Digital Commons Network^™

Does Reducing Videofluoroscopy Frame Rate Affect Dige/St Grades In Modified Barium Swallow Studies?, Shitong Mao, Carla L Warneke, Sheila N Buoy, Ariana J Sahli, Brinda Rao Korivi, Carly E A Barbon, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Understanding the effects of reduced frame rates on the reliability of Modified Barium Swallow (MBS) ratings for swallowing safety and efficiency is essential for clinical practice. While previous research has examined frame rate (simulated pulse rates) implications concerning penetration, aspiration, and residue ratings, the impact on summary grading systems like the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) remains unclear. This study analyzed a total of 315 full MBS videos collected from 278 patients, and 76.25% of patients were diagnosed with head and neck cancer (mean age 62.51 years, SD 8.53; 12.23% female). We performed pairwise comparisons of DIGEST grades …

Secretory Iga Dysfunction Underlies Poor Prognosis In Fusobacterium-Infected Colorectal Cancer, Ilseok Choi, Kyung-A Kim, Sang Cheol Kim, Donghwan Park, Ki Taek Nam, Jun Hyung Cha, Seungbyn Baek, Junha Cha, Hye-Yeong Jo, Minsun Jung, Melody Y Zeng, Irina Matei, Susan Bullman, Joong Bae Ahn, Yoon Dae Han, Han Sang Kim, Insuk Lee

Faculty, Staff and Student Publications

Fusobacterium nucleatum (Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-positive and Fn-negative tumors. We discovered that Fn impairs IgA plasma cell development and secretory IgA (sIgA) production by disrupting communication with tumor-associated macrophages. Additional experiments in germ-free mice, together with our re-analysis of a publicly available single-cell RNA-seq data set from a CRC mouse model with an intact gut microbiome–both models having been orally gavaged with Fn–jointly validated the causal …

Tumor Intrinsic Mettl5 Modulates Atf4 Translation To Prevent T Cell-Induced Ferroptosis In Ovarian Cancer, Jiakai Hou, Cheng-Wei Ju, Nicholas A Egan, Yanjun Wei, Yunfei Wang, Minghao Dang, Tianyi Zhou, Leilei Shi, Ningbo Zheng, Si Chen, Ashley M Guerrero, Xiaofang Liang, Wanfu Wu, Areej Akhtar, Chitra Dhiman, Debanwita Roy Burman, Andro E Gerges, Mason D Flores, Han Li, Li-Sheng Zhang, Marleen Kok, Xiaobo Mao, Linghua Wang, Qin Feng, Yiwen Chen, Sanghoon Lee, Daniel J Mcgrail, Nidhi Sahni, Chuan He, Amir A Jazaeri, Weiyi Peng

Faculty, Staff and Student Publications

Poor clinical responses to immune checkpoint blockade (ICB) observed in ovarian cancer (OC) highlight an unmet need to understand the mechanisms driving immune evasion in this disease. To address this, an integrative analysis is conducted by combining in vitro genome‐wide immune screens, in vivo ICB screens, and clinical data mining, and METTL5 is identified as a crucial OC‐intrinsic factor that promotes immune resistance. Immunologically “cold” OC tumors and poor responders to ICB exhibit elevated METTL5 expression. Mechanistically, knocking out (KO) METTL5 in OC disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to the downregulation of SLC7A11 and SLC3A2 …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A Colleran, Meagan Choates, Syed Hashmi, Brittanie Shelton, Aranza Gonzalez Cendejas, Angela Haynes Burgess, Blair K Stevens

Faculty, Staff and Student Publications

Current reproductive guidelines call for offering expanded carrier screening (ECS) for genetic conditions. Currently available panels can include screening for carrier status of tens to hundreds of autosomal recessive and/or X-linked conditions. Clinical utility is based on alterations to reproductive decision-making, but study cohorts supporting the utility of ECS largely consist of individuals of European ancestry who are highly educated, of high income, and who often receive preconception counseling. There is a lack of research on the views of patients from diverse backgrounds. Therefore, we aimed to assess and compare perceptions of the utility of ECS and targeted carrier screening …

