Digital Commons Network^™

Functional Connectivity Associations With Markers Of Disease Progression In Grn Pathogenic Variant Carriers, Taru M Flagan, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Autosomal dominant progranulin (GRN) pathogenic variants are a genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that asymptomatic GRN variant carriers exhibit thalamocortical hyperconnectivity that increases with age, presumably as they are approaching symptom onset. Whether hyperconnectivity arises concomitantly with markers of neurodegeneration remains unclear.

METHODS: Utilizing T1 and task-free functional magnetic resonance imaging from 49 asymptomatic and 26 symptomatic GRN variant carriers, we determined the relationships between functional connectivity, as measured by voxelwise …

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%. …

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 …

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 …

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

2020-Current year OA Pubs

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

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

RESULTS: 306 patients were included: 124 …

Trainee Perspectives On Diversity, Equity, And Inclusion: A Group Concept Mapping Study, Nicholas Szoko, Ana Radovic, Jennifer E Wolford, Loreta Matheo, Orquidia Torres

2020-Current year OA Pubs

Growing work highlights the importance of diversity, equity, and inclusion (DEI) initiatives in graduate medical education. Few studies have employed participatory research approaches to solicit trainee perspectives related to DEI. Our goal was to utilize group concept mapping (GCM), a mixed-methods participatory research approach, to describe resident perspectives on DEI within a large pediatric residency program. To organize and represent their perspectives on DEI, trainees completed brainstorming, sorting/rating, and interpretation activities in accordance with GCM methodology. Activities occurred via two synchronous discussion sessions (brainstorming and interpretation) and an electronic survey (sorting/rating). Items from the brainstorming session were sorted (i.e. grouped …

Telemedicine Preexposure Prophylaxis Prescribing From A Large Online Us Company, Aaron J Siegler, Shi Hao Ernest Koh, Tristan Schukraft, Simon Mazzoni, Edwin Corbin-Gutierrez, Rupa R Patel, Patrick S Sullivan, Wenting Huang

2020-Current year OA Pubs

IMPORTANCE: HIV preexposure prophylaxis (PrEP) is highly effective in HIV prevention; telemedicine is a promising avenue for delivering PrEP care.

OBJECTIVE: To explore telemedicine delivery of PrEP care (telePrEP) by the largest telePrEP company in the US.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, single-arm cohort study used health record data of patients receiving telePrEP from MISTR LLC, a for-profit telehealth company, from November 27, 2018, to March 5, 2025. Patient characteristics and AIDSVu data were assessed to determine levels of PrEP use nationally. Retention in care was assessed for persons initiating PrEP in 2020, 2021, and 2022. Data were analyzed …

State Of Omics-Based Microbial Diagnostics Of Crc, Jerome Prusa, Mark G Gorelik, Kevin S Blake, Gautam Dantas

2020-Current year OA Pubs

Colorectal cancer (CRC) remains a major burden of cancer-related morbidity and mortality globally, especially when detected at later stages. Early detection through improved and more accessible diagnostics is critical for reducing the severity of CRC. As our understanding of CRC and the microbial inhabitants of the gastrointestinal tract continues to improve, it has become increasingly recognized that the bacterial component of the gut microbiome may provide diagnostic utility for detecting CRC. This is because CRC is often accompanied by shifts in bacterial taxa, and the metabolites produced or utilized by the CRC-associated gut bacterial community. Advances in sequencing and metabolite …

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 …

Single Cell Viral Tagging Of Faecalibacterium Prausnitzii Reveals Rare Bacteriophages Omitted By Other Techniques, Danielle E Campbell, Xiaofen Wu, Lindsey R Hall, Dylan Lawrence, Jerome M Molleston, Lawrence A Schriefer, Lindsay Droit, James S Weagley, Benjamin S Olson, Joanna Rimmer, Miles Parkes, Scott A Handley, Megan T Baldridge

2020-Current year OA Pubs

The associations of the gut microbiome and virome with human health and disease are increasingly numerous and clear. The mechanistic roles of bacteriophages (phages) in the microbiome, however, are especially unclear, as their cultivation is exceedingly difficult and their diversity so immense. We use viral tagging (VT), a technique wherein fluorescently stained uncultivated viruses are allowed to adsorb to host cells and then host cells are singly sorted. This method identifies interacting phage-bacteria pairs to better sample and characterize the phages in human stool samples from healthy and inflammatory bowel disease (IBD)-affected patients. First, we apply VT to uncultivated bacteria …

Lymphoid Gene Expression Supports Neuroprotective Microglia Function, Pinar Ayata, Maud Gratuze, Jason D Ulrich, David M Holtzman, Et Al.

2020-Current year OA Pubs

Microglia, the innate immune cells of the brain, play a defining role in the progression of Alzheimer's disease (AD)

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 …

Introducing The Outpace Framework For Health Care Quality Improvement, Michele Bolles, Heather M. Alger, Mitchell S. V. Elkind, Howard Haft, Sabra C. Lewsey, Mariell Jessup, Karen E. Joynt Maddox, Chiadi E. Ndumele, Clyde W. Yancy, Christine Rutan, Michelle Congdon, Katherine Overton, Lynn Serdynski, Kathie Thomas, Gregg C. Fonarow

2020-Current year OA Pubs

Equitable, timely, and evidence-based care remains a central goal across health care ecosystems, yet significant quality gaps, care variability, and health disparities persist. Professional societies, including the American Heart Association, have long developed clinical practice guidelines to provide standardized, evidence-based recommendations across the cardiovascular care continuum. These guidelines are operationalized into quality measures to monitor care, identify gaps, and guide improvement. Professional societies, agencies, and health systems have applied implementation science strategies, such as education, data sharing, and evaluation, to improve care quality and achieve quality measures defined in the clinical practice guidelines. American Heart Association's Get With The Guidelines …

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 …

Proteogenomics In Cerebrospinal Fluid And Plasma Reveals New Biological Fingerprint Of Cerebral Small Vessel Disease, Ilana Caro, Daniel Western, Chengran Yang, Jigyasha Timsina, Laura Ibanez, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences …

Clinical Characteristics And Real-World Outcomes In Patients With Mucopolysaccharidosis Ii Over 18 Years: Final Report Of The Hunter Outcome Survey, Joseph Muenzer, Jaco Botha, Hernan Amartino, Roberto Giugliani, Paul Harmatz, Christoph Kampmann, Bianca Link, Shuan-Pei Lin, David Molter, Julian Raiman, Maurizio Scarpa, Anna Tylki-Szymańska, Siddharth Jain, David A H Whiteman, Barbara K Burton

2020-Current year OA Pubs

BACKGROUND: Mucopolysaccharidosis II (MPS II) is a rare, progressive, X-linked lysosomal storage disease. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase has been approved for the treatment of patients with MPS II since 2005. The Hunter Outcome Survey (HOS; NCT03292887) was established as a condition of approval to monitor the long-term safety and effectiveness of idursulfase. Here, we report the final results from HOS.

METHODS: HOS was a multicenter, long-term, observational registry that enrolled patients with a biochemically and/or genetically confirmed diagnosis of MPS II who were untreated or treated with idursulfase and/or bone marrow transplant. Patients were enrolled prospectively …

Semi-Annual And Annual Mass Drug Administration Of Diethylcarbamazine And Albendazole Are Equally Effective Regimens For Eliminating Lymphatic Filariasis In Papua New Guinea, Michael C. Payne, Nelly Sanuku, Brooke E. Mancuso, Yao-Chieh Cheng, Gary J. Weil, Peter U. Fischer, Moses Laman, Leanne J. Robinson, Daniel J. Tisch, Christopher L King

2020-Current year OA Pubs

Annual mass drug administration (MDA) is currently recommended for the local elimination of lymphatic filariasis (LF). Modeling studies of LF transmission suggest that conducting MDA twice a year could accelerate LF elimination. To test this idea, we compared the effects of 3 rounds of yearly MDA and 5 rounds of semiannual MDA using diethylcarbamazine with albendazole on LF infection measures in Papua New Guinea (PNG) across 2 treatment areas with high LF prevalence. From 2013 to 2018, we conducted 4 annual community surveys at 4 sentinel sites in each treatment area. We sampled 2,854 people at the start and 2,746, …

Molecular Response To The Non-Lytic Peptide Bac7 (1-35) Triggers Disruption Of Klebsiella Pneumoniae Biofilm, Robert L Beckman I V, Berta Martinez, Flor Z. Santiago, Gabriela N. Echeverria, Bruno V. Pinheiro, Marcelo D. T. Torres, Logan Suits, Shantal Garcia, Paeton L. Wantuch, Cesar De La Fuente-Nunez, Prahathees Eswara, David A. Rosen, Renee M. Fleeman

