Digital Commons Network^™

Effect Of Feeding A Saccharomyces Cerevisiae Fermentation Product On Immune Response To Vaccines Against Newcastle Disease Virus, Avian Influenza Virus, And The Prevalence Of Chronic Respiratory Disease And Coccidiosis In Chickens Raised In A Low Biosecurity Production System, Bui Thi Hien, Ho Thi Dung, Pham Hoang Son Hung, Le Duc Thao, Nguyen Van Chao, Tran Quang Vui, Nguyen Thi Hoa, Anjan Mondal, Nsereko Victor, Le Dinh Phung

The Thai Journal of Veterinary Medicine

This study was carried out in a low biosecurity production system to explore the effects of a Saccharomyces cerevisiae fermentation product (SCFP) on immune responses to vaccination against Newcastle disease virus (NDV) and Avian influenza (H5N1) and prevalence of common diseases in chickens including chronic respiratory disease (CRD) and coccidiosis. One hundred and ninety two 1-day-old chickens were randomly assigned into control (a standard basal diet) and treatment (a standard basal diet containing 1.25 kg/MT of Diamond V XPC™ – a Saccharomyces cerevisiae fermentation product). Immunity data on antibody titers to NDV and H5N1 were collected at 3 weeks and …

Synthetic Protein Mimetic Based Therapies For Neurodegeneration, Nicholas H. Stillman

Electronic Theses and Dissertations

Protein-protein interactions (PPIs) are crucial for the regulation of a majority of, if not every fundamental cellular process. Despite their role in regular biological processes, dysregulated and/or aberrant protein-protein interactions (aPPIs) are often related to the onset of disease including cancer, viral infection, and amyloid diseases. aPPIs have historically been deemed ‘undruggable’ due to their large surface area and lack of a binding cavity; however, today, more than 40 disease-related aPPIs have been targeted with small molecules and several of those have reached clinical trials.

A class of synthetic protein mimetics called oligopyridylamides (OPs) has been shown to inhibit disease-related …

The Importance Of Recruitment Of Low-Income Pregnant Persons In Interdisciplinary Research To Understand The Impact Of Social And Environmental Determinants: Lessons Learned About Implementation And Recruitment, Erika R. Marquez, Amanda Haboush-Deloye, Elizabeth M. Lawrence, Selam Ayele, Courtney Coughenour, Nora Doyle, Wynona Dizon, Lizbeth Perez Rodriguez, Chloe Bombara

Environmental & Global Health Faculty Research

Background: Prior research indicates that enrolling underrepresented populations in clinical research is challenging. Although research has identified some barriers to participation and strategies to overcome them, studies have made little progress in being inclusive and representative. There remains a great need for including racial/ethnic minorities, low-income families, and pregnant women in research. The purpose of this article is to describe the implementation of enrollment strategies used in our study to understand the feasibility of building a maternal cohort and better understand the relationship between environmental and social impacts on maternal exposure and child outcomes.

Methods: Working across multiple academic units, …

Rare Damaging Ccr2 Variants Are Associated With Lower Lifetime Cardiovascular Risk, Jiang Li, Reinier W P Tack, Tamara N Kimball, Yaw Asare, Alanna C Morrison, Noah L Tsao, Renae Judy, Braxton D Mitchell, Huichun Xu, May E Montasser, Ron Do, Eimear E Kenny, Ruth J F Loos, James G Terry, John Jeffrey Carr, Joshua C Bis, Bruce M Psaty, W T Longstreth, Sharon M Lutz, Michael H Cho, Jai Broome, Alyna T Khan, Fei Fei Wang, Nancy Heard-Costa, Sudha Seshadri, Ramachandran S Vasan, Nicholette D Palmer, Barry I Freedman, Donald W Bowden, Lisa R Yanek, Brian G Kral, Lewis C Becker, Patricia A Peyser, Lawrence F Bielak, Farah Ammous, April P Carson, Michael E Hall, Laura M Raffield, Stephen S Rich, Wendy S Post, Russel P Tracy, Kent D Taylor, Xiuqing Guo, Michael C Mahaney, Joanne E Curran, John Blangero, Shoa L Clarke, Jeffrey W Haessler, Yao Hu, Themistocles L Assimes, Charles Kooperberg, Jürgen Bernhagen, Christopher D Anderson, Scott M Damrauer, Ramin Zand, Jerome I Rotter, Paul S De Vries, Martin Dichgans

Faculty, Staff and Student Publications

BACKGROUND: Previous work has shown a role of CCL2, a key chemokine governing monocyte trafficking, in atherosclerosis. However, it remains unknown whether targeting CCR2, the cognate receptor of CCL2, provides protection against human atherosclerotic cardiovascular disease.

METHODS: Computationally predicted damaging or loss-of-function (REVEL > 0.5) variants within CCR2 were detected in whole-exome-sequencing data from 454,775 UK Biobank participants and tested for association with cardiovascular endpoints in gene-burden tests. Given the key role of CCR2 in monocyte mobilization, variants associated with lower monocyte count were prioritized for experimental validation. The response to CCL2 of human cells transfected with these variants was tested …

Delivering Guideline-Directed Medical Therapy For Heart Failure With Reduced Ejection Fraction As An Over-Encapsulated Polypill: Rationale And Protocol For The Combo-Hf-X Pilot Crossover Randomised Clinical Trial, Colette Dejong, Mark D Huffman, Anubha Agarwal, Et Al.

2020-Current year OA Pubs

INTRODUCTION: A four-drug regimen of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is underused, in part due to prescriber inertia and low patient adherence. Although fixed-dose combination pills ('polypills') have improved adherence and clinical outcomes for other conditions, there are no polypills available that combine multiple classes of GDMT for HFrEF. Pharmacy-level over-encapsulation, in which several tablets are combined into one capsule, offers an opportunity to create customised HFrEF polypills with the goal of improving delivery of HFrEF therapies.

METHODS AND ANALYSIS: In the COMBO-HF-X pilot crossover randomised clinical trial, we will enrol 30-40 patients …

Antimicrobial Performance Of A Novel Drug-Eluting Bioenvelope, M Rizwan Sohail

Faculty, Staff and Students Publications

No abstract provided.

Persistent Barriers To Implementation Of Long-Acting Injectable Antiretroviral Therapy, Jessica Hack, Adati Tarfa, Harlan Sayles, Nada Fadul

EMET Projects

No abstract provided.

Characteristics And Outcomes Of Cancer Patients Admitted To The Hospital With Community-Acquired Pneumonia, Anoud Al-Saleh, Dana Hassouneh, Sara Faqeer, Nour

Sultan Qaboos University Medical Journal

Objectives: Community-acquired pneumonia (CAP) poses a significant risk of complications in cancer patients. However, limited studies have evaluated hospitalised cancer patients with CAP. This study aimed to evaluate the characteristics and outcomes of cancer patients hospitalised with CAP. Methods: This retrospective study included adult cancer patients diagnosed with CAP admitted at the King Hussein Cancer Center, Jordan, from January 2021 to August 2022, following the Infectious Diseases Society of America guidelines. Patient characteristics, microbiological cultures, length of hospital stay, intensive care unit (ICU) transfers and all-cause mortality were recorded. Early clinical stability was defined as temperature ≤37.8°C, heart …

Mpox In The Gulf Cooperation Council Countries: Addressing A New Challenge To Regional Health Security, Salah Al Awaidy, Jaffar A. Al-Tawfiq, Faryal Maslamani, Muna Al, Jameela Al Salman, Sk Md Mamunur Rahman Malik

Sultan Qaboos University Medical Journal

No abstract provided.

Comparison Of Syndromic Surveillance And Hospital Discharge Data For Unintentional Drowning In Metropolitan Houston, Texas, Usa, Ned Norman Levine, Rohit P Shenoi

Faculty, Staff and Students Publications

Background: Syndromic surveillance, which provides real-time data, may provide timely drowning surveillance compared with hospital discharge data where the release of data may be delayed. We compared data on hospital visits for unintentional drowning identified in hospital discharge and syndromic surveillance data sets for accuracy and completeness.

Methods: We compared data for hospital visits for unintentional drowning identified in the Texas Health Care Information Collection hospital discharge and syndromic surveillance data sets for metropolitan Houston, Texas, USA from 2019 to 2021. Hospital visits included emergency department-only visits and hospital admissions. We compared time-series visualisation of hospital visits between data sets. …

Attitudes And Barriers Toward Antiretroviral Therapeutic Drug Monitoring Among Infectious Disease Providers, Bich N Dang, Dong Liang

Faculty, Staff and Students Publications

Background/Objectives: Effective HIV treatment and prevention rely heavily on patient adherence to the prescribed regimen. Therapeutic drug monitoring (TDM), which involves measuring medication concentrations in blood circulation, offers an objective method to evaluate toxic or ineffective drug levels. TDM is not routinely used in HIV treatment in clinical practice. Therefore, the purpose of this study is to survey infectious disease providers’ attitudes and barriers toward therapeutic drug monitoring for antiretroviral therapy in people living with HIV. Materials and

Methods: A 15-item online survey was distributed to infectious disease providers in the Greater Houston area, including physicians, pharmacists, and mid-level practitioners …

Editorial: Old Drugs: Confronting Recent Advancements And Challenges, Anna Wiktorowska-Owczarek, Diego Iacono, Magdalena Jasińska-Stroschein

Department of Neurology Faculty Papers

No abstract provided.

Molecular Assays For The Diagnosis Of Sepsis In Neonates: A Diagnostic Test Accuracy Review, James Versalovic, Mariska Mg Leeflang, Chris Cooper, Mohan Pammi

Faculty, Staff and Students Publications

Background: Microbial cultures for diagnosis of neonatal sepsis have low sensitivity and reporting delay. Advances in molecular microbiology have fostered new molecular assays that are rapid and may improve neonatal outcomes.

Objectives: To assess the diagnostic accuracy of various molecular methods for the diagnosis of culture-positive bacterial and fungal sepsis in neonates and to explore heterogeneity among studies by analyzing subgroups classified by gestational age and type of sepsis onset and compare molecular tests with one another.

Search methods: We searched CENTRAL, MEDLINE, Embase and trial registries in August 2023. We checked reference lists of included studies and systematic reviews …

A Narrative Review Of The Covid-19 Infodemic And Censorship In Healthcare, Mitchell Liester, Sohaib Ashraf, Patricia Callisperis, Hector Carvallo, Shankara Chetty, Robert Enzenauer, Carlos Franco-Paredes, Raul Pineda, Panagis Polykretis, Rachel Wilkenson, Peter Mccullough

Secrecy and Society

Ideological and financial motivations have undermined science for decades. In this narrative review, we explore how organizations and governments used misinformation, disinformation, censorship, and secrecy to manage the COVID-19 pandemic. Various rationales for employing censorship and secrecy during the COVID-19 pandemic are examined including how organizations and governments create confusion about the risks associated with their products and blame avoidance to shift responsibility and to avoid accountability for their actions. Methods of censorship employed during the COVID-19 pandemic are reviewed, examples are provided, and the consequences of these actions are reviewed. Information included in this review was obtained from scientific …

Dried Blood Spots To Assess Cardiovascular-Kidney-Metabolic Health, Tyler A Jacobson, Mark D Huffman, Et Al.

2020-Current year OA Pubs

Dried blood spot sampling offers a scalable strategy to close diagnostic gaps and improve global surveillance for cardiovascular-kidney-metabolic syndrome. However, assay performance and the extent of validity vary widely between biomarkers used in cardiovascular-kidney-metabolic health assessment under different settings and have not been well described. To fill this gap, we conducted a systematic search of the literature and a narrative synthesis through April 2024 and included reports with laboratory or field validation measuring biomarkers that can be used in cardiovascular-kidney-metabolic health assessment. We categorized assays into categories based on laboratory validation: excellent performance (r>0.95 with gold standard methods and …

The Autophagy Protein Atg14 Safeguards Against Unscheduled Pyroptosis Activation To Enable Embryo Transport During Early Pregnancy, Pooja Popli, Arin K Oestreich, Vineet K Maurya, Marina N Rowen, Yong Zhang, Michael J Holtzman, Ramya Masand, John P Lydon, Shizuo Akira, Kelle Moley, Ramakrishna Kommagani

2020-Current year OA Pubs

Recurrent pregnancy loss, characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, our understanding of the biological processes that preserve the oviductal cellular structure and functional integrity is limited. Here, we report that autophagy-related protein ATG14 plays a crucial role in maintaining the cellular integrity of the oviduct by …

The Autophagy Protein Atg14 Safeguards Against Unscheduled Pyroptosis Activation To Enable Embryo Transport During Early Pregnancy, Marina N Rowen, Yong Zhang, Michael J Holtzman, Ramya Masand, John P Lydon, Shizuo Akira, Kelle Moley, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Recurrent pregnancy loss, characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, our understanding of the biological processes that preserve the oviductal cellular structure and functional integrity is limited. Here, we report that autophagy-related protein ATG14 plays a crucial role in maintaining the cellular integrity of the oviduct by …

Emerging Clostridioides Difficile Ribotypes Have Divergent Metabolic Phenotypes, Colleen K Ardis, Kevin W Garey, Jennifer K Spinler, Robert A Britton

Faculty, Staff and Students Publications

Clostridioides difficile is a gram-positive spore-forming pathogen that commonly causes diarrheal infections in the developed world. Although C. difficile is a genetically diverse species, certain ribotypes are overrepresented in human infections, and it is unclear if metabolic adaptations are essential for the emergence of these epidemic ribotypes. To identify ribotype-specific metabolic differences, we therefore tested carbon substrate utilization by 88 C. difficile isolates and looked for differences in growth between 22 ribotypes. As expected, C. difficile was capable of growing on a variety of carbon substrates. Further, C. difficile strains clustered by phylogenetic relationship and displayed ribotype-specific and clade-specific …

Genetic Associations With C-Peptide Levels Before Type 1 Diabetes Diagnosis In At-Risk Relatives, Taylor M Triolo, Hemang M Parikh, Mustafa Tosur, Lauric A Ferrat, Lu You, Peter A Gottlieb, Richard A Oram, Suna Onengut-Gumuscu, Jeffrey P Krischer, Stephen S Rich, Andrea K Steck, Maria J Redondo

Children’s Nutrition Research Center Staff Publications

Objective: We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms are associated with C-peptide preservation before type 1 diabetes diagnosis.

Methods: We conducted a retrospective analysis of 713 autoantibody-positive participants who developed type 1 diabetes in the TrialNet Pathway to Prevention Study who had T1DExomeChip data. We evaluated the relationships of 16 known single nucleotide polymorphisms and T1D-GRS2 with area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted in the 9 months before diagnosis.

Results: Higher T1D-GRS2 was associated with lower C-peptide AUC in the 9 months before …

Correction: Ellsworth, M.; Ostrosky-Zeichner, L. Isavuconazole: Mechanism Of Action, Clinical Efficacy, And Resistance, Misti Ellsworth, Luis Ostrosky-Zeichner

Faculty, Staff and Student Publications

In the original article [1], in Section 6.3, “Treatment groups received caspofungin 750 mg IV on day 1” should be “70 mg” instead of “750 mg”. We made a mistake in the process of writing. The corrected paragraph is as follows:

“Treatment groups received caspofungin 70 mg IV on day 1 followed by 50 mg IV daily or 200 mg of isavuconazole IV q8h on days 1–2 followed by 200 mg once daily.”

The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated.

Phase I Trial Of Tti-101, A First-In-Class Oral Inhibitor Of Stat3, In Patients With Advanced Solid Tumors, Apostolia M Tsimberidou, David J Vining, Sukeshi P Arora, Sofia De Achaval, Jeffrey Larson, Carrie Cartwright, Imran Alibhai, David J Tweardy, Ahmed O Kaseb

Faculty, Staff and Student Publications

Purpose: Signal transducer and activator of transcription 3 is a transcription factor that is essential for the survival and immune sequestration of cancer cells. We conducted a phase I study of TTI-101, a first-in-class, selective small-molecule inhibitor of signal transducer and activator of transcription 3, in patients with advanced metastatic cancer.

Patients and methods: Patients were treated with TTI-101 orally twice daily in 28-day cycles at four dose levels (DL): 3.2 (DL1), 6.4 (DL2), 12.8 (DL3), and 25.6 (DL4) mg/kg/day ("3+3" design). Three TTI-101 formulations were used in a stepwise manner (NCT03195699).

Results: Sixty-four patients were treated (median …

Association Of Messenger Rna Coronavirus Disease 2019 (Covid-19) Vaccination And Reductions In Post Covid Conditions Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection In A Us Prospective Cohort Of Essential Workers, Josephine Mak, Sana Khan, Amadea Britton, Spencer Rose, Lisa Gwynn, Katherine D Ellingson, Jennifer Meece, Leora R Feldstein, Harmony Tyner, Laura J Edwards, Matthew S Thiese, Allison Naleway, Manjusha Gaglani, Natasha Solle, Jefferey L Burgess, Julie Mayo Lamberte, Meghan Shea, Taryn Hunt-Smith, Alberto Caban-Martinez, Cynthia Porter, Ryan Wiegand, Ramona Rai, Kurt T Hegmann, James Hollister, Ashley Fowlkes, Meredith Wesley, Andrew L Philips, Patrick Rivers, Robin Bloodworth, Gabriella Newes-Adeyi, Lauren E W Olsho, Sarang K Yoon, Sharon Saydah, Karen Lutrick

Center for Medical Ethics and Health Policy Staff Publications

Background: Data are limited on whether vaccination reduces post COVID conditions (PCCs) risk after less severe nonhospitalized coronavirus disease 2019 (COVID-19). This study assessed whether COVID-19 vaccination protected against PCCs in persons with mild initial infections during Delta and Omicron variant predominance.

Methods: This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with test-confirmed severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) between 28 June 2021 and 14 September 2022 were surveyed for PCCs, defined by symptoms lasting >4 weeks after initial infection. Cases self-reported PCCs and controls self-reported no PCCs. The exposure was …

Dengue Cases In Hanoi, Vietnam: Unseasonal Surge Foreshadows Increased Incidence That Demands Organized Preventive Action, Andrew W. Taylor-Robinson

Chulalongkorn Medical Journal

Letter to the Editor - Abstract not required.

Cracking The Code Of Hbv Persistence: Cutting-Edge Approaches To Targeting Cccdna In Chronic Hepatitis B With Or Without Pyogenic Liver Abscesses, Umar Saeed, Zahra Zahid Piracha, Mahmood Khan, Muhammad Nouman Tariq, Syed Shahan Gilani, Muhammad Raza, Rakshana Munuswamy, Naveen Bose, Dilber Uzun Ozsahin, Ilker Özşahin, Surya M. Nauli

Pharmacy Faculty Articles and Research

Chronic Hepatitis B Virus (HBV) infection remains a formidable global health challenge, driving severe liver complications such as hepatocellular carcinoma (HCC) and pyogenic liver abscesses (PLA). At the core of HBV persistence lies covalently closed circular DNA (cccDNA), a viral reservoir that fuels ongoing infection despite antiviral treatments. This review highlights molecular mechanisms governing cccDNA formation, maintenance, and clearance, spotlighting innovative therapeutic strategies to disrupt this key viral element. We explore cutting-edge approaches, including epigenetic modulation to silence cccDNA, RNA interference (RNAi) for viral RNA degradation, and CRISPR/Cas genome editing to excise cccDNA directly. Additionally, emerging antiviral therapies and immunotherapies, …

From Pregnancy To Beyond: Renewed Emphasis On Comprehensive Hiv Prevention In South Africa., Chibuzor M. Babalola, Remco P.H. Peters, Christina A. Muzny, Dvora Joseph Davey, Christopher M. Taylor, Mandisa M. Mdingi, Freedom Mukomana, Lindsey De Vos, Andrew Medina-Marino, Jeffrey D. Klausner

School of Medicine Faculty Publications

No abstract provided.

Inflammation And Gut Barrier Function-Related Genes And Colorectal Cancer Risk In Western European Populations, Hannah B Mandle, Mazda Jenab, Marc J Gunter, Anne Tjønneland, Anja Olsen, Jie Zhang, Joseph Rothwell, Gianluca Severi, Rudolf Kaaks, Verena A Katzke, Matthias B Schulze, Giovanna Masala, Sabina Sieri, Salvatore Panico, Carlotta Sacerdote, Catalina Bonet, Maria-Jose Sánchez, Pilar Amiano, José María Huerta, Marcela Guevara, Richard Palmqvist, Thyra Löwenmark, Aurora Perez-Cornago, Elisabete Weiderpass, Alicia K Heath, Amanda J Cross, Paolo Vineis, David J Hughes, Veronika Fedirko

Faculty, Staff and Student Publications

Gut barrier dysfunction and related inflammation are known to be associated with the development and progression of colorectal cancer (CRC). We investigated associations of 292 single-nucleotide polymorphisms (SNPs) from 27 genes related to endotoxins/lipopolysaccharide (LPS) sensing and tolerance, mucin synthesis, inflammation, and Crohn's disease with colon and rectal cancer risks. Incident CRC cases (N = 1374; colon = 871, rectum = 503) were matched 1:1 to controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. Previously measured serum concentrations of gut barrier function and inflammation biomarkers (flagellin/LPS-specific immunoglobulins and C-reactive protein [CRP]) were available for a sub-set …

Exploring Health Equity With Culturally Specific Providers Of Permanent Supportive Housing, Judith Solomon

University Honors Theses

Chronic homelessness is an important public health issue. Permanent Supportive Housing (PSH) is a promising opportunity for transitioning people experiencing homelessness into housing, however there remain unaddressed racial inequities in service provision and outcomes. The aim of this study is to better understand the role of culturally specific (CS) providers of PSH in improving health equity. I analyzed interviews with CS PSH providers for themes related to health and healthcare. Providers spoke about the importance of connecting clients to healthcare. Providers stressed the importance of honesty and lived experience, highlighting the strong sense of responsibility to the community. Providers also …

Exploring The Mechanistic Interplay Between Chronic Inflammation And Gastrointestinal Cancer In The Gut Microbiome: A Review, Hanan Mohamed Abd Elmoneim

Saudi Toxicology Journal

There are complex and heterogeneous immunological milieus of the gastrointestinal system, so there is a high mortality rate from malignancies affecting the gastrointestinal system. The pathophysiology of cancer has long been thought to be significantly influenced by inflammation. However, several of the mechanisms underlying its tumor-promoting activities have only lately been discovered. Both beneficial and harmful microorganisms play a crucial role in controlling the host immune system and, eventually, inflammation. Furthermore, bacteria may also influence how a tumor develops through different mechanisms, including long-term inflammation activation, changes to the tumor microenvironment, and genotoxic response induction. A significant percentage of cancers …

High-Throughput Repurposing Screen Reveals Compounds With Activity Against Toxoplasma Gondii Bradyzoites, Taher Uddin, Jing Xia, Yong Fu, Case W Mcnamara, Arnab K Chatterjee, L David Sibley

2020-Current year OA Pubs

No abstract provided.

C10-Benzoate Esters Of Anhydrotetracycline Inhibit Tetracycline Destructases And Recover Tetracycline Antibacterial Activity, Emily E Williford, Yao-Peng Xue, Wai Kwan Tang, Ruihao Li, Katherine V Jones, Kevin S Blake, Helen C Blaine, Xiang Lian, Christina L Stallings, Niraj H Tolia, Gautam Dantas, Timothy A Wencewicz

2020-Current year OA Pubs

Tetracyclines (TCs) are an important class of antibiotics threatened by enzymatic inactivation. These tetracycline-inactivating enzymes, also known as tetracycline destructases (TDases), are a subfamily of class A flavin monooxygenases (FMOs) that catalyze hydroxyl group transfer and oxygen insertion (Baeyer-Villiger type) reactions on TC substrate scaffolds. Semisynthetic modification of TCs (e.g., tigecycline, omadacycline, eravacycline, and sarecycline) has proven effective in evading certain resistance mechanisms, such as ribosomal protection and efflux, but does not protect against TDase-mediated resistance. Here, we report the design, synthesis, and evaluation of a new series of 22 semisynthetic TDase inhibitors that explore D-ring substitution of anhydrotetracycline (aTC) …