Digital Commons Network^™

Serological Evidence Of Severe Fever With Thrombocytopenia Syndrome Virus And Igm Positivity Were Identified In Healthy Residents In Vietnam, Xuan Chuong Tran, Sung Hye Kim, Jeong-Eun Lee, So-Hee Kim, Su Yeon Kang, Nguyen D Binh, Pham V Duc, Phan T K Phuong, Nguyen T P Thao, Wonwoo Lee, Joon-Yong Bae, Man-Seong Park, Misun Kim, Jeong Rae Yoo, Sang Taek Heo, Kyeong Ho An, Jung Mogg Kim, Nam-Hyuk Cho, Sun-Ho Kee, Keun Hwa Lee

Faculty, Staff and Student Publications

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne viral disease, is prevalent in East Asia and has also been reported in Southeast Asia since 2019. SFTS patients in Vietnam were first reported in 2019. However, the seroprevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) in Vietnam has not been reported. To investigate the seroprevalence of SFTSV in Vietnam, we collected serum samples from 714 healthy residents in Thua Thien Hue and Quang Nam Province, Vietnam, and the seroprevalence of SFTSV was assessed using immunofluorescence antibody assay (IFA), Enzyme-Linked Immunosorbent Assays (ELISAs) and the 50% focus reduction neutralization test …

Scgwas: Landscape Of Trait-Cell Type Associations By Integrating Single-Cell Transcriptomics-Wide And Genome-Wide Association Studies, Peilin Jia, Ruifeng Hu, Fangfang Yan, Yulin Dai, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: The rapid accumulation of single-cell RNA sequencing (scRNA-seq) data presents unique opportunities to decode the genetically mediated cell-type specificity in complex diseases. Here, we develop a new method, scGWAS, which effectively leverages scRNA-seq data to achieve two goals: (1) to infer the cell types in which the disease-associated genes manifest and (2) to construct cellular modules which imply disease-specific activation of different processes.

RESULTS: scGWAS only utilizes the average gene expression for each cell type followed by virtual search processes to construct the null distributions of module scores, making it scalable to large scRNA-seq datasets. We demonstrated scGWAS in …

Federated Learning Algorithms For Generalized Mixed-Effects Model (Glmm) On Horizontally Partitioned Data From Distributed Sources, Wentao Li, Jiayi Tong, Md Monowar Anjum, Noman Mohammed, Yong Chen, Xiaoqian Jiang

Faculty, Staff and Student Publications

OBJECTIVES: This paper developed federated solutions based on two approximation algorithms to achieve federated generalized linear mixed effect models (GLMM). The paper also proposed a solution for numerical errors and singularity issues. And showed the two proposed methods can perform well in revealing the significance of parameter in distributed datasets, comparing to a centralized GLMM algorithm from R package ('lme4') as the baseline model.

METHODS: The log-likelihood function of GLMM is approximated by two numerical methods (Laplace approximation and Gaussian Hermite approximation, abbreviated as LA and GH), which supports federated decomposition of GLMM to bring computation to data. To solve …

Central Nervous System (Cns) Inflammatory Demyelinating Diseases (Idds) Associated With Covid-19: A Case Series And Review, Parissa Feizi, Kanika Sharma, Shreya R Pasham, Lalit Nirwan, Joe Joseph, Shruti Jaiswal, Shitiz Sriwastava

Faculty, Staff and Student Publications

BACKGROUND: Over the past two years, SARS-CoV-2 has frequently been documented with various post and para-infectious complications, including cerebrovascular, neuromuscular, and some demyelinating conditions such as acute disseminated encephalomyelitis (ADEM). We report two rare neurological manifestations post-COVID-19 infection; multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Further, we reviewed other CNS inflammatory demyelinating diseases (IDDs) associated with SARS-CoV-2, including optic neuritis (ON) and neuromyelitis optica spectrum disorders (NMOSD).

METHODS: A descriptive analysis and literature search of Google Scholar and PubMed was conducted by two independent reviewers from December 1st, 2019, to March 30th, 2022, and included all the …

Combined Trip13 And Aurora Kinase Inhibition Induces Apoptosis In Human Papillomavirus-Driven Cancers, Soma Ghosh, Tuhina Mazumdar, Wei Xu, Reid T Powell, Clifford Stephan, Li Shen, Pooja A Shah, Curtis R Pickering, Jeffery N Myers, Jing Wang, Mitchell J Frederick, Faye M Johnson

Faculty, Staff and Student Publications

PURPOSE: Human papillomavirus (HPV) causes >5% of cancers, but no therapies uniquely target HPV-driven cancers.

EXPERIMENTAL DESIGN: We tested the cytotoxic effect of 864 drugs in 16 HPV-positive and 17 HPV-negative human squamous cancer cell lines. We confirmed apoptosis in vitro and in vivo using patient-derived xenografts. Mitotic pathway components were manipulated with drugs, knockdown, and overexpression.

RESULTS: Aurora kinase inhibitors were more effective in vitro and in vivo in HPV-positive than in HPV-negative models. We hypothesized that the mechanism of sensitivity involves retinoblastoma (Rb) expression because the viral oncoprotein E7 leads to Rb protein degradation, and basal Rb protein …

Machine Learning On Syngeneic Mouse Tumor Profiles To Model Clinical Immunotherapy Response, Zexian Zeng, Shengqing Stan Gu, Cheryl J Wong, Lin Yang, Nofal Ouardaoui, Dian Li, Wubing Zhang, Myles Brown, X Shirley Liu

Faculty, Staff and Student Publications

Most patients with cancer are refractory to immune checkpoint blockade (ICB) therapy, and proper patient stratification remains an open question. Primary patient data suffer from high heterogeneity, low accessibility, and lack of proper controls. In contrast, syngeneic mouse tumor models enable controlled experiments with ICB treatments. Using transcriptomic and experimental variables from >700 ICB-treated/control syngeneic mouse tumors, we developed a machine learning framework to model tumor immunity and identify factors influencing ICB response. Projected on human immunotherapy trial data, we found that the model can predict clinical ICB response. We further applied the model to predicting ICB-responsive/resistant cancer types in …

Human Nop2/Nsun1 Regulates Ribosome Biogenesis Through Non-Catalytic Complex Formation With Box C/D Snornps, Han Liao, Anushri Gaur, Hunter Mcconie, Amirtha Shekar, Karen Wang, Jeffrey T Chang, Ghislain Breton, Catherine Denicourt

Faculty, Staff and Student Publications

5-Methylcytosine (m5C) is a base modification broadly found on various RNAs in the human transcriptome. In eukaryotes, m5C is catalyzed by enzymes of the NSUN family composed of seven human members (NSUN1-7). NOP2/NSUN1 has been primarily characterized in budding yeast as an essential ribosome biogenesis factor required for the deposition of m5C on the 25S ribosomal RNA (rRNA). Although human NOP2/NSUN1 has been known to be an oncogene overexpressed in several types of cancer, its functions and substrates remain poorly characterized. Here, we used a miCLIP-seq approach to identify human NOP2/NSUN1 RNA substrates. Our analysis revealed that NOP2/NSUN1 catalyzes the …

Prevalence Of Polypharmacy And Associated Adverse Outcomes And Risk Factors Among Children With Asthma In The Usa: A Cross-Sectional Study, Luyu Xie, Andrew Gelfand, Caitlin C Murphy, M Sunil Mathew, Folefac Atem, George L Delclos, Sarah Messiah

Faculty, Staff and Student Publications

OBJECTIVE: to estimate the prevalence of polypharmacy, identify risk factors and examine related adverse outcomes in the US children with asthma.

DESIGN, SETTING AND PARTICIPANTS: This population-based, cross-sectional study included 1776 children with asthma from the 2011-2020 National Health and Nutrition Examination Surveys.

EXPOSURES: Polypharmacy is defined as taking ≥2 medications concurrently for ≥1 day over the past 30 days.

MAIN OUTCOMES AND MEASURES: (1) Weighted prevalence estimates of polypharmacy in children with asthma; (2) asthma attacks and emergency department (ED) visits.

RESULTS: The estimated prevalence of polypharmacy in the US children with asthma was 33.49% (95% CI 31.81% to …

2022 Practice Recommendation Updates From The World Consensus Conference On Bia-Alcl, Fabio Santanelli Di Pompeo, Mark W Clemens, Michael Atlan, Giovanni Botti, Peter G Cordeiro, Daphne De Jong, Arianna Di Napoli, Dennis Hammond, Cara L Haymaker, Steven M Horwitz, Kelly Hunt, Peter Lennox, Patrick Mallucci, Roberto N Miranda, Alexandre M Munhoz, Eric Swanson, Suzanne D Turner, Guido Firmani, Michail Sorotos

Faculty, Staff and Student Publications

BACKGROUND: Laboratory and clinical research on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is rapidly evolving. Changes in standard of care and insights into best practice were recently presented at the 3rd World Consensus Conference on BIA-ALCL.

