Digital Commons Network^™

Foxp1 And Klf2 Reciprocally Regulate Checkpoints Of Stem-Like To Effector Transition In Car T Cells, Ziang Zhu, Guohua Lou, Xiao-Lu Teng, Haixia Wang, Ying Luo, Wangke Shi, Kiddist Yihunie, Shumeng Hao, Kole Degolier, Chengheng Liao, Huocong Huang, Qing Zhang, Terry Fry, Tao Wang, Chen Yao, Tuoqi Wu

Faculty, Staff and Student Publications

During cancers and infections, self-renewing stem-like CD8+ T cells mediate the response of immunotherapies and replenish terminally exhausted T cells and effector-like T cells. However, the programs governing the lineage choice in chimeric antigen receptor (CAR) T cells are unclear. Here, by simultaneously profiling single-cell chromatin accessibility and transcriptome in the same CAR T cells, we identified heterogeneous chromatin states within CD8+ T cell subsets that foreshadowed transcriptional changes and were primed for regulation by distinct transcription factors. Transcription factors that controlled each CD8+ T cell subset were regulated by high numbers of enhancers and positioned as hubs of gene …

Editorial: Advances And Methods In Mesenchymal Stem Cells, Pamela L Wenzel

Faculty, Staff and Student Publications

No abstract provided.

A Systematic Review Of Infant Mental Health Prevention And Treatment Programs, Megan M Hare, Taylor D Landis, Melissa L Hernandez, Paulo A Graziano

Faculty, Staff and Student Publications

Although many prevention and treatment programs exist for children and families, there have been no reviews specifically examining their impact on infant mental health at the program level. Therefore, the purpose of the current review was to a) systematically examine prevention and treatment programs targeting infant mental health outcomes (i.e., internalizing problems, externalizing problems, social-emotional development, trauma) or the parent-infant relationship/ attachment in children from pregnancy to 2 years; b) classify each program by level of empirical support; and c) highlight strengths and identify gaps in the existing literature to inform future mental health intervention science. From over 121,341 publications …

Increased Rate Of Multidrug-Resistant Gram-Negative Bacterial Infections In Hospitalized Immunocompromised Pediatric Patients, Sarah Khafaja, Yara Salameh, Celina F Boutros, Cherine Awad, Kawthar Faour, Nadim Tfaily, Sarah Merhi, Zeinab El Zein, Samer Bou Karroum, Dana Oweini, Danielle Fayad, George F Araj, Ramia Zakhour, Ghassan S Dbaibo

Faculty, Staff and Student Publications

Introduction: Multidrug resistant Gram-negative bacterial infections are considered a major public health threat. Immunocompromised pediatric patients are at a great risk of severe or overwhelming infections. The aim of this study was to describe the frequency of infections with multidrug resistant (MDR) Gram-negative bacteria (GNB) in immunocompromised pediatric patients and to determine the risk factors. In addition, we aimed to identify the antimicrobial resistance patterns of these isolates.

Materials and methods: This was a retrospective observational study conducted at the American University of Beirut Medical Center (AUBMC) from 2009 to 2017. The study included immunocompromised patients 18 years of age …

Botulinum Toxin Treatment May Improve Myoelectric Pattern Recognition In Robot-Assisted Stroke Rehabilitation, Zhiyuan Lu, Yingchun Zhang, Sheng Li, Ping Zhou

Faculty, Staff and Student Publications

No abstract provided.

Effect Of Pioglitazone On Inflammatory Response And Clinical Outcome In T2dm Patients With Covid-19: A Randomized Multicenter Double-Blind Clinical Trial, Khaled Baagar, Thamer Alessa, Mohamed Abu-Farha, Jehad Abubaker, Heba Alhumaidi, Jose Antonio Franco Ceruto, Mohammad Khair Hamad, Ali Omrani, Salma Abdelrahman, Muhammad Zaka-Ul Haq, Abdul Wajid Safi, Bassem Alhariri, Manish Barman, Alaaeldin Abdelmajid, Humberto Vidal Denis Cancio, Eman Elmekaty, Irina Al-Khairi, Preethi Cherian, Lina Jayyousi, Mohammed Ahmed, Mohammed Qaddoumi, Sulaiman Hajji, Ahmad Esmaeel, Ali Al-Andaleeb, Arshad Channanath, Sriraman Devarajan, Hamad Ali, Thangavel Alphonse Thanaraj, Salman Al-Sabah, Fahd Al-Mulla, Muhammad Abdul-Ghani, Amin Jayyousi

