Medicine and Health Sciences Commons^™

Lipidomic And Proteomic Insights From Extracellular Vesicles In The Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes, Chioma M Okeoma, Wasifa Naushad, Bryson C Okeoma, Carlos Gartner, Yulica Santos-Ortega, Calvin Vary, Savio Lima-Bastos, Victor Corasolla Carregari, Martin R Larsen, Alessio Noghero, Consuelo Walss-Bass, Rodrigo Grassi-Oliveira

Faculty, Staff and Student Publications

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to reactive astrogliosis and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD. In particular, our study investigated neuroinflammatory signatures in SUD patients by isolating EVs from the dorsolateral prefrontal cortex (dlPFC) Brodmann's area 9 (BA9) from postmortem subjects. We isolated BA9-derived …

Randomised, Placebo-Controlled Trial Of Oral Hymecromone In Adults With Pulmonary Hypertension, Kathryn Czepiel, Nadine Nagy, Tamera Panjalingam, Anissa Kalinowski, Adam R Frymoyer, Harry Karmouty-Quintana, Bo Gu, Haley Hedlin, Gernot Kaber, Sylvie Dobrota Lai, Joelle I Rosser, Paul L Bollyky, Vinicio De Jesus Perez, Roham T Zamanian

Faculty, Staff and Student Publications

Background: Pulmonary hypertension (PH) is a progressive cardiopulmonary condition associated with increased morbidity and mortality. The extracellular matrix component hyaluronan (HA) is linked to vascular remodelling and interstitial fibrosis in PH. We hypothesised that inhibition of HA synthesis with hymecromone could serve as a reverse-remodelling therapy in PH.

Methods: We performed a proof-of-concept phase IIa randomised, double-blind, placebo-controlled study in adults with pulmonary arterial hypertension and PH associated with interstitial lung disease (PH-ILD). Patients were randomised to a 5:3 ratio and stratified by PH group to receive oral hymecromone or placebo two times per day over 24 weeks. The primary …

Mathematical Modeling And Association Analysis Decipher The Impact Of The Gut Microbiome On Cancer Immunotherapy, Andreas G Hadjigeorgiou, Constantinos Harkos, Aditya K Mishra, Golnaz Morad, Sarah B Johnson, Nadim J Ajami, Jennifer A Wargo, Lance L Munn, Triantafyllos Stylianopoulos, Rakesh K Jain

Faculty, Staff and Student Publications

The gut microbiome has emerged as a key regulator of response to cancer immunotherapy. However, a better understanding of the underlying mechanisms by which the microbiome influences immunotherapy is needed to identify strategies to optimize outcomes. To this end, we developed a mathematical model to obtain insights into the effect of the microbiome on the immune system and immunotherapy response. This model was based on (i) gut microbiome data derived from preclinical studies, (ii) mathematical modeling of the antitumor immune response, (iii) association analysis of microbiome profiles with model-predicted immune profiles, and (iv) statistical models that correlate model parameters with …

Clinical, Tumor, And Product Features Associated With Outcomes After Axicabtagene Ciloleucel Therapy In Follicular Lymphoma, Soumya Poddar, Jiali Yan, Gayatri Tiwari, Darawan Rinchai, Justin Budka, Wangshu Zhang, Weixin Peng, Shruti Salunkhe, Madison Davis, Qinghua Song, Sara Beygi, Harry Miao, Mike Mattie, Rhine S Shen, Caron A Jacobson, Davide Bedognetti, Simone Filosto, Sattva S Neelapu

Faculty, Staff and Student Publications

Background: Axicabtagene ciloleucel (axi-cel), anti-CD19 chimeric antigen receptor (CAR) T cell therapy, demonstrated remarkable efficacy with manageable toxicity in relapsed/refractory indolent B cell lymphomas in the ZUMA-5 trial.

Methods:Here, we report associations of product attributes, serum biomarkers, clinical features, and tumor characteristics with outcome in 124 patients with follicular lymphoma (FL).

Results: In univariate and multivariate analyses, pretreatment inflammatory markers, including TNF-α and IL-12p40, as well as total metabolic tumor volume (TMTV), associated with disease progression. Conversely, T-naive–like product phenotype associated with improved outcome, particularly in patients with high TMTV. These covariates improved risk stratification when combined with the …

Contemporary Outcomes Of Octa-Nonagenarians With Newly Diagnosed Acute Myeloid Leukemia, Jayastu Senapati, Hagop M Kantarjian, Tapan M Kadia, Jeannot Kekedjian, Gautam Borthakur, Naval Daver, Courtney D Dinardo, Elias Jabbour, Prithviraj Bose, Nicholas J Short, Musa Yilmaz, Nitin Jain, Naveen Pemmaraju, Hussein A Abbas, Ghayas C Issa, Abhishek Maiti, Guillermo Montalban Bravo, Indraneel Deshmukh, Elizabeth Shpall, Partow Kebriaei, Uday Popat, Sanam Loghavi, Beenu Thakral, Guilin Tang, Fadi G Haddad, Yesid Alvarado, Guillermo Garcia Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Background: Octa-nonagenarians with acute myeloid leukemia (AML) represent a high-risk group due to frequently poor performance status, adverse genomics (e.g., TP53 mutations, complex karyotype), a high incidence of secondary AML, and inability to undergo an allogeneic stem cell transplantation. Evaluating their outcomes with modern treatment approaches is important.

Methods: This retrospective study analyzed outcomes of patients ≥80 years old with newly diagnosed AML treated at our center from 2013-2023.

Results: A total of 289 patients (median age, 83 years; range, 80-95 years) were included. Venetoclax containing low-intensity therapy was administered to 107 patients (37.0%). AML subtypes included de novo (123, …

Biological Control Mitigates Spread Of Vector-Borne Plant Pathogens, Kris A.G. Wyckhuys, Yi Zou, David W. Crowder, Evie Adriani, Annabelle B. Albaytar, Marie Joy B. Beltran, Ibtissem Ben Fekih, Carolina Camargo-Gil, Filomena C. Filomena, Lizette Cicero, Yelitza C. Colmenarez, Claudia M. Cuellar-Palacios, Thomas Dubois, Sanford D. Eigenbrode, Frederic Francis, Alberto Fereres, Khalid Haddi, Fathiya M. Khamis, Cécile Le Lann, Anne Le Ralec, Lorena Lopez, Baoqian Lyu, James Montoya-Lerma, Karen Muñoz-Cardenas, Ihsan Nurkomar, Paola A. Palmeros-Suarez, Jermaine D. Perier, Ricardo Ramírez-Romero

All Peer-Reviewed Publications

Diseases caused by vector-borne plant pathogens cause adverse impacts on yield resilience, food security, and farmer livelihoods, which are bound to aggravate under global change. Biological control is routinely discounted as a mitigation strategy for plant diseases, partially due to scarce and inconclusive empirical support. Here, using curated field survey data for 58 persistently or semi-persistently transmitted pathogens, we employ a multi-method approach to assess the role of resident (i.e., naturally occurring) biological control agents in these pathosystems. Our meta-analyses show how in planta pathogen incidence is strongly affected by vector abundance and infectivity. Meanwhile, biological control agent density negatively …

Role Of Immunosuppressive Jnk Pathway In The Tumor Microenvironment Among Tnbc Subtypes In Ibcsg Trial 22–00, Andrea Joaquin Garcia, Takashi Semba, Mattia Rediti, Daniel J Mcgrail, Xuemei Xie, Xiaoping Wang, Dileep R Rampa, David Venet, Laurence Buisseret, Samira Majjaj, Roswitha Kammler, Marco Colleoni, Sherene Loi, Giuseppe Viale, Meredith M Regan, Françoise Rothé, Christos Sotiriou, Naoto T Ueno

Faculty, Staff and Student Publications

Phosphorylation of the JNK (pJNK) protein promotes an immunosuppressive tumor microenvironment (TME), enhancing aggressiveness in inflammatory triple-negative breast cancer (TNBC). This study evaluated the role of JNK signaling using a gene signature. RNA sequencing was performed on 347 TNBC tumors from the phase 3 International Breast Cancer Study Group (IBCSG) 22-00 trial, which evaluated adjuvant low-dose cyclophosphamide and methotrexate (CM). Immune-related tumors were identified by TNBC subtype or tumor-infiltrating lymphocytes (TILs). Associations between JNK and outcomes were analyzed using Cox models. Low pJNK levels were associated with better disease-free survival (DFS) in immune-related tumors. These tumors also had lower Treg …

Effects Of Body Armor On Respiratory Muscle Fatigue And Muscle Blood Flow During Progressive Treadmill Marching, Kathryn Bell

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: Torso-borne loads such as body armor are essential for modern military operations but impose mechanical and metabolic strain. These physiological stressors can trigger the inspiratory metaboreflex, which redirects blood flow from locomotor to respiratory muscles, further reducing muscle oxygen and endurance. While aerobic fitness has been shown to alleviate these effects, the interaction between sex, aerobic capacity, and oxygenation under load is not well understood. This study examined the physiological effects of torso-borne load carriage on respiratory muscle fatigue, skeletal muscle oxygenation, and exercise performance to volitional exhaustion and the degree to which sex and aerobic capacity influence these …

Hot Spring Associated Infectious Diseases In The Great Basin And Southwest, Matthew Bentz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Like all bodies of freshwater, natural hot springs can harbor pathogenic microorganisms that carry the threat of infectious disease. The unique chemistry, increased temperature, and popularity for bathing may alter the risk profile of hot springs compared to other natural bodies of water. Despite this risk, the role of hot springs as a reservoir for infectious diseases remains understudied, particularly within the context of regional public health. Nevada and the Great Basin/Southwest have increasingly promoted hot springs for the purposes of tourism, and they share a strong link to the cultural heritage of the region. The unknown risk profile and …

An Analysis Of The Influence Of Human Disease Pathogens On Core Behaviors Of The Black-Legged Tick, Emily F. Marinko

UNLV Theses, Dissertations, Professional Papers, and Capstones

Ixodes scapularis, the black-legged or deer tick, is a vector for several different disease-causing microbes, including the causative agent of Lyme disease. As such, it is a major health concern for people living within its range in the eastern half of the United States, a habitation area that is increasing due to climate change. Despite its medical relevance as a disease vector, there is still much to learn about the basic behavior of these arachnids in the wild. Thus, the major hypothesis of this thesis is that ticks that are infected with specific human disease-causing microbes behave differently than those …

Exploring The Processing Of Objects, Settings, And Global Properties In Natural Auditory Scenes, Margaret A. Mcmullin

UNLV Theses, Dissertations, Professional Papers, and Capstones

Our auditory system has a remarkable ability to make sense of complex environments, allowing us to identify what we are hearing and where sounds come from. This process of auditory scene analysis is essential for situational awareness, decision-making, and effective communication in daily life. While much is known about how listeners segregate and identify individual sound sources (e.g., voices), less is understood about how global properties of a scene (e.g., openness, naturalness) contribute to perception. This dissertation examined how object- and setting-level information in natural auditory scenes are processed, and whether they rely on distinct or overlapping mechanisms. In Experiment …

Sox2 Regulates Foregut Squamous Epithelial Homeostasis And Is Lost During Barrett’S Esophagus Development, Ramon U Jin, Yuanwei Xu, T Mamie Lih, Yang-Zhe Huang, Toni M Nittolo, Blake E Sells, Olivia M Dres, Jean S Wang, Qing K Li, Hui Zhang, Jason C Mills

Faculty, Staff and Students Publications

Esophageal adenocarcinoma is increasingly prevalent and is thought to arise from Barrett's esophagus (BE), a metaplastic condition in which chronic acid and bile reflux transforms the esophageal squamous epithelium into a gastric-intestinal glandular mucosa. The molecular determinants driving this metaplasia are poorly understood. We developed a human BE organoid biobank that recapitulates BE's molecular heterogeneity. Bulk and single-cell transcriptomics, supported by patient tissue analysis, revealed that BE differentiation reflects a balance between SOX2 (foregut/esophageal) and CDX2 (hindgut/intestinal) transcription factors. Using squamous-specific inducible Sox2-KO (Krt5CreER/+ Sox2Δ/Δ ROSA26tdTomato/+) mice, we observed increased basal proliferation, reduced squamous differentiation, and expanded metaplastic glands at …

The Morphologic Structure Of Some Wing Muscles In The Common Pheasant (Phasianus Colchicus), Beste Demi̇rci̇, Murat Erdem Gülti̇ken

Turkish Journal of Veterinary & Animal Sciences

Avians use significant amounts of energy during flight that is supplied by muscles. The Common Pheasant, a member of the Phasianidae family, can fly swiftly over short distances and flies to evade predators. Pheasant species are terrestrial and have a global distribution. This investigation aimed to analyze the anatomical structure of skeletal muscles in pheasants. A cohort of 20 adult pheasants consisting of an equal number of females and males (10 each) was used. Dissections were performed on 5 females and 5 male pheasants for macroscopic evaluation. The remaining samples underwent immunohistochemical staining using an antimyoglobin antibody to measure the …

An Investigation Of The Association Of Gdf9-C.260g>A Polymorphism With Lamb Live Weight In The Akkaraman Breed, Şeyma Kökkaya, Fadi̇me Daldaban, Davut Bayram, Mehmet Ulaş Çinar, Korhan Arslan, Bi̇lal Akyüz

Turkish Journal of Veterinary & Animal Sciences

In this study, the relationship between the Growth Differentiation Factor-9 (GDF9) gene polymorphism and birth weight, as well as weights on days 30, 60, 90, was investigated in Akkaraman lambs, one of the indigenous sheep breeds of Türkiye. For this purpose, a total of 314 lambs were genotyped by PCR-RFLP method for the single nucleotide polymorphism (SNP) c.260G>A in the GDF9 gene. While GG and GA genotypes were observed in the studied breed, the AA genotype was not observed. The results showed that Akkaraman lambs were in Hardy–Weinberg (H–W) equilibrium for the GDF9-c.260G>A polymorphism (p < 0.05). In this study, a significant association was observed between GDF9-HhaI polymorphism and 30th day weight and 60th day weight in Akkaraman lambs. When the animals were analyzed according to birth type, it was observed that this factor was associated with birth weight, as well as weights on days 30, 60, and 90. It is suggested that the c.260G>A coded SNP …

Growth Curve And Serum Calcium And Magnesium Concentrations In Duck Breeders (Anas Boschas) From Hatching To The Prelaying Period Reared Under Subtropical Conditions, Vanessa Peripolli, Fabiano Dahlke, Ellen Karen Dos Santos, Maila Palmeira, Stelamaris Dezen, Robert Lenock, Elizabeth Schwegler, Juahil Martins De Oliveira Júnior, Ivan Bianchi, Paula Gabriela Da Silva Pires, Betina Raquel Cunha Dos Santos, Andressa Fernanda Campos, Fabiana Moreira

Turkish Journal of Veterinary & Animal Sciences

Optimizing duck production requires understanding growth variability and monitoring serum calcium and magnesium levelsas health indicators. This study aimed to analyze the growth curve, mortality, and serum calcium (Ca) and magnesium (Mg) levels in White Mallard ducks from hatching to the prelaying period in subtropical conditions. A total of 1100 females and 270 males were raised for 146 days. At hatch, day 6 (D6), D13, D23, D34, D50, D64, D80, D94, D111, and D146, ducks were weighed separately to assess body weight (BW). Blood samples were collected at hatch, D50, D94, and D146 to determine serum calcium and magnesium levels. …

Erratum To “Nitrate And Nitrite Le Ate And Nitrite Levels In Cattle F Els In Cattle Feed, Drinking Water Eed, Drinking Water, Rumen , Rumen Content, And Blood Methemoglobin Le Content, And Blood Methemoglobin Levels In Bur Els In Burdur Province Of Vince Of Türkiye”[Turkish Journal Of Veterinary And Animal Sciences 49 (3) 2025 94-101], Reyda Kiyici, Hasan Altan Akkan, Mehmet Karaca, Esra Zeybek, Bayram Kudret Karaayvaz, Fi̇rdevs Mor Savaş, Yahya Öztürk, Asim Kart, Ramazan Yildiz, Murat Bayezi̇t

Turkish Journal of Veterinary & Animal Sciences

We hereby issue this erratum to address a concern regarding Tables 6, 7, and 8 in the manuscript titled “Nitrate and nitrite levels in cattle feed, drinking water, rumen content, and blood methemoglobin levels in Burdur Province of Türkiye”. Some of the numbers in Tables 6, 7, and 8 were misprinted by mistake during the typesetting process. To ensure the accuracy of the published work, the correct tables are included for your reference.

The original article can be accessed at: https://doi.org/10.55730/1300-0128.4376

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 …

Large-Scale Crispr Screening In Primary Human 3d Gastric Organoids Enables Comprehensive Dissection Of Gene-Drug Interactions, Yuan-Hung Lo, Hudson T Horn, Mo-Fan Huang, Wei-Chieh Yu, Chia-Mei Young, Qing Liu, Madeline Tomaske, Martina Towers, Antonia Dominguez, Michael C Bassik, Dung-Fang Lee, Lei S Qi, Jonathan S Weissman, Jin Chen, Calvin J Kuo

Faculty, Staff and Student Publications

Understanding how genes influence drug responses is critical for advancing personalized cancer treatments. However, identifying these gene-drug interactions in a physiologically relevant human system remains a challenge, as it requires a model that reflects the complexity and heterogeneity among individuals. Here we show that large-scale CRISPR-based genetic screens, including knockout, interference (CRISPRi), activation (CRISPRa), and single-cell approaches, can be applied in primary human 3D gastric organoids to systematically identify genes that affect sensitivity to cisplatin. Our screens uncover genes that modulate cisplatin response. By combining CRISPR perturbations with single-cell transcriptomics, we resolve how genetic alterations interact with cisplatin at the …

Iterative Intraoperative 3t Mri (Imri)-Guided Brachytherapy: A Prospective Study On Enhancing Implantation Precision And Dosimetric Gains In Advanced Gynecologic Cancers, Shrikiriti S Rajan, Matthew S Ning, Megan Jacobson, Samantha J Simiele, Teresa Bruno, Ramez Kouzy, Kyoko Yoshida-Court, Tatiana Cisneros-Napravnik, Henry Yu, Jason Stafford, Yusung Kim, Geena Mathew, Rauda Alicia Cordova, Maliah Domingo, Anuja Jhingran, Lilie L Lin, Melissa Joyner, Travis T Sims, Lauren Colbert, Aradhana M Venkatesan, Ann Klopp

Faculty, Staff and Student Publications

Purpose: To report on primary outcomes and dosimetric results of a prospective clinical trial and protocol for use of iterative intraoperative magnetic resonance imaging (iMRI) in gynecologic brachytherapy.

Methods: Patients with locally advanced cervical or vaginal cancer (FIGO stages IB2 - IVA, and stage II-IVA, respectively) undergoing pulsed dose rate (PDR) brachytherapy were enrolled in a prospective clinical trial (NCT03634267) using iterative 3T iMRI during brachytherapy implant placement. Applicator and optional interstitial needles were placed under iMRI guidance in a 3T clinical MRI scanner. Imaging, dosimetry and clinical outcomes (local control (LC), recurrence-free survival (RFS), overall survival (OS)), …

Genome Sequences Of Eight Fusobacterium Watanabei Sp Isolates, Martha A Zepeda-Rivera, Falk Ponath, Kaitlyn N Lewis, Rutika P Gavate, Floyd E Dewhirst, Junko Tomida, Yoshiaki Kawamura, Kaori Tanaka, Susan Bullman, Christopher D Johnston

Faculty, Staff and Student Publications

We report draft genome sequences of eight Fusobacterium watanabei clinical isolates, ranging from 1.95 to 2.09 Mbp. Analysis against the Genome Taxonomy Database indicates that F. watanabei genomes are part of the "Fusobacterium nucleatum_J" group.

Bacteria Recovered From Ear Swab Samples Of Cats With Otitis Externa And Their Antimicrobial Resistance Profiles In Kayseri, Türkiye, Emre Karakaya, Doğancan Yarim, Özgür Güran, Cansu Güran, Umut Alpman, İzzet Burçi̇n Saticioğlu, Gülteki̇n Atalan, Seçi̇l Abay, Fuat Aydin

Turkish Journal of Veterinary & Animal Sciences

This study aimed to isolate and identify bacteria from ear swab samples from cats with otitis externa and to detect the antimicrobial resistance profiles of the recovered isolates. For this purpose, ear swab samples from 100 domestic cats that were detected to have otitis externa were used. The samples collected from the animals were inoculated onto 7% defibrinated sheep blood agar and MacConkey agar, and the media were incubated at 37°C for 24-72h under aerobic/microaerobic conditions. The definition of the isolates was carried out by phenotypic tests, MALDI-TOF MS analysis, and 16S rRNA gene sequencing. Antimicrobial susceptibilities of the obtained …

A Morphological Study On Acanthocephalan Species From Wild Birds In Northern Türkiye, Mehmet Öztürk, Şi̇nasi̇ Umur

Turkish Journal of Veterinary & Animal Sciences

The phylum Acanthocephala contains approximately 1300 acanthocephalan species. So far, only nine acanthocephalan species of wild birds have been reported in Türkiye. To study the context of acanthocephalan diversity in wild birds in Türkiye, we examined 193 birds from 69 species belonging to 16 orders. Acanthocephalans were found in seven bird species: Centrorhynchus aluconis in Buteo buteo and Buteo rufinus, Centrorhynchus spinosus in Buteo buteo and Strix aluco, Mediorhynchus papillosus in Iduna icterina, Mediorhynchus tenuis in Luscinia svecica, Plagiorhynchus cylindraceus in Erithacus rubecula and Turdus merula, Polymorphus contortus in Anas platyrhynchos, and Sphaerirostris turdi in Turdus merula. Except for Plagiorhynchus …

Proteomics-Based Aging Clocks In Midlife Or Late-Life And Their Associated Risk Of Dementia, Sanaz Sedaghat, Saeun Park, Rob F Walker, Shuo Wang, Jialing Liu, Timothy M Hughes, Behnam Sabayan, Weihong Tang, Josef Coresh, James S Pankow, Keenan A Walker, Ramon Casanova, Ruth Dubin, Rajat Deo, Jerome I Rotter, Alexis C Wood, Peter Ganz, Pamela L Lutsey, Weihua Guan, Anna Prizment

Children’s Nutrition Research Center Staff Publications

Background: Biological age can be quantified by composite proteomic scores, called proteomics-based aging clocks (PACs). We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk.

Methods: We used two longitudinal population-based studies: the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA). PACs were created in ARIC at midlife (mean age: 58 years, 57% female, n = 11,758) and late-life (mean age: 77 years, 56% female, n = 4934) using elastic net regression models in two-thirds of dementia-free participants and validated in the remaining one-third …

Co-Targeting Bcl-Xl With Mcl-1 Induces Lethal Mitochondrial Dysfunction In Diffuse Mesothelioma, Yuan Xu, Cristian G Medina, Deborah R Surman, Lacey E Dobrolecki, Monica Vilchis, Maheshwari Ramineni, Susan G Hilsenbeck, Yanming Li, Naren Li, Siqi Wu, Jaylon C Aggison, Xi Chen, Yi Zhu, Ying H Shen, R Taylor Ripley

Faculty, Staff and Students Publications

Diffuse mesothelioma (DM) is a rare but highly aggressive and treatment resistant neoplasm with low survival rates. Effective therapeutic strategies are limited, and resistance to treatment is a major obstacle. Myeloid Cell Leukemia (MCL)-1 and B-cell leukemia (BCL)-xL are anti-apoptotic B-cell lymphoma 2 (Bcl-2) family proteins that block cell-intrinsic apoptosis through interactions on the mitochondrial outer membrane which contribute to therapeutic resistance.

We investigated whether B-cell homology domain (BH)-3 profiles were consistent between intra-patient fresh tumor sample, patient-derived cells (PDC), and patient-derived xenografts (PDX) by BH3 profiling; we observed striking consistency which enabled cross model comparisons. Next, we co-targeted BCL-xl …

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 …

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 …

Reduced Computed Tomography Scan Speed Improves Alignment Errors For Patients Undergoing Thoracic Stereotactic Body Radiation Therapy, Ramaswamy Sadagopan, Rachael M Martin-Paulpeter, Christopher R Peeler, Xiaochun Wang, Paige Nitsch, Julianne M Pollard-Larkin

Faculty, Staff and Student Publications

Objectives: We investigated the performance of a slow computed tomography (CT) protocol to reduce alignment errors arising from motion when using CT-on-rail (CTOR) for image guidance for patients receiving thoracic stereotactic body radiation therapy (SBRT).

Methods: A Quasar lung phantom with a moving tumor was programmed with three breathing rates and three motion amplitudes. MIP and average 4DCT images were used for contouring and alignment, respectively. Ten CTOR images were obtained for each of the breathing rates and amplitudes, under both CT protocols. We used in-house CAT software for image guidance, centering the tumor in the lung window …

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 …

Identification Of Alkynyl Nicotinamide Hsn748 As A Ret Solvent-Front Mutant Inhibitor With Intracranial Efficacy, Ujjwol Khatri, Neetu Dayal, Kofi B Owusu, Mandeep Kaur Hunjan, Shriya Pandey, Haley Anne Harper, Carli Mcmahan, Bennett D Elzey, Tao Shen, Xueqing Hu, Kurt W Evans, Ahmed El-Sheikh, Seong Jun Jo, Frederick W Holtsberg, M Javad Aman, Funda Meric-Bernstam, Sukyung Woo, Herman O Sintim, Jie Wu

Faculty, Staff and Student Publications

RET solvent-front G810C/R/S mutations confer resistance to the currently approved RET protein tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib. Moreover, RET fusion-positive lung adenocarcinoma frequently metastasizes to the brain. To address these challenges, it is imperative to develop a RET TKI that is effective against solvent-front mutations and exhibits intracranial activity. We synthesized alkynyl nicotinamide-based RET TKIs and tested their efficacy in cell cultures in inhibiting selpercatinib/pralsetinib-resistant RET solvent-front mutants G810C/R/S found in cancer patients, and in BaF3/KIF5B-RET(G810C) cell-derived subcutaneous and intracranial tumors in vivo. We also evaluated alkynyl nicotinamide RET TKIs in KIF5B-RET-induced lung tumors in immune competent …

Defining Treatment-Resistant Bipolar Depression: Recommendations From The Isbd Task Force, Eduard Vieta, Roger S Mcintyre, Trisha Suppes, Tamsyn E Van Rheenen, Balwinder Singh, Kamilla Woznica Miskowiak, Allan H Young, Lakshmi N Yatham, Kyooseob Ha, Michael Berk, Holly A Swartz, Chantal Henry, Maja Pantovic Stefanovic, Gerard Anmella Diaz, Aysegul Ozerdem, Wiesław J Cubała, Diego Hidalgo-Mazzei, Mauricio Tohen, Isabella Pacchiarotti, Paula Villela Nunes, Carlos Lopez-Jaramillo, Ana Gonzalez-Pinto, Paolo Brambilla, Robert Post, Jair C Soares, Michael Bauer, Ana C Andreazza, Xavier Justes Fradera, Montserrat Cosials-Lopez, Giovanna Fico

Faculty, Staff and Student Publications

Objective: Despite the availability of approved treatments, a substantial proportion of patients with bipolar disorder experience treatment-resistant bipolar depression (TRBD), characterized by persistent depressive symptoms unresponsive to standard therapies. However, a universally accepted definition of TRBD is lacking. This consensus document, developed by the International Society for Bipolar Disorders (ISBD) Task Force on TRBD, aims to provide a standardized definition of TRBD to facilitate clinical trials, research, and treatment strategies.

Methods: The Task Force employed a literature review, clinical trials analysis, and expert consensus meetings to define TRBD.

Results: TRBD was defined as the failure to achieve a significant and …