OBJECTIVES: The authors sought to provide practice recommendations from a consensus of experts, supplemented with a literature review regarding epidemiology, etiology, pathogenesis, diagnosis, treatment, socio-psychological aspects, and international authority guidance.

METHODS: A literature search of all manuscripts between 1997 and August 2021 for the above areas of BIA-ALCL was conducted with the PubMed database. Manuscripts in different languages, on non-human subjects, and/or discussing …

Public Health Burden Of Secondhand Smoking: Case Reports Of Lung Cancer And A Literature Review, Ladislav Štěpánek, Jarmila Ševčíková, Dagmar Horáková, Mihir Sanjay Patel, Radka Durďáková

Faculty, Staff and Student Publications

Secondhand smoke (SHS), composed of mainstream and sidestream smoke, is a known human carcinogen. It contains a variety of harmful substances at even higher concentrations than mainstream smoke itself, which is inhaled during firsthand smoking. Exposure to SHS, affecting more than a third of the worldwide population, increases the likelihood of lung cancer by roughly 30%, with specific contributions depending on the histological type of cancer. This study aimed to present the harmful potential of SHS through case reports and describe the burden of SHS via a literature review. From a collection of lung cancer case reports occurring in never …

Structural And Functional Diversity Of Type Iv Secretion Systems, Melissa R Cruz, Shane Cristy, Shantanu Guha, Giuseppe Buda De Cesare, Elena Evdokimova, Hiram Sanchez, Dominika Borek, Pedro Miramón, Junko Yano, Paul L Fidel, Alexei Savchenko, David R Andes, Peter J Stogios, Michael C Lorenz, Danielle A Garsin

Faculty, Staff and Student Publications

Fungal pathogens are a continuing challenge due to few effective antifungals and a rise in resistance. In previous work, we described the inhibition of Candida albicans virulence following exposure to the 68 amino acid bacteriocin, EntV, secreted by Enterococcus faecalis. Here, to optimize EntV as a potential therapeutic and better understand its antifungal features, an X-ray structure is obtained. The structure consists of six alpha helices enclosing a seventh 16 amino acid helix (α7). The individual helices are tested for antifungal activity using in vitro and nematode infection assays. Interestingly, α7 retains antifungal, but not antibacterial activity and is also …

Neoadjuvant Toripalimab Combined With Gemcitabine And Cisplatin In Resectable Locally Advanced Head And Neck Squamous Cell Carcinoma (Neotgp01): An Open Label, Single-Arm, Phase Ib Clinical Trial, Xiaotao Huang, Qiaodan Liu, Guihua Zhong, Yingpeng Peng, Ye Liu, Lizhong Liang, Haiyu Hong, Weineng Feng, Shuang Yang, Yaqin Zhang, Shiping Xian, Zhanyu Li, Yuling Zhou, Zhaoyuan Zhang, Wen Jiang, Jun Liang, Zhi-Gang Liu

Faculty, Staff and Student Publications

BACKGROUND: Neoadjuvant programmed death receptor-1 (PD-1) inhibitors have drawn increasing attention in locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the safety and efficacy of gemcitabine and cisplatin (GP), combined with a PD-1 inhibitor, in patients with locally advanced HNSCC.

MATERIALS AND METHODS: A total of 23 eligible patients were administered two cycles of toripalimab and GP followed by surgical resection. The primary endpoints were safety, treatment-related adverse events (TRAEs), and non-operation delay rates. The secondary endpoints consisted of pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), and …

The Temporal Impulse Response Function In Infantile Nystagmus, Gal Avital, Felicia Kuperwaser, Andrew W Pountain, Keenan A Lacey, Erin E Zwack, Magdalena Podkowik, Bo Shopsin, Victor J Torres, Itai Yanai

Faculty, Staff and Student Publications

Innate immune recognition of bacterial pathogens is a key determinant of the ensuing systemic response, and host or pathogen heterogeneity in this early interaction can impact the course of infection. To gain insight into host response heterogeneity, we investigate macrophage inflammatory dynamics using primary human macrophages infected with Group B Streptococcus. Transcriptomic analysis reveals discrete cellular states within responding macrophages, one of which consists of four sub-states, reflecting inflammatory activation. Infection with six additional bacterial species—Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Yersinia pseudotuberculosis, Shigella flexneri, and Salmonella enterica—recapitulates these states, though at …

Whole Genome Sequence Analysis Of Blood Lipid Levels In >66,000 Individuals, Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Akhil Pampana, David Y Zhang, Joseph Park, Stella Aslibekyan, Joshua C Bis, Jennifer A Brody, Brian E Cade, Lee-Ming Chuang, Ren-Hua Chung, Joanne E Curran, Lisa De Las Fuentes, Paul S De Vries, Ravindranath Duggirala, Barry I Freedman, Mariaelisa Graff, Xiuqing Guo, Nancy Heard-Costa, Bertha Hidalgo, Chii-Min Hwu, Marguerite R Irvin, Tanika N Kelly, Brian G Kral, Leslie Lange, Xiaohui Li, Martin Lisa, Steven A Lubitz, Ani W Manichaikul, Preuss Michael, May E Montasser, Alanna C Morrison, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Patricia A Peyser, Muagututia S Reupena, Jennifer A Smith, Xiao Sun, Kent D Taylor, Russell P Tracy, Michael Y Tsai, Zhe Wang, Yuxuan Wang, Wei Bao, John T Wilkins, Lisa R Yanek, Wei Zhao, Donna K Arnett, John Blangero, Eric Boerwinkle, Donald W Bowden, Yii-Der Ida Chen, Adolfo Correa, L Adrienne Cupples, Susan K Dutcher, Patrick T Ellinor, Myriam Fornage, Stacey Gabriel, Soren Germer, Richard Gibbs, Jiang He, Robert C Kaplan, Sharon L R Kardia, Ryan Kim, Charles Kooperberg, Ruth J F Loos, Karine A Viaud-Martinez, Rasika A Mathias, Stephen T Mcgarvey, Braxton D Mitchell, Deborah Nickerson, Kari E North, Bruce M Psaty, Susan Redline, Alexander P Reiner, Ramachandran S Vasan, Stephen S Rich, Cristen Willer, Jerome I Rotter, Daniel J Rader, Xihong Lin, Gina M Peloso, Pradeep Natarajan

Faculty, Staff and Student Publications

Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid …

Crossmodal Correspondences Between Basic Tastes And Visual Design Features: A Narrative Historical Review, Byron P Lee, Charles Spence

Faculty, Staff and Student Publications

People tend to associate abstract visual features with basic taste qualities. This narrative historical review critically evaluates the literature on these associations, often referred to as crossmodal correspondences, between basic tastes and visual design features such as color hue and shape curvilinearity. The patterns, discrepancies, and evolution in the development of the research are highlighted while the mappings that have been reported to date are summarized. The review also reflects on issues of cross-cultural validity and deviations in the matching patterns that are observed when correspondences are assessed with actual tastants versus with verbal stimuli. The various theories that have …

Evolution And Modulation Of Antigen-Specific T Cell Responses In Melanoma Patients, Jani Huuhtanen, Liang Chen, Emmi Jokinen, Henna Kasanen, Tapio Lönnberg, Anna Kreutzman, Katriina Peltola, Micaela Hernberg, Chunlin Wang, Cassian Yee, Harri Lähdesmäki, Mark M Davis, Satu Mustjoki

Faculty, Staff and Student Publications

Analyzing antigen-specific T cell responses at scale has been challenging. Here, we analyze three types of T cell receptor (TCR) repertoire data (antigen-specific TCRs, TCR-repertoire, and single-cell RNA + TCRαβ-sequencing data) from 515 patients with primary or metastatic melanoma and compare it to 783 healthy controls. Although melanoma-associated antigen (MAA) -specific TCRs are restricted to individuals, they share sequence similarities that allow us to build classifiers for predicting anti-MAA T cells. The frequency of anti-MAA T cells distinguishes melanoma patients from healthy and predicts metastatic recurrence from primary melanoma. Anti-MAA T cells have stem-like properties and frequent interactions with regulatory …

2021 Saem Consensus Conference Proceedings: Research Priorities For Developing Emergency Department Screening Tools For Social Risks And Needs, Jacqueline Furbacher, Callan Fockele, Ben Del Buono, Laura Janneck, Cooper March, Melanie Molina, Herbet C Duber, Kelly M Doran, Michelle P Lin, Richelle J Cooper, Payal Modi

Faculty, Staff and Student Publications

INTRODUCTION: The Emergency Department (ED) acts as a safety net for our healthcare system. While studies have shown increased prevalence of social risks and needs among ED patients, there are many outstanding questions about the validity and use of social risks and needs screening tools in the ED setting.

METHODS: In this paper, we present research gaps and priorities pertaining to social risks and needs screening tools used in the ED, identified through a consensus approach informed by literature review and external expert feedback as part of the 2021 SAEM Consensus Conference -- From Bedside to Policy: Advancing Social Emergency …

Metarnn: Differentiating Rare Pathogenic And Rare Benign Missense Snvs And Indels Using Deep Learning, Chang Li, Degui Zhi, Kai Wang, Xiaoming Liu

Faculty, Staff and Student Publications

Multiple computational approaches have been developed to improve our understanding of genetic variants. However, their ability to identify rare pathogenic variants from rare benign ones is still lacking. Using context annotations and deep learning methods, we present pathogenicity prediction models, MetaRNN and MetaRNN-indel, to help identify and prioritize rare nonsynonymous single nucleotide variants (nsSNVs) and non-frameshift insertion/deletions (nfINDELs). We use independent test sets to demonstrate that these new models outperform state-of-the-art competitors and achieve a more interpretable score distribution. Importantly, prediction scores from both models are comparable, enabling easy adoption of integrated genotype-phenotype association analysis methods. All pre-computed nsSNV scores …

Dissection Of A Sensorimotor Circuit Underlying Pathogen Aversion In C Elegans, Adam Filipowicz, Jonathan Lalsiamthara, Alejandro Aballay

Faculty, Staff and Student Publications

BACKGROUND: Altering animal behavior to reduce pathogen exposure is a key line of defense against pathogen attack. In Caenorhabditis elegans, alterations in intestinal physiology caused by pathogen colonization and sensation of microbial metabolites may lead to activation of pathogen aversive behaviors ranging from aversive reflexes to learned avoidance. However, the neural circuitry between chemosensory neurons that sense pathogenic bacterial cues and the motor neurons responsible for avoidance-associated locomotion remains unknown.

RESULTS: Using C. elegans, we found that backward locomotion was a component of learned pathogen avoidance, as animals pre-exposed to Pseudomonas aeruginosa or Enterococcus faecalis showed reflexive aversion to drops …

Clinical Decision Support Malfunctions Related To Medication Routes: A Case Series, Adam Wright, Scott Nelson, David Rubins, Richard Schreiber, Dean F Sittig

Faculty, Staff and Student Publications

OBJECTIVE: To identify common medication route-related causes of clinical decision support (CDS) malfunctions and best practices for avoiding them.

MATERIALS AND METHODS: Case series of medication route-related CDS malfunctions from diverse healthcare provider organizations.

RESULTS: Nine cases were identified and described, including both false-positive and false-negative alert scenarios. A common cause was the inclusion of nonsystemically available medication routes in value sets (eg, eye drops, ear drops, or topical preparations) when only systemically available routes were appropriate.

DISCUSSION: These value set errors are common, occur across healthcare provider organizations and electronic health record (EHR) systems, affect many different types of …

Risk Factors For Thoracic Aortic Dissection, Zhen Zhou, Alana C Cecchi, Siddharth K Prakash, Dianna M Milewicz

Faculty, Staff and Student Publications

Thoracic aortic aneurysms involving the root and/or the ascending aorta enlarge over time until an acute tear in the intimal layer leads to a highly fatal condition, an acute aortic dissection (AAD). These Stanford type A AADs, in which the tear occurs above the sinotubular junction, leading to the formation of a false lumen in the aortic wall that may extend to the arch and thoracoabdominal aorta. Type B AADs originate in the descending thoracic aorta just distal to the left subclavian artery. Genetic variants and various environmental conditions that disrupt the aortic wall integrity have been identified that increase …

Critical Role Of Lncepat In Coupling Dysregulated Egfr Pathway And Histone H2a Deubiquitination During Glioblastoma Tumorigenesis, Linlin Li, Aidong Zhou, Yanjun Wei, Feng Liu, Peng Li, Runping Fang, Li Ma, Sicong Zhang, Longqiang Wang, Jinze Liu, Hope T Richard, Yiwen Chen, Hengbin Wang, Suyun Huang

Faculty, Staff and Student Publications

Histone 2A (H2A) monoubiquitination is a fundamental epigenetics mechanism of gene expression, which plays a critical role in regulating cell fate. However, it is unknown if H2A ubiquitination is involved in EGFR-driven tumorigenesis. In the current study, we have characterized a previously unidentified oncogenic lncRNA (lncEPAT) that mediates the integration of the dysregulated EGFR pathway with H2A deubiquitination in tumorigenesis. LncEPAT was induced by the EGFR pathway, and high-level lncEPAT expression positively correlated with the glioma grade and predicted poor survival of glioma patients. Mass spectrometry analyses revealed that lncEPAT specifically interacted with deubiquitinase USP16. LncEPAT inhibited USP16's recruitment to …

Respiratory Virus Surveillance Among Children With Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021, Ariana Perez, Joana Y Lively, Aaron Curns, Geoffrey A Weinberg, Natasha B Halasa, Mary Allen Staat, Peter G Szilagyi, Laura S Stewart, Monica M Mcneal, Benjamin Clopper, Yingtao Zhou, Brett L Whitaker, Elizabeth Lemasters, Elizabeth Harker, Janet A Englund, Eileen J Klein, Rangaraj Selvarangan, Christopher J Harrison, Julie A Boom, Leila C Sahni, Marian G Michaels, John V Williams, Gayle E Langley, Susan I Gerber, Angela Campbell, Aron J Hall, Brian Rha, Meredith Mcmorrow

Faculty, Staff and Student Publications

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN …

Feasibility Of A Novel Non-Invasive Swab Technique For Serial Whole-Exome Sequencing Of Cervical Tumors During Chemoradiation Therapy, Julianna K Bronk, Chiraag Kapadia, Xiaogang Wu, Bhavana V Chapman, Rui Wang, Tatiana V Karpinets, Xingzhi Song, Andrew M Futreal, Jianhua Zhang, Ann H Klopp, Lauren E Colbert

Faculty, Staff and Student Publications

BACKGROUND: Clinically relevant genetic predictors of radiation response for cervical cancer are understudied due to the morbidity of repeat invasive biopsies required to obtain genetic material. Thus, we aimed to demonstrate the feasibility of a novel noninvasive cervical swab technique to (1) collect tumor DNA with adequate throughput to (2) perform whole-exome sequencing (WES) at serial time points over the course of chemoradiation therapy (CRT).

METHODS: Cervical cancer tumor samples from patients undergoing chemoradiation were collected at baseline, at week 1, week 3, and at the completion of CRT (week 5) using a noninvasive swab-based biopsy technique. Swab samples were …

Molecular Pathways Of Major Depressive Disorder Converge On The Synapse, Gabriel R Fries, Valeria A Saldana, Johannes Finnstein, Theo Rein

Faculty, Staff and Student Publications

Major depressive disorder (MDD) is a psychiatric disease of still poorly understood molecular etiology. Extensive studies at different molecular levels point to a high complexity of numerous interrelated pathways as the underpinnings of depression. Major systems under consideration include monoamines, stress, neurotrophins and neurogenesis, excitatory and inhibitory neurotransmission, mitochondrial dysfunction, (epi)genetics, inflammation, the opioid system, myelination, and the gut-brain axis, among others. This review aims at illustrating how these multiple signaling pathways and systems may interact to provide a more comprehensive view of MDD's neurobiology. In particular, considering the pattern of synaptic activity as the closest physical representation of mood, …

Identification Of Minimum Essential Therapeutic Mixtures From Cannabis Plant Extracts By Screening In Cell And Animal Models Of Parkinson’S Disease, Michael G Morash, Jessica Nixon, Lori M N Shimoda, Helen Turner, Alexander J Stokes, Andrea L Small-Howard, Lee D Ellis

Faculty, Staff and Student Publications

Medicinal cannabis has shown promise for the symptomatic treatment of Parkinson's disease (PD), but patient exposure to whole plant mixtures may be undesirable due to concerns around safety, consistency, regulatory issues, and psychoactivity. Identification of a subset of components responsible for the potential therapeutic effects within cannabis represents a direct path forward for the generation of anti-PD drugs. Using an

Single-Cell Sequencing Reveals Trajectory Of Tumor-Infiltrating Lymphocyte States In Pancreatic Cancer, Aislyn Schalck, Donastas Sakellariou-Thompson, Marie-Andrée Forget, Emi Sei, Tara G Hughes, Alexandre Reuben, Shanshan Bai, Min Hu, Tapsi Kumar, Mark W Hurd, Matthew H G Katz, Ching-Wei D Tzeng, Shubham Pant, Milind Javle, David R Fogelman, Anirban Maitra, Cara L Haymaker, Michael P Kim, Nicholas E Navin, Chantale Bernatchez

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) has few effective treatments. Immunotherapy, an attractive alternative strategy, remains challenging with the lack of knowledge on the tumor-infiltrating lymphocyte (TIL) landscape in PDAC. To generate a reference of T-cell subpopulations, we profiled 80,000 T cells from 57 PDAC samples, 22 uninvolved/normal samples, and cultured TIL using single-cell transcriptomic and T-cell receptor analysis. These data revealed 20 cell states and heterogeneous distributions of TIL populations. The CD8+ TIL contained a putative transitional GZMK+ population based on T-cell receptor clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical …

Effectiveness And Feasibility Of Telerehabilitation In Patients With Covid-19: A Systematic Review And Meta-Analysis, Abubeker Alebachew Seid, Setognal Birara Aychiluhm, Ahmed Adem Mohammed

Faculty, Staff and Student Publications

OBJECTIVES: To determine the pooled effectiveness and feasibility of telerehabilitation in patients with COVID-19.

DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs).

DATA SOURCES: PubMed, CINAHL, Science Direct, PEDro, Google Scholar and Cochrane Library databases were systematically searched to the end of March 2022.

ELIGIBILITY CRITERIA AND OUTCOMES: RCTs investigating the effects of telerehabilitation in the management of patients with COVID-19 were included. The outcomes of interest were functional capacity, cardiopulmonary exercise tests, quality of life and other variables where data are available.

DATA EXTRACTION AND SYNTHESIS: Two reviewers screened, extracted data and performed methodological quality assessment independently. …

Peripheral Blood Monocytes As A Therapeutic Target For Marrow Stromal Cells In Stroke Patients, Nikunj Satani, Kaushik Parsha, Courtney Davis, Adrian Gee, Scott D Olson, Jaroslaw Aronowski, Sean I Savitz

Faculty, Staff and Student Publications

BACKGROUND: Systemic administration of marrow stromal cells

METHODS: Peripheral blood from stroke patients was collected at 5-7 days (

RESULTS: Our results show that there is a higher release of IFN-γ and IL-10 from monocytes isolated from peripheral blood at day 5-7 after stroke compared with monocytes from healthy controls. In trans-well co-cultures of MSCs and monocytes isolated from stroke patients, we found statistically significant increased levels of IL-4 and MCP-1, and decreased levels of IL-6, IL-1β, and TNF-α. Addition of MSCs to monocytes increased the secretions of Fractalkine, IL-6, and MCP-1, while the secretions of TNF-α decreased, as compared …

Single-Cell Transcriptomic Profiling Reveals The Tumor Heterogeneity Of Small-Cell Lung Cancer, Yanhua Tian, Qingqing Li, Zhenlin Yang, Shu Zhang, Jiachen Xu, Zhijie Wang, Hua Bai, Jianchun Duan, Bo Zheng, Wen Li, Yueli Cui, Xin Wang, Rui Wan, Kailun Fei, Jia Zhong, Shugeng Gao, Jie He, Carl M Gay, Jianjun Zhang, Jie Wang, Fuchou Tang

Faculty, Staff and Student Publications

Small-cell lung cancer (SCLC) is the most aggressive and lethal subtype of lung cancer, for which, better understandings of its biology are urgently needed. Single-cell sequencing technologies provide an opportunity to profile individual cells within the tumor microenvironment (TME) and investigate their roles in tumorigenic processes. Here, we performed high-precision single-cell transcriptomic analysis of ~5000 individual cells from primary tumors (PTs) and matched normal adjacent tissues (NATs) from 11 SCLC patients, including one patient with both PT and relapsed tumor (RT). The comparison revealed an immunosuppressive landscape of human SCLC. Malignant cells in SCLC tumors exhibited diverse states mainly related …