Medical Specialties Commons^™

Investigating The Physiological Mechanisms Between Resistance Training And Pain Relief In The Cancer Population: A Literature Review, Yvonne Jiang, Peter C. Angeletti, Amy J. Hoffman

Nebraska Center for Virology: Faculty Publications

This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: breast, prostate, and lung, will be examined. A number of experimental studies have been conducted to confirm the effectiveness of resistance training on pain relief as well as the biochemical pathways that relate to this process. In this review, we will examine 5 randomized controlled trials. For the purposes of this review, pain is defined as physical suffering or discomfort associated with illness. Pain is the body’s natural …

Enabling Endpoint Development For Interventional Clinical Trials In Individuals With Angelman Syndrome: A Prospective, Longitudinal, Observational Clinical Study (Freesias), Jorrit Tjeertes, Carlos A Bacino, Terry Jo Bichell, Lynne M Bird, Mariana Bustamante, Rebecca Crean, Shafali Jeste, Robert W Komorowski, Michelle L Krishnan, Meghan T Miller, David Nobbs, Cesar Ochoa-Lubinoff, Kimberly A Parkerson, Alexander Rotenberg, Anjali Sadhwani, Mark D Shen, Lisa Squassante, Wen-Hann Tan, Brenda Vincenzi, Anne C Wheeler, Joerg F Hipp, Elizabeth Berry-Kravis

Faculty, Staff and Students Publications

BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by the absence of a functional UBE3A gene, which causes developmental, behavioral, and medical challenges. While currently untreatable, comprehensive data could help identify appropriate endpoints assessing meaningful improvements in clinical trials. Herein are reported the results from the FREESIAS study assessing the feasibility and utility of in-clinic and at-home measures of key AS symptoms.

METHODS: Fifty-five individuals with AS (aged < 5 years: n = 16, 5-12 years: n = 27, ≥ 18 years: n = 12; deletion genotype: n = 40, nondeletion genotype: n = 15) and 20 typically developing children (aged 1-12 years) were enrolled across six USA sites. Several clinical outcome assessments and digital health technologies were tested, together with overnight 19-lead electroencephalography (EEG) and additional polysomnography (PSG) sensors. Participants were assessed at baseline (Clinic Visit 1), 12 months later (Clinic Visit 2), and during intermittent home visits.

RESULTS: The participants achieved high completion rates for the clinical outcome assessments (adherence: 89-100% [Clinic Visit 1]; 76-91% [Clinic Visit 2]) and varied feasibility of and adherence to digital health …

Islet: Individual-Specific Reference Panel Recovery Improves Cell-Type-Specific Inference, Hao Feng, Guanqun Meng, Tong Lin, Hemang Parikh, Yue Pan, Ziyi Li, Jeffrey Krischer, Qian Li

Faculty, Staff and Student Publications

We propose a statistical framework ISLET to infer individual-specific and cell-type-specific transcriptome reference panels. ISLET models the repeatedly measured bulk gene expression data, to optimize the usage of shared information within each subject. ISLET is the first available method to achieve individual-specific reference estimation in repeated samples. Using simulation studies, we show outstanding performance of ISLET in the reference estimation and downstream cell-type-specific differentially expressed genes testing. We apply ISLET to longitudinal transcriptomes profiled from blood samples in a large observational study of young children and confirm the cell-type-specific gene signatures for pancreatic islet autoantibody. ISLET is available at https://bioconductor.org/packages/ISLET …

Comprehensive Analysis Of The Prognostic Significance Of The Trim Family In The Context Of Tp53 Mutations In Cancers, Trung Vu, Annaliese Fowler, Nami Mccarty

Faculty, Staff and Student Publications

The p53 protein is an important tumor suppressor, and TP53 mutations are frequently associated with poor prognosis in various cancers. Mutations in TP53 result in a loss of p53 function and enhanced expression of cell cycle genes, contributing to the development and progression of cancer. Meanwhile, several tripartite motif (TRIM) proteins are known to regulate cell growth and cell cycle transition. However, the prognostic values between TP53 and TRIM family genes in cancer are unknown. In this study, we analyzed the relationship between the

Tissue-Specific Features Of The T Cell Repertoire After Allogeneic Hematopoietic Cell Transplantation In Human And Mouse, Susan Dewolf, Yuval Elhanati, Katherine Nichols, Nicholas R Waters, Chi L Nguyen, John B Slingerland, Natasia Rodriguez, Olga Lyudovyk, Paul A Giardina, Anastasia I Kousa, Hana Andrlová, Nick Ceglia, Teng Fei, Rajya Kappagantula, Yanyun Li, Nathan Aleynick, Priscilla Baez, Rajmohan Murali, Akimasa Hayashi, Nicole Lee, Brianna Gipson, Madhumitha Rangesa, Zoe Katsamakis, Anqi Dai, Amanda G Blouin, Maria Arcila, Ignas Masilionis, Ronan Chaligne, Doris M Ponce, Heather J Landau, Ioannis Politikos, Roni Tamari, Alan M Hanash, Robert R Jenq, Sergio A Giralt, Kate A Markey, Yanming Zhang, Miguel-Angel Perales, Nicholas D Socci, Benjamin D Greenbaum, Christine A Iacobuzio-Donahue, Travis J Hollmann, Marcel R M Van Den Brink, Jonathan U Peled

Faculty, Staff and Student Publications

T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood …

Clinical Evidence Of Human Pathogens Implicated In Alzheimer’S Disease Pathology And The Therapeutic Efficacy Of Antimicrobials: An Overview, Celso S G Catumbela, Vijayasree V Giridharan, Tatiana Barichello, Rodrigo Morales

Faculty, Staff and Student Publications

A wealth of pre-clinical reports and data derived from human subjects and brain autopsies suggest that microbial infections are relevant to Alzheimer's disease (AD). This has inspired the hypothesis that microbial infections increase the risk or even trigger the onset of AD. Multiple models have been developed to explain the increase in pathogenic microbes in AD patients. Although this hypothesis is well accepted in the field, it is not yet clear whether microbial neuroinvasion is a cause of AD or a consequence of the pathological changes experienced by the demented brain. Along the same line, the gut microbiome has also …

Pharmaco-Proteogenomic Characterization Of Liver Cancer Organoids For Precision Oncology, Shuyi Ji, Li Feng, Zile Fu, Gaohua Wu, Yingcheng Wu, Youpei Lin, Dayun Lu, Yuanli Song, Peng Cui, Zijian Yang, Chen Sang, Guohe Song, Shangli Cai, Yuanchuang Li, Hanqing Lin, Shu Zhang, Xiaoying Wang, Shuangjian Qiu, Xiaoming Zhang, Guoqiang Hua, Junqiang Li, Jian Zhou, Zhi Dai, Xiangdong Wang, Li Ding, Pei Wang, Daming Gao, Bing Zhang, Henry Rodriguez, Jia Fan, Hans Clevers, Hu Zhou, Yidi Sun, Qiang Gao

Faculty, Staff and Students Publications

Organoid models have the potential to recapitulate the biological and pharmacotypic features of parental tumors. Nevertheless, integrative pharmaco-proteogenomics analysis for drug response features and biomarker investigation for precision therapy of patients with liver cancer are still lacking. We established a patient-derived liver cancer organoid biobank (LICOB) that comprehensively represents the histological and molecular characteristics of various liver cancer types as determined by multiomics profiling, including genomic, epigenomic, transcriptomic, and proteomic analysis. Proteogenomic profiling of LICOB identified proliferative and metabolic organoid subtypes linked to patient prognosis. High-throughput drug screening revealed distinct response patterns of each subtype that were associated with specific …

When Phased Without Water: Biophysics Of Cellular Desiccation, From Biomolecules To Condensates, Paulette Sofia Romero-Perez, Yanniv Dorone, Eduardo Flores, Shahar Sukenik, Steven Boeynaems

Faculty, Staff and Students Publications

The molecular machinery that enables life has evolved in water, yet many of the organisms around us are able to survive even extreme desiccation. Especially remarkable are single-cell and sedentary organisms that rely on specialized biomolecular machinery to survive in environments that are routinely subjected to a near-complete lack of water. In this review, we zoom in on the molecular level of what is happening in the cellular environment under water stress. We cover the various mechanisms by which biochemical components of the cell can dysfunction in dehydrated cells and detail the different strategies that organisms have evolved to eliminate …

Gender Differences In A Mouse Model Of Hepatocellular Carcinoma Revealed Using Multi-Modal Imaging, Brian J Engel, Vincenzo Paolillo, Md Nasir Uddin, Kristyn A Gonzales, Kathryn M Mcginnis, Margie N Sutton, Madhavi Patnana, Brian J Grindel, Gregory J Gores, David Piwnica-Worms, Laura Beretta, Federica Pisaneschi, Seth T Gammon, Steven W Millward

Faculty, Staff and Student Publications

The worldwide incidence of hepatocellular carcinoma (HCC) continues to rise, in part due to poor diet, limited exercise, and alcohol abuse. Numerous studies have suggested that the loss or mutation of PTEN plays a critical role in HCC tumorigenesis through the activation of the PI3K/Akt signaling axis. The homozygous knockout of PTEN in the livers of mice results in the accumulation of fat (steatosis), inflammation, fibrosis, and eventually progression to HCC. This phenotype bears a striking similarity to non-alcoholic steatohepatitis (NASH) which is thought to occupy an intermediate stage between non-alcoholic fatty liver disease (NAFLD), fibrosis, and HCC. The molecular …

Sindrom Respons Inflamasi Sistemik, Yefta Moenadjat

Department of Surgery Teaching Materials and Monographs

Materi perkuliahan memuat uraian respons inflamasi pascatrauma yang berkembang menjadi sindrom respons inflamasi sistemik, berakhir dengan kegagalan organ multipel ditinjau dari aspek biomolekuler.

Buku ini merupakan bagian pertama dari seri inflamasi yang disusun dalam bentuk digital dan dipublikasi menurut konsep lisensi Commons Attribution-NonCommercial 4.0 International License untuk tujuan diseminasi.

Omega-3 Fatty Acids And Risk For Atrial Fibrillation: Big Fish Or Small Fry?, Christie M Ballantyne, Xiaoming Jia

Faculty, Staff and Students Publications

No abstract provided.

Pseudohypercreatininemia After Surgery For Aortic Dissection: A Case Report, Ayako Tasaki, Makoto Fukuda, Yuki Ikeda, Masatora Yamasaki, Ikko Yamaguchi, Shinichi Aishima, Motoaki Miyazono

Children’s Nutrition Research Center Staff Publications

Background: Elevated creatinine concentrations often indicate acute renal injury and renal biopsies are considered in this situation. However,pseudohypercreatininemia is potential cause of elevated creatinine concentrations, and invasive interventions should be avoided.

Case presentation: A 54-year-old woman underwent surgery for descending aortic dissection.Nine days postoperatively, her creatinine concentration increased from 1 mg/dl to 5.78 mg/dl (normal range, 0.47-0.7 mg/dl). Azotemia and hyperkalemia were absent and physical examination findings were unremarkable. Cystatin C concentration was 1.56 mg/l (normal range, 0.56-0.8 mg/l) and pseudohypercreatininemia was suspected. Testing with different reagents showed a creatinine concentration of 0.84 mg/dl. Immunoglobulin (Ig)G was markedly elevated, and …

Alemtuzumab And Cxcl9 Levels Predict Likelihood Of Sustained Engraftment After Reduced-Intensity Conditioning Hct, Ashley V Geerlinks, Brooks Scull, Christa Krupski, Ryan Fleischmann, Michael A Pulsipher, Mary Eapen, James A Connelly, Catherine M Bollard, Sung-Yun Pai, Christine N Duncan, Leslie S Kean, K Scott Baker, Lauri M Burroughs, Jeffrey R Andolina, Shalini Shenoy, Philip Roehrs, Rabi Hanna, Julie-An Talano, Kirk R Schultz, Elizabeth O Stenger, Howard Lin, Adi Zoref-Lorenz, Kenneth L Mcclain, Michael B Jordan, Tsz-Kwong Man, Carl E Allen, Rebecca A Marsh

Faculty, Staff and Students Publications

Overall survival after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using alemtuzumab, fludarabine, and melphalan is associated with high rates of mixed chimerism (MC) and secondary graft failure (GF). We hypothesized that peritransplantation alemtuzumab levels or specific patterns of inflammation would predict these risks. We assessed samples from the Bone Marrow Transplant Clinical Trials Network 1204 (NCT01998633) to study the impact of alemtuzumab levels and cytokine patterns on MC and impending or established secondary GF (defined as donor chimerism < 5% after initial engraftment and/or requirement of cellular intervention). Thirty-three patients with hemophagocytic lymphohistiocytosis (n = 25) and other IEIs (n = 8) who underwent HCTs with T-cell–replete grafts were included. Patients with day 0 alemtuzumab levels ≤0.32 μg/mL had a markedly lower incidence of MC, 14.3%, vs 90.9% in patients with levels >0.32 μg/mL (P = .008). Impending or established secondary GF was only observed in patients with day …

Agrp Neurons Are Not Indispensable For Body Weight Maintenance In Adult Mice, Jing Cai, Jing Chen, Joshua Ortiz-Guzman, Jessica Huang, Benjamin R Arenkiel, Yuchen Wang, Yan Zhang, Yuyan Shi, Qingchun Tong, Cheng Zhan

Faculty, Staff and Student Publications

In addition to their role in promoting feeding and obesity development, hypothalamic arcuate agouti-related protein/neuropeptide Y (AgRP/NPY) neurons are widely perceived to be indispensable for maintaining normal feeding and body weight in adults, and consistently, acute inhibition of AgRP neurons is known to reduce short-term food intake. Here, we adopted complementary methods to achieve nearly complete ablation of arcuate AgRP/NPY neurons in adult mice and report that lesioning arcuate AgRP/NPY neurons in adult mice causes no apparent alterations in ad libitum feeding or body weight. Consistent with previous studies, loss of AgRP/NPY neurons blunts fasting refeeding. Thus, our studies show …

Editorial: Targeting Dna Damage Response To Enhance Antitumor Innate Immunity In Radiotherapy, Victoria Valvo, Emanuele Vitale, Marco Tigano, Rachel Evans, Meredith A. Morgan, Qiang Zhang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Gene Signature Reveals Decreased Sox10-Dependent Transcripts In Malignant Cells From Immune Checkpoint Inhibitor-Resistant Cutaneous Melanomas, Timothy J. Purwin, Signe Caksa, Ahmet Sacan, Claudia Capparelli, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Evidence is mounting for cross-resistance between immune checkpoint and targeted kinase inhibitor therapies in cutaneous melanoma patients. Since the loss of the transcription factor, SOX10, causes tolerance to MAPK pathway inhibitors, we used bioinformatic techniques to determine if reduced SOX10 expression/activity is associated with immune checkpoint inhibitor resistance. We integrated SOX10 ChIP-seq, knockout RNA-seq, and knockdown ATAC-seq data from melanoma cell models to develop a robust SOX10 gene signature. We used computational methods to validate this signature as a measure of SOX10-dependent activity in independent single-cell and bulk RNA-seq SOX10 knockdown, cell line panel, and MAPK inhibitor drug-resistant datasets. Evaluation …

Impact Of Type Of Induction Therapy On Outcomes In Older Adults With Aml After Allogeneic Stem Cell Transplantation, Nicholas J Short, Faustine Ong, Farhad Ravandi, Graciela Nogueras-Gonzalez, Tapan M Kadia, Naval Daver, Courtney D Dinardo, Marina Konopleva, Gautam Borthakur, Betul Oran, Gheath Al-Atrash, Rohtesh Mehta, Elias J Jabbour, Musa Yilmaz, Ghayas C Issa, Abhishek Maiti, Richard E Champlin, Hagop Kantarjian, Elizabeth J Shpall, Uday Popat

Faculty, Staff and Student Publications

Although venetoclax-based lower-intensity regimens have greatly improved outcomes for older adults with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy, the optimal induction for older patients with newly diagnosed AML who are suitable candidates for hematopoietic stem cell transplant (HSCT) is controversial. We retrospectively analyzed the post HSCT outcomes of 127 patients ≥60 years of age who received induction therapy at our institution with intensive chemotherapy (IC; n = 44), lower-intensity therapy (LIT) without venetoclax (n = 29), or LIT with venetoclax (n = 54) and who underwent allogeneic HSCT in the first remission. The 2-year relapse-free survival …

Deep Learning-Based Tem Image Analysis For Fully Automated Detection Of Gold Nanoparticles Internalized Within Tumor Cell, Amrit Kaphle, Sandun Jayarathna, Hem Moktan, Maureen Aliru, Subhiksha Raghuram, Sunil Krishnan, Sang Hyun Cho

Faculty, Staff and Student Publications

Transmission electron microscopy (TEM) imaging can be used for detection/localization of gold nanoparticles (GNPs) within tumor cells. However, quantitative analysis of GNP-containing cellular TEM images typically relies on conventional/thresholding-based methods, which are manual, time-consuming, and prone to human errors. In this study, therefore, deep learning (DL)-based methods were developed for fully automated detection of GNPs from cellular TEM images. Several models of "you only look once (YOLO)" v5 were implemented, with a few adjustments to enhance the model's performance by applying the transfer learning approach, adjusting the size of the input image, and choosing the best optimization algorithm. Seventy-eight original …

Dual Targeting Of Cdk4/6 And Bcl-2 Exhibits A Potent Antitumor Effect On Mantle Cell Lymphoma, Yuxuan Che, Yang Liu, Yijing Li, Joseph M Mcintosh, Alexa Jordan, Fangfang Yan, Wei Wang, Lei Nie, Heng-Huan Lee, Jingling Jin, Yixin Yao, Zhongming Zhao, Vivian Changying Jiang, Michael Wang

Faculty, Staff and Student Publications

No abstract provided.

Rad51c-Xrcc3 Structure And Cancer Patient Mutations Define Dna Replication Roles, Michael A Longo, Sunetra Roy, Yue Chen, Karl-Heinz Tomaszowski, Andrew S Arvai, Jordan T Pepper, Rebecca A Boisvert, Selvi Kunnimalaiyaan, Caezanne Keshvani, David Schild, Albino Bacolla, Gareth J Williams, John A Tainer, Katharina Schlacher

Faculty, Staff and Student Publications

RAD51C is an enigmatic predisposition gene for breast, ovarian, and prostate cancer. Currently, missing structural and related functional understanding limits patient mutation interpretation to homology-directed repair (HDR) function analysis. Here we report the RAD51C-XRCC3 (CX3) X-ray co-crystal structure with bound ATP analog and define separable RAD51C replication stability roles informed by its three-dimensional structure, assembly, and unappreciated polymerization motif. Mapping of cancer patient mutations as a functional guide confirms ATP-binding matching RAD51 recombinase, yet highlights distinct CX3 interfaces. Analyses of CRISPR/Cas9-edited human cells with RAD51C mutations combined with single-molecule, single-cell and biophysics measurements uncover discrete CX3 regions for DNA replication …

Longitudinal Diffusion And Volumetric Kinetics Of Head And Neck Cancer Magnetic Resonance On A 15 T Mr-Linear Accelerator Hybrid System: A Prospective R-Ideal Stage 2a Imaging Biomarker Characterization/Pre-Qualification Study, Joint Head And Neck Radiation Therapy-Mri Development Cooperative, Mr-Linac Consortium Head And Neck Tumor Site Group

Faculty, Staff and Student Publications

Objectives: We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5 T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker characterization effort.

Methods:Thirty patients with HNSCC who received curative-intent RT at MD Anderson Cancer Center, were included. Baseline and weekly MRI were obtained, and various ADC parameters were extracted from the regions of interest (ROIs). Baseline and weekly ADC parameters were …

Simplified And Highly-Reliable Automated Production Of [8f]Fspg For Clinical Studies, Mai Lin, Robert T Ta, H Charles Manning

Faculty, Staff and Student Publications

Background: (S)-4-(3-18F-Fluoropropyl)-L-Glutamic Acid ([18F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc-), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of [18F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results. In particular, low background uptake in the brain, lung, liver, and bowel was observed that further leads to excellent imaging contrasts of [18F]FSPG PET. However, reliable production-scale cGMP-compliant automated procedures for [18F]FSPG production are still lacking to further increase the utility and …

Recombinant Adamts-13 Improves Survival Of Mice Subjected To Endotoxemia, Daniel Gao, Zhou Zhou, Ruidong Ma, Huaizhu Wu, Trung Nguyen, Li Liu, Jingfei Dong

Faculty, Staff and Students Publications

When stimulated by proinflammatory mediators, endothelial cells release ultra-large von Willebrand factor (ULVWF) multimers that are hyperactive in activating and aggregating platelets. These ULVWF multimers can accumulate in the circulation and on the inflamed endothelium because they are insufficiently cleaved by the metalloprotease ADAMTS-13, which becomes moderately deficient under conditions of systemic inflammation. This moderate ADAMTS-13 deficiency may lead to thrombotic complications that contribute to ischemic tissue injury and organ failure that are associated with severe infections. To test this hypothesis, we investigated whether recombinant ADAMTS-13 improves the pathological course of endotoxemia in lipopolysaccharide (LPS)-treated mice. C57BL/J6 mice received a …

Correcting Calculation And Data Errors Reveals That The Original Conclusions Were Incorrect In “The Best Drug Supplement For Obesity Treatment: A Systematic Review And Network Meta-Analysis”, Xiaoxin Yu, Patrice L Capers, Roger S Zoh, David B Allison

Children’s Nutrition Research Center Staff Publications

The goal of this study was to reproduce and evaluate the reliability of the network meta-analysis performed in the article "The best drug supplement for obesity treatment: A systematic review and network meta-analysis" by Salari et al. In recent years, it has become more common to employ network meta-analysis to assess the relative efficacy of treatments often used in clinical practice. To duplicate Salari et al.'s research, we pulled data directly from the original trials and used Cohen's D to determine the effect size for each treatment. We reanalyzed the data since we discovered significant differences between the data we …

Correlative Cryo-Fib And Cryo-Et Of Dendritic Spines And Synaptic Connections, Erik D Anderson, Christopher A Cronkite, Kimberley F Tolias, Steven J Ludtke

Faculty, Staff and Students Publications

No abstract provided.

Homeobox Transcription Factor Hbxa Influences Expression Of Over One Thousand Genes In The Model Fungus Aspergillus Nidulans, Sandesh S. Pandit, Jinfang Zheng, Yanbin Yan, Sophie Lorber, Olivier Puel, Sourabh Dhingra, Eduardo A. Espeso, Ana M. Calvo

Food for Health: Publications

In fungi, conserved homeobox-domain proteins are transcriptional regulators governing development. In Aspergillus species, several homeobox-domain transcription factor genes have been identified, among them, hbxA/hbx1. For instance, in the opportunistic human pathogen Aspergillus fumigatus, hbxA is involved in conidial production and germination, as well as virulence and secondary metabolism, including production of fumigaclavines, fumiquinazolines, and chaetominine. In the agriculturally important fungus Aspergillus flavus, disruption of hbx1 results in fluffy aconidial colonies unable to produce sclerotia. hbx1 also regulates production of aflatoxins, cyclopiazonic acid and aflatrem. Furthermore, transcriptome studies revealed that hbx1 has a broad effect on …

Comparison Of Dna Vaccines With As03 As An Adjuvant And An Mrna Vaccine Against Sars-Cov-2, Praveen Neeli, Dafei Chai, Xu Wang, Navid Sobhani, George Udeani, Yong Li

Faculty, Staff and Students Publications

Emerging variants of SARS-CoV-2 call for frequent changes in vaccine antigens. Nucleic acid-based vaccination strategies are superior as the coding sequences can be easily altered with little impact on downstream production. mRNA vaccines, including variant-specific boosters, are approved for SARS-CoV-2. Here, we tested the efficacy of DNA vaccines against the SARS-CoV-2 Spike aided by the AddaS03 adjuvant using electroporation and compared their immunogenicity with an approved mRNA vaccine (mRNA-1273). DNA vaccination elicited robust humoral and cellular immune responses in C57BL/6 mice with Spike-specific antibody neutralization and T cells produced from 20 μg DNA vaccines similar to that from 0.5 μg …

Targeting Polyploid Giant Cancer Cells Potentiates A Therapeutic Response And Overcomes Resistance To Parp Inhibitors In Ovarian Cancer, Xudong Zhang, Jun Yao, Xiaoran Li, Na Niu, Yan Liu, Richard A Hajek, Guang Peng, Shannon Westin, Anil K Sood, Jinsong Liu

Faculty, Staff and Student Publications

To understand the mechanism of acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) olaparib, we induced the formation of polyploid giant cancer cells (PGCCs) in ovarian and breast cancer cell lines, high-grade serous cancer (HGSC)-derived organoids, and patient-derived xenografts (PDXs). Time-lapse tracking of ovarian cancer cells revealed that PGCCs primarily developed from endoreplication after exposure to sublethal concentrations of olaparib. PGCCs exhibited features of senescent cells but, after olaparib withdrawal, can escape senescence via restitutional multipolar endomitosis and other noncanonical modes of cell division to generate mitotically competent resistant daughter cells. The contraceptive drug mifepristone blocked PGCC formation and daughter cell …

Clinical And Functional Correlates Of Parkinsonism In A Population-Based Sample Of Individuals Aged 75 +: The Pietà Study, Thiago Cardoso Vale, Francisco Eduardo Costa Cardoso, Danilo Jorge Da Silva, Elisa De Paula Franca Resende, Débora Palma Maia, Mauro César Quintão Cunningham, Henrique Cerqueira Guimarães, João Carlos Barbosa Machado, Antônio Lúcio Teixeira, Paulo Caramelli, Maira Tonidandel Barbosa

Faculty, Staff and Student Publications

BACKGROUND: Parkinsonism is strongly associated with ageing, and many studies have suggested that parkinsonian signs may affect up to half of older adults and is associated with a wide range of adverse health outcomes. We compared clinical and functional characteristics of oldest-old community-dwelling individuals with parkinsonism (parkinsonian group [PG]) to individuals without parkinsonism (non-parkinsonian group [NPG].

METHODS: The Pietà study is a population-based study conducted in Caeté, southeast Brazil, involving 607 individuals aged 75 + years submitted to an extensive clinical evaluation. A subset of 65 PG individuals (61.5% women, median age of 82 years) was compared to 542 NPG …

Differential Effects Of Bariatric Surgery And Caloric Restriction On Hepatic One-Carbon And Fatty Acid Metabolism, Arnon Haran, Michael Bergel, Doron Kleiman, Liron Hefetz, Hadar Israeli, Sarah Weksler-Zangen, Bella Agranovich, Ifat Abramovich, Rachel Ben-Haroush Schyr, Eyal Gottlieb, Danny Ben-Zvi

Faculty, Staff and Student Publications

Weight loss interventions, including dietary changes, pharmacotherapy, or bariatric surgery, prevent many of the adverse consequences of obesity, and may also confer intervention-specific benefits beyond those seen with decreased weight alone. We compared the molecular effects of different interventions on liver metabolism to understand the mechanisms underlying these benefits. Male rats on a high-fat, high-sucrose diet underwent sleeve gastrectomy (SG) or intermittent fasting with caloric restriction (IF-CR), achieving equivalent weight loss. The interventions were compared to