Kras Inhibition Activates An Actionable Cd24 "Do Not Eat Me" Signal In Pancreatic Cancer, Yongkun Wei, Minghui Liu, Er-Yen Yen, Jun Yao, Zhenzhen Xun, Phuoc T Nguyen, Xiaofei Wang, Zecheng Yang, Abdelrahman Yousef, Dean Pan, Yanqing Jin, Ching-Fei Li, Madelaine S Theardy, Jangho Park, Yiming Cai, Mitsunobu Takeda, Matthew Vasquez, Elizabeth M Park, David H Peng, Yong Zhou, Hong Zhao, Timothy P Heffernan, Andrea Viale, Huamin Wang, Stephanie S Watowich, Han Liang, Dan Zhao, Ronald A Depinho, Wantong Yao, Haoqiang Ying

Faculty, Staff and Student Publications

KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C-driven PDAC model. Compared to the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a ‘hot’ tumor immune microenvironment. Immunoprofiling revealed that CD24, a ‘don’t eat me’ signal, is significantly upregulated on cancer …

Clinical Outcomes Of Adult Patients With Newly Diagnosed Mixed Phenotype Acute Leukemia, Hannah Goulart, Farhad Ravandi, Nicholas J Short, Nitin Jain, Naval Daver, Tapan M Kadia, Courtney Dinardo, Gautam Borthakur, Koichi Takahashi, Naveen Pemmaraju, Fadi G Haddad, Guillermo Montalban Bravo, Yesid Alvarado, Ghayas C Issa, Alex Bataller, Sherry Pierce, Sanam Loghavi, Guilin Tang, Sa A Wang, Beenu Thakral, Elizabeth Shpall, Richard Champlin, Issa Khouri, Partow Kebriaei, Guillermo Garcia-Manero, Koji Sasaki, Elias J Jabbour, Jayastu Senapati

Faculty, Staff and Student Publications

Purpose: Mixed phenotype acute leukemia (MPAL) is a rare clinical entity with historically poor outcomes.

Methods: We conducted a retrospective analysis of adults 18 years and older with newly diagnosed B-cell (B/M) or T-cell/myeloid (T/M) MPAL treated at our institution between 2017 and 2024.

Results: We identified 42 patients (median age 70 years); 20 (48%) had B/M MPAL, and 22 (52%) had T/M MPAL; 57% of patients had adverse risk cytogenetics, and 41% had a TP53 mutation. Sixty-two percent of patients were treated with a hybrid regimen, and 45% of patients received intensive therapy. A composite complete remission (CRc; CR …

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 …

Addressing Controversy In Fusobacterium Nomenclature: What Exactly Does “F Nucleatum” Refer To?, Martha A Zepeda-Rivera, Floyd E Dewhirst, Susan Bullman, Christopher D Johnston

Faculty, Staff and Student Publications

The F. nucleatum group (sensu lato) is historically composed of four subspecies (F. nucleatum subsp. animalis, F. nucleatum subsp. nucleatum, F. nucleatum subsp. polymorphum, F. nucleatum subsp. vincentii). Although F. nucleatum sensu lato members are typically associated with oral disease, they have recently been shown to disseminate to the gastrointestinal tract and are associated with adverse health conditions such as inflammatory bowel disease and colorectal cancer (CRC). A growing debate over the nomenclature applied to Fusobacterium taxonomy has resulted in different names for these lineages, shifting them from their historic subspecies designations to …

Knowledge Mapping And Visualized Analysis Of Research Progress In Onconephrology: A Bibliometric Analysis, Yiwei Wang, Shuling Fan, Wei Wang

Faculty, Staff and Student Publications

Objectives: Onconephrology is an expanding subspecialty focused on the management of cancer patients with renal injury. This study used a comprehensive bibliometric analysis to emphasize the need for cooperation between oncologists and nephrologists, exploring current trends and future research areas in onconephrology.

Methods: Relevant literature on onconephrology published between 1 January 2000 and 27 April 2024 was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection, followed by manual screening. Bibliometric analyses were performed using CiteSpace, VOSviewer, and Bibliometrix software.