2020-Current year OA Pubs

Klebsiella pneumoniae is becoming increasingly difficult to treat as multidrug-resistant (MDR) strains become more prevalent. The formation of biofilm heightens this threat by embedding bacterial cells in a polysaccharide-rich matrix that limits antibiotic penetration. Here we dissect the anti-biofilm bovine host-defense cathelicidin peptide fragment bac7 (1-35), exploring its anti-biofilm mechanism, evaluating its ability to curb colonization of the vital organs by hypervirulent K. pneumoniae, and testing its breadth of activity against diverse clinical isolates. Transcriptomic profiling revealed that bac7 (1-35) simultaneously compromises the bacterial membrane and inhibits ribosomal function, a dual assault that precipitates rapid biofilm collapse and blocks bacterial …

The Impact Of Sleep In High-Risk Infants, Ann-Cathrine Neukamm, Mirja Quante, Christian F Poets, Renée A Shellhaas, “Neonatal Sleep Talks (Nest)” Group

2020-Current year OA Pubs

Most of an infant's day is devoted to sleep - and normal sleep is vital to normal brain development. Sleep disruptions may impair overall health, well-being, and neurodevelopment. Disruptors of sleep and circadian health, such as noise, light, respiratory support, and clinical interventions, are highly prevalent in hospital and nursing care facilities. These factors particularly affect infants who already have an increased risk of sleep disorders and their consequences due to an underlying disease. Preterm infants and infants with disorders such as neonatal abstinence syndrome, craniofacial malformations, congenital heart disease, hypoxic-ischemic encephalopathy, Chiari-malformation/myelomeningocele, congenital musculoskeletal disease, and Down syndrome are …

Does Health Insurance Coverage Improve Cardiometabolic Risk Factor Levels? Quasi-Experimental Evidence From India, Kavita Singh, Anubha Agarwal, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Chronic conditions cause notable health and economic burdens. While health insurance enables access to healthcare, its effects on chronic care outcomes remain under-explored.

OBJECTIVE: To examine the association between health insurance coverage and cardiometabolic risk factors among people with chronic conditions in India.

METHODS: Data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) and Solan studies, including 2,926 adults with chronic conditions were analyzed using propensity score weighting to evaluate the associations between health insurance and cardiometabolic risk factors (HbA1c, low-density lipoprotein cholesterol [LDLc], and blood pressure [BP]) and self-reported health status (measured using European Quality …

Cholinergic Dysfunction In Occupational Manganese Exposure, T Noah Hutson, Susan Searles Nielsen, Natalie Senini, John O'Donnell, Hubert P Flores, Tamara Hershey, Joel S Perlmutter, Anil Kumar Soda, Stephen M Moerlein, Zhude Tu, Michael Kasper, Lianne Sheppard, Brad A Racette, Susan R Criswell

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVE: Excessive exposure to manganese (Mn) produces a clinical syndrome of parkinsonism and cognitive impairment. However, our understanding of the mechanisms of Mn neurotoxicity remains limited. This study aimed to evaluate the relationships between Mn exposure, cholinergic function, and cognitive impairment in exposed workers.

METHODS: We assessed brain cholinergic function using vesicular acetylcholine transporter (VAChT) radiotracer (-)-(1-(8-(2-[(18)F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone (VAT) with positron emission tomography (PET) in 21 Mn-exposed workers. We estimated occupational Mn exposure from work histories and the MRI pallidal index. A cognitive control battery consisting of the Verbal Fluency (VF), Letter Number Sequencing (LNS), Two-Back Letter Task (2B), …

Rhinovirus C15 Infection Induces Airway Epithelial Cell Remodeling And Robust Inflammatory Responses: Potential Implications For Airway Obstruction In Children, Yiran Li, Shilpi Singh, Hannah L Briggs, Jordan E Kreger, Alex L Sliwicki, Emily L Eberhardt, Shiuhyang Kuo, Jessica A Czapla, J Kelley Bentley, Heidi R Flori, Amjad Horani, Steven L Brody, Marc B Hershenson

2020-Current year OA Pubs

Despite recognition of rhinovirus-C (RV-C) as a cause of severe respiratory exacerbations, little is known about the pathogenesis of RV-C infections. We infected mucociliary-differentiated primary tracheobronchial epithelial cells with RV-C15 or RV-A16. Initial RNASeq data showed that, compared to RV-A16, RV-C15 decreased expression of genes related to ciliary function while increasing expression of genes associated with mucus secretion and inflammation. Using different airway epithelial cell isolates, we confirmed greater reduction in DNAI2 and FOXJ1 (regulates production of motile cilia) and increased FOXA3 (regulates mucin -related gene expression) after RV-C15 infection compared to RV-A16. Similarly, nasal swab samples from children with …

Application Of The Surgical Apgar Score To Predict Intensive Care Unit Admission And Post-Operative Outcomes In Cesarean Hysterectomy For Placenta Accreta Spectrum, Emily Root, Jacqueline Curbelo, Patrick Ramsey, Jessian L Munoz

Faculty, Staff and Students Publications

Background and Objective: Placenta Accreta Spectrum (PAS) encompasses a continuum of abnormal placentation conditions associated with significant maternal and fetal morbidity. Management of PAS requires coordinated cesarean hysterectomy. Associated morbidities include blood transfusion, coagulopathy, and intensive care unit (ICU) admission. Accurate prediction of ICU admission allows for enhanced multidisciplinary management, coordination of care and utilization of resources. Scoring systems exist in other surgical specialties that can predict the likelihood of ICU admission, but these have not been applied to an obstetric population. The SAS is a 10-point scale that has been validated for the prediction of ICU-level care requirements within …

Implementing And Evaluating Visual Key Information Pages Compared To Text-Based Key Information: Protocol For A Stepped-Wedge Cluster Randomized Trial, Krista E Cooksey, Eliana C Goldstein, Clara N Lee, Jessica Mozersky, Kimberly A Kaphingst, Jingxia Liu, Shuang Wu, Molly Volkmar, Victor Catalan-Gallegos, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Informed consent is a key aspect of conducting research studies, yet many participants do not understand critical study details after reviewing long, complex consent documents. The 2018 Common Rule aimed to address this challenge by requiring a key information section, a "concise and focused" presentation of important and relevant study information. In our ongoing work, we developed a template and toolkit to improve the presentation of key information by incorporating health literacy best practices, including color and visual icons. The goal of this study is to assess the impact of the visual key information (KI) pages at both the …

Impact Of Common Variants On Brain Gene Expression From Rna To Protein To Schizophrenia Risk, Qiuman Liang, Yi Jiang, Annie W Shieh, Dan Zhou, Rui Chen, Feiran Wang, Meng Xu, Mingming Niu, Xusheng Wang, Dalila Pinto, Yue Wang, Lijun Cheng, Ramu Vadukapuram, Chunling Zhang, Kay Grennan, Gina Giase, Kevin P White, Junmin Peng, Bingshan Li, Chunyu Liu, Chao Chen, Sidney H Wang

The Brown Foundation: Institute of Molecular Medicine

Genetic variants influencing gene expression have been extensively studied at the transcriptional level. How these variants affect downstream processes remains unclear. We quantitated ribosome occupancy in prefrontal cortex samples from the BrainGVEX cohort and integrated these data with transcriptomic and proteomic profiles from the same individuals. Through cis-QTL mapping, we identified genetic variants associated with transcript level (eQTLs), ribosome occupancy (rQTLs), and protein level (pQTLs). Notably, only 34% of eQTLs have their effects propagated to the protein levels, suggesting widespread post-transcriptional attenuation. Using both a gene-based approach and a variant-based approach we identified omics-specific QTLs that associated with brain disorder …

The Impact Of Extramedullary And Paraskeletal Plasmacytomas On Treatment Outcomes In Multiple Myeloma Treated With Teclistamab: U.S. Myeloma Immunotherapy Consortium Real-World Experience, Aimaz Afrough, Danai Dima, Beatrice Razzo, Utkarsh Goel, Aishwarya Sannareddy, Oren Pasvolsky, Mariola Vazquez-Martinez, Christopher Ferreri, Rahul Banerjee, Jack Khouri, James Davis, Mahmoud Gaballa, Alex Lieberman-Cribbin, Masooma Rana, Kelley Julian, Faiz Anwer, Leyla Shune, Shaun Dejarnette, Ariel Grajales-Cruz, Evguenia Ouchveridze, Gabriel De Avila, Sandra Susanibar-Adaniya, Andrew Portuguese, Daniel Schrum, Erin Eberwein, Hitomi Hosoya, Lekha Mikkilineni, Gurbakhash Kaur, Joseph Mcguirk, Adriana Rossi, Megan Herr, Omar Castaneda, Frederick Locke, Shahzad Raza, Yi Lin, Shebli Atrash, Douglas Sborov, Peter Voorhees, Shambavi Richard, Alfred Garfall, Surbhi Sidana, Krina Patel, Doris Hansen, Andrew Cowan, Larry Anderson, Hans Lee

Department of Medical Oncology Faculty Papers

Teclistamab, a bispecific antibody targeting B-cell maturation antigen (BCMA), is effective in relapsed or refractory multiple myeloma (RRMM), but its impact on patients with soft tissue plasmacytomas is unclear. We studied 385 RRMM patients treated with teclistamab at 13 U.S. centers through September 2023, with follow-up to April 2024. Soft tissue plasmacytomas were classified as true extramedullary disease (EMD; not contiguous with bone) or paraskeletal plasmacytomas (PSK; contiguous with bone). Patients with the simultaneous presence of both were classified as true-EMD, reflecting its adverse prognosis. Of those, 109 (28%) had true EMD, 33 (9%) had PSK, and 243 (63%) had …

Benchmarking Dna Foundation Models For Genomic And Genetic Tasks, Haonan Feng, Lang Wu, Bingxin Zhao, Chad Huff, Jianjun Zhang, Jia Wu, Lifeng Lin, Peng Wei, Chong Wu

Faculty, Staff and Student Publications

The rapid evolution of DNA foundation models promises to revolutionize genomics, yet comprehensive evaluations are lacking. Here, we present a comprehensive, unbiased benchmark of five models (DNABERT-2, Nucleotide Transformer V2, HyenaDNA, Caduceus-Ph, and GROVER) across diverse genomic and genetic tasks including sequence classification, gene expression prediction, variant effect quantification, and topologically associating domain (TAD) region recognition, using zero-shot embeddings. Our analysis reveals that mean token embedding consistently and significantly improves sequence classification performance, outperforming other pooling strategies. Model performance varies among tasks and datasets; while general purpose DNA foundation models showed competitive performance in pathogenic variant identification, they were less …

Mecp2 Interacts With The Super Elongation Complex To Regulate Transcription, Jun Young Sonn, Wonho Kim, Marta Iwanaszko, Yuki Aoi, Yan Li, Guantong Qi, Luke Parkitny, Janice L Brissette, Lorin Weiner, Juan Botas, Ismael Al-Ramahi, Ali Shilatifard, Huda Y Zoghbi

Faculty, Staff and Students Publications

Loss-of-function mutations in methyl-CpG binding protein 2 (MECP2) cause Rett syndrome. While we know that MeCP2 binds to methylated cytosines on DNA, the full breadth of the molecular mechanisms by which MeCP2 regulates gene expression remains incompletely understood. Here, using a genetic modifier screen, we identify the super elongation complex, a P-TEFb–containing elongation factor that releases promoter-proximally paused RNA polymerase II, as a genetic interactor of MECP2. MeCP2 physically interacts with SEC subunits and directly binds AFF4, the scaffold of the SEC, via the transcriptional repression domain. Furthermore, MeCP2 facilitates the binding of AFF4 on a subset …

Microbial Associations And Viruses On The Risk Of Celiac Disease (Mavric): A Longitudinal Post-Hoc Case-Cohort Study, Kristian F Lynch, Eric W Triplett, Heikki Hyöty, Angelica P Ahrens, Jutta E Laiho, Joseph F Petrosino, Richard E Lloyd, Daniel Agardh

Faculty, Staff and Students Publications

Celiac disease etiopathogenesis requires genetic predisposition and exposure to gluten, yet these factors alone are not sufficient. Larger longitudinal studies are needed to determine the role of time-varying infections and gut microorganisms. The aim was to design a celiac disease case-cohort longitudinal study using The Environmental Determinants of Diabetes in the Young (TEDDY) study. By age 3-years, persistent tissue transglutaminase autoantibodies (tTGA), i.e., celiac disease autoimmunity (CDA), was confirmed in 704 of the 6132 genetically at-risk TEDDY children. Celiac disease onset (CD-onset) was defined as the age CDA developed when followed by a biopsy-proven diagnosis. A competing risk analysis on …

Participatory Implementation Science To Enhance Knowledge And Build The Capacity To Increase The Uptake And Sustainability Of Hpv Vaccination Among Girls In Nigeria, Peter Kalulu, Olufunto A Olusanya, Nkiruka Obodoechina, Maria A Afadapa, Temitope Ojo, Priscilla A Kabutey, Caven N Ngoe, Ashley Bardon, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Human papillomavirus (HPV) vaccination can prevent cancer in low- and middle-income countries (LMICs), but its uptake remains low, especially in Nigeria. Understanding participatory approaches can help identify local strategies to increase, build capacity for, and sustain vaccine uptake. This study evaluated the effectiveness of an innovation bootcamp in enhancing the knowledge and skills of youth implementers about HPV and cervical cancer as a strategy to increase vaccine uptake among Nigerian girls aged 9-14 years. An innovation bootcamp is an intensive training program that engages end users to build capacity and skills.

METHODS: This was a five-week hybrid bootcamp guided …