year recurrence-free survival in pancreas …
Identification Of Predictive Pretreatment Biomarkers For Neoadjuvant Chemotherapy Response In Latino Invasive Breast Cancer Patients, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos A. Orozco, Sandra Diaz-Casas, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba L. Combita
Identification Of Predictive Pretreatment Biomarkers For Neoadjuvant Chemotherapy Response In Latino Invasive Breast Cancer Patients, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos A. Orozco, Sandra Diaz-Casas, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba L. Combita
School of Medicine Faculty Publications
Background: Breast cancer (BC) exhibits significant heterogeneity in incidence and mortality worldwide. Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced BC; however, its efficacy varies by subtype. This study examined the gene expression profiles associated with NAC response in Colombian women with invasive BC. Methods: RNA sequencing of pre-treatment tissues from 58 patients (29 responders and 29 non-responders) identified differentially expressed genes (DEGs) for each molecular subtype, and prognostic performance was evaluated using risk scores. Results: Functional enrichment analysis highlighted the immune system pathways in non-responders. Changes in cytokine target activity and immune cell populations were analyzed to …
Overview Of Huntington's Disease And Emerging Treatment Strategies: A Narrative Review, Alexis J. Vega, Gabriel V. Hernandez, Pearse A. O'Malley, Connor J. Robin, Amanda N. Parra, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye
Overview Of Huntington's Disease And Emerging Treatment Strategies: A Narrative Review, Alexis J. Vega, Gabriel V. Hernandez, Pearse A. O'Malley, Connor J. Robin, Amanda N. Parra, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye
School of Medicine Faculty Publications
Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by a cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin (HTT) gene. The symptoms of HD include severe motor dysfunction, cognitive issues, and emotional dysregulation. These combined issues are not only debilitating but also lead to depression/anxiety, increased suicide rates, and caregiver burnout. Our narrative review summarizes several recent studies examining the efficacy and differences among emerging treatment strategies for HD. A systematic search of peer-reviewed literature was conducted, focusing on recent studies that describe molecular genetic manipulation of the HTT gene/huntingtin protein. The results of our narrative review reveal …
Nirsevimab Effectiveness Against Intensive Care Unit Admission For Respiratory Syncytial Virus In Infants - 24 States, December 2024-April 2025, Laura D. Zambrano, Regina M. Simeone, Margaret M. Newhams, Amanda B. Payne, Natasha B. Halasa, Amber O. Orzel-Lockwood, Jemima M. Calixte, Satoshi Kamidani, Hillary Crandall, Melissa A. Cameron, Jennifer E. Schuster, Aline B. Maddux, Kathleen Chiotos, Katherine Irby, Steven L. Shein, Mary Allen Staat, Lora M. Martin, Samina S. Bhumbra, Ryan A. Nofziger, Jigar C. Chauhan, Danielle M. Zerr, Shira J. Gertz, Judith A. Guzman-Cottrill, Michele Kong, Janet R. Hume, Bria M. Coates, Kelly N. Michelson, Tamara T. Bradford, Et Al
Nirsevimab Effectiveness Against Intensive Care Unit Admission For Respiratory Syncytial Virus In Infants - 24 States, December 2024-April 2025, Laura D. Zambrano, Regina M. Simeone, Margaret M. Newhams, Amanda B. Payne, Natasha B. Halasa, Amber O. Orzel-Lockwood, Jemima M. Calixte, Satoshi Kamidani, Hillary Crandall, Melissa A. Cameron, Jennifer E. Schuster, Aline B. Maddux, Kathleen Chiotos, Katherine Irby, Steven L. Shein, Mary Allen Staat, Lora M. Martin, Samina S. Bhumbra, Ryan A. Nofziger, Jigar C. Chauhan, Danielle M. Zerr, Shira J. Gertz, Judith A. Guzman-Cottrill, Michele Kong, Janet R. Hume, Bria M. Coates, Kelly N. Michelson, Tamara T. Bradford, Et Al
School of Medicine Faculty Publications
Respiratory syncytial virus (RSV) is a leading cause of intensive care unit (ICU) admission and respiratory failure among infants (children aged < year) in the United States. In August 2023, CDC’s Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect against RSV-associated lower respiratory tract infection among all infants aged < 8 months born during or entering their first RSV season. Following licensure, nirsevimab effectiveness has been demonstrated against RSV-associated infant hospitalization, but evidence regarding effectiveness against RSV-associated critical illness is limited. In a 27-hospital case-control investigation, nirsevimab effectiveness against both RSV-associated infant ICU admission and acute respiratory failure (illness requiring continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation) after hospital admission was evaluated during December 1, 2024-April 15, 2025. Among 457 case-patients who received a positive RSV test result and 302 control patients who received a negative RSV test result admitted to an ICU with respiratory symptoms, 14% and 45%, respectively, had received nirsevimab ≥ 7 days before symptom onset. Nirsevimab was 80% effective (95% CI = 70%-86%) against RSV-associated ICU admission and 83% effective (95% CI = 74%-90%) against acute respiratory failure when received a median of 52 days (IQR = 32-89 days) and 50 days (IQR = 32-86 days) before onset for each respective endpoint. These estimates support the recommendation for use of nirsevimab as a prevention strategy to protect infants against severe outcomes from RSV infection.
Colorectal Cancer: Differential Gene Expression And In Vitro Response To 5-Fluorouracil, Novel Fluoropyrimidine F10, And Potential Synergy With Lupeol, Shrey D. Thaker, Jenny Paredes, Jone Garai, Laura A. Martello, William H. Gmeiner, Jovanny Zabaleta, Jennie Williams
Colorectal Cancer: Differential Gene Expression And In Vitro Response To 5-Fluorouracil, Novel Fluoropyrimidine F10, And Potential Synergy With Lupeol, Shrey D. Thaker, Jenny Paredes, Jone Garai, Laura A. Martello, William H. Gmeiner, Jovanny Zabaleta, Jennie Williams
School of Medicine Faculty Publications
Colorectal cancer (CRC) remains one of the most lethal malignancies in the United States, with African American (AA) patients experiencing disproportionately higher incidence and mortality compared to Caucasian Americans (CAs). These disparities have been linked to tumor-intrinsic genomic differences, including microsatellite instability (MSI) and p53 mutation status, which may influence chemotherapeutic response, particularly to the standard-of-care agent 5-fluorouracil (5-FU). However, mechanistic insights have been limited by the lack of racially diverse preclinical models. Here, we evaluated the efficacy of F10 (a novel fluoropyrimidine polymer) vs. 5-FU using AA- and CA-derived CRC cell lines with distinct MSI and p53 profiles. MTT …
Intercellular Signaling And Synaptic Deconstruction Uncovered By Single-Cell And Spatial Transcriptomics In An Ad Tauopathy Model, Jeff X. Ji, Brian L. Giles, Surjyadipta Bhattacharjee, Marie-Audrey I. Kautzmann, Alasdair P. Masson, Sonia Do Carmo, A Claudio Cuello, Nicolas G. Bazan
Intercellular Signaling And Synaptic Deconstruction Uncovered By Single-Cell And Spatial Transcriptomics In An Ad Tauopathy Model, Jeff X. Ji, Brian L. Giles, Surjyadipta Bhattacharjee, Marie-Audrey I. Kautzmann, Alasdair P. Masson, Sonia Do Carmo, A Claudio Cuello, Nicolas G. Bazan
School of Medicine Faculty Publications
Alzheimer's disease (AD) is the leading cause of dementia in elderly individuals worldwide; however, all mechanisms leading to disease onset and progression are not well understood. Here, we report brain single-cell multiome and spatial transcriptomics in a transgenic rat model of human-like tauopathy. We have identified new markers of tau-driven AD pathology and provided single-cell evidence for genes implicated in AD. Our findings reveal how tau hyperphosphorylation and aging alter ligand-receptor communication, transcription factor regulatory networks, and specific cellular networks. Notably, we found intriguing changes in cell communication involving glutamatergic transmission and Netrin signaling as a taupathy consequence. Overall, this …
Roux-En-Y Gastric Bypass Is Associated With Increased Intestinal Glucose Uptake In Humans, Florina Corpodean, Maryam Naseri, Michael Kachmar, Julia St Amant, Denis P. Blondin, Owen T. Carmichael, Vance L. Albaugh
Roux-En-Y Gastric Bypass Is Associated With Increased Intestinal Glucose Uptake In Humans, Florina Corpodean, Maryam Naseri, Michael Kachmar, Julia St Amant, Denis P. Blondin, Owen T. Carmichael, Vance L. Albaugh
School of Medicine Faculty Publications
CONTEXT: In animal models, Roux-en-Y gastric bypass (RYGB) is associated with increased Roux limb intestinal glucose uptake that may contribute to early metabolic benefits, though prospective clinical studies are lacking. OBJECTIVE: The present study aimed to test the hypothesis that Roux limb glucose uptake would increase relative to baseline in a cohort of patients undergoing RYGB. METHODS: RYGB patients underwent preoperative baseline, and 3- and 6-month positron emission tomography/computed tomography postoperative imaging. Maximum and mean standardized uptake values (SUV) were measured from the following predefined regions of interest: cecum, hepatic flexure, splenic flexure, sigmoid colon, duodenal bulb, Roux limb, and …
Atypical Abdominal Pain: Uncovering Malignant Peritoneal Mesothelioma In Suspected Crohn's Disease: A Case Report, Catherine Loehr, Lara Boudreaux, Ann Porter Uhlhorn, Nisha Loganantharaj