Results: A total of 1,853 publications, including 1,647 articles and 206 reviews, by 11,606 authors …

The Role Of Neutrophils In Vasospasm And Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: Is It Time For A Sah Clinical Trial Targeting Neutrophils?, William W Wroe, Hussein A Zeineddine, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease, and one of the primary drivers of morbidity after aneurysm rupture is the phenomenon of delayed cerebral ischemia (DCI). Significant knowledge has been gained over the past two decades of the impact of neuroinflammation in DCI; and neutrophils are now believed to play a major role. There is significant human subject data showing the rise of neutrophil related inflammatory markers and neutrophil's association with poor outcome after aSAH, but as of yet no trials involving human subjects have been done specifically targeting neutrophils. There is however a growing body of evidence …

Categorizing Weight Growth Of Infants Born Before 32 Weeks' Gestation Using The 2023 Postnatal Growth Charts For Preterm Infants., Fu-Sheng Chou, Hung-Wen Yeh, Crystal Hsueh, Jing Zhang, Maria Fe B. Villosis, Karine Barseghyan, Ashwini Lakshmanan, Reese H. Clark

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To categorize growth and correlate growth categories with morbidities in infants born before 32 weeks of gestation.

STUDY DESIGN: This retrospective study categorized weight growth by correlating mean growth velocity (GV) with growth trajectory z-score changes (ΔGTZ ), as measured using 2023 Postnatal Growth Charts for Preterm Infants. The associations between weight categories and morbidities were assessed.

RESULTS: Weight gain of infants without morbidities was categorized into three groups based on correlating ΔGTZ with mean GV: slower ( ΔGTZ < -0.1), in-parallel ( ΔGTZ -0.1 to 0.3), and faster ( ΔGTZ > 0.3). The proportions of infants with and without morbidities in these categories were evaluated across two distinct cohorts, revealing similar …

Trends In Hospital Resource Use For Children With Complex Chronic Conditions., Nathaniel D. Bayer, Matthew Hall, Maria Osipovich, John M. Morrison, Christian D. Pulcini, Jana C. Leary, Joanna E. Thomson, Tamara D. Simon, Dennis Z. Kuo, Jeffrey D. Colvin, Eyal Cohen, Jay G. Berry

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Despite a small prevalence, children with complex chronic conditions (CCCs) use substantial inpatient resources.

OBJECTIVE: To assess national trends in hospital discharges, bed days, and hospital charges for children with and without CCCs in the US from 2000 to 2022.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, repeated cross-sectional study used hospital discharge data from the Kids' Inpatient Database (KID) from the years 2000, 2003, 2006, 2009, 2012, 2016, 2019, and 2022 for US children aged 0 to 18 years, excluding uncomplicated newborn discharges.

EXPOSURE: Presence of 0, 1, 2, or 3 or more CCCs.

MAIN OUTCOMES AND MEASURES: Trends …

Bypassing Cisplatin Resistance In Nrf2 Hyperactivated Head And Neck Cancer Through Effective Pi3kinase Targeting, Pedram Yadollahi, Kelli A Mccord, Yang Li, Hussam Dayoub, Kalil Saab, Fonma Essien, Sean Hyslop, Emerald Kan, Kazi M Ahmed, Parker R Kirby, Vasanta Putluri, Chandra Shekar R Ambati, Karthik Reddy Kami Reddy, Patricia Castro, Heath D Skinner, Cristian Coarfa, William K Decker, Abdullah A Osman, Rutulkumar Patel, Jeffrey N Myers, Stephen Y Lai, Nagireddy Putluri, Faye M Johnson, Mitchell J Frederick, William H Hudson, Vlad C Sandulache

Faculty, Staff and Students Publications

Background: For patients with head and neck squamous cell carcinoma (HNSCC), failure of definitive radiation combined with cisplatin nearly universally results in death. Although hyperactivation of the Nrf2 pathway can drive radiation and cisplatin resistance along with suppressed anti-tumor immunity, treatment-refractory HNSCC tumors may retain sensitivity to targeted agents secondary to synergistic lethality with other oncogenic drivers (e.g., NOTCH1 mutations).

Methods: Using state of the science mechanistic, metabolomic and spatial transcriptomic approaches combined with preclinical models of HNSCC, we tested whether a novel PI3K inhibitor, gedatolisib, can bypass hyperactivation of the Nrf2 pathway.

Results: The PI3K pathway is activated in …

Alternative Splicing Of The Snap23 Microexon Is Regulated By Mbnl, Qki, And Rbfox2 In A Tissue-Specific Manner And Is Altered In Striated Muscle Diseases, Gabrielle M Gentile, R Eric Blue, Grant A Goda, Bryan B Guzman, Rachel A Szymanski, Eunice Y Lee, Nichlas M Engels, Emma R Hinkle, Hannah J Wiedner, Aubriana N Bishop, Jonathan T Harrison, Hua Zhang, Xander H T Wehrens, Daniel Dominguez, Jimena Giudice

Faculty, Staff and Students Publications

The reprogramming of alternative splicing networks during development is a hallmark of tissue maturation and identity. Alternative splicing of microexons (small, genomic regions ≤ 51 nucleotides) functionally regulate protein-protein interactions in the brain and is altered in several neuronal diseases. However, little is known about the regulation and function of alternatively spliced microexons in striated muscle. Here, we investigated alternative splicing of a microexon in the synaptosome-associated protein 23 (Snap23) encoded gene. We found that inclusion of this microexon is developmentally regulated and tissue-specific, as it occurs exclusively in adult heart and skeletal muscle. The alternative region is …

Adrenomedullin Overexpression Protects Mice From Experimental Bronchopulmonary Dysplasia And Associated Pulmonary Hypertension, Shyam Thapa, Poonam Sarkar, M Waleed Gaber, Roberto Barrios, Madhulata Chauhan, Chandrasekhar Yallampalli, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) or BPD-PH is a lung disease of infants with significant morbidity. Adrenomedullin (Adm) is an angiogenic peptide that signals through calcitonin receptor-like receptor (Calcrl) and receptor activity modifying protein 2 (RAMP2). Adm deficiency potentiates hyperoxia-induced experimental BPD-PH in mice; however, whether Adm overexpression can mitigate this lung disease is unclear. Thus, we tested the hypothesis that Adm overexpression attenuates hyperoxia (HO)-induced murine experimental BPD-PH by using a novel transgenic mouse that overexpresses Adm globally (Admhi/hi mice). One-day-old Admhi/hi mice or their wild-type littermates (Adm+/+ mice) were exposed to …

Bilateral Breast Treatment In A Single Arc Using Rapidarc Dynamic: A Planning Comparison With Conventional Volumetric Modulated Arc Therapy, Taoran Li, Luca Cozzi, Lesley Rosa, Ryan Clark, Priyanka Agarwal, Yin Gao, Yun Yang, Boon-Keng Kevin Teo, Anthony Magliari, Himank Kalra, Francisco Reynoso, Patrick Kupelian, Sushil Beriwal

2020-Current year OA Pubs

PURPOSE: Synchronous bilateral breast cancer (SBBC) presents significant radiotherapy planning challenges due to complex target volumes near critical organs. This study evaluated RapidArc Dynamic (RAD), a novel technique integrating dynamic arcs with static angle modulated ports (STAMPs) via simultaneous GPU-accelerated optimization, against conventional volumetric modulated arc therapy (VMAT) for SBBC treatment planning and delivery efficiency.

METHODS: Ten retrospective SBBC cases involving comprehensive nodal irradiation were planned using both multi-arc VMAT (six arcs) and RAD (one arc plus six STAMPs) in Eclipse (v18.1) with AcurosXB. A prescription dose of 40.05 Gy in 15 fractions was normalized to PTV D95% = 95%. …

Brain Functional Connectivity, But Not Neuroanatomy, Captures The Interrelationship Between Sex And Gender In Preadolescents, Athanasia Metoki, Roselyne J Chauvin, Evan M Gordon, Timothy O Laumann, Benjamin P Kay, Babatunde Adeyemo, Samuel R Krimmel, Scott Marek, Anxu Wang, Andrew N Van, Noah J Baden, Vahdeta Suljic, Kristen M Scheidter, Julia Monk, Forrest I Whiting, Nadeshka J Ramirez-Perez, Deanna M Barch, Aristeidis Sotiras, Nico U F Dosenbach

2020-Current year OA Pubs

Understanding sex differences in the adolescent brain is crucial, as they relate to sex-specific neurological and psychiatric conditions. Predicting sex from adolescent brain data may reveal how these differences influence neurodevelopment. Recently, attention has shifted toward socially-identified gender (distinct from sex assigned at birth) recognizing its explanatory power. This study evaluates whether resting-state functional connectivity (rsFC), cortical thickness, or cortical volume better predicts sex and sex/gender alignment (congruence between sex and gender) in preadolescents. Using Adolescent Brain Cognitive Development (ABCD) Study data and machine learning, rsFC predicted sex more accurately (85 %) than cortical thickness (76 %) and cortical volume …

Current Practices And Trends In Surgical Decision-Making For Children With Lennox-Gastaut Syndrome: A Cross-Sectional Survey By The Pediatric Epilepsy Research Consortium, Michelle Y Chiu, Renée A Shellhaas, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The objective of this study is to characterize contemporary surgical management practices and factors influencing surgical decision-making in the management of Lennox-Gastaut Syndrome (LGS) across pediatric epilepsy centers in the United States.

METHODS: A 45-item cross-sectional survey was developed and distributed to Pediatric Epilepsy Research Consortium centers. Domains included institutional demographics, surgical evaluation timing and goals, presurgical workup, procedural utilization and outcomes, and barriers to surgery. Descriptive statistics and thematic analysis were performed.

RESULTS: Thirty-two pediatric epilepsy centers participated (38% response), the majority comprising pediatric epileptologists at Level 4 National Association of Epilepsy Centers. Most centers (66%) considered surgery …

Fast And Accurate Measurement Of Small Field Dosimetry Using A Novel Scintillation Detector, Yiding Han, Jingzhu Xu, Yao Hao, Baozhou Sun

2020-Current year OA Pubs

BACKGROUND: The most used instruments for small-field dosimetry have notable limitations, including the need for correction of output factors, limited scanning speeds, and challenges in alignment for percentage depth dose (PDD) measurements, particularly for extremely small fields. However, plastic scintillation detectors (PSDs) are an attractive alternative for small-field dosimetry due to their correction-free nature, linear dose response, and fast response time.

PURPOSE: This study evaluates the robustness and accuracy of the dosimetric measurements using a new water-equivalent PSD in small-field dosimetry. The study also aims to report accurate measurements of output factors, profiles, and an indirect method for measuring PDD …

Meniscal Repair In The Setting Of Revision Anterior Cruciate Ligament Reconstruction: 6-Year Follow-Up Results From The Mars Cohort, Mars Group, Amanda K Haas, Robert H Brophy, Matthew J Matava, Matthew V Smith, Et Al.

2020-Current year OA Pubs

BACKGROUND: Meniscal preservation has been demonstrated to contribute to long-term knee health and has been a successful intervention in isolation and in patients with anterior cruciate ligament reconstruction (ACLR). The long-term results of meniscal repair in the setting of revision ACLR have yet to be documented.

PURPOSE: To report the incidence of meniscal repair failures at the 6-year follow-up in a cohort of patients who underwent concurrent revision ACLR and primary meniscal repair.

STUDY DESIGN: Prospective cohort study; Level of evidence, 2.

METHODS: All revision ACLRs with concomitant primary meniscal repair cases from a multicenter group between 2006 and 2011 …

Eus-Guided Fine-Needle Biopsy Sampling Of Solid Pancreatic Masses With And Without Rapid Onsite Evaluation For Commercial Next-Generation Genomic Profiling, Mohamad Dbouk, Brenton G Davis, Matthew Peller, Erika Sloan, Thomas Hollander, Juan Pablo Reyes-Genere, Ahmad Bazarbashi, Mohammad K Ismail, Gabriel Lang, Vladimir Kushnir, Dayna Early, Samuel Ballentine, Sun-Chuan Dai, Abdul Kouanda, Koushik K Das

2020-Current year OA Pubs

BACKGROUND AND AIMS: Although EUS-guided fine-needle biopsy sampling (EUS-FNB) of solid pancreatic lesions with or without the use of rapid onsite evaluation (ROSE) provides a high diagnostic yield, the utility of ROSE for commercial genomic analysis is unclear.