Faculty, Staff and Student Publications

Background: Coronavirus disease 2019 (COVID-19) caused by the coronavirus SARS-CoV-2, has emerged as a rapidly spreading contagious disease across the globe. Recent studies showed that people with diabetes mellitus, severe obesity, and cardiovascular disease are at higher risk of mortality from COVID-19. It has been suggested that the increased risk is due to the chronic inflammatory state associated with type 2 diabetes. This study aimed to evaluate the efficacy of pioglitazone, a strong insulin sensitizer with anti-inflammatory properties, in improving the clinical outcomes of patients with type 2 diabetes admitted with moderate-severe COVID-19.

Method: We enrolled 350 patients with type …

Endoscopic Innovations In Diagnosis And Management Of Pancreatic Cancer: A Narrative Review And Future Directions, Prateek Suresh Harne, Vaishali Harne, Curtis Wray, Nirav Thosani

Faculty, Staff and Student Publications

Background: Noncompressible torso hemorrhage is a leading cause of preventable death. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to control hemorrhage but full aortic occlusion is limited by distal ischemia. Partial REBOA (pREBOA) allows some distal perfusion to prolong occlusion, but precise balloon titration is difficult with standard devices. The COBRA-OS 4 French (Fr) aortic occlusion catheter was evaluated in vitro and in vivo for partial REBOA.

Methods: Bench-top (in vitro) and porcine (in vivo) models were used. The titration window of the device was evaluated in a non-hemorrhage porcine model and in a pulsatile aortic model. …

Postsurgical Pyoderma Gangrenosum After Penile Inversion Vaginoplasty: Case With Review Of Diagnostic And Management Strategies, Michael M Talanker, Jessica R Nye, David T Mitchell, Daniel J Freet

Faculty, Staff and Student Publications

BACKGROUND: Postsurgical pyoderma gangrenosum (PSPG) is a highly uncommon and unpredictable wound healing complication. Rapid progression of ulcers at incisions can cause unfettered dehiscence. Most commonly, PSPG involves breast procedures; however, in this work, we detail a case of a patient who developed PSPG 10 days postoperatively after penile inversion vaginoplasty.

METHODS: The patient in this case underwent a penile inversion vaginoplasty with orchiectomy in the standard fashion. She had no risk factors for PSPG. Following an uncomplicated hospital stay, the patient developed difficulty with pain control and increasing serous drainage on the 10th postoperative day. On readmission, the patient …

Explainable Suicide Phenotyping From Initial Psychiatric Evaluation Notes Using Reasoning Large Language Models, Zehan Li, Wanjing Wang, Lokesh Shahani, Rodrigo M Vieira, Salih Selek, Jair Soares, Hongfang Liu, Ming Huang

Faculty, Staff and Student Publications

Clinical phenotyping is the process of extracting patient's observable symptoms and traits to better understand their disease condition. Suicide phenotyping focuses more on behavioral and cognitive characteristics, such as suicide ideation, attempt, and self-injury, to identify suicide risks and improve interventions. In this study, we leveraged the latest reasoning models, namely 4o, o1, and o3-mini, to perform note-level multi-label classification and reasoning generation tasks using previously annotated psychiatric evaluation notes from a safety-net psychiatric inpatient hospital in Harris County, Texas. Compared with the previously finetuned GPT-3.5 model, the out-of-box reasoning models prompted with in-context learning achieved comparable and better performance, …

Enhancing Associative Learning In Rats With A Computationally Designed Training Protocol, Xu O Zhang, Yili Zhang, Claire E Cho, Douglas S Engelke, Paul Smolen, John H Byrne, Fabricio H Do-Monte

Faculty, Staff and Student Publications

Background

Learning requires the activation of protein kinases with distinct temporal dynamics. In Aplysia, nonassociative learning can be enhanced by a computationally designed learning protocol with intertrial intervals (ITIs) that maximize the interaction between fast-activated PKA (protein kinase A) and slow-activated ERK (extracellular signal-regulated kinase). Whether a similar strategy can enhance associative learning in mammals is unknown.

Methods

We simulated 1000 training protocols with varying ITIs to predict an optimal protocol based on empirical data for PKA and ERK dynamics in rat hippocampus. Adult male rats received the optimal protocol or control protocols in auditory fear conditioning and fear …

Monet: A Database For Prediction Of Neoantigens Derived From Microsatellite Loci, Nan Deng, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

BACKGROUND: Microsatellite instability (MSI) secondary to mismatch repair (MMR) deficiency is characterized by insertions and deletions (indels) in short DNA sequences across the genome. These indels can generate neoantigens, which are ideal targets for precision immune interception. However, current neoantigen databases lack information on neoantigens arising from coding microsatellites. To address this gap, we introduce The MicrOsatellite Neoantigen Discovery Tool (MONET).

METHOD: MONET identifies potential mutated tumor-specific neoantigens (neoAgs) by predicting frameshift mutations in coding microsatellite sequences of the human genome. Then MONET annotates these neoAgs with key features such as binding affinity, stability, expression, frequency, and potential pathogenicity using …

Synaptic Vesicle Dynamics In Mouse Rod Bipolar Cells, Sara S Patterson, Rebecca J Girresch, Marcus A Mazzaferri, Andrea S Bordt, Wendy L Piñon-Teal, Brett D Jesse, Dinukie-Chantal W Perera, Melanie A Schlepphorst, James A Kuchenbecker, Alice Z Chuang, Jay Neitz, David W Marshak, Judith Mosinger Ogilvie

Faculty, Staff and Student Publications

Considerable progress has been made in studying the receptive fields of the most common primate retinal ganglion cell (RGC) types, such as parasol RGCs. Much less is known about the rarer primate RGC types and the circuitry that gives rise to noncanonical receptive field structures. The goal of this study was to analyze synaptic inputs to smooth monostratified RGCs to determine the origins of their complex spatial receptive fields, which contain isolated regions of high sensitivity called "hotspots." Interestingly, smooth monostratified RGCs co-stratify with the well-studied parasol RGCs and are thus constrained to receiving input from bipolar and amacrine cells …

A Bibliometric Analysis Of Literatures On Uterine Leiomyosarcoma In The Last 20 Years, Jinhua Huang, Yu Chen, Ziyin Li, Mimi Chen, Dingwen Huang, Peixin Zhu, Xintong Han, Yi Zheng, Xiaochun Chen, Zhiying Yu

Faculty, Staff and Student Publications

Background: Uterine leiomyosarcoma(uLMS) is a rare malignant tumor with low clinical specificity and poor prognosis.There are many studies related to uLMS, however, there is still a lack of metrological analyses with generalization. This study provides a bibliometric study of uLMS.

Methods and materials: We chose the Web of Science (WoS) as our main database due to its extensive interdisciplinary coverage. We specifically focused on the literature from the last 20 years to ensure relevance and practicality. By utilizing the WOS core dataset and leveraging the R package "bibliometric version 4.1.0" and Citespace, we performed a comprehensive bibliometric analysis. This allowed …

Structures Of Channelrhodopsin Paralogs In Peptidiscs Explain Their Contrasting K+ And Na+ Selectivities, Shu Kikuta, Shin Nagayama, Sanae Hasegawa-Ishii

Faculty, Staff and Student Publications

The olfactory epithelium (OE) is directly exposed to environmental agents entering the nasal cavity, leaving OSNs prone to injury and degeneration. The causes of olfactory dysfunction are diverse and include head trauma, neurodegenerative diseases, and aging, but the main causes are chronic rhinosinusitis (CRS) and viral infections. In CRS and viral infections, reduced airflow due to local inflammation, inflammatory cytokine production, release of degranulated proteins from eosinophils, and cell injury lead to decreased olfactory function. It is well known that injury-induced loss of mature OSNs in the adult OE causes massive regeneration of new OSNs within a few months through …

Role Of A Pdlim5:Palmd Complex In Directing Dendrite Morphology, Yogesh Srivastava, Maxsam Donta, Lydia L Mireles, Adriana Paulucci-Holthauzen, M Neal Waxham, Pierre D Mccrea

Faculty, Staff and Student Publications

Neuronal connectivity is regulated during normal brain development with the arrangement of spines and synapses being dependent on the morphology of dendrites. Further, in multiple neurodevelopmental and aging disorders, disruptions of dendrite formation or shaping is associated with atypical neuronal connectivity. We showed previously that Pdlim5 binds delta-catenin and promotes dendrite branching. We report here that Pdlim5 interacts with PalmD, a protein previously suggested by others to interact with the cytoskeleton (e.g.,

Her4 And Egfr Activate Cell Signaling In Nrg1 Fusion-Driven Cancers: Implications For Her2-Her3-Specific Versus Pan-Her Targeting Strategies, Hibiki Udagawa, Monique B Nilsson, Jacqulyne P Robichaux, Junqin He, Alissa Poteete, Hong Jiang, Simon Heeke, Yasir Y Elamin, Yuji Shibata, Shingo Matsumoto, Kiyotaka Yoh, Shogo Okazaki, Takashi Masuko, Igor Odintsov, Romel Somwar, Marc Ladanyi, Koichi Goto, John V Heymach

Faculty, Staff and Student Publications

Introduction: NRG1 gene fusions are clinically actionable alterations identified in NSCLC and other tumors. Previous studies have reported that NRG1 fusions signal through HER2 and HER3 but, thus far, strategies targeting HER3 specifically or HER2-HER3 signaling have exhibited modest activity in patients with NSCLC bearing NRG1 fusions. Although NRG1 fusion proteins can bind HER4 in addition to HER3, the contribution of HER4 and other HER family members in NRG1 fusion-positive cancers is not fully understood.

Methods: We investigated the role of HER4 and EGFR-HER3 signaling in NRG1 fusion-positive cancers using Ba/F3 models engineered to express various HER family members in …

Establishment Of A Brain Tumor Consortium Of Africa: Advancing Collaborative Research And Advocacy For Brain Tumors In Africa, Lateef A Odukoya, Kwadwo Darko, Francis Zerd, Nathalie C Ghomsi, Gloria Kabare, David O Kamson, Jeanette E Eckel-Passow, Robert B Jenkins, Gaspar J Kitange, Andrea O Akinjo, Kabir B Badmos, Olufemi Bankole, Olufemi E Idowu, Claire Karekezi, Elias Edrick, Chukwuyem Ekhator, Victoria M Katasi, Desmond A Brown, Jason Huse, Henry Llewellyn, Margreth Magambo, Michael Magoha, Umaru Barrie, Advera Ngaiza, Arsene D Nyalundja, Minda Okemwa, Lawrence Osei-Tutu, Bernard Petershie, W Elorm Yevudza, Charles C Anunobi, Liadi Tiamiyu, Gbetoho Fortuné Gankpe, Kashaigili Heronima, Dominique Higgins, Kristin Schroeder, Teddy Totimeh, James Balogun, Beverly Cheserem, Arnold B Etame, Ekokobe Fonkem

Faculty, Staff and Student Publications

Background: Brain tumors represent a significant global health challenge, with rising incidence and mortality impacting individuals worldwide and contributing to cancer-related morbidity and mortality. In Africa, this burden is exacerbated by limited access to advanced diagnostics, treatment options, and multidisciplinary care, compounded by the absence of standardized cancer registration and tumor biobanking. The introduction of molecular diagnostics, as outlined in the 2021 World Health Organization central nervous system (CNS) tumor classification, adds complexity to brain tumor management, particularly in regions with scarce resources.