Atypical Abdominal Pain: Uncovering Malignant Peritoneal Mesothelioma In Suspected Crohn's Disease: A Case Report, Catherine Loehr, Lara Boudreaux, Ann Porter Uhlhorn, Nisha Loganantharaj
School of Medicine Faculty Publications
BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare and aggressive cancer from the serosal membranes of the abdominal cavity. In the United States, MPM accounts for about 10-15% of all mesothelioma cases, and translates into approximately 600 new cases diagnosed annually. It is typically diagnosed in Caucasian individuals, and while asbestos exposure is a well-established risk factor for pleural mesothelioma, its association with peritoneal mesothelioma remains less clear. Clinical symptoms of MPM, such as abdominal pain, bloating, and weight loss, overlap with other gastrointestinal disorders, which often leads to delayed diagnosis. This case report presents a unique instance of MPM …
Fine Mapping Regulatory Variants By Characterizing Native Cpg Methylation With Nanopore Long-Read Sequencing, Yijun Tian, Shannon K. Mcdonnell, Lang Wu, Nicholas B. Larson, Liang Wang
Fine Mapping Regulatory Variants By Characterizing Native Cpg Methylation With Nanopore Long-Read Sequencing, Yijun Tian, Shannon K. Mcdonnell, Lang Wu, Nicholas B. Larson, Liang Wang
School of Medicine Faculty Publications
5-Methylcytosine (5mC) is the most common DNA modification in the human genome. Bisulfite conversion combined with short-read sequencing captures this modification at single-nucleotide resolution but introduces PCR duplication bias and limits co-methylation analysis between distant cytosines. To resolve these limitations, we used nanopore long-read sequencing to profile human methylation and performed long-range co-methylation analysis with native DNA modification information. We analyzed the nanopore demo data in the adaptive sampling sequencing targeting the CpG islands and applied the linkage disequilibrium (LD) R to identified methylation haplotype blocks (MHBs). We found that the cancer genome exhibited significantly smaller MHBs, higher CpG density, …
Bromelain-Based Enzymatic Debridement Of A Third-Degree Burn To Skin-Grafted Bowel, Shengqing Wang, Janie Faris, Kareem Abdelfattah, Samuel Mandell, M Victoria Miles
Bromelain-Based Enzymatic Debridement Of A Third-Degree Burn To Skin-Grafted Bowel, Shengqing Wang, Janie Faris, Kareem Abdelfattah, Samuel Mandell, M Victoria Miles
School of Medicine Faculty Publications
Burn injuries over previously grafted tissue present a formidable challenge for excision and debridement, particularly when there are critical underlying structures such as bowel. Enzymatic debridement with the recently approved anacaulase-bcdb, a bromelain-based enzymatic debridement gel (Nexobrid), presents an additional method of burn excision that may be useful in such a situation. This brief report presents the management of a complex third-degree burn over a remotely skin-grafted bowel mass using anacaulase-bcdb gel. This report is written with documented patient consent and approval by the Human Research Protection Program office in compliance with institutional policy. A 52-year-old man presented to our …
Isolated Transaminitis As A Sentinel Sign Of Duchenne Muscular Dystrophy In An Infant: A Case Report, Ayesha Khalid, Tuba Chaudhry, Ayesha Liaqat, Lauren Tufts
Isolated Transaminitis As A Sentinel Sign Of Duchenne Muscular Dystrophy In An Infant: A Case Report, Ayesha Khalid, Tuba Chaudhry, Ayesha Liaqat, Lauren Tufts
School of Medicine Faculty Publications
Duchenne muscular dystrophy (DMD) is an X-linked recessive muscular dystrophy (MD) that typically presents after ambulation due to progressive proximal muscle weakness. The average age of diagnosis is 4.83 years. However, there are some subtle signs that can help in early diagnosis and delay the progression of the disease. We present a non-classical DMD case in a six-month-old infant with failure to thrive, persistent emesis, transaminitis, and truncal weakness, leading to an early diagnosis of DMD. Initial workup for failure to thrive was unremarkable, other than persistently elevated liver enzymes aspartate aminotransferase (AST) and alanine transaminase (ALT) with normal alkaline …
Opposing Synovial Cannabinoid Receptor Type 2 And Transient Receptor Potential Vanilloid 1 Expression In Painful Osteoarthritis, Collin A. Toups, Lauren G. Guillot, Kaitlyn Redondo, Sydney Jensen, Jennifer Klein, Luis Marrero
Opposing Synovial Cannabinoid Receptor Type 2 And Transient Receptor Potential Vanilloid 1 Expression In Painful Osteoarthritis, Collin A. Toups, Lauren G. Guillot, Kaitlyn Redondo, Sydney Jensen, Jennifer Klein, Luis Marrero
School of Medicine Faculty Publications
Knee osteoarthritis (kOA) poses a major health challenge worldwide, but current non-surgical treatments have limited long-term success and do not address the underlying disease process. This study explores the complex relationship between the endocannabinoid system (ECS) and the endovanilloid system (EVS) in the synovial membrane of patients with kOA undergoing total knee replacement, focusing on how these systems relate to patient-reported pain and histological synovitis. Synovial tissues and fluid from patients grouped into high and low pain categories based on the Knee Injury and Osteoarthritis Outcome Score (KOOS) were examined for cannabinoid receptor type 2 (CB2R), transient receptor potential vanilloid …
Targeting Kinin B1r Attenuates Hypertension Through At1r-Dependent Mechanisms, Drew Theobald, Riley N. Bessetti, Yumei Feng Earley, Eric Lazartigues, Karen Litwa, Srinivas Sriramula
Targeting Kinin B1r Attenuates Hypertension Through At1r-Dependent Mechanisms, Drew Theobald, Riley N. Bessetti, Yumei Feng Earley, Eric Lazartigues, Karen Litwa, Srinivas Sriramula
School of Medicine Faculty Publications
BACKGROUND: Neurogenic hypertension is chronically high blood pressure that is initiated and maintained through excessive sympathetic nervous system activity and has been associated with increased B1R (kinin B1 receptor) activation. We previously reported a central role for B1R in mediating inflammatory pathways in the development of deoxycorticosterone acetate salt hypertension. Additionally, we identified a causal relationship between B1R expression after Ang II (angiotensin II) stimulation, and that B1R can mediate the bidirectional interaction between neuroinflammation and oxidative stress. However, whether there are any interactions between AT1R (Ang II-type I receptor) and B1R, and if B1R can mediate the effects of …
In-Hospital Exposure And Opioids Prescribed After Total Knee Arthroplasty, Clifton Daigle, Robert Branstetter, Leland Van Deventer, Ravi Rajendra, Claudia Leonardi, Amy Bronstone, Vinod Dasa
In-Hospital Exposure And Opioids Prescribed After Total Knee Arthroplasty, Clifton Daigle, Robert Branstetter, Leland Van Deventer, Ravi Rajendra, Claudia Leonardi, Amy Bronstone, Vinod Dasa
School of Medicine Faculty Publications
BACKGROUND: Opioids are frequently used intraoperatively and during postanesthesia care unit care in total knee arthroplasty (TKA) cases and are commonly prescribed after surgery despite known adverse effects. This study examined whether in-hospital opioid exposure is related to postoperative opioid prescribing in opioid-naïve TKA patients. METHODS: This retrospective study included opioid-naïve patients (no opioid prescriptions filled during the three months before TKA) who had unilateral primary TKA between May 1, 2020, and November 30, 2023, performed by an orthopaedic surgeon. All patients were treated using the same multimodal pain protocol. Opioid prescriptions filled by patients during the three months following …
Interleukin-22 And Interleukin-22 Binding Protein Signaling Axis Influences Intubation Status In Trauma, Augustus E. Anderson, Jacob Broome, Aaron L. Albuck, Megan Shenk, Valeria Noguera, Wid Covey, Alison Smith, Juan Duchesne, Danielle Tatum, Christine M. Bojanowski, Derek Pociask, Jay K. Kolls, Olan Jackson-Weaver, Sharven Taghavi
Interleukin-22 And Interleukin-22 Binding Protein Signaling Axis Influences Intubation Status In Trauma, Augustus E. Anderson, Jacob Broome, Aaron L. Albuck, Megan Shenk, Valeria Noguera, Wid Covey, Alison Smith, Juan Duchesne, Danielle Tatum, Christine M. Bojanowski, Derek Pociask, Jay K. Kolls, Olan Jackson-Weaver, Sharven Taghavi
