Digital Commons Network^™

Local Or Systemic Antibody-Targeted Sting Activation Drives Pro- Inflammatory Stromal Metabolic Changes And Downregulates C-Myc Oncoprotein, Akash Boda

Dissertations and Theses (Open Access)

The past decade has witnessed remarkable advances in the field of cancer immunotherapy. Immune checkpoint blockade (ICB) has emerged as a cornerstone, achieving long-lasting tumor regression in several types of cancer. However, its effectiveness is often limited, particularly in certain tumor types. Immunologically "cold" tumors, such as pancreatic ductal adenocarcinoma (PDAC), remain clinically unresponsive to ICB, presenting a significant challenge in oncology. Amidst these challenges, the stimulation of the STING pathway via small molecule synthetic agonists has surfaced as a promising strategy. Acting as an in-situ vaccine, STING activation has the potential to transform the immune landscape of cold tumors …

The Role Of Ganglioside Gd2 And Gd3 Synthase (St8sia1) In The Regulation Of Immune Suppression In Breast Cancer, Bolutyfe Oderinde

Dissertations and Theses (Open Access)

Gangliosides are acidic glycosphingolipids involved in cell adhesion, proliferation, and modulation of signal transduction pathways. It has been reported that tumor-shed gangliosides influence the activity of immune cells including macrophages, NK cells, and T cells. GD3 synthase (GD3S) is the key enzyme that regulates the biosynthesis of the b and c series gangliosides, particularly GD3 and GD2, and studies have shown that GD3S is upregulated in most tumors and plays a role in tumor progression. Similarly, we have previously found GD3S to be significantly upregulated in GD2+ breast cancer stem cells (BCSC) compared to GD2- cells, and the knockdown of …

Covid-19 Risk Assessment Among Vulnerable Small Business Owners In El Paso County, Texas, Sadie H Conway, Denise Vasquez, Kristina D Mena, Louis D Brown, Soyoung Kwon, Janelle Rios

Faculty, Staff and Student Publications

Background: Our objective was to deliver actionable, worksite-specific COVID-19 risk assessments and mitigation strategies tailored to vulnerable workers in one of the highest-risk areas in the US.

Methods: Four trained, bilingual (English/Spanish) community health workers (CHWs) recruited small businesses (ie, ≤20 employees) across various industries and executed novel on-site infectious disease risk assessment surveys of at least one employer and one employee.

Results: Of 102 participating businesses (95% Hispanic-owned), 96% were characterized as "high risk" or "very high risk" for disease transmission. All businesses reported implementing at least one practice to reduce disease transmission; however, almost half of businesses lacked …

Surfactant Protein-C Regulates Alveolar Type 2 Epithelial Cell Lineages Via The Cd74 Receptor, Krishan G Jain, Yang Liu, Runzhen Zhao, Preeti J Muire, Nan-Miles Xi, Hong-Long Ji

Faculty, Staff and Student Publications

Background: Deficiency of surfactant protein-C (SPC) increases susceptibility to lung infections and injury, and suppressed expression of SPC has been associated with the severity of acute respiratory distress syndrome (ARDS). Alveolar type 2 epithelial cells (AT2) are critical for maintenance and repair of the lung. However, the role of the SPC in the regulation of AT2 cell lineage and the underlying mechanisms are not completely understood.

Methods: This study aimed to investigate the mechanisms by which SPC regulates AT2 lineages. Sftpc-/- mice were used to model the SPC deficiency in ARDS patients. We utilized three-dimensional (3D) organoids to compare AT2 …

Nasal Virus Infection Induces Asthma Exacerbation Through B-Cell-Dependent Recruitment Of Inflammatory Monocytes, Kody A Waldstein, Arman Issimov, Maria Ganama, Valerie Jinge, Stephen Tilley, Xiaoyang Hua

Faculty, Staff and Student Publications

Background: Upper respiratory viral infections (URVIs) are responsible for 80% of asthma exacerbation episodes. However, the underlying mechanisms remain poorly understood.

Methods: In this study, we used a mouse model of URVI and examined the impact of URVI on asthma phenotypes and the underlying mechanisms.