Methods: To address these issues, the Brain Tumor Consortium for Africa (BTCA) was established in 2023, bringing …

Circulating Cancer-Associated Macrophage-Like Cells And Macrophage-Related Cytokines In Obese Patients With Advanced Breast Cancer Who Undergo Neoadjuvant Chemotherapy, Toshiaki Iwase, Aaroh Parikh, Dong Wenli, Yu Shen, Daniel L Adams, Cha-Mei Tang, Evan N Cohen, James M Reuben, Tushaar Vishal Shrimanker, Sudpreeda Chainitikun, Kumiko Kida, Akshara Singareeka Raghavendra, Maryanne E Sapon, Onur Sahin, Anjali James, Nithya Sridhar, Ann H Klopp, Debasish Tripathy, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Cancer-associated macrophage-like cells (CAMLs) are rare, gigantic, and atypical circulating cells found exclusively in the peripheral blood of patients with solid cancers. Obesity-induced hypoxia attracts macrophages to the tumor microenvironment, where they contribute to establishing chronic inflammation, leading to cancer progression. We hypothesized that obese patients with advanced breast cancer may have CAML profiles different from those of nonobese patients, and these profiles may correlate with proinflammatory markers or other macrophage-related markers.

Methods: We prospectively collected 20 mL of peripheral blood from patients diagnosed with stage 2-4 breast cancer. We identified CAMLs using the CellSieve microfiltration system and in …

Blood-Based Microrna Biomarker Signature Of Early-Stage Pancreatic Ductal Adenocarcinoma With Lead-Time Trajectory In Prediagnostic Samples, Warapen Treekitkarnmongkol, Jianliang Dai, Suyu Liu, Deivendran Sankaran, Tristian Nguyen, Seetharaman Balasenthil, Mark W Hurd, Meng Chen, Hiroshi Katayama, Sinchita Roy-Chowdhuri, George A Calin, Randall E Brand, Paul D Lampe, Tony Y Hu, Anirban Maitra, Eugene J Koay, Ann M Killary, Subrata Sen

Faculty, Staff and Student Publications

Background and aims: Clinically validated biomarker of pancreatic ductal adenocarcinoma (PDAC), carbohydrate antigen 19-9 (CA19-9), has limited sensitivity and specificity for early-stage disease. Circulating miRNAs in plasma associated with cancer relevant pathways were developed as early detection biomarkers.

Methods: 2083 miRNAs in 15 μl of plasma from multicenter age-matched cohorts (N = 203: healthy controls, n = 46; pancreatitis controls, n = 36; diagnosed cases: n = 121) and a prediagnostic Prostate, Lung, Colorectal, and Ovarian age- and gender-matched cohort (N = 96; controls, n = 48; prediagnosed cases, n = 48) were interrogated. A three-miRNA biomarker signature …

The Mir-17-92 Cluster In Cardiac Health And Disease, Yuhan Cao, Mingjie Zheng, Maham A Sewani, Jun Wang

Faculty, Staff and Student Publications

MicroRNAs (miRs) are small noncoding RNAs that play important roles in both physiological and pathological processes through post-transcriptional regulation. The miR-17-92 cluster includes six individual members: miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1. The miR-17-92 cluster has been extensively studied and reported to broadly function in cancer biology, immunology, neurology, pulmonology, and cardiology. This review focuses on its roles in heart development and cardiac diseases. We briefly introduce the nature of the miR-17-92 cluster and its crucial roles in both normal development and the pathogenesis of various diseases. We summarize the recent progress in understanding the versatile roles of miR-17-92 …

Proportional Sway-Based Electrotactile Feedback Improves Lateral Standing Balance, V S Raghav Hari Krishna, Jeonghee Kim, Shuo-Hsiu Chang, Yoonsuck Choe, Hangue Park

Faculty, Staff and Student Publications

INTRODUCTION: Plantar cutaneous augmentation is a promising approach in balance rehabilitation by enhancing motion-dependent sensory feedback. The effect of plantar cutaneous augmentation on balance has been mainly investigated in its passive form (e.g., textured insole) or on lower-limb amputees. In this study, we tested the effect of plantar cutaneous augmentation on balance in its active form (i.e., electrical stimulation) for individuals with intact limbs.

METHODS: Ten healthy subjects participated in the study and were instructed to maintain their balance as long as possible on the balance board, with or without electrotactile feedback evoked on the medial side of the heel, …

Single-Molecule Fret Analyses Of Nmda Receptors, Ryan J Durham, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Single-molecule fluorescence resonance energy transfer (smFRET) enables the real-time observation of conformational changes in a single protein molecule of interest. These observations are achieved by attaching fluorophores to proteins of interest in a site-specific manner and investigating the FRET between the fluorophores. Here we describe the method wherein the FRET is studied by adhering the protein molecules to a slide using affinity-based interactions and measuring the fluorophores' fluorescence intensity from a single molecule over time. The resulting information can be used to derive distance values for a point-to-point measurement within a protein or to calculate kinetic transition rates between various …

Hormone Regulation Of Corticotropin-Releasing Factor Receptor 1 In The Female Mouse Brain, Rose M De Guzman, Jason S Jacobskind, Zachary J Rosinger, Krystyna A Rybka, Katherine E Parra, Aya L Caballero, Massoud S Sharif, Nicholas J Justice, Damian G Zuloaga

Faculty, Staff and Student Publications

Introduction: Corticotropin-releasing factor receptor 1 (CRFR1) is a key regulator of neuroendocrine and behavioral stress responses. Previous studies have demonstrated that CRFR1 in certain hypothalamic and preoptic brain areas is modified by chronic stress and during the postpartum period in female mice, although the potential hormonal contributors to these changes are unknown.

Methods: This study focused on determining the contributions of hormones associated with stress and the maternal period (glucocorticoids, prolactin, estradiol/progesterone) on CRFR1 levels using a CRFR1-GFP reporter mouse line and immunohistochemistry.

Results: Administration of dexamethasone, an agonist of the glucocorticoid receptor, elevated CRFR1 in the anteroventral periventricular nucleus …

Tissue Transglutaminase: A Multifunctional And Multisite Regulator In Health And Disease, Zhouzhou Yao, Yuhua Fan, Lizhen Lin, Rodney E Kellems, Yang Xia

Faculty, Staff and Student Publications

Tissue transglutaminase (TG2) is a widely distributed multifunctional protein involved in a broad range of cellular and metabolic functions carried out in a variety of cellular compartments. In addition to transamidation, TG2 also functions as a Gα signaling protein, a protein disulfide isomerase (PDI), a protein kinase, and a scaffolding protein. In the nucleus, TG2 modifies histones and transcription factors. The PDI function catalyzes the trimerization and activation of heat shock factor-1 in the nucleus and regulates the oxidation state of several mitochondrial complexes. Cytosolic TG2 modifies proteins by the addition of serotonin or other primary amines and in this …

Anticancer Effects Of Wild Baicalin On Hepatocellular Carcinoma: Downregulation Of Akr1b10 And Pi3k/Akt Signaling Pathways, Longjun Sun, Wenjuan Chen, Peixi Zhao, Bin Zhao, Guangyan Lei, Le Han, Yili Zhang

Faculty, Staff and Student Publications

ntroduction

Hepatocellular carcinoma (HCC) is a common and deadly malignancy. Traditional Chinese medicine, such as the compound Astragalus (wild Baicalin), has shown promise in improving outcomes for HCC patients. This study aimed to investigate the effects of wild Baicalin on the human hepatoma cell line HepG2 and elucidate the underlying mechanisms, particularly the role of the AKR1B10 and PI3K/AKT signaling pathways.

