Digital Commons Network^™

Exploring Lingering Covid-19 Vaccine Hesitancy In Three Diverse U.S. States: Alabama, Illinois, And Texas, Sinan Almukhtar, Noah Mcwhirter, Anaïs Mendiola, Shekwonya Samuel, Olivia Dominguez, Danielle Pester Boyd, Stephen Flores, Pooja Gandhi, Francis Kazungu, Manorama Khare, Paula Cuccaro, Maria E Fernández, Ronald C Hershow, Sage Kim, Emily Stiehl

Faculty, Staff and Student Publications

During the COVID-19 pandemic, vaccine uptake was slower than expected, with some people experiencing concern about the safety and effectiveness of the COVID-19 vaccine even after being vaccinated. This manuscript explores a phenomenon called lingering hesitancy, or the concern that people experience even after receiving an initial dose of a vaccine. Leveraging survey findings from three individual Prevention Research Centers (PRCs) in Alabama, Illinois, and Texas, we compare the attitudes of individuals across three vaccine status groups: those who received their complete COVID-19 vaccine series, those who received an initial dose but no subsequent doses (lingering hesitancy), and those who …

It Takes A Village: Addressing Community Needs To Implement Firearm Prohibitions For Domestic Violence Protective Order Respondents, Kellie R Lynch, Michael K Gusmano, Jeff R Temple, Sarah Lane

Faculty, Staff and Student Publications

Prohibiting domestic violence protective order (DVPO) respondents from firearms is an effective strategy to prevent intimate partner homicide. However, DVPO gun laws vary considerably across states, and the implementation of such laws is inconsistent across localities. Local context, such as resource availability, priorities, and politics, differs across types of communities and impacts the implementation of laws. We conducted in-depth key informant interviews with victim service and criminal justice professionals (N = 27) working in urban communities, rural communities, and statewide organizations to better understand: (a) what communities need to effectively prohibit DVPO respondents from firearms (i.e., the DVPO gun …

Dissection Of Surface Area-Dependent Lipolysis At A Single Organelle Level, Chengxin Ma, Yan Liang, Xinmeng Che, Yuqi Li, Jin Wu, Li Xu, Hongyuan Yang, Tong-Jin Zhao, Feng-Jung Chen, Peng Li

Faculty, Staff and Student Publications

Lipid droplets are dynamic organelles whose size and number signify their role in energy. However, owing to cellular heterogeneity and technological limitations, the relationship between the lipolytic ability and lipid droplet morphology is unclear. Here, we developed a live-cell imaging assay using geometric analysis to quantify cellular lipolysis at a single organelle level, designated imaging lipolysis. Using imaging lipolysis and super-resolution imaging, we found that lipolysis is controlled by both lipase-accessible lipid droplet surface area and lipase activity. Moreover, lipid droplet fusion regulatory proteins CLSTN3β/CIDEs promote lipolysis by increasing the total lipid droplet surface area-to-volume ratio in biophysical regulation. We …

Evaluating The Efficacy And Safety Of Milrinone For Prevention Of Post-Patent Ductus Arteriosus Closure Syndrome (The Midas Trial) In Extremely Preterm Infants: A Multicentre, Double-Masked, Randomised, Placebo-Controlled Trial, Patrick J Mcnamara, Valerie Y Chock, Adrianne Rahde-Bischoff, Jenna Gabrio, Karen J Johnson, Heidi M Harmon, Diana Montoya-Williams, Tarah T Colaizy, Anup C Katheria, Felix Ines, Keira Sorrells, Cheryl Battersby, Philip T Levy, Matthew A Rysavy, Shazia Bhombal, Matthew M Laughon, Ben Carper, Susan R Hintz, Abhik Das, Edward F Bell

Faculty, Staff and Student Publications

Introduction: Post-ligation cardiac syndrome (PLCS) represents a state of severe post-intervention cardiopulmonary instability, seen in up to 50% of extremely premature infants after surgical closure of the patent ductus arteriosus (PDA); yet an evidence-based approach to treatment of this condition does not exist. The objective of this study is to determine the efficacy and safety of prophylactic milrinone in reducing incidence of PLCS and/or mortality within the first 7 days following PDA closure. The central hypothesis is that administration of intravenous milrinone will reduce the incidence of PLCS or death within 7 days of PDA closure either by percutaneous device …

The Role Of Recruited Adipose Stromal Cells And Their Fibroblastic Differentiation In Cancer, Lingyi Cai, Mikhail G Kolonin, Dimitris Anastassiou

Faculty, Staff and Student Publications

Adipose stromal cells (ASCs) are perivascular mesenchymal progenitors of adipose tissue. In cancer patients, ASCs can mobilize and migrate to the tumor, where they subsequently play an important role in cancer progression. This biological process involves the conversion of recruited ASCs into cancer-associated fibroblasts (CAFs). ASC-derived CAFs influence the tumor microenvironment through extracellular matrix remodeling, vascularization, and immunomodulation. These and other processes mediated by secreted paracrine factors also affect gene expression in carcinoma cells to promote the epithelial-mesenchymal transition (EMT), metabolic adaptation, survival, and invasiveness of cancer cells. ASC-derived CAFs can enhance tumor aggressiveness, accounting in part for the link …

Suppression Of Cardiac Allograft Vasculopathy By A Macrophage Efferocytosis Receptor, Sahil Shah, Aparnaa Ananthakrishnan, Matthew Deberge, Kristofor Glinton, Rebecca T L Jones, Mallory Filipp, Ivana Shen, Joey Lockhart, Connor W Lantz, Edward B Thorp

Faculty, Staff and Student Publications

Cardiac allograft vasculopathy remains a major cause of late morbidity following heart transplantation. While accumulating evidence implicates innate macrophages in the inflammatory progression of CAV, the underlying mechanisms remain incompletely understood. In murine models of CAV, we identified proteolytic cleavage of MERTK, a key anti-inflammatory receptor on macrophages, as a contributing factor to CAV progression. In a model of CAV, MERTK deficiency accelerated allograft rejection and increased intimal leukocyte infiltration. In contrast, mice expressing a genetically cleavage-resistant form of MERTK (MertkCR/CR) exhibited prolonged graft survival, reduced intimal thickening, diminished immune cell infiltration, and decreased circulating effector T cells. …

Phase 1 Clinical Trial Of ¡Iniciando! La Adultez: A Culturally Tailored Intervention For Transitioning Latino Young Adults With Autism, Antonio F Pagán, Ana Esparza, Ana Ramirez, Miriam Ortiz, Linda Hernandez, Mary Beth Morgan, Geohanna Noel, Alejandro L Pagán, Jada Salas, Katherine Maurano, Grace Sattem, Leela Sydow, Noor Ahmed, Katherine A Loveland, Cecilia Montiel-Nava, Ron Acierno

Faculty, Staff and Student Publications

This Phase 1 clinical trial evaluated ¡Iniciando! la Adultez, a culturally adapted intervention for Latino autistic young adults (n = 56) and their parents (n = 63). Young adults showed significant post-treatment improvements on measures of social responsiveness (SRS-2), adaptive behavior (ABAS-3), executive functioning (BRIEF-A), quality of life (WHOQOL-BREF), transition readiness (TRS-A), coping self-efficacy (CSES), and emotion regulation (DERS-SF). Parents reported significant improvements in their perceptions of their child’s social responsiveness, adaptive behavior, and executive functioning, as well as increased transition readiness ratings. Notably, parents evinced a significant decrease in acculturative stress (RASI) and depressive symptoms (PHQ-9), however, …

Using The R = Mc2 Heuristic To Assess Whole-Of-School Physical Activity Implementation In Elementary Schools: A Cross-Sectional Study, Derek W Craig, Kevin Lanza, Christopher D Pfledderer, Andjelka Pavlovic, Kempson Onadeko, Natalia I Heredia, Jizyah Injil, Laura F Defina, Timothy J Walker

Faculty, Staff and Student Publications

Background: Schools are recommended to use a whole-of-school (WOS) approach to promote physical activity opportunities before, during, and after school. Yet, the barriers and facilitators to implementing a WOS approach successfully are not well understood. The R = MC2 heuristic, which defines readiness for implementation as a combination of an organization's motivation and capacity to implement, can enhance our understanding of implementation in the school setting. This study examines associations between constructs from the R = MC2 heuristic and schools' implementation of a WOS approach.

Methods: We conducted a secondary analysis of cross-sectional data from U.S. elementary schools participating in …

Predicting Regional Cerebral Blood Flow Using Voxel-Wise Resting-State Functional Mri, Hongjie Ke, Bhim M Adhikari, Yezhi Pan, David B Keator, Daniel Amen, Si Gao, Yizhou Ma, Paul M Thompson, Neda Jahanshad, Jessica A Turner, Theo G M Van Erp, Mohammed R Milad, Jair C Soares, Vince D Calhoun, Juergen Dukart, L Elliot Hong, Tianzhou Ma, Peter Kochunov

Faculty, Staff and Student Publications

Background: Regional cerebral blood flow (rCBF) is a putative biomarker for neuropsychiatric disorders, including major depressive disorder (MDD).

Methods: Here, we show that rCBF can be predicted from resting-state functional MRI (rsfMRI) at the voxel level while correcting for partial volume averaging (PVA) artifacts. Cortical patterns of MDD-related CBF differences decoded from rsfMRI using a PVA-corrected approach showed excellent agreement with CBF measured using single-photon emission computed tomography (SPECT) and arterial spin labeling (ASL). A support vector machine algorithm was trained to decode cortical voxel-wise CBF from temporal and power-spectral features of voxel-level rsfMRI time series while accounting for PVA. …

Caf-Macrophage Crosstalk Fuels Immunotherapy Resistance, Yang Liu, Linghua Wang

Faculty, Staff and Student Publications

No abstract provided.

Association Of Glucagon-Like Peptide-1 Receptor Agonists With Cancer Risk In Older Adults With Type 2 Diabetes, Ying Lu, Hao Dai, Huilin Tang, William T Donahoo, Thomas J George, Ramon C Sun, Sizun Jiang, Aik Choon Tan, Yi Guo, Jonathan D Licht, John M Allen, Kelvin P Lee, Jingchuan Guo, Jiang Bian

Faculty, Staff and Student Publications

Objective: The real-world evidence on the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and cancer risk remains limited and mixed.

Methods: In 2013-2020 national Medicare claims data, we included cancer-naïve patients with type 2 diabetes (T2D). We identified those who initiated GLP-1 RA, sodium-glucose cotransporter 2 inhibitor (SGLT2i), or dipeptidyl peptidase 4 inhibitor (DPP4i) and conducted 1:1 propensity score matching for confounding adjustment. Cox proportional hazards models were used to estimate hazard ratios (HR) of nine obesity-associated cancers (thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, and prostate cancer).

Results: In the matched GLP-1RA versus SGLT2i cohort (n = 21,362 …

Circzfr/Ythdf3 Axis Drives Lymph Node Metastasis In Cervical Cancer Via Fasn Translation, Mingyi Zhou, Yan Gao, Yong Zhang, Lian He, Bo Gao, Yue Zhang, Francois X Claret, George A Calin, Danbo Wang

Faculty, Staff and Student Publications

Background: Lymph node metastasis is a key driver of poor outcomes in cervical cancer. However, the molecular mechanisms of circular RNAs (circRNAs) driving cervical cancer lymph node metastasis remain unclear.

Methods: We identified circZFR, fatty acid synthase (FASN) and YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) protein expression in the cervical cancer patients with long and short disease-free survival (DFS). Functional experiments were performed to investigate the function of circZFR, FASN and YTHDF3 on cell migration and invasion. MeRIP-qPCR, RNA pulldown, RNA Immunoprecipitation (RIP), and Co-Immunoprecipitation (Co-IP) assays were executed to investigate the mechanism of circZFR regulating FASN protein expression. …

Deep Phenotyping Of Obesity: Electronic Health Record-Based Temporal Modeling Study, Xiaoyang Ruan, Shuyu Lu, Liwei Wang, Andrew Wen, Sameer Murali, Hongfang Liu

Faculty, Staff and Student Publications

Background: Obesity affects approximately 40% of adults and 15%-20% of children and adolescents in the United States, and poses significant economic and psychosocial burdens. Currently, patient responses to any single antiobesity medication (AOM) vary significantly, making obesity deep phenotyping and associated precision medicine important targets of investigation.

Objective: This study aimed to evaluate the potential of electronic health records (EHR) as a primary data source for obesity deep phenotyping. We conducted an in-depth analysis of the data elements and quality available from obesity patients prior to pharmacotherapy and applied a multimodal longitudinal deep autoencoder to investigate the feasibility, data requirements, …

Targeted Proteomic Analysis Identifies Acvrl1 As A Marker Of Cerebral Edema In Aneurysmal Subarachnoid Hemorrhage, Bosco Seong Kyu Yang, Lena O'Keefe, Sarah Hinds, Hua Chen, Athziry Paz, Jude Savarraj, Han-Gil Jeong, Moon-Ku Han, Aaron Gusdon, Xuefang Sophie Ren, Spiros Blackburn, Huimahn Alex Choi

Faculty, Staff and Student Publications

Cerebral edema (CE) is a major component of early brain injury from aneurysmal subarachnoid hemorrhage (SAH). Despite the utility of blood-based protein markers, biomarkers targeting cerebral edema have yet to be developed. We performed a targeted proteomic search analyzing 141 proteins in plasma samples taken from 80 adult patients within 48 hours after aneurysmal rupture to identify plasma biomarkers of cerebral edema. The protein expression profiles were analyzed for associations with a higher level of the subarachnoid hemorrhage early brain edema score measured in admission computed tomography scans. Five differentially expressed proteins-brorin, ectodysplasin A2 receptor, layilin, scavenger receptor class A …

Genomic Editing Of A Pathogenic Sequence Variant In Acta2 Rescues Multisystemic Smooth Muscle Dysfunction Syndrome In Mice, Qianqian Ding, Peiheng Gan, Zhisheng Xu, Hui Li, Lei Guo, Camryn Macdonald, Wei Tan, Efrain Sanchez-Ortiz, John R Mcanally, Yu Zhang, Dileep Karri, Lin Xu, Ning Liu, Eric N Olson

Faculty, Staff and Student Publications

Background: Vascular smooth muscle cells (SMCs), the predominant cell type in the aortic wall, play a crucial role in maintaining aortic integrity, blood pressure, and cardiovascular function. Vascular SMC contractility and function depend on ACTA2 (smooth muscle α-actin 2). The pathogenic variant ACTA2 c.536G>A (p.R179H) causes multisystemic smooth muscle dysfunction syndrome, a severe disorder marked by widespread smooth muscle abnormalities, resulting in life-threatening aortic disease and high risk of early death from aneurysms or stroke. No effective treatments exist for multisystemic smooth muscle dysfunction syndrome.

Methods: To develop a comprehensive therapy for multisystemic smooth muscle dysfunction syndrome, we used …

Lipid-Laden Microglia: Characterization And Roles In Diseases, Jiani Xing, Takese Mckenzie, Jian Hu

Faculty, Staff and Student Publications

Microglia are resident phagocytes of the central nervous system that play an essential role in brain development and homeostasis. When the intracellular lipid content exceeds the metabolic capacity of microglia, lipid droplets accumulate, giving rise to a distinct population termed lipid-laden microglia (LLMs). LLMs have been implicated in various neuroinflammatory and neurodegenerative diseases, functioning as both regulators/indicators of inflammation and potential therapeutic targets. This review summarizes the current research on LLMs, focusing on disease-specific regulators and functions, protective roles, interactions with neighboring cells, and advances in diagnostic and analytical tools. We also discuss the blurred distinction between LLMs and macrophages, …

Trpc4 Regulates Limbic Behavior And Neuronal Development By Stabilizing Dendrite Branches Through Actomyosin-Driven Integrin Activation, Jaepyo Jeon, Travis I Moore, Insuk So, Marc Freichel, Veit Flockerzi, Lutz Birnbaumer, Michael X Zhu

Faculty, Staff and Student Publications

Transient Receptor Potential Canonical 4 (TRPC4) channels have been implicated in multiple neurological functions, including anxiety and sociability. TRPC4 variants were also found in patients with autism. However, the contributions of TRPC4 to neurodevelopment remain undefined. Here, we show that neurobehavioral deficits appear early in young TRPC4 knockout (Trpc4^−/−) mice immediately after weaning, manifesting as alterations in multiple, limbic-related behaviors, such as nesting, marble burying, burrowing, self-grooming, and social interactions. Hippocampal neurons of Trpc4−/− mice exhibit reduced dendritic arborization both in vivo and in vitro. Mechanistically, we found that TRPC4 expression in dendrites surged at the …

Simulated Emergency Room Sign-Outs: What They Tell Us About Diagnostic Accuracy And Opportunities For Improvement, Roni Matin, Brent R King, Amit M Mehta, Susan H Fenton, Nathan R Hoot, David J Robinson, Charles L Maddow, Amy Franklin

Faculty, Staff and Student Publications

Objective: Emergency department (ED) sign-outs provide continuity of care for patients at shift changes. However, these periods have been associated with communication breakdowns and medical errors. We explored information factors (stage-of-the-case and the explicitness of the sign-out narrative) to determine their impact on clinicians' diagnostic accuracy and confidence.

Methods: Clinicians from 2 academic ED sites reviewed patient vignettes sign-out narratives (N=69). Using a within-subjects experiment, the explicitness of the sign-out information (i.e., broad statement about labs versus stating each test) and the patient's stage in the diagnostic process (e.g., labs pending, treatment occurring, etc.) at the time of sign-out varied. …

Old Vs New Local Ancestry Inference In Hchs/Sol: A Comparative Study, Xueying Chen, Hao Wang, Iris Broce, Anders Dale, Bing Yu, Laura Y Zhou, Xihao Li, Maria Argos, Martha L Daviglus, Jianwen Cai, Nora Franceschini, Tamar Sofer

Faculty, Staff and Student Publications

Hispanic/Latino populations are admixed, with genetic contributions from multiple ancestral populations. To uncover genetic associations in these populations, researchers often turn to admixture mapping, which relies on inferred counts of "local" ancestry, i.e. the source ancestral population at a locus. Local ancestries are inferred using external reference panels that represent ancestral populations, making the choice of inference method and reference panel critical. This study used a dataset of Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) to evaluate how updates in local ancestry inference (LAI) affect results, specifically, the 'old' LAI performed using a popular inference method …

Kdm2b Variants In The Cxxc Domain Impair Its Dna-Binding Ability And Cause A Distinct Neurodevelopmental Syndrome, Amber S E Van Oirsouw, Michael A Hadders, Martijn Koetsier, Edith D J Peters, Nurit Assia Batzir, Tahsin Stefan Barakat, Diana Baralle, Adelyn Beil, Marie-Noëlle Bonnet-Dupeyron, Philip M Boone, Arjan Bouman, Deanna Alexis Carere, Benjamin Cogne, Leslie Dunnington, Laura S Farach, Casie A Genetti, Bertrand Isidor, Louis Januel, Aakash Joshi, Nayana Lahiri, Kristen N Lee, Idit Maya, Meriel Mcentagart, Hope Northrup, Mathilde Pujalte, Kate Richardson, Susan Walker, Bobby P C Koeleman, Mariëlle Alders, Richard H Van Jaarsveld, Renske Oegema

Faculty, Staff and Student Publications

Rare variants affecting the epigenetic regulator KDM2B cause a recently delineated neurodevelopmental disorder. Interestingly, we previously identified both a general KDM2B-associated episignature and a subsignature specific to variants in the DNA-binding CxxC domain. In light of the existence of a distinct subsignature, we set out to determine if KDM2B CxxC variants are associated with a unique phenotype and disease mechanism. We recruited individuals with heterozygous CxxC variants and assessed the variants' effect on protein expression and DNA-binding ability. We analyzed clinical data from 19 individuals, including ten previously undescribed individuals with seven novel CxxC variants. The core phenotype of the …

Multidimensional Analysis Of B7 Homolog 3 Rna Expression In Small Cell Lung Cancer Molecular Subtypes, Carl M Gay, Taofeek K Owonikoko, Lauren A Byers, Noura J Choudhury, Sajid Ahmed, Zachary Cain, Xiaozhong Qian, Matthew Brentnall, Simon Heeke, Ming Poi, Sharon Wu, Charles M Rudin

Faculty, Staff and Student Publications

Purpose: B7 homolog 3 (B7-H3) is a promising target for antibody-drug conjugates, with ifinatamab deruxtecan demonstrating an objective response rate of 54.8% in previously treated extensive-stage small cell lung cancer (SCLC). This analysis aimed to characterize B7-H3 RNA expression with reference to SCLC molecular subtypes (SCLC-A, SCLC-N, SCLC-P, and SCLC-I) and immune-related parameters.

Experimental design: Tumor RNA expression and mutational burden for 1,721 patients with SCLC were derived from a real-world database (Caris Life Sciences). A predominant molecular subtype was assigned based on RNA expression using a gene-ratio classifier. PD-L1 expression was assessed by IHC (antibody 22C3; positive cutoff: tumor …

Advanced Specificity And Sensitivity Studies Relative To A Research Use Only Transcription-Mediated Amplification-Based Assay For Treponema Pallidum Rna Detection, Trinity Krueger, Grace Kadonsky, Elizabeth Thelen, Amanda Zapp, Josephine Moore, Ahmet Muslu, Allan Pillay, Irene A Stafford, Erik Munson

Faculty, Staff and Student Publications

Preliminary experimentation has suggested that a research-use-only real-time transcription-mediated amplification assay for Treponema pallidum (RUO T. pallidum TMA) yields instances of T. pallidum nucleic acid detection that coincide with non-treponemal serology in men who have sex with men (MSM) at increased risk for sexually transmitted infection. To further characterize the specificity of RUO T. pallidum TMA testing, 3,586 rectal swab specimens reported as “not detected” by the assay generated a mean endpoint FAM fluorescence of 637.5 units. Introduction of Treponema denticola, Treponema phagedenis, and Treponema refringens nucleic acid into matrices generated mean endpoint FAM fluorescence ranging from 620.7 …

Military Launching! To Adulthood: A Cultural Adaptation Of A Group Therapy Program For Military-Dependent Young Adults With Autism Spectrum Disorder Transitioning To Adulthood, Antonio F Pagán, Jordan Kenemore, Linda Hernandez, Stephen Armstrong, Katherine A Loveland, Mark Ahlenius, Ron Acierno

Faculty, Staff and Student Publications

Objectives: The transition to adulthood poses distinct challenges for young adults with autism spectrum disorder (ASD) (ages 18-25), particularly in establishing and achieving long-term goals. This is further complicated for those within the military and veteran communities. This study aimed to evaluate the feasibility, acceptability, and cultural fit of "Launching! to Adulthood," a 12-week telehealth intervention, adapted for military-dependent young adults with ASD and their military/veteran parents.

Methods: Building on previous research and incorporating stakeholder feedback, the intervention addressed key transition challenges such as executive functioning, mental health, vocational skills, and social engagement, while also aligning with military cultural values. …

An Exciting Future For Microbial Molecular Biology And Physiology, Andrew A Bridges, Leah Guthrie, Mckenzie Lehman, Elizabeth H Kellogg, Samantha Wellington Miranda, Andrew Pountain, Anthony L Shiver, Andrew Varble, Molecular Biology And Physiology Community Of The Council On Microbial Sciences, Heidi B Kaplan, Elizabeth A Shank, Gisela Storz

Faculty, Staff and Student Publications

Continuous advances in technologies ranging from deep sequencing and genetic manipulation to mass spectrometry, single cell imaging, and structural biology have led to previously unimaginable advances in our understanding of microbial physiology and the molecular mechanisms underlying microbial responses in a multitude of environments. Simultaneously, these advances are revealing how much more there is to learn. At the 2024 virtual retreat of the Molecular Biology and Physiology (MBP) Community of the Council on Microbial Sciences (COMS) of the American Society for Microbiology (ASM), eight early-career investigators, along with retreat attendees, discussed some of these astounding advances, as well as the …

Csf-Exosomal Mirnas And Delayed Cerebral Ischemia: Insights Into Pathophysiology But No Definitive Biomarkers, Chathathayil M Shafeeque, Devin W Mcbride, Yuanqing Yan, Hussein A Zeineddine, John P Hagen, H Alex Choi, Jude P Savarraj, Ari Dienel, Spiros L Blackburn, Peeyush Kumar Thankamani

Faculty, Staff and Student Publications

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is notoriously known for its high mortality and morbidity. Approximately one-third of the patients who survive aneurysm rupture are reported to develop delayed cerebral ischemia (DCI), which contributes to a poor clinical outcome. Currently, there are no biomarkers for identifying which aSAH patients are at risk of developing DCI. We aimed to determine the feasibility of cerebrospinal fluid (CSF) exosomal microRNAs (miRNAs) for predicting DCI post-aSAH.

Methods: aSAH patients were prospectively enrolled, and CSF samples were collected at two time points (< 24 h and 72 h post-aSAH) from individuals undergoing external ventricular drainage. Exosomal miRNAs were isolated from the CSF for analysis. In the initial group of patients (discovery cohort), an exploratory analysis was conducted using a CSF panel containing 84 miRNAs, assessed by quantitative real-time PCR (RT-qPCR). Based on this analysis, 27 miRNAs were selected for further evaluation in a second group of patients (validation cohort). Among these, 10 miRNAs had previously been reported in SAH-related CSF studies, supporting their relevance for continued investigation.

Results: In this study, RT-qPCR analysis of 84 miRNAs in CSF samples from …

Ribosome Deficiency Induces Salmonella Filamentation Within Host Cells, Zhihui Lyu, Cierra Wilson, Kalyn Weiss, Spencer Lewis, Kurt Fredrick, William Margolin, Jiqiang Ling

Faculty, Staff and Student Publications

The ribosome is the central hub for protein synthesis and is heavily targeted by antibiotics. Ribosomal mutations, antibiotic treatment, and nutrient starvation can alter translational efficiency and lead to stressed cells. Ribosome deficiency plays a critical role in stress responses and disease progression; yet, how it affects bacteria-host interactions remains poorly understood. In this study, we show that a ribosome-deficient strain exhibits a surprising morphological change from rod shape to filamentous in Salmonella cells growing inside host macrophages. Such filamentation depends on an acidic condition within macrophages and in a defined medium mimicking macrophage conditions. Further genetic analyses revealed that …

Dalbavancin For Treatment Of Staphylococcus Aureus Bacteremia: The Dots Randomized Clinical Trial, Nicholas A Turner, Toshimitsu Hamasaki, Sarah B Doernberg, Thomas P Lodise, Heather A King, Varduhi Ghazaryan, Sara E Cosgrove, Timothy C Jenkins, Catherine Liu, Shrabani Sharma, Smitha Zaharoff, Lana Wahid, Valerie J Renard, Paul Cook, Issam Raad, Ray Hachem, Anne-Marie Chaftari, Matthew Sims, Carmen Demarco, Loren G Miller, Matthew W Mccarthy, Caryn G Morse, Chris Lucasti, Graeme N Forrest, Kartikeya Cherabuddi, Christopher Polk, Tasaduq Fazili, Mark E Rupp, George R Thompson, Kami Kim, Luke Strnad, Amanda E Schnee, James A Mckinnell, Mayur Ramesh, Fernanda P Silveira, Todd P Mccarty, Todd C Lee, Emily G Mcdonald, Kristopher Paolino, Katie Wiegand, Alison Wall, Todd Riccobene, Rinal Patel, Urania Rappo, Scott Evans, Henry F Chambers, Vance G Fowler, Thomas L Holland

Faculty, Staff and Student Publications

Importance: Dalbavancin is a long-acting intravenous lipoglycopeptide that may be effective for treatment of complicated Staphylococcus aureus bacteremia without requiring long-term intravenous access.

Objective: To evaluate the efficacy and safety of dalbavancin vs standard therapy for completion of treatment of complicated S aureus bacteremia.

Design, setting, and participants: Open-label, assessor-masked, randomized clinical trial conducted from April 2021 to December 2023 at 23 medical centers in the US (n = 22) and Canada (n = 1). Participant follow-up lasted 70 days (180 days for participants with osteomyelitis); date of final follow-up was December 1, 2023. Hospitalized adults with complicated S aureus …

Tracing Sars-Cov-2 Clusters Across Local Scales Using Genomic Data, Leke Lyu, Mandev Gill, Guppy Stott, Sachin Subedi, Cody Dailey, Gabriella Veytsel, Magdy Alabady, Kayo Fujimoto, Ryker Penn, Pamela Brown, Roger Sealy, Justin Bahl

Faculty, Staff and Student Publications

A quantitative understanding of local transmission dynamics is essential for designing effective prevention strategies. In this study, we developed a computational workflow to identify viral introductions and trace locally circulating clusters. We analyzed over 26,000 SARS-CoV-2 genomes and their associated metadata, collected between January and October 2021, to explore introduction and local dispersal patterns in Greater Houston, a major metropolitan area known for its demographic diversity. Our analysis identified more than 1,000 independent introduction events, resulting in clusters of varying sizes. The majority of introductions originated from domestic sources, while international introductions occurred earlier and were associated with larger cluster …

Assessing The Muc5b Promoter Variant In A Large Cohort Of Systemic Sclerosis-Associated Interstitial Lung Disease, Carlos Rosa-Baez, Carlos Rangel-Pelaez, Inmaculada Rodriguez-Martin, Martin Kerick, Alfredo Guillen-Del-Castillo, Carmen P Simeon-Aznar, José Luis Callejas, Alexandre E Voskuyl, Alexander Kreuter, Oliver Distler, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Jeska K De Vries-Bouwstra, Ariane L Herrick, Yannick Allanore, Lorenzo Beretta, Maureen D Mayes, Christopher P Denton, Shervin Assassi, Javier Martin, Marialbert Acosta-Herrera

Faculty, Staff and Student Publications

Objective: The common gain-of-function variant rs35705950, located in the promoter of MUC5B gene, has been strongly associated with interstitial lung diseases (ILDs) of different aetiology, such as idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated ILD (RA-ILD). In this study, we aimed to investigate the association of this variant and its nearby single nucleotide polymorphisms (SNPs) in the largest cohort of systemic sclerosis-associated ILD (SSc-ILD) to date.

Methods: Samples were collected from blood/saliva, followed by DNA extraction and genotyping using SNP arrays. Data for rs35705950 and additional 903 variants within 100 Kb were obtained using genomic imputation. Subsequently, we tested their …

Hippocampal Avoidance During Prophylactic Cranial Irradiation For Patients With Small Cell Lung Cancer: Randomized Phase Ii/Iii Trial Nrg-Cc003, Vinai Gondi, Stephanie L Pugh, Minesh P Mehta, Jeffrey S Wefel, Wolfgang A Tomé, Alexander Y Sun, John Grecula, Kristin J Redmond, Shannon Fogh, Laurie Gaspar, Andre Konski, Joseph Bovi, Clifford G Robinson, Benjamin Corn, Gregory M Videtic, Benjamin H Lok, Harold A Yoon, John H Heinzerling, Albert S Denittis, Ronald C Mcgarry, Kiran Devisetty, Vijayananda Kundapur, Abraham J Wu, Edward C Mccarron, Isabelle Thibault, Edmund L Simon, Andrew M Baschnagel, Samir Narayan, Jondavid Pollock, Rebecca Paulus, Lisa A Kachnic

Faculty, Staff and Student Publications

Purpose: Hippocampal avoidance (HA) during therapeutic whole-brain radiotherapy reduces the risk of neurocognitive function (NCF) toxicity in patients with brain metastasis. This trial hypothesized that HA during prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) leads to noninferior intracranial relapse (ICR) and reduction in NCF toxicity.

Methods: This randomized phase II/III trial enrolled patients with SCLC, no brain metastases, and response to chemotherapy. The primary end points were 12-month ICR (noninferiority design, randomized phase II) and 6-month Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall (DR) failure (phase III). Secondary end points were failure in any NCF …