METHODS: A multicenter retrospective review was conducted of consecutive patients where genomic analysis was requested from EUS-FNB of solid pancreatic lesions, performed with 22-gauge fine-needle biopsy (FNB) needles. Data were collected at 2 academic centers, one that routinely uses ROSE to assess adequacy for all EUS-FNB cases (University of California San Francisco, n = 44) and one that does not use ROSE …

Obesity Promotes Conserved Inflammatory And Metabolic Transcriptional Programs In Colon Tumors: Evidence From Mouse Models And The Colocare Study Patient Cohort, Elaine M Glenny, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: The global prevalence of obesity, an established risk and progression factor for colon cancer, is high and rising. Unfortunately, the mechanisms underlying the obesity-colon cancer association are incompletely understood, and new molecular targets enabling more effective intervention strategies to break the obesity-colon cancer link are urgently needed.

OBJECTIVES: This study integrated RNA sequencing data from mouse and human colon tumor samples, as well as human adipose samples, to rigorously establish obesity-associated transcriptomic signatures conserved between the 2 species.

METHODS: We employed a mouse colon cancer model with colonoscopy-guided orthotopic transplantation of syngeneic Apc

RESULTS: Diet-induced obesity reduced survival in …

A Novel Lncrna Fam151b-Dt Regulates Degradation Of Aggregation Prone Proteins, Arun Renganathan, Miguel A Minaya, Matthew Broder, Isabel Alfradique-Dunham, Rebecca L Miller, Dhruva D Dhavale, Reshma Bhagat, Jacob Marsh, Anthony Verbeck, Grant Galasso, Emma Starr, Paul T Kotzbauer, Carlos Cruchaga, Celeste M Karch, Et Al.

2020-Current year OA Pubs

Neurodegenerative diseases share common features of protein aggregation along with other pleiotropic traits, including shifts in transcriptional patterns, neuroinflammation, disruption in synaptic signaling, mitochondrial dysfunction, oxidative stress, and impaired clearance mechanisms like autophagy. However, key regulators of these pleiotropic traits have yet to be identified. Here, we used transcriptomics, mass spectrometry, and biochemical assays to define the role of a novel lncRNA on tau pathophysiology. We discovered a long non-coding RNA (lncRNA), FAM151B-DT, that is reduced in a stem cell model of frontotemporal lobar dementia with tau inclusions (FTLD-tau) and in brains from FTLD-tau, progressive supranuclear palsy, Alzheimer's disease, and …

Five-Year Analysis Of Efficacy And Safety Of A Bidirectional Aav Gene Therapy In Tay-Sachs Sheep, Toloo Taghian, Xuntian Jiang, Et Al.

2020-Current year OA Pubs

Tay-Sachs disease (TSD) and Sandhoff disease are fatal neurodegenerative diseases without an effective therapy that are caused by mutations in the HEXA and HEXB genes, respectively. Together they encode the heterodimeric isozyme of hexosaminidase, hexosaminidase A (HexA), that degrades GM2 ganglioside. This report describes a 5-year-long study using a bidirectional adeno-associated virus 9 (AAV9) vector (AAV9-Bic_HexA/HexB) encoding both HEXA and HEXB in the TSD sheep model. Bidirectional AAV9 was delivered i.v. or through various cerebrospinal fluid (CSF) delivery routes: intracerebroventricular (ICV), cisterna magna (CM), and lumbar intrathecal space (LIT). The longest survival and best distribution were achieved by multipoint CSF …

Buprenorphine Treatment During The Extended Postpartum Period: A Survey Of Patient Experiences, Bridget Galati, Heather Jacobsen, Melissa Krauss, Melissa Mills, Brittaney Vaughn, Sam Williams, Michael Wenzinger, Cynthia Rogers, Nandini Raghuraman, Jeannie Kelly

2020-Current year OA Pubs

OBJECTIVE: The late postpartum period, defined as greater than 6 weeks to 12 months, is a high-risk time for individuals with opioid use disorder (OUD). Discontinuation rates of buprenorphine treatment for OUD during this period are high. Little is known about patients' subjective experience with buprenorphine treatment during this time. We sought to assess patient treatment experience, goals, facilitators and barriers to continued buprenorphine treatment throughout the extended postpartum period.

METHODS: We performed a cross-sectional survey of postpartum patients who received buprenorphine treatment, including sublingual and long-acting injectable formulations, in an interdisciplinary, wrap-around clinic for maternal OUD between February 2022 …

Long-Term Illness In Adults Hospitalized For Respiratory Syncytial Virus Disease, United States, February 2022-September 2023, Aleda M Leis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

Respiratory syncytial virus (RSV) can cause severe illness, but little is known about long-term consequences in hospitalized adults. We surveyed adults (>18 years of age) who survived hospitalization for RSV or COVID-19 during February 2022-September 2023 about physical functioning and quality of life; surveys were conducted 6-12 months after hospitalization. We compared outcomes after RSV hospitalization by age (< 60 vs. >60 years) and to those hospitalized for COVID-19 by using multivariable regression models. Among 146 adults hospitalized with RSV, 27.4% reported severe breathlessness and 21.9% poor quality of life at follow-up. Few differences were seen in posthospital illness by age. …

Impact Of Silencing Automated Penicillin Cross-Reactivity Alerts On Perioperative Antibiotic Prescribing And Surgical Site Infection Rates, Michael J Durkin, Joshua Nordman, Alice Bewley, Andrew Atkinson, Jonas Marschall, Helen Newland, Kimberly G Blumenthal

2020-Current year OA Pubs

We evaluated the impact of silencing penicillin cross-reactivity alerts on perioperative antibiotic prescribing and surgical site infections (SSIs) in 6 hospitals using an interrupted time series analysis. Silencing the alerts minimally increased cefazolin prescribing among penicillin allergy labeled patients (sensitivity analysis only;

A Multi-Center Retrospective Cohort Study Of Neurosarcoidosis Myelitis: Current Observations And Future Directions, Giovanna S Manzano, David B Clifford, Steven Richard Dunham, Masoud Majed, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The optimal treatment for neurosarcoidosis myelitis is uncertain. We characterize incident neurosarcoidosis myelitis and assess treatment response by MRI and clinical scales.

METHODS: Incident probable or definite neurosarcoidosis myelitis in adults was retrospectively identified from 13 academic medical centers. Cases were analyzed by initial treatment. The primary outcome was T1 post-contrast gadolinium enhancement resolution at 6 months post-treatment. Secondary outcomes were changes in modified Rankin scale (mRS) and Expanded Disability Status Scale (EDSS) from nadir to final follow-up.

RESULTS: Two hundred two patients were identified (median diagnosis age: 47 years (IQR 39-55); male: female 1.3:1). Median nadir mRS and …

Differential Microrna Profiling Of Blood L1cam And Bulk Extracellular Vesicles In Bipolar Disorder, Gabriel R Fries, Salahudeen Mirza, Jun Wang, Camila N C Lima, Wei Zhang, Marcela Carbajal Tamez, Giselli Scaini, Jair C Soares, Joao Quevedo

Faculty, Staff and Students Publications

Objective: This preliminary study aimed to identify microRNA (miRNA) signatures associated with bipolar disorder (BD) by profiling blood-derived extracellular vesicles (EVs) of both putative neuronal origin and from all sources.

Method: In two parallel studies of individuals with BD and controls (CON), we characterized miRNA expression profiles of blood EVs selected for L1CAM, a putative marker of neuronal origin (n = 20 BD/20 CON), as well as bulk EVs (n = 21 BD/20 CON). For each study, analyses identified miRNAs differentially expressed between groups, followed by functional interrogation and testing for associations with clinical features.

Results: Results of …

Plasma Metabolomic And Proteomic Signatures Of Blood Pressure Management After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Juan Pablo Lewinger, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Carmen Chen, Todd M Jenkins, Stephanie Sisley, Stephen R Daniels, Douglas I Walker, Max T Aung, Erika Garcia, Rob Mcconnell, Sandrah P Eckel, Michele A La Merrill, Tanya L Alderete, Zhuanghua Chen, Frank D Gilliland, Thomas H Inge, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Background: Emerging omics approaches, including metabolomics and proteomics, can be integrated into obesity treatment for better blood pressure management. We tested whether preoperative metabolomic and proteomic profiles predict long-term elevated blood pressure (EBP) changes better than known risk factors in adolescents undergoing bariatric surgery.

Methods: We included 108 participants from the Teen-LABS (Teen-Longitudinal Assessment of Bariatric Surgery). Plasma untargeted metabolomics (via liquid chromatography with high-resolution mass spectrometry) and Olink proteomics were assessed pre surgery. An elastic net model with stability selection was used to identify features predictive of EBP reductions 5 years post surgery. Models including identified metabolites, proteins, and …