Results: Previously, we have reported that nasal-restricted infection with respiratory syncytial virus (RSV) only produces mild sino-nasal inflammation and mucus production, without causing direct lung infection. However, such nasal-restricted infection dramatically enhanced TH2 and TH17 inflammatory responses in the lungs and increased airway hyperresponsiveness (AHR) in mice with house dust mite (HDM)-induced asthma. Additionally, nasal-restricted …

Immunopeptidomic Mhc-I Profiling And Immunogenicity Testing Identifies Tcj2 As A New Chagas Disease Mrna Vaccine Candidate, Leroy Versteeg, Rakesh Adhikari, Gonteria Robinson, Jungsoon Lee, Junfei Wei, Nelufa Islam, Brian Keegan, William K Russell, Cristina Poveda, Maria Jose Villar, Kathryn Jones, Maria Elena Bottazzi, Peter Hotez, Edwin Tijhaar, Jeroen Pollet

Faculty, Staff and Students Publications

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease. Globally 6 to 7 million people are infected by this parasite of which 20-30% will progress to develop Chronic Chagasic Cardiomyopathy (CCC). Despite its high disease burden, no clinically approved vaccine exists for the prevention or treatment of CCC. Developing vaccines that can stimulate T. cruzi-specific CD8+ cytotoxic T cells and eliminate infected cells requires targeting parasitic antigens presented on major histocompatibility complex-I (MHC-I) molecules. We utilized mass spectrometry-based immunopeptidomics to investigate which parasitic peptides are displayed on MHC-I of T. cruzi infected cells. Through duplicate experiments, we identified an …

Fournier's Gangrene Severity Index And Charlson Comorbidity Index Predict Mortality, Intensive Care Unit Admission, And Length Of Hospital Stay In Patients With Fournier's Gangrene: An Analysis Of 264 Consecutive Patients, Nicholas Hauser, Chenlin Huang, Girija Vaidya, Timothy Chrusciel, Krithika Narayana Kumarasan, John Culhane, Sameer Siddiqui

Faculty, Staff and Students Publications

Introduction

Fournier’s gangrene (FG) is a rapidly progressing necrotizing fasciitis. The Fournier's Gangrene Severity Index (FGSI), in conjunction with the Charlson Comorbidity Index (CCI), has been used as a mortality predictor during hospitalization. Patients with diabetes have also been shown to be at an increased risk for the development of FG. This study explores the potential of using FGSI, CCI, and patient diabetes status in predicting more extensive patient outcomes, including intensive care unit (ICU) admission and length of hospital stay.

Methods

From 2013 to 2023, inpatient admissions with the diagnosis of FG were selected from the EPIC Clarity database …

Google Trends And Syphilis, Theodore Rosen, Maci Terrell

Faculty, Staff and Students Publications

Objective: This study aims to assess the correlation between Centers for Disease Control-reported syphilis incidence rates and case burden and public interest in syphilis as indicated by Google search trends.

Methods: This study utilized Google Trends data to analyze popular syphilis-related search terms from 2013 to 2023. The latest Centers for Disease Control-reported syphilis incidence rates for 2022 were compared to Google Trends data to identify patterns or correlations.

Results: Google Trends data showed a 37.65-percent increase in average annual searches for syphilis-related terms in the United States from 2013 to 2023. The largest increase in search volume was observed …

Association Between Microsatellite Instability Status, Clinicopathological Features And Mitochondrial Dna Amplification In Patients With Colorectal Cancer, Junmi Lu, Hong Tan, Tao Guo, Xi Chen, Zhongyi Tong

Faculty, Staff and Students Publications

The relationship between BRAF-V600E mutations, mitochondrial DNA amplification and microsatellite instability-high (MSI-H) in colorectal cancer (CRC) has yet to be fully elucidated. The aim of the present study was to assess the association between the MSI status and BRAF-V600E gene mutations/clinicopathological features/mitochondrial DNA amplification in CRC. A non-interventional study analysis was performed using the clinicopathological features of 455 patients with CRC. Immunohistochemistry was used to evaluate four mismatch repair proteins (MutS homolog 2, MutS homolog 6, MutL homolog 1 and postmeiotic segregation increased 2), Ki-67 index, and programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) expression. …

Medical School Ranking And Provider Outpatient Medicare Part D Claims For Antibiotics Among Older Patients In The Usa, Mayar Al Mohajer, David Slusky, David Nix, Catia Nicodemo

Faculty, Staff and Students Publications

BACKGROUND: Our study aimed to assess whether there was a relationship between graduating from higher-ranked medical schools and the rate of prescribing antibiotics among Medicare Part D providers in the USA.

METHODS: The study obtained data from the Medicare Part D Prescribers (FY2013-2021) and the Doctor and Clinicians National repositories. A regression model was fitted to assess the relationship between provider medical school ranking and the rate of antibiotic days supplied per 100 beneficiaries at the provider level.

RESULTS: A total of 197 540 providers were included. No association was found between the medical school ranking and the rate of …

Increasing Access To Behavioral Health Care: Examples Of Task Shifting In Two Us Government Health Care Systems, Kathryn E Kanzler, Mark E Kunik, Chase A Aycock

Faculty, Staff and Students Publications

Introduction: Addressing U.S. health disparities in behavioral health care requires innovative solutions to expand access beyond the traditional specialty behavioral health (BH) service model. One evidence-based strategy to increase access is task shifting, whereby tasks usually reserved for licensed clinicians are delegated to less specialized but uniquely capable health workers. Health care systems in the United States have been slow to adopt this approach, despite the widespread success of task shifting in other countries. However, two large government health care systems have employed unique task-shifting models for decades, integrating nonclinician health workers into BH settings: the Defense Health Agency (behavioral …

Bst2 Facilitates Activation Of Hematopoietic Stem Cells Through Erk Signaling, Marcus A Florez, Apoorva Thatavarty, Duy T Le, Holly A Hill, Youngjae Jeong, Brian M Ho, Pawel Kus, Trisha K Wathan, Bailee N Kain, Shixia Huang, Dongsu Park, Katherine Y King

Faculty, Staff and Students Publications

The proinflammatory cytokine interferon-gamma (IFNγ) is upregulated in a variety of infections and contributes to bone marrow failure through hematopoietic stem cell (HSC) activation and subsequent exhaustion. The cell surface protein, bone marrow stromal antigen 2 (BST2), is a key mediator of this process, as it is induced upon interferon stimulation and required for interferon-dependent HSC activation. To identify the mechanism by which BST2 promotes interferon-dependent HSC activation, we evaluated its role in niche localization, immune cell function, lipid raft formation, and intracellular signaling. Our studies indicated that knock out (KO) of BST2 in a murine model does not disrupt …

Fournier's Gangrene Severity Index And Charlson Comorbidity Index Predict Mortality, Intensive Care Unit Admission, And Length Of Hospital Stay In Patients With Fournier's Gangrene: An Analysis Of 264 Consecutive Patients, Nicholas Hauser, Chenlin Huang, Girija Vaidya, Timothy Chrusciel, Krithika Narayana Kumarasan, John Culhane, Sameer Siddiqui

Faculty, Staff and Students Publications

Introduction: Fournier’s gangrene (FG) is a rapidly progressing necrotizing fasciitis. The Fournier's Gangrene Severity Index (FGSI), in conjunction with the Charlson Comorbidity Index (CCI), has been used as a mortality predictor during hospitalization. Patients with diabetes have also been shown to be at an increased risk for the development of FG. This study explores the potential of using FGSI, CCI, and patient diabetes status in predicting more extensive patient outcomes, including intensive care unit (ICU) admission and length of hospital stay.

Methods: From 2013 to 2023, inpatient admissions with the diagnosis of FG were selected from the EPIC Clarity database …

Strategies To Enhance Diagnostic Capabilities For The New Drug-Resistant Tuberculosis (Dr-Tb) Drugs, Antonia Morita Iswari Saktiawati, Anca Vasiliu, Francesca Saluzzo, Onno W Akkerman

Faculty, Staff and Students Publications

The global burden of drug-resistant tuberculosis (DR-TB) continues to challenge healthcare systems worldwide. There is a critical need to tackle DR-TB by enhancing diagnostics and drug susceptibility testing (DST) capabilities, particularly for emerging DR-TB drugs. This endeavor is crucial to optimize the efficacy of new therapeutic regimens and prevent the resistance and overuse of these invaluable weapons. Despite this urgency, there remains a lack of comprehensive review of public health measures aimed at improving the diagnostics and DST capabilities. In this review, we outline strategies to enhance the capabilities, especially tailored to address the challenges posed by resistance to new …

Neurohospitalist Core Competencies, Jana J Wold, Jetter Robertson, Jerome A Jeevarajan, Molly G Knox, Prateek Thatikunta, Guillermo E Solorzano, Kristin Galetta, Shefali Dujari, Tarini Goyal, Matthew E Ehrlich, Jonathan P Donnelly, Elizabeth Marriott, Vishal A Mandge, Roshni S Dhoot, Matthew W Luedke, Matthew B Maas, Margaret Y Yu, Michel Toledano, Rafid Mustafa, Jamie L Palaganas, Kathryn Kvam, Rachelle Dugue, Ethan Meltzer, Lahoud Touma, Maulik P Shah, Vanja C Douglas, Karen Orjuela, Brian J Scott, Joshua P Klein, David J Likosky, Jennifer R Simpson, Megan B Richie, Carolin Dohle, Jane G Morris, Carl A Gold

Faculty, Staff and Student Publications

The Neurohospitalist Core Competencies comprise a set of competency-based learning objectives that encapsulate the knowledge, skills, and attitudes of neurohospitalitists who specialize in the care of hospitalized patients with neurologic conditions. These competencies serve to characterize the rapidly expanding field of neurohospitalist medicine. The 27 chapters are divided into 3 sections entitled: neurological conditions, clinical interventions and interpretation of ancillary studies, and neurohospitalist role in the healthcare system. Each individual learning objective in the chapters describes a specific concept with an action verb to illustrate the behavior that the neurohospitalist exhibits. The individual neurohospitalist may not exhibit mastery in each …

Insights Into Human Norovirus Cultivation In Human Intestinal Enteroids, Khalil Ettayebi, Gurpreet Kaur, Ketki Patil, Janam Dave, B Vijayalakshmi Ayyar, Victoria R Tenge, Frederick H Neill, Xi-Lei Zeng, Allison L Speer, Sara C Di Rienzi, Robert A Britton, Sarah E Blutt, Sue E Crawford, Sasirekha Ramani, Robert L Atmar, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are a significant cause of epidemic and sporadic acute gastroenteritis worldwide. The lack of a reproducible culture system hindered the study of HuNoV replication and pathogenesis for almost a half-century. This barrier was overcome with our successful cultivation of multiple HuNoV strains in human intestinal enteroids (HIEs), which has significantly advanced HuNoV research. We optimized culture media conditions and generated genetically modified HIE cultures to enhance HuNoV replication in HIEs. Building upon these achievements, we now present new insights into this culture system, which involve testing different media, unique HIE lines, and additional virus strains. HuNoV infectivity …

Discovery Of Highly Potent And Alk2/Alk1 Selective Kinase Inhibitors Using Dna-Encoded Chemistry Technology, Ravikumar Jimmidi, Diana Monsivais, Hai Minh Ta, Kiran L Sharma, Kurt M Bohren, Srinivas Chamakuri, Zian Liao, Feng Li, John M Hakenjos, Jian-Yuan Li, Yuji Mishina, Haichun Pan, Xuan Qin, Matthew B Robers, Banumathi Sankaran, Zhi Tan, Suni Tang, Yasmin M Vasquez, Jennifer Wilkinson, Damian W Young, Stephen S Palmer, Kevin R Mackenzie, Choel Kim, Martin M Matzuk

Faculty, Staff and Students Publications

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non–small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer. Using DNA-encoded chemistry technology, we screened 3.94 billion unique compounds from our diverse …

Discovery Of Highly Potent And Alk2/Alk1 Selective Kinase Inhibitors Using Dna-Encoded Chemistry Technology, Ravikumar Jimmidi, Diana Monsivais, Hai Minh Ta, Kiran L Sharma, Kurt M Bohren, Srinivas Chamakuri, Zian Liao, Feng Li, John M Hakenjos, Jian-Yuan Li, Yuji Mishina, Haichun Pan, Xuan Qin, Matthew B Robers, Banumathi Sankaran, Zhi Tan, Suni Tang, Yasmin M Vasquez, Jennifer Wilkinson, Damian W Young, Stephen S Palmer, Kevin R Mackenzie, Choel Kim, Martin M Matzuk

Faculty, Staff and Students Publications

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non-small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer. Using DNA-encoded chemistry technology, we screened 3.94 billion unique compounds from our diverse …

The Impact Of Diabetes Mellitus On Hiv Virologic Control: Results Of The Macs/Wihs Combined Cohort Study, Sarah C Mann, Weiqun Tong, Alison G Abraham, Frank Palella, Anjali Sharma, Phyllis C Tien, Margaret A Fischl, Samy I Mcfarlane, Cecile D Lahiri, Susan Koletar, Daniel Merenstein, Michelle Floris-Moore, Jordan E Lake, Elizabeth Daubert, Aubri Hickman, Todd T Brown, Jose Castillo-Mancilla

Faculty, Staff and Student Publications

Objective: Diabetes mellitus (DM) is associated with lower antiretroviral (ART) drug exposure among persons with HIV (PWH) compared to PWH without DM. The association between DM and virologic control in PWH, however, remains unknown.

Methods: We included participants in the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) who had initiated ART between 1999 and 2020 and had a suppressed HIV viral load (≤200 copies/ml) within 1 year of ART initiation. We compared the frequency of incident HIV viremia (HIV-1 RNA >200 copies/ml) between adult PWH with and without DM. Poisson regression was used to examine the …

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

Faculty, Staff and Students Publications

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

Systematic Review Of Immune Checkpoint Inhibitor-Related Gastrointestinal, Hepatobiliary, And Pancreatic Adverse Events, Malek Shatila, Hao Chi Zhang, Anusha Shirwaikar Thomas, Antonio Pizuorno Machado, Sidra Naz, Nitish Mittal, Christine Catinis, Krishnavathana Varatharajalu, Carolina Colli Cruz, Eric Lu, Deanna Wu, Julie R Brahmer, Franck Carbonnel, Stephen B Hanauer, Bret Lashner, Bryan Schneider, John A Thompson, Michel Obeid, David P Farris, Yinghong Wang

Faculty, Staff and Student Publications

Gastrointestinal immune-related adverse events (GI irAEs) are common manifestations of immune checkpoint inhibitor (ICI) toxicity. We present a comprehensive systematic review of the incidence, management, and clinical course of irAEs across the entire GI system, including the luminal GI tract, liver, and pancreas. MEDLINE, Embase, Web of Science Core Collection, and Cochrane Library were used to conduct this review. All studies pertaining to GI irAEs were included. Both abstracts and full manuscripts were eligible if they included human subjects and were written in the English language. Articles not available in English, animal studies, or research not specific to GI toxicity …

Complete Genome Sequence Of Borrelia Miyamotoi Strain Mn18-0001, An Am-East-2 Strain Type Isolate Derived From An Ixodes Scapularis Tick (Minnesota), Alexander R Kneubehl, Lynn M Osikowicz, Christina M Parise, Taylor J Van Gundy, Adam J Replogle, Job E Lopez, Rebecca J Eisen, Andrias Hojgaard

Faculty, Staff and Students Publications

We report the genomic sequence of the hard tick relapsing fever spirochete Borrelia miyamotoi strain MN18-0001. B. miyamotoi causes human illness and is geographically widespread in Ixodes spp. (Acari: Ixodidae) ticks. This is a chromosome- and plasmid-resolved genome assembly of an Am-East-2 strain type isolate from the midwestern United States.

Seroprevalence And Risk Factors For Cysticercosis In Mexican Americans In Starr County, Texas, Megan M Duffey, Elise M O'Connell, Morgan Jibowu, Fanny E Moron, Lauren M Leining, Nina L Tang, Craig L Hanis, Eric L Brown, Sarah M Gunter

Faculty, Staff and Students Publications

Cysticercosis is a parasitic infection and neglected tropical disease caused by Taenia solium, or the pork tapeworm. Cysticercosis with central nervous system involvement, or neurocysticercosis, is a leading cause of chronic headaches and epilepsy in endemic regions, including Latin America and Asia. In the United States, the epidemiology of cysticercosis has not been well described. We conducted a cross-section serosurvey of Mexican-American adults residing along the Texas–Mexico border (Starr County, Texas) and identified an overall seroprevalence of 7.4% (45/605) for cysticercosis. Brain imaging studies conducted on seropositive study participants identified lesions consistent with calcified neurocysticercosis in 2 of the …

The 2024 Report Of The Lancet Countdown On Health And Climate Change: Facing Record-Breaking Threats From Delayed Action, Marina Romanello, Maria Walawender, Shih-Che Hsu, Annalyse Moskeland, Yasna Palmeiro-Silva, Daniel Scamman, Zakari Ali, Nadia Ameli, Denitsa Angelova, Sonja Ayeb-Karlsson, Sara Basart, Jessica Beagley, Paul J Beggs, Luciana Blanco-Villafuerte, Wenjia Cai, Max Callaghan, Diarmid Campbell-Lendrum, Jonathan D Chambers, Victoria Chicmana-Zapata, Lingzhi Chu, Troy J Cross, Kim R Van Daalen, Carole Dalin, Niheer Dasandi, Shouro Dasgupta, Michael Davies, Robert Dubrow, Matthew J Eckelman, James D Ford, Chris Freyberg, Olga Gasparyan, Georgiana Gordon-Strachan, Michael Grubb, Samuel H Gunther, Ian Hamilton, Yun Hang, Risto Hänninen, Stella Hartinger, Kehan He, Julian Heidecke, Jeremy J Hess, Louis Jamart, Slava Jankin, Harshavardhan Jatkar, Ollie Jay, Ilan Kelman, Harry Kennard, Gregor Kiesewetter, Patrick Kinney, Dominic Kniveton, Rostislav Kouznetsov, Pete Lampard, Jason K W Lee, Bruno Lemke, Bo Li, Yang Liu, Zhao Liu, Alba Llabrés-Brustenga, Melissa Lott, Rachel Lowe, Jaime Martinez-Urtaza, Mark Maslin, Lucy Mcallister, Celia Mcmichael, Zhifu Mi, James Milner, Kelton Minor, Jan Minx, Nahid Mohajeri, Natalie C Momen, Maziar Moradi-Lakeh, Karyn Morrisey, Simon Munzert, Kris A Murray, Nick Obradovich, Megan B O'Hare, Camile Oliveira, Tadj Oreszczyn, Matthias Otto, Fereidoon Owfi, Olivia L Pearman, Frank Pega, Andrew J Perishing, Ana-Catarina Pinho-Gomes, Jamie Ponmattam, Mahnaz Rabbaniha, Jamie Rickman, Elizabeth Robinson, Joacim Rocklöv, David Rojas-Rueda, Renee N Salas, Jan C Semenza, Jodi D Sherman, Joy Shumake-Guillemot, Pratik Singh, Henrik Sjödin, Jessica Slater, Mikhail Sofiev, Cecilia Sorensen, Marco Springmann, Zélie Stalhandske, Jennifer D Stowell, Meisam Tabatabaei, Jonathon Taylor, Daniel Tong, Cathryn Tonne, Marina Treskova, Joaquin A Trinanes, Andreas Uppstu, Fabian Wagner, Laura Warnecke, Hannah Whitcombe, Peng Xian, Carol Zavaleta-Cortijo, Chi Zhang, Ran Zhang, Shihui Zhang, Ying Zhang, Qiao Zhu, Peng Gong, Hugh Montgomery, Anthony Costello

Faculty, Staff and Student Publications

Despite the initial hope inspired by the 2015 Paris Agreement, the world is now dangerously close to breaching its target of limiting global multiyear mean heating to 1·5°C. Annual mean surface temperature reached a record high of 1·45°C above the pre-industrial baseline in 2023, and new temperature highs were recorded throughout 2024. The resulting climatic extremes are increasingly claiming lives and livelihoods worldwide.

Tumor-Associated Edema In Children With Kaposi Sarcoma: 14 Years' Experience At Kamuzu Central Hospital, Lilongwe, Malawi, Fatsani Rose Manase, Allison Silverstein, William Kamiyango, Jimmy Villiera, Clement Dziwe, Claudia Wallrauch, Tom Heller, Mark Zobeck, Tamiwe Tomoka, Michael E Scheurer, Carl E Allen, Nmazuo Ozuah, Rizine Mzikamanda, Nader Kim El-Mallawany, Casey L Mcatee

Center for Medical Ethics and Health Policy Staff Publications

Background/objectives: Kaposi sarcoma (KS) is a common lymphatic endothelial cancer among children with and without HIV in central and eastern Africa. Despite its clinical heterogeneity, its various clinical phenotypes are often grouped together in staging and treatment algorithms. Patients with KS tumor-associated edema, referring to hard, non-pitting lesions which often lead to chronic disability, represent a unique, understudied subgroup of children with KS. To continue our work defining the distinct phenotypes of pediatric KS, this study aimed to assess the clinical progression and outcomes of KS edema in children.

Methods: A retrospective cohort study was conducted at Kamuzu Central Hospital …

Estimating The Number Of Polygenic Diseases Among Six Mutually Exclusive Entities Of Non-Tumors And Cancer, C I Edvard Smith, Jan A Burger, Rula Zain

Faculty, Staff and Student Publications

In the era of precision medicine with increasing amounts of sequenced cancer and non-cancer genomes of different ancestries, we here enumerate the resulting polygenic disease entities. Based on the cell number status, we first identified six fundamental types of polygenic illnesses, five of which are non-cancerous. Like complex, non-tumor disorders, neoplasms normally carry alterations in multiple genes, including in 'Drivers' and 'Passengers'. However, tumors also lack certain genetic alterations/epigenetic changes, recently named 'Goners', which are toxic for the neoplasm and potentially constitute therapeutic targets. Drivers are considered essential for malignant transformation, whereas environmental influences vary considerably among both types of …

High Incidence And Geographic Distribution Of Cleft Palate In Finland Are Associated With The Irf6 Gene, Fedik Rahimov, Pekka Nieminen, Priyanka Kumari, Emma Juuri, Tiit Nikopensius, Kitt Paraiso, Jakob German, Antti Karvanen, Mart Kals, Abdelrahman G Elnahas, Juha Karjalainen, Mitja Kurki, Aarno Palotie, Estonian Biobank Research Team, Finngen, Arja Heliövaara, Tõnu Esko, Sakari Jukarainen, Priit Palta, Andrea Ganna, Anjali P Patni, Daniel Mar, Karol Bomsztyk, Julie Mathieu, Hannele Ruohola-Baker, Axel Visel, Walid D Fakhouri, Brian C Schutte, Robert A Cornell, David P Rice

Faculty, Staff and Student Publications

In Finland, the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study in the Finnish population and identified rs570516915, a single nucleotide polymorphism highly enriched in Finns, as strongly associated with CP (P = 5.25 × 10-34, OR = 8.65, 95% CI 6.11-12.25), but not with CL/P (P = 7.2 × 10-5), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence …

Skn-1 Activation During Infection Of Caenorhabditis Elegans Requires Cdc-48 And Endoplasmic Reticulum Proteostasis, Carolaing Gabaldón, Ozgur Karakuzu, Danielle A Garsin

Faculty, Staff and Student Publications

During challenge of Caenorhabditis elegans with human bacterial pathogens such as Pseudomonas aeruginosa and Enterococcus faecalis, the elicited host response can be damaging if not properly controlled. The activation of Nrf (nuclear factor erythroid-related factor)/CNC (Cap-n-collar) transcriptional regulators modulates the response by upregulating genes that neutralize damaging molecules and promote repair processes. Activation of the C. elegans Nrf ortholog, SKN-1, is tightly controlled by a myriad of regulatory mechanisms, but a central feature is an activating phosphorylation accomplished by the p38 mitogen-activated kinase (MAPK) cascade. In this work, loss of CDC-48, an AAA+ ATPase, was observed to severely compromise SKN-1 …

Gene Discovery From Microbial Gene Libraries I: Protection Against Reactive Oxygen Species-Driven Dna Damage, John C Taylor, Carmen Gu Liu, James D Chang, Brianna E Thompson, Anthony W Maresso

Faculty, Staff and Students Publications

Reactive oxygen species (ROS) pose a lethal risk for all life forms by causing damage to cell processes, genome-wide DNA damage-driving mutation, replicative instability, and death. Thus, the development of mechanisms to resist or repair ROS-induced DNA damage is critical for the reliable replication of nucleic acids. DNA repair and protection mechanisms have been discovered in all forms of life. However, the vast array of microbes that may harbor novel repair or protection mechanisms, especially bacterial viruses, have not been adequately assessed. Here, we screened a microbial gene library composed primarily of phage open reading frames (ORFs) to uncover elements …

Nepali Oral Microbiomes Reflect A Gradient Of Lifestyles From Traditional To Industrialized, Erica P Ryu, Yoshina Gautam, Diana M Proctor, Dinesh Bhandari, Sarmila Tandukar, Meera Gupta, Guru Prasad Gautam, David A Relman, Ahmed A Shibl, Jeevan Bahadur Sherchand, Aashish R Jha, Emily R Davenport

Faculty, Staff and Student Publications

Background: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called "vanishing microbiomes" potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes …