Digital Commons Network^™

A Class Of Benzofuranoindoline-Bearing Heptacyclic Fungal Ripps With Anticancer Activities, Qiuyue Nie, Fanglong Zhao, Xuerong Yu, Mithun C Madhusudhanan, Caleb Chang, Siting Li, Sandipan Roy Chowdhury, Bryce Kille, Andy Xu, Rory Sharkey, Chunxiao Sun, Hongzhi Zeng, Shuai Liu, Dishu Zhou, Xin Yu, Kevin Yang, Sandra A C Figueiredo, Maria Zotova, Zichen Hu, Alan Y Du, Dongyin Guan, Rui Tang, Todd Treangen, Jin Wang, Pedro N Leão, Yang Gao, Junjie Chen, Peng Liu, Hans Renata, Xue Gao

Children’s Nutrition Research Center Staff Publications

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored. Here, we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases. Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus. A derivative with a C-11 linear fatty …

Acceptability Of Corticosteroid Use In The Treatment Of Infant Bronchiolitis: Utilizing The Theoretical Framework Of Acceptability To Design Research Instruments, Caroline R. Smetanka

Capstone Experience: Master of Public Health

Bronchiolitis is the leading cause of hospitalization among infants under six months, yet treatment remains largely supportive due to clinical guidelines that discourage pharmacologic intervention. Recent research suggests that bronchiolitis is not a uniform condition, and a subgroup of infants (those classified within “Profile A”) may benefit from targeted corticosteroid therapy. However, these treatments remain outside current clinical guidelines, and their successful adoption depends on stakeholder acceptability. This Capstone project developed and refined four data collection instruments- two questionnaires and two interview guides- designed to assess how healthcare providers and caregivers perceive the acceptability of corticosteroid treatment for Profile A …

Advancing Trypanosoma Cruzi N-Myristoyltransferase As A Drug Target For Chagas Disease Through In Silico Discovery And Biochemical Evaluation, Diana Citlali González García

Open Access Theses & Dissertations

Chagas disease remains one of the most persistent and neglected parasitic infections in the Americas, advancing silently through the intracellular replication of Trypanosoma cruzi amastigotes and the invasive spread of trypomastigotes. The survival of the parasite is critically reliant on protein N-myristoylation, a lipid modification catalyzed by N-myristoyltransferase (NMT). This dissertation aims to advance beyond prior studies by systematically investigating NMT inhibition across multiple biological levels, spanning from the characterization of the purified enzyme, through cellular infection models, to the global proteomic remodeling induced within the parasite, thereby evaluating TcNMT as a potential therapeutic vulnerability in T.cruzi.Recombinant TcNMT was expressed, …

Representation Of Neuro-Oncology In American Neurology Departments: An Analysis Of Grand Rounds And Perspectives From Faculty And Residents, Elizabeth C Neil, Aubree Bruhnding, Zubair A Ahmed, Priya U Kumthekar, Nicholas A Blondin, Christian Grommes, Chirag B Patel, Sigmund Hsu, Feng Wang, Hongyu Miao, Noah L Rosen, Rashmi B Halker Singh, Mark J Burish, Zachary A Corbin

Faculty, Staff and Student Publications

Background: Neuro-oncology education in American neurology departments is highly variable, with no clear guidelines on appropriate practices. To better understand its current state, we focus on the perspective of departmental Grand Rounds (GR), views of adult neurology residency program directors (ANRPD), neuro-oncologists, and residents.

Methods: First, we obtained GR series from academic years 2017-2018 and 2018-2019 via an online search and direct emails to neurology residency programs. Second, two online surveys were dispensed to ANRPD and neuro-oncologists. Third, a cohort of neurology residents completed surveys with pre/post-didactic tests.

Results: Neuro-oncology consisted of 7% (28/ 411) GR in 2017-2018 and 6% …

Fusobacterium Sphaericum Sp Nov, Isolated From A Human Colon Tumor Adheres To Colonic Epithelial Cells And Induces Il-8 Secretion, Martha A Zepeda-Rivera, Yannick Eisele, Alexander Baryiames, Hanrui Wu, Claudia Mengoni, Gianmarco Piccinno, Elsa F Mcmahon, Kaitlyn D Lacourse, Dakota S Jones, Hans Hauner, Samuel S Minot, Nicola Segata, Floyd E Dewhirst, Christopher D Johnston, Susan Bullman

Faculty, Staff and Student Publications

Cancerous tissue is a largely unexplored microbial niche that provides a unique environment for the colonization and growth of specific bacterial communities, and with it, the opportunity to identify novel bacterial species. Here, we report distinct features of a novel Fusobacterium species, F. sphaericum sp. nov. (Fs), isolated from primary colon adenocarcinoma tissue. We acquire the complete closed genome and associated methylome of this organism and phylogenetically confirm its classification into the Fusobacterium genus, with F. perfoetens as its closest neighbor. Fs is phenotypically and genetically distinct, with morphological analysis revealing its coccoid shape, that while similar to …

Association Of Area Deprivation Index With Perinatal And Covid-19 Outcomes During The Early Pandemic: A Secondary Analysis Of A Prospective Cohort Study, Abigail Bell, Megan Foeller, Candice Woolfolk, Emily Diveley, Fan Zhang, Amy Scheffer, Ruizhi Huang, Daniel Jackson, Nandini Raghuraman, Ebony Carter, Indira U Mysorekar, Jeannie C Kelly

Center on Aging Staff Publications

Objective: We sought to evaluate the relationship between neighborhood-level deprivation and perinatal outcomes, particularly preterm birth, as well as COVID-19 outcomes among pregnant patients during the early pandemic.

Methods: We performed a secondary analysis of a prospective longitudinal cohort study that investigated the impact of prenatal COVID-19 exposure on perinatal outcomes. Pregnant patients were recruited 12/23/20-7/18/22 and serially assessed for COVID-19 exposure during pregnancy, with serum antibody testing, electronic medical record review, and patient report. For this secondary analysis, address at the time of delivery was used to categorize patients into low ADI (≤50th percentile Area Deprivation Index, indicating low …

Evaluating Covid-19 Severity Prediction And Immune Dynamics With Nulisaseq: Insights From The Impacc Study, Koji Abe, Tyson H Holmes, Tran T Nguyen, Seunghee Kim-Schulze, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, Ruth R Montgomery, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Joanna Schaenman, Elaine F Reed, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Holden T Maecker

Faculty, Staff and Students Publications

The National Institutes of Health-funded IMPACC (IMmunoPhenotyping Assessment in a COVID-19 Cohort) evaluated longitudinal clinical and immunological features of human patients hospitalized for COVID-19. This study focuses on comparing the novel NULISAseq assay with the Olink platform using a subset of participants to assess their efficacy in predicting COVID-19 severity and understanding immune response dynamics. Our findings reveal that NULISAseq could provide superior detectability and dynamic range across various targets. Elastic net analysis demonstrated that specific proteins, including amphiregulin, effectively predict COVID-19 severity from sera at admission (samples drawn within 96 h of admission), with a test area under the …

Hemophagocytic Lymphohistiocytosis In A Pediatric Lung Transplant Recipient, Sunil Chickmagalur, Anna Schrader, Dallas Parrish, David Moreno Mcneill, Maria C Gazzaneo, Ernestina Melicoff-Portillo, Nahir Cortes-Santiago

Faculty, Staff and Students Publications

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare complication of solid organ transplantation and is a syndrome of systemic hyperinflammation secondary to dysregulation of the inflammatory response, primarily involving lymphocytes and macrophages. It is often fatal and therefore early recognition and treatment are crucial. Among 11 adult cases of HLH in post-lung transplant cases found in the literature, only one patient survived.

Case: We report the first known pediatric case of HLH following lung transplantation. The patient, a previously healthy adolescent, developed end-stage bullous lung disease secondary to acute respiratory distress syndrome (ARDS) and underwent bilateral lung transplantation. Two months posttransplant, …

Bridging The Gap: From Early Recognition To Timely Referral For Cardiac Implantable Electronic Devices Infections, M Rizwan Sohail, Sarwat Khalil, Molly L Paras, Christopher B Granger, Andrew Uehlin, Yu-Rong Gao, Zerelda Esquer Garrigos

Faculty, Staff and Students Publications

An increasing number of patients are living with cardiac implantable electronic devices (CIEDs). When a patient with a CIED is hospitalized with concern for infection or positive blood cultures from any source, recognizing and managing a possible CIED infection is critical due to its significant morbidity and mortality risk. Internists are often the first to evaluate these patients and must consider the possibility of an underlying device infection. Gram-positive bacteremia carries a high risk of CIED infection, often necessitating cardiac imaging. In contrast, hematogenous seeding with gram-negative bacteremia is infrequent. Patients with clinical or imaging evidence of device infection should …

Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The United States, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo

Faculty, Staff and Students Publications

(Abstracted from JAMA 2025;333(24):2176-2187) The development of childhood vaccine protocols has led to the elimination of many infectious diseases from the United States, including measles, rubella, diphtheria, and polio, by maintaining herd immunity. In recent years, especially since the COVID-19 pandemic, vaccination rates have declined due to policy changes, misinformation, distrust, and broader societal shifts.

Bilateral Endogenous Fungal Endophthalmitis Following Elective Surgical Abortion: A Single Center Case Series, Viet Q. Chau, Jesse D. Sengillo, Flavius A. Beca, Julia L. Hudson, Thomas A. Albini, Harry W. Flynn

Wills Eye Hospital Papers

BACKGROUND: To describe the clinical features and management of three cases of bilateral endogenous fungal endophthalmitis following elective surgical abortion performed at the same outpatient surgical center.

METHODS: Case series.

OBSERVATIONS: Three immunocompetent women presented with vision loss days to weeks following elective surgical abortions performed at a single outpatient clinic. Initial visual acuities ranged from 20/20 to 20/300. Fundoscopic examination revealed multiple white round chorioretinal lesions with vitreous infiltration bilaterally in all three patients. Vitreous tap samples were obtained for culture and broad-spectrum intravitreal antimicrobials were administered. Despite negative cultures and systemic workup, the clinical presentation was consistent with …

Single-Cell Transcriptomic Analysis Of Peripheral Blood Mononuclear Cells Reveals Key Immune Responses In St-Segment Elevation Myocardial Infarction, Zheng Zhang, Shengfang Wang, Yahui Liu, Gaohan Li, Qianqian Cheng, Wei Yang, Gan-Xin Yan, Chuanyu Gao

Department of Medicine Faculty Papers

BACKGROUND: Inflammation plays a crucial role in the pathogenesis of ST-segment elevation myocardial infarction (STEMI). However, the precise immunological mechanisms remain incompletely understood. Single-cell RNA sequencing (scRNA-seq) provides a powerful approach to dissect immune cell heterogeneity and dynamic changes at single-cell resolution.

METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from 7 STEMI patients (within 6h after primary percutaneous coronary intervention) and 3 healthy controls. Single-cell suspensions were prepared and subjected to scRNA-seq using the 10x Genomics Chromium platform and Illumina NovaSeq 6000. Data were processed using Cell Ranger and analyzed with Seurat for quality control, clustering, and annotation. Differentially …

Mycobacterium Chelonae Outbreak Investigation At A Quaternary Pediatric Hospital Following The Opening Of A Leed-Certified Critical Care Tower: Where Does Water Sustainability Intersect With Infection Control?, Andrea L Ankrum, Silvia M Caceres, Michael Torsell, Elaine Epperson, Vinicius Calado Nogueira De Moura, Jennifer J Gilick, Michael Strong, Qingyun Liu, Matthew J Strand, Rachel N Wilsey, Jennifer R Honda, Jane E Gross, Felicia A Scaggs-Huang

Faculty, Staff and Student Publications

Objective: Investigate the increased incidence of Mycobacterium chelonae positive respiratory cultures in hospitalized patients.

Design: Apply the Healthcare-Associated Links in Transmission of Nontuberculous Mycobacteria (HALT NTM) toolkit to an outbreak investigation of M. chelonae.

Setting: Quaternary-care pediatric hospital and medical center in the United States with a recently opened LEED-certified critical care tower.

Patients: Adult and pediatric patients with M. chelonae positive respiratory cultures between June 2022 and January 2024.

Methods: An epidemiological investigation involving clinical and laboratory practices, water management, building construction and renovation projects. Environmental sampling of air vents, water sources and endoscope reprocessing equipment was performed. M. …

Nirsevimab Effectiveness Against Intensive Care Unit Admission For Respiratory Syncytial Virus In Infants - 24 States, December 2024-April 2025., Laura D. Zambrano, Regina M. Simeone, Margaret M. Newhams, Amanda B. Payne, Natasha B. Halasa, Amber O. Orzel-Lockwood, Jemima M. Calixte, Satoshi Kamidani, Hillary Crandall, Melissa A. Cameron, Jennifer E. Schuster, Aline B. Maddux, Kathleen Chiotos, Katherine Irby, Steven L. Shein, Mary Allen Staat, Lora M. Martin, Samina S. Bhumbra, Ryan A. Nofziger, Jigar C. Chauhan, Danielle M. Zerr, Shira J. Gertz, Judith A. Guzman-Cottrill, Michele Kong, Janet R. Hume, Bria M. Coates, Kelly N. Michelson, Emily R. Levy, Tamara T. Bradford, Stephanie P. Schwartz, Tracie C. Walker, Melissa S. Stockwell, Austin Biggs, Alexander H. Hogan, Katherine Lindsey, Angela P. Campbell, Adrienne G. Randolph, Overcoming Rsv Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Respiratory syncytial virus (RSV) is a leading cause of intensive care unit (ICU) admission and respiratory failure among infants (children aged < 1 year) in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect against RSV-associated lower respiratory tract infection among all infants aged < 8 months born during or entering their first RSV season. Following licensure, nirsevimab effectiveness has been demonstrated against RSV-associated infant hospitalization, but evidence regarding effectiveness against RSV-associated critical illness is limited. In a 27-hospital case-control investigation, nirsevimab effectiveness against both RSV-associated infant ICU admission and acute respiratory failure (illness requiring continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation) after hospital admission was evaluated during December 1, 2024-April 15, 2025. Among 457 case-patients who received a positive RSV test result and 302 control patients who received a negative RSV test result admitted to an ICU with respiratory symptoms, 14% and 45%, respectively, had received nirsevimab ≥7 days before symptom onset. Nirsevimab was 80% effective (95% CI = 70%-86%) against RSV-associated ICU admission and 83% effective (95% CI = 74%-90%) against acute respiratory failure when received a median of 52 days (IQR = 32-89 days) and 50 days (IQR = 32-86 days) before onset for each respective endpoint. These estimates support the recommendation for use of nirsevimab as a prevention strategy to protect infants against severe outcomes from RSV infection.

Providencia Rettgeri As An Unusual Pathogen In Diabetic Foot Osteomyelitis: A Case Report And Literature Review, Stephanie N. Campbell, Madeleine Mehaffey, Nikita Gambhir, Amanda L. Killeen

School of Podiatric Medicine Publications

Providencia rettgeri is a Gram-negative bacterium, rarely reported as a cause of diabetic wound infections. Its frequent resistance to β-lactams and carbapenems limits treatment options, especially in immunocompromised patients. We present the case of a 59-year-old unhoused male living with diabetes, peripheral artery disease, and prior bilateral transmetatarsal amputations who presented with a University of Texas 3B diabetic foot ulcer. Magnetic resonance imaging showed osteomyelitis of metatarsals 2–4, and bone biopsy grew Providencia rettgeri and Proteus mirabilis. The patient declined further surgery and was treated with 6 weeks of cefepime and metronidazole, with outpatient wound care, achieving wound closure …

Infection And Nonunion Rates In Open Fractures, Roman M. Natoli, Lucas S. Marchand, Sofia Bzovsky, Jennifer E. Hagen, Mark J. Gage, Christina A. Stennett, Nathan N. O’Hara, Kyle J. Jeray, Brad Petrisor, Sheila Sprague, Gerard P. Slobogean, Jeffrey Wells, Mohit Bhandari, Anthony D. Harris, C. Daniel Mullins, Lehana Thabane, Amber Wood, Gregory J. Della Rocca, Joan Hebden, Lyndsay M. O’Hara, Robert Zura, Christopher Lee, Joseph Patterson, Michael J. Gardner, Jenna Blasman, Jonah Davies, Stephen Liang, Monica Taljaard, The Flow Investigators, The Prep-It Investigators

Orthopaedic Surgery Faculty Publications

Background: Infection and nonunion are common sequelae of open fractures. Studies have shown infection and nonunion rates ranging from 2% to 52% and 12% to 17%, respectively. The present article describes the rates of surgical site infection (SSI) and delayed union/nonunion following open fractures in a large contemporary series of patients from prospective clinical trials with adjudicated outcomes. Methods: A descriptive analysis was performed with use of patient data from the FLOW, Aqueous-PREP, and PREPARE-Open studies. These studies, published within the past 10 years, included multiple international trauma centers and shared definitions for SSI and delayed union/nonunion. SSI and delayed …

A Week-Long Departmental Scholarship Curriculum For Pediatric Subspecialty Fellows, Amy Creel, Amanda Messer, Robin English

School of Medicine Faculty Publications

BACKGROUND: Scholarly activity is a key requirement in pediatric subspecialty fellowship training. However, clear guidance on how to effectively support fellows in their scholarly endeavors remains limited. OBJECTIVE: This study assesses the impact of a week-long departmental scholarship curriculum designed to enhance fellows' research competencies. METHODS: In 2024, a curriculum was designed and delivered to first-year pediatric subspecialty fellows over 5 days, combining group learning sessions with individualized tasks. Pre- and post-curriculum surveys assessed fellows' confidence and knowledge across key scholarly domains. Daily session evaluations provided additional feedback. Fourteen fellows from 9 pediatric subspecialty programs participated. RESULTS: All first-year fellows …

Be Faster Community Of Practice To Increase Rapid Initiation Of Antiretroviral Therapy In Houston, Texas: A Pre-Post Intervention Study, Naomi Sequeira, Bich N Dang, Melanie Goebel, Monisha Arya, Avishek Ghosh-Hajra, Kathryn Fergus, Shital M Patel

Faculty, Staff and Students Publications

Background: Rapid initiation of antiretroviral therapy (Rapid ART) is a key strategy of the Ending the HIV Epidemic (EHE) initiative. The Baylor College of Medicine Extension for Community Healthcare Outcomes (ECHO) Facilitating Antiretroviral Start Earlier (BE FASTER) program was developed to address this call-to-action. The program uses the ProjectECHO tele-mentoring model as an implementation tool in Harris County, a priority EHE jurisdiction. The authors present results on the acceptability and feasibility of the BE FASTER program.

Methods: Multidisciplinary health professionals from 5 Ryan White Part A funded agencies formed the community of practice. The BE FASTER program included 9 monthly …

Multiomic Analysis Reveals A Key Bcat1 Role In Mtor Activation By B Cell Receptor And Tlr9, Rui Guo, Yizhe Sun, Matthew Y Lim, Hardik Shah, Joao A Paulo, Rahaman A Ahmed, Weixing Li, Yuchen Zhang, Haopeng Yang, Liang Wei Wang, Daniel Strebinger, Nicholas A Smith, Meng Li, Merrin Man Long Leong, Michael Lutchenkov, Jin Hua Liang, Zhixuan Li, Yin Wang, Rishi Puri, Ari Melnick, Michael R Green, John M Asara, Adonia E Papathanassiu, Duane R Wesemann, Steven P Gygi, Vamsi K Mootha, Benjamin E Gewurz

Faculty, Staff and Student Publications

B lymphocytes play major adaptive immune roles, producing antibodies and driving T cell responses. However, how immunometabolism networks support B cell activation and differentiation in response to distinct receptor stimuli remains incompletely understood. To gain insights, we systematically investigated acute primary human B cell transcriptional, translational, and metabolomic responses to B cell receptor (BCR), TLR9, CD40-ligand (CD40L), IL-4, or combinations thereof. T cell-independent BCR/TLR9 costimulation, which drives malignant and autoimmune B cell states, highly induced transaminase branched chain amino acid transaminase 1 (BCAT1), which localized to lysosomal membranes to support branched chain amino acid synthesis and mTORC1 activation. BCAT1 inhibition …

Application Of Freezetb, A Targeted Nanopore Sequencing Assay, For Identification Of Drug Resistance And Lineages Among Pulmonary Tuberculosis Cases In Alaska, Bryce Inman, Jeremy Butler, Soren George-Nichol, Ganna Kovalenko, Theresa Savidge, Yvette Vergnetti, Catherine Pongratz, Elizabeth Bee, Andrew R Dinardo, Alexander Kay, Anna Mandalakas, Eric Bortz, Tara E Ness

Faculty, Staff and Students Publications

Alaska has the highest incidence of tuberculosis (TB) in the United States, with 8% mortality while undergoing TB treatment. With a quarter of TB cases lacking sputum culture to enable drug resistance testing, FreezeTB aimed to develop tools tailored to meet the challenges in Alaska while being translatable to other settings. We designed a rapid and cost-effective laboratory workflow and software to identify drug-resistant mutations in Mycobacterium tuberculosis using targeted next-generation sequencing (tNGS). FreezeTB, a Fast, Reliable, Economical Evaluation tool to Zap Endemic Tuberculosis, amplifies 22 gene loci associated with resistance to 16 anti-tuberculosis drugs. M. tuberculosis isolates from Alaska …

Prevalence Of Potentially Inappropriate Medications In People Living With Hiv: A Systematic Review And Meta-Analysis, Mustapha Muhammed Abubakar, Abdulmuminu Isah, Ruth Jeminiwa, Ibraheem Abioye, Ismaeel Yunusa, Mohammed Abba-Aji, Osagie Kenneth Cole, Jamila Sani, Mukhtar Ijaiya, Chukwuemeka Nwachuya, Yusuf Ibrahim, Mustapha Usman, Duke Daniels, Oluwaseun Samuel Ilugbuhi, Blessing Onyinye Ukoha-Kalu

College of Pharmacy Faculty Papers

BACKGROUND: Potentially inappropriate medications (PIM) are associated with adverse health outcomes. The use of PIM among persons living with HIV (PLHIV) could be more problematic due to peculiarities such as antiretroviral toxicity and drug-disease interactions. However, PIM among PLHIV continues to receive little attention. Therefore, we aimed to systematically review and estimate the prevalence of PIM among PLHIV.

METHODS: We searched the PubMed, Scopus, and Web of Science databases to identify relevant studies from 1 January 2014 to 30 June 2024. Studies included were peer-reviewed articles that determined PIM prevalence using validated explicit or implicit tools and provided statistical information …

Slc35g3 Is A Udp-N-Acetylglucosamine Transporter For Sperm Glycoprotein Formation And Underpins Male Fertility In Mice, Daisuke Mashiko, Shingo Tonai, Haruhiko Miyata, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Despite the recognized importance of glycans in biological phenomena, their complex roles in spermatogenesis and sperm function remain unclear. SLC35G3, a 10-transmembrane protein specifically found in early round spermatids, belongs to the sugar-nucleotide transporter family, indicating its involvement in glycan formation. In this study, we found that Slc35g3 knockout male mice were sterile due to impaired sperm functions in uterotubal junction passage, zona pellucida binding, and oocyte fusion. Mouse SLC35G3 has UDP-GlcNAc transporter activity, and its ablation caused abnormal processing of the sperm plasma membrane and acrosome membrane proteins. Reported human SLC35G3 mutations (F267L and T179HfsTer27) diminished the UDP-GlcNAc transporter …

‘In Texas, Everybody Wants Antibiotics’: Reducing Inappropriate Antibiotic Expectations And Use With A Provider-Patient Communication Tool In Primary Care, Ashley Collazo, Paige Wermuth, Johanan Luna Rodriguez, Kiara Olmeda, Azalia Mancera, Fabrizia Faustinella, Michael K Paasche-Orlow, Roger Zoorob, Barbara Wells Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Background/objective: Patients often expect antibiotics for self-limiting diseases, pressuring providers to prescribe antibiotics unnecessarily. These expectations also contribute to the unsafe practice of taking antibiotics without a prescription (non-prescription use), such as pills retained from prior prescriptions or antibiotics from non-medical sources. Previous work shows that non-prescription use is due to strong, widely held misconceptions regarding the curative power of antibiotics. To reduce unnecessary use of antibiotics, we developed and pilot-tested a patient-focused, bilingual (English and Spanish) educational tool with patient and provider stakeholder input. The tool, a trifold brochure, included information on safe antibiotic use, potential antibiotic harms and …

Antimicrobial Resistance In Ukraine—What Healthcare Providers Need To Know When Treating Ukrainian Refugees, Olga Vasylyeva

Advances in Clinical Medical Research and Healthcare Delivery

The scoping review assesses the trends in clinical infectious diseases reporting antimicrobial resistance (AMR) in Ukraine following a year of full-scale Russo-Ukrainian war (2022) to offer recommendations for healthcare providers caring for patients traveling from Ukraine.

Background: Until 2019, antibiotics were available to Ukrainians over the counter, and there was no systematic program to monitor bacterial resistance. Only in 2023 did a document standardizing the rational use of antibacterial and antifungal drugs become available for Ukrainian healthcare providers. By 2020, high levels of carbapenem-resistant bacteria were reported in military hospitals, 29.5%–64.2%, with Acinetobacter baumannii particularly problematic. Nosocomial infections were significantly …

Accidental Daily Dosing: Severe Methotrexate Toxicity In A Patient With Rheumatoid Arthritis, Sidra Memon, Kavitha Vemuri, Syed Uzair Mahmood, Darshit Patel

Advances in Clinical Medical Research and Healthcare Delivery

This case highlights a crucial complication of oral methotrexate therapy: toxicity due to dosing errors. A patient’s daily dosing regimen, instead of the intended weekly schedule, led to a significantly excessive cumulative dose of methotrexate over a short period, resulting in severe hematologic and mucosal toxicity. This underscores the importance of clear patient education and vigilant prescription practices to prevent such errors.

Impact Of Frailty On Inpatient Outcomes Of Covid-19 Patients: Evidence From A Us National Inpatient Sample, Ali Jaan, Priyanshi Shah, Ashish Dhawan, Saria Qaiser, Azka Ali, Hla Myo Thwe, Oluwatosin Abimbolu, Clara Chimuanya Okpara, Michael Rajnik

Advances in Clinical Medical Research and Healthcare Delivery

Introduction: The global impact of Coronavirus Disease 2019 (COVID-19), caused by severe-acute-respiratory-syndrome coronavirus 2 (SARS-CoV-2), has been profound, claiming the lives of more than 3 million individuals within a year and a half. Among the affected population, heightened vulnerability is observed among older and frailer individuals, leading to more severe symptoms and adverse outcomes compared to their younger, non-frail counterparts. This study to analyze the impact of frailty on the outcomes of adult patients admitted with COVID-19.

Methods: Using the National Inpatient Sample (NIS) database 2020, we identified adult patients admitted with a principal diagnosis of COVID-19. The …

A Multiomics Recovery Factor Predicts Long Covid In The Impacc Study, Gisela Gabernet, Jessica Maciuch, Jeremy P Gygi, John F Moore, Annmarie Hoch, Caitlin Syphurs, Tianyi Chu, Naresh Doni Jayavelu, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick-Pierre Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Nadine Rouphael, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, Catherine L Hough, William B Messer, Mark M Davis, Kari C Nadeau, Bali Pulendran, Monica Kraft, Chris Bime, Elaine F Reed, Joanna Schaenman, David J Erle, Carolyn S Calfee, Mark A Atkinson, Scott C Brakenridge, Esther Melamed, Albert C Shaw, David A Hafler, Alison D Augustine, Patrice M Becker, Al Ozonoff, Steven E Bosinger, Walter Eckalbar, Holden T Maecker, Seunghee Kim-Schulze, Hanno Steen, Florian Krammer, Kerstin Westendorf, Bjoern Peters, Slim Fourati, Matthew C Altman, Ofer Levy, Kinga K Smolen, Ruth R Montgomery, Joann Diray-Arce, Steven H Kleinstein, Leying Guan, Lauren Ir Ehrlich

Faculty, Staff and Students Publications

Background: Following SARS-CoV-2 infection, approximately 10%–35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.

Methods: We utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics “recovery factor,” trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor …

Proteomic Perspectives On Kras-Driven Cancers And Emerging Therapeutic Approaches, Ramesh Karki, Ru Chen, Sheng Pan

Faculty, Staff and Student Publications

KRAS mutations are implicated in approximately 23% of all human malignancies, with particularly high prevalence in pancreatic ductal adenocarcinoma (PDAC) (~92%), colorectal cancer (CRC) (~49%), and non-small cell lung cancer (NSCLC) (~35%). The recent approval of the KRASG12C-specific inhibitors for NSCLC represents a pivotal advancement in KRAS-targeted therapy. Nevertheless, the emergence of intrinsic and acquired resistance to KRAS-targeted therapies poses a significant clinical obstacle to targeting KRAS, which necessitates a deeper understanding of the resistance mechanisms. Recent progress in proteomic studies has enabled comprehensive profiling of the proteomic alterations driven by KRAS mutations, offering valuable insights into the disrupted KRAS …

Gut Bacterial Dysbiosis In Pediatric Severe Malaria Associates With Post-Discharge Mortality, Olivia Bednarski, Sawyer Lehman, David Mzinza, Caroline Kazinga, Ruth Namazzi, Robert Opoka, Jie Ren, Tuan Tran, Terrie Taylor, Karl Seydel

Paediatrics and Child Health, East Africa

Gut microbiota have been implicated in severe malaria in murine models, but their contribution to the pathogenesis of severe malaria in children is unknown. Here we show through analysis of gut bacteria in stool samples from two separate African studies enrolling children with severe malaria, and children from local communities, that children with severe malaria have gut bacteria dysbiosis. Among children with severe malaria, there is increased abundance of Enterobacteriaceae that associates with multiple clinical complications of severe malaria. Moreover, increased abundance of Escherichia coli was a predictor of post-discharge mortality. Metagenome analysis identify elevated metabolic pathways and genes supporting …

Avasopasem Manganese Treatment For Severe Oral Mucositis From Chemoradiotherapy For Locally Advanced Head And Neck Cancer: Phase 3 Randomized Controlled Trial (Roman), Carryn Anderson, Christopher M. Lee, Joseph Randall Kelley, Gary V. Walker, Neal E. Dunlap, Voichita Bar-Ad, Douglas A. Miller, Vernon J. King, Abhinand V. Peddada, Douglas F. Ciuba, Francois Vincent, Brian C. Muzyka, Amanda Lynn Gillespie-Twardy, Stephen T. Sonis, Jon Holmlund, Robert A Beardsley, Eugene P Kennedy, Deborah Saunders

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Of patients who receive standard concomitant chemoradiation (CRT; intensity-modulated radiation therapy [IMRT] plus cisplatin) for locally advanced head and neck cancer (HNC), approximately two-thirds will develop severe oral mucositis (SOM), limiting their ability to eat solids (WHO grade 3) or drink liquids (WHO grade 4). In a randomized, double-blind phase 2b trial, avasopasem manganese substantially reduced duration and incidence of SOM versus placebo. This phase 3 trial further assessed avasopasem's reduction of SOM due to CRT.

METHODS: In this double-blind, placebo-controlled trial (Clinicaltrials.gov: NCT03689712), patients receiving 60-72 Gy IMRT (>50 Gy to ≥2 oral mucosal sites) plus cisplatin …