School of Medicine Faculty Publications
Background: Interleukin-22 is a cytokine involved in mucosal immunity, whereas interleukin-22 binding protein is a soluble receptor that can potently block interleukin-22. The role of interleukin-22 and interleukin-22 binding protein in trauma remains unclear. This study investigates whether IL-22 levels are associated with intubation in patients with trauma. We hypothesized interleukin-22 levels would be lower in intubated patients. Methods: Plasma samples were prospectively obtained in the trauma bay at consecutive Level 1 activations from November 2021 to November 2022. Patients were categorized as having respiratory failure (intubated) or as controls (nonintubated). Two-to-one case-control matching was conducted based on age, sex, …
Temporal Trends Of A Cellular Host Response Test For Sepsis And A Comparison With Selected Biomarkers Of Inflammation And Infection, Matthew S. Berlinger, Matt Sorrells, Christopher B. Thomas, Tonya Jagneaux, James E. Walker, Jennifer Daigle, Heather Quiriarte, Youyoung Kim, Guillaume Spielmann, Debbie Robertson, Susan Park Ochsner, Gideon Avornu, Katherine Fenstermacher, Elijah James Kurien, Camille King, Adenine Cembellin-Kao, Chase Yonamine, Querino Maia, Maciej Obrebski, David N. Hager, Roya Sheybani, Henry T.K. Tse, Ajay M. Shah, Robert Scoggins, Hollis R. O’Neal, Richard Rothman
Temporal Trends Of A Cellular Host Response Test For Sepsis And A Comparison With Selected Biomarkers Of Inflammation And Infection, Matthew S. Berlinger, Matt Sorrells, Christopher B. Thomas, Tonya Jagneaux, James E. Walker, Jennifer Daigle, Heather Quiriarte, Youyoung Kim, Guillaume Spielmann, Debbie Robertson, Susan Park Ochsner, Gideon Avornu, Katherine Fenstermacher, Elijah James Kurien, Camille King, Adenine Cembellin-Kao, Chase Yonamine, Querino Maia, Maciej Obrebski, David N. Hager, Roya Sheybani, Henry T.K. Tse, Ajay M. Shah, Robert Scoggins, Hollis R. O’Neal, Richard Rothman
School of Medicine Faculty Publications
Sepsis, a condition characterized by immune dysregulation, is the leading cause of in-hospital mortality and requires rapid treatment. Assessing immune dysregulation has been challenging. The IntelliSep Index (ISI), a novel biomarker which leverages microfluidic deformability cytometry to assess immune activation, has been evaluated as a test for Emergency Department use but it is unclear how the signal evolves as patient condition evolves. In a 47-patient cohort with hospital stays ≤ 14 days, ISI provided a good indicator of disease progression by blinded physician review. ISI trends correlated with clinical improvement over time. During the first 12 h following presentation, ISI …
Dietary Protein’S Effect On The Gut Microbiome And Its Metabolites: Protocol Description And Virtual Recruitment Efforts For A Remote Randomized Controlled Trial, Karyn M. Gallivan, Kristin S. Ondrak, Denise M. Danos, Meng Luo, Christopher M. Taylor, Lauren E. Meyer, Ann M. Byerley, Alexander W. Nguyen, Sabyasachi Chatterjee, Jiri Adamec, Lauri O. Byerley
Dietary Protein’S Effect On The Gut Microbiome And Its Metabolites: Protocol Description And Virtual Recruitment Efforts For A Remote Randomized Controlled Trial, Karyn M. Gallivan, Kristin S. Ondrak, Denise M. Danos, Meng Luo, Christopher M. Taylor, Lauren E. Meyer, Ann M. Byerley, Alexander W. Nguyen, Sabyasachi Chatterjee, Jiri Adamec, Lauri O. Byerley
School of Medicine Faculty Publications
Fiber’s effect on our gut microbes has been studied extensively, while knowledge of the effect of protein is sparse. Colonic putrefaction of dietary protein is known to produce several potentially detrimental compounds. This randomized controlled trial (RCT) uses a pre- and post-study design to investigate the effect of consuming higher levels of dietary protein on the gut microbiota and the metabolites it produces. Here, we describe our virtual recruitment efforts and RCT protocol. Potential participants lived throughout the contiguous US. Several recruitment methods were employed, of which email reached the largest group of people (approximately 9,100) and generated a 0.3% …
Cholesterol Crystal Embolization Induced Kidney Disease, Shohan Pervaze, Shreya Mohandas, Pushkas Gopalan, Stephen A. Morse, Siddhartha Bajracharya, Landon A. Krone, Farshid Yazdi
Cholesterol Crystal Embolization Induced Kidney Disease, Shohan Pervaze, Shreya Mohandas, Pushkas Gopalan, Stephen A. Morse, Siddhartha Bajracharya, Landon A. Krone, Farshid Yazdi
School of Medicine Faculty Publications
Cholesterol crystal embolization (CCE) results from the release of cholesterol crystals from ruptured atherosclerotic plaques into circulation, resulting in the occlusion of small arteries and arterioles in various organs. Ischemia triggers a systemic inflammatory response resulting in vascular obstruction and organ dysfunction. Kidneys are often involved because of the proximity to the aorta and CCE in the kidneys can result in acute, sub-acute, or chronic kidney disease. There are many known risk factors for renal involvement of CCE, including iatrogenic and spontaneous causes. The pathophysiology of CCE includes complex pathways that lead to acute and chronic effects that can have …
Effectiveness And Safety Of Abobotulinumtoxina In Pediatric Lower Limb Spasticity: A Phase Iv, Prospective, Observational, Multicenter Study, Mark E. Gormley, Edward Dabrowski, Mauricio R. Delgado, Ann Tilton, Asare Christian, Sarah Helen Evans, Anne-Sophie Grandoulier, Jumaah Goldberg
Effectiveness And Safety Of Abobotulinumtoxina In Pediatric Lower Limb Spasticity: A Phase Iv, Prospective, Observational, Multicenter Study, Mark E. Gormley, Edward Dabrowski, Mauricio R. Delgado, Ann Tilton, Asare Christian, Sarah Helen Evans, Anne-Sophie Grandoulier, Jumaah Goldberg
School of Medicine Faculty Publications
Aim: To assess the longitudinal attainment of patient-centered, function-related Goal Attainment Scaling Total (GAS T)-score after repeated abobotulinumtoxinA (AboBoNT-A) injections over a period of up to 30 months and up to 10 cycles. Method: In this prospective observational study, the investigators' clinical practices recruited patients aged 2 to 17 years with pediatric lower limb spasticity (PLLS). GAS T-scores were assessed for each injection, and goals could be redefined at each visit; scores of 50 reflected goal achievement. Adverse events were recorded. Results: Of 210 patients in the effectiveness population, 171 had cerebral palsy and 163 were previously treated with a …
First-In-Human Phase I Open-Label Study Of The Anti-Tim-3 Monoclonal Antibody Incagn02390 In Patients With Select Advanced Or Metastatic Solid Tumors, Martin E. Gutierrez, Shou Ching Tang, John D. Powderly, Ani S. Balmanoukian, Paul E. Hoyle, Zhiwan Dong, Lulu Cheng, Xiaohua Gong, John E. Janik, Nawel Bourayou, Omid Hamid
First-In-Human Phase I Open-Label Study Of The Anti-Tim-3 Monoclonal Antibody Incagn02390 In Patients With Select Advanced Or Metastatic Solid Tumors, Martin E. Gutierrez, Shou Ching Tang, John D. Powderly, Ani S. Balmanoukian, Paul E. Hoyle, Zhiwan Dong, Lulu Cheng, Xiaohua Gong, John E. Janik, Nawel Bourayou, Omid Hamid
School of Medicine Faculty Publications
Background T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is an immune checkpoint receptor upregulated during anti-programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy for cancer. TIM-3 blockade may improve the antitumor activity of PD-1/PD-L1inhibition. This phase 1 study evaluated INCAGN02390, a novel, fully human Fc-engineered antibody against TIM-3. Methods INCAGN02390 was evaluated by dose escalation at 10-1600 mg infused in 14-day cycles (every 2 weeks [Q2W]) in pretreated patients with select advanced/metastatic immunogenic solid tumors. Objectives included evaluation of safety/tolerability and maximum tolerated dose (MTD) (primary), pharmacokinetics, preliminary antitumor activity, pharmacodynamics, and immunogenicity (secondary). Results Forty patients were enrolled and …
Ifi16 Mediates Deacetylation Of Kshv Chromatin Via Interaction With Nurd And Sin3a Co-Repressor Complexes, Anandita Ghosh, Bala Chandran, Arunava Roy
Ifi16 Mediates Deacetylation Of Kshv Chromatin Via Interaction With Nurd And Sin3a Co-Repressor Complexes, Anandita Ghosh, Bala Chandran, Arunava Roy
School of Medicine Faculty Publications
IFI16 is a well-characterized nuclear innate immune DNA sensor that detects foreign dsDNA, including herpesviral genomes, to activate the inflammasome and interferon pathways. Beyond immune signaling, IFI16 also functions as an antiviral restriction factor, promoting the silencing of invading viral genes through transcriptional and epigenetic mechanisms. We recently demonstrated another role of IFI16, in which it interacts with and recruits the class I histone deacetylases, HDAC1 and 2, to the KSHV latency protein LANA, modulating its acetylation and function. In this study, we asked whether these IFI16-HDAC1/2 interactions contribute to broader epigenetic regulation of the KSHV chromatin. Our findings reveal …
Economic Value Of Intra-Articular Knee Oa Therapies: A U.S. Perspective, Vinod Dasa, Wilson Ngai, Kevin Steele, Ronald Preblick, Heather Watson, Kevin L. Ong
Economic Value Of Intra-Articular Knee Oa Therapies: A U.S. Perspective, Vinod Dasa, Wilson Ngai, Kevin Steele, Ronald Preblick, Heather Watson, Kevin L. Ong
School of Medicine Faculty Publications
AIMS: This study compared the six-month medical/pharmacy costs and healthcare resource utilization (HCRU) for knee OA patients undergoing intra-articular therapy with different classes of hyaluronic acid (HA) (by molecular weight) or corticosteroid (ICS). MATERIALS AND METHODS: Patients across high molecular weight (HMW) HA, medium molecular weight (MMW) HA, low molecular weight (LMW) HA, and ICS therapy groups were matched from a U.S. claims database (Optum's de-identified Clinformatics Data Mart Database), with a final size of 6,234 patients per group. Adjusted six-month medical/prescription costs per patient per month (PPPM), and HCRU rates and costs, were determined. Secondary endpoints included complication rates …
Supra Inguinal Fascia Iliac Versus Peng Block For Post-Operative Pain Management Of Hip Arthroplasty: A Narrative Review, Shahab Ahmadzadeh, Megan S. Walker, Mary O'Dell Duplechin, Drake P. Duplechin, Charles J. Fox, Sahar Shekoohi, Alan D. Kaye
Supra Inguinal Fascia Iliac Versus Peng Block For Post-Operative Pain Management Of Hip Arthroplasty: A Narrative Review, Shahab Ahmadzadeh, Megan S. Walker, Mary O'Dell Duplechin, Drake P. Duplechin, Charles J. Fox, Sahar Shekoohi, Alan D. Kaye
School of Medicine Faculty Publications
Effective post-operative pain management following hip arthroplasty is critical to improving recovery, reducing opioid consumption, enhancing mobility, and reducing the risk of complications for patients. Multimodal anesthesia strategies, including the supra inguinal fascia iliac block (SIFIB) and the periarticular nerve group (PENG) block have become the new point of focus as opposed to traditional methods previously used. This narrative review compares the SIFIB and the PENG block in their efficacy to treat post-operative pain management. Mechanism of action, safety, patient outcomes, and clinical applications are compared between the two blocks for evaluation. Clinical studies have indicated that both blocks reduce …
Elv-N34, Rvd6-Isomer, Or Npd1 Halt Replication Of Sars-Cov-2 Omicron Ba.5 Virus In Human Lung And Nasal Cells, Jorgelina M. Calandria, Haydee E. Bazan, Surjyadipta Bhattacharjee, Marie-Audrey I. Kautzmann, Nicholas J. Maness, Nicolas G. Bazan
Elv-N34, Rvd6-Isomer, Or Npd1 Halt Replication Of Sars-Cov-2 Omicron Ba.5 Virus In Human Lung And Nasal Cells, Jorgelina M. Calandria, Haydee E. Bazan, Surjyadipta Bhattacharjee, Marie-Audrey I. Kautzmann, Nicholas J. Maness, Nicolas G. Bazan
School of Medicine Faculty Publications
Current vaccines rely on the sequence of Spike (S) protein to induce immunity against the severe acute respiratory coronavirus-2 (SARS-CoV-2) virus. Because of the high mutation rate of the viral S protein, new mutant strains are developed to generate new infectivity profiles. Bioactive lipid mediators (LMs) derived from docosahexaenoic acid (DHA) are synthesized on demand to sustain homeostasis. The purpose of this study was to determine the action of selected LMs in the viral replication of SARS-CoV-2 Omicron BA.5 variant in human lung and nasal epithelial cells. Cells from healthy donors were infected with Omicron BA.5 for one hour and …
Chronic Inflammatory Pain And Chronic Thc Vapor Inhalation Alter Midbrain Neuronal Activity, Leslie K. Kelley, Nicholas W. Gilpin, Jason W. Middleton
Chronic Inflammatory Pain And Chronic Thc Vapor Inhalation Alter Midbrain Neuronal Activity, Leslie K. Kelley, Nicholas W. Gilpin, Jason W. Middleton
School of Medicine Faculty Publications
In an effort to reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain. We tested chronic delta-9 tetrahydrocannabinol (THC) vapor inhalation effects on intrinsic and synaptic properties of ventrolateral periaqueductal gray (vlPAG) neurons in male and female rats treated with complete Freund's adjuvant (CFA). We report that chronic THC vapor inhalation modulates intrinsic and synaptic properties of vlPAG neurons, including reductions in action potential firing rate and spontaneous inhibitory synaptic transmission in males, and that these effects occur specifically …
Rationally Designed Pentapeptide Analogs Of Aβ19-23 Fragment As Potent Inhibitors Of Aβ42 Aggregation, Sachin B. Baravkar, Yan Lu, Qi Zhao, Hongying Peng, Weilie Zhou, Song Hong
Rationally Designed Pentapeptide Analogs Of Aβ19-23 Fragment As Potent Inhibitors Of Aβ42 Aggregation, Sachin B. Baravkar, Yan Lu, Qi Zhao, Hongying Peng, Weilie Zhou, Song Hong
School of Medicine Faculty Publications
Amyloid beta (Aβ42 and Aβ40) aggregation, along with neurofibrillary tangles, is one of the major neurotoxic events responsible for the onset of Alzheimer's disease. Many potent peptide-based inhibitors mainly focusing on central hydrophobic core Aβ16-20 (KLVFF) have been reported in recent years. Herein, we report pentapeptides -, based on the β-turn-inducing fragment Aβ19-23 (FFAED). The synthesis of peptides - was carried out using Fmoc/tBu-based solid-phase peptide synthesis technique, and it was found that pentapeptide potently inhibit the aggregation propensity of Aβ42, when incubated with it at 37 °C for 48 h. The aggregation inhibition study was conducted using thioflavin T-based …
A Mean Field Theory For Pulse-Coupled Neural Oscillators Based On The Spike Time Response Curve, Carmen C. Canavier
A Mean Field Theory For Pulse-Coupled Neural Oscillators Based On The Spike Time Response Curve, Carmen C. Canavier
School of Medicine Faculty Publications
A mean field method for pulse-coupled oscillators with delays used a self-connected oscillator to represent a synchronous cluster of N - 1 oscillators and a single oscillator assumed to be perturbed from the cluster. A periodic train of biexponential conductance input was divided into a tonic and a phasic component representing the mean field input. A single cycle of the phasic conductance from the cluster was applied to the single oscillator embedded in the tonic component at different phases to measure the change in the cycle length in which the perturbation was initiated, that is, the first-order phase response curve …
5-Ht Receptors: Pharmacology And Functional Selectivity, Benjamin R. Cummins, Gerald B. Billac, David E. Nichols, Charles D. Nichols
5-Ht Receptors: Pharmacology And Functional Selectivity, Benjamin R. Cummins, Gerald B. Billac, David E. Nichols, Charles D. Nichols
School of Medicine Faculty Publications
Serotonin 5-HT receptors were one of the first serotonin receptors to be pharmacologically characterized. In mammals, they are expressed throughout the body in nearly every cell and tissue type, with the highest density in cortical layer V of the brain. They are involved in several aspects of normal physiological processes and behaviors and have been implicated in the etiology of neuropsychiatric diseases such as schizophrenia. Atypical antipsychotics have targeted blockade of 5-HT receptors as part of their therapeutic mechanism. More recently, 5-HT receptors have come to prominence for their role as the primary target for psychedelic drugs, which activate this …