Methods

HepG2 cells were treated with varying concentrations of wild Baicalin. Cell proliferation, apoptosis, migration, invasion, and cell cycle were evaluated using CCK-8, flow cytometry, scratch, Transwell, and clonogenic assays, respectively. Transcriptome sequencing was performed to analyze gene expression …

Clearance Of Neutrophils From Ich-Affected Brain By Macrophages Is Beneficial And Is Assisted By Lactoferrin And Cd91, Xiurong Zhao, Shun-Ming Ting, Guanghua Sun, Jesus Bautista Garrido, Lidiya Obertas, Jaroslaw Aronowski

Faculty, Staff and Student Publications

Background: Within hours after intracerebral hemorrhage (ICH) onset, masses of polymorphonuclear neutrophils (PMNs) infiltrate the ICH-affected brain. After degranulation involving controlled release of many toxic antimicrobial molecules, the PMNs undergo rapid apoptosis and then are removed by phagocytic microglia/macrophages (MΦ) through a process called efferocytosis. Effective removal of PMNs may limit secondary brain damage and inflammation; however, the molecular mechanisms governing these cleanup activities are not well understood. We propose that scavenger receptor CD91 on myeloid phagocytes especially in presence of CD91 ligand, LTF (lactoferrin, protein abundant in PMNs), plays an important role in clearance of dead apoptotic PMNs (ANs). …

Accelerate Vaccine Development Using Seamless Phase 2/3 Trial Designs, Jia-Ying Yang, Guo-Chun Li, Ying Yuan

Faculty, Staff and Student Publications

Background: Traditional vaccine development, often a lengthy and costly process of three separated phases. However, the swift development of COVID-19 vaccines highlighted the critical importance of accelerating the approval of vaccines. This article showcases a seamless phase 2/3 trial design to expedite the development process, particularly for multi-valent vaccines.

Research design and methods: This study utilizes simulation to compare the performance of seamless phase 2/3 design with that of conventional trial design, specifically by re-envisioning a 9-valent HPV vaccine trial. Across three cases, several key performance metrics are evaluated: overall power, type I error rate, average sample size, trial duration, …

Circulating Tumor Dna (Ctdna) As A Biomarker Of Response To Therapy In Advanced Hepatocellular Carcinoma Treated With Nivolumab, Yehia I Mohamed, Sunyoung S Lee, Tarik Demir, Shadi Chamseddine, Zishuo Ian Hu, Lianchun Xiao, Khaled Elsayes, Jeffrey S Morris, Robert A Wolff, Rikita Hiatia, Aliya Qayyum, Asif Rashid, Dan G Duda, James C Yao, Michael Lapelusa, Eugene J Koay, Armeen Mahvash, Ahmed Al Azzam, Ecaterina E Dumbrava, Manal Hassan, Hesham M Amin, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

Background: Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC).

Objective: This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab.

Methods: We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions.

Results: Of 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had …

Lifestyle Management Of Hypertension: International Society Of Hypertension Position Paper Endorsed By The World Hypertension League And European Society Of Hypertension, Fadi J Charchar, Priscilla R Prestes, Charlotte Mills, Siew Mooi Ching, Dinesh Neupane, Francine Z Marques, James E Sharman, Liffert Vogt, Louise M Burrell, Lyudmila Korostovtseva, Manja Zec, Mansi Patil, Martin G Schultz, Matthew P Wallen, Nicolás F Renna, Sheikh Mohammed Shariful Islam, Swapnil Hiremath, Tshewang Gyeltshen, Yook-Chin Chia, Abhinav Gupta, Aletta E Schutte, Britt Klein, Claudio Borghi, Colette J Browning, Marta Czesnikiewicz-Guzik, Hae-Young Lee, Hiroshi Itoh, Katsuyuki Miura, Mattias Brunström, Norm R C Campbell, Olutope Arinola Akinnibossun, Praveen Veerabhadrappa, Richard D Wainford, Ruan Kruger, Shane A Thomas, Takahiro Komori, Udaya Ralapanawa, Véronique A Cornelissen, Vikas Kapil, Yan Li, Yuqing Zhang, Tazeen H Jafar, Nadia Khan, Bryan Williams, George Stergiou, Maciej Tomaszewski

Faculty, Staff and Student Publications

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on …

Hypoxia-Adenosine Axis As Therapeutic Targets For Acute Respiratory Distress Syndrome, Katherine Figarella, Jieun Kim, Wei Ruan, Tingting Mills, Holger Klaus Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially …