Digital Commons Network^™

Disentangling The Unique Contributions Of Age, Pubertal Stage, And Pubertal Hormones To Brain Structure In Childhood And Adolescence, Mark Curtis, John C Flournoy, Sridhar Kandala, Ashley F P Sanders, Michael P Harms, Adam Omary, Leah H Somerville, Deanna M Barch

2020-Current year OA Pubs

Puberty and associated changes in pubertal hormones influence structural brain development. Hormones such as dehydroepiandrosterone (DHEA) and progesterone remain understudied, and it remains unclear how these aspects of puberty contribute uniquely to structural brain development. We used the Human Connectome Project in Development cross-sectional sample of 1304 youth (aged 5-21 years) to investigate unique contributions of sex, age, pubertal stage, DHEA, testosterone, estradiol, and progesterone to cortical thickness, surface area, and subcortical volume development within functionally-relevant networks. Sex and age explain the most unique variance in all three aspects of structural development. Pubertal stage and pubertal hormones uniquely contribute more …

Nivolumab Plus Relatlimab And Nivolumab Plus Ipilimumab For Patients With Advanced Renal Cell Carcinoma: Results From The Open-Label, Randomised, Phase Ii Fraction-Rcc Trial, T K Choueiri, R K Pachynski, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology study in patients with aRCC (FRACTION-RCC) was designed to assess new immuno-oncology (IO) combinations in patients with advanced renal cell carcinoma (aRCC). We present results in IO-naive patients treated with nivolumab (NIVO) + relatlimab (RELA) or NIVO + ipilimumab (IPI) in track 1.

METHODS: The open-label, randomised, phase II FRACTION-RCC trial enrolled patients with aRCC from 32 hospitals and cancer centres across six countries. Patients were enrolled in track 1 (IO-naive) or track 2 (IO-experienced). IO-naive patients were stratified by previous tyrosine kinase inhibitor therapy and randomised to NIVO (240 …

Analysis Of 1386 Epileptogenic Brain Lesions Reveals Association With Dyrk1a And Egfr, Christian M Boßelmann, Costin Leu, Tobias Brünger, Lucas Hoffmann, Sara Baldassari, Mathilde Chipaux, Roland Coras, Katja Kobow, Hajo Hamer, Daniel Delev, Karl Rössler, Christian G Bien, Thilo Kalbhenn, Tom Pieper, Till Hartlieb, Kerstin Becker, Lisa Ferguson, Robyn M Busch, Stéphanie Baulac, Peter Nürnberg, Imad Najm, Ingmar Blümcke, Dennis Lal

Faculty, Staff and Student Publications

Lesional focal epilepsy (LFE) is a common and severe seizure disorder caused by epileptogenic lesions, including malformations of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT). Understanding the genetic etiology of these lesions can inform medical and surgical treatment. We conducted a somatic variant enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( > 1600x) targeted panel sequencing. Here we confirm four known associations (BRAF, SLC35A2, MTOR, PTPN11), support eight associations without prior statistical support (FGFR1, PIK3CA, AKT3, NF1, PTEN, RHEB, KRAS, NRAS), and identify novel associations for two genes, …

Building Capacity In Dissemination And Implementation Research: The Presence And Impact Of Advice Networks, Allison J L'Hotta, Rebekah R Jacob, Stephanie Mazzucca-Ragan, Russell E Glasgow, Sharon E Straus, Wynne E Norton, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: As dissemination and implementation (D&I) research increases, we must continue to expand training capacity and research networks. Documenting, understanding, and enhancing advice networks identifies key connectors and areas where networks are less established. In 2012 Norton et al. mapped D&I science advice and collaboration networks. The current study builds on this work and aims to map current D&I research advice networks.

METHODS: D&I researchers in the United States (US) and Canada were identified through a combination of publication metrics, and key persons identified networks and were invited to participate (n = 1,576). In this social network analysis study, participants …

A Comprehensive Analysis Of In-Hospital Adverse Events After Scopolamine Administration: Insights From A Retrospective Cohort Study Using A Large Nationwide Inpatient Database, George Sun, Marc Torjman, Kevin Min

Department of Anesthesiology Faculty Papers

BACKGROUND: Scopolamine is a widely used antiemetic in anesthetic practice, particularly for postoperative and post-discharge nausea and vomiting. Despite its frequent usage and recognized efficacy, concerns have emerged regarding the potential for increased side effects, particularly in elderly patients. Further research is needed to assess safety and determine age thresholds for adverse events. This study hypothesizes associations between perioperative scopolamine use, worse clinical outcomes, increased pneumonia, delirium, urinary retention, and readmissions.

METHODS: A large, retrospective cohort study was performed using the TriNetX Analytics Network database on patients undergoing major surgical procedures between Jan 1, 2009, and March 21, 2018, to …

Human Single Cell Rna-Sequencing Reveals A Targetable Cd8+ Exhausted T Cell Population That Maintains Mouse Low-Grade Glioma Growth, Rasha Barakat, Jit Chatterjee, Rui Mu, Xuanhe Qi, Xingxing Gu, Igor Smirnov, Olivia Cobb, Karen Gao, Angelica Barnes, Jonathan Kipnis, David H Gutmann

2020-Current year OA Pubs

In solid cancers, T cells typically function as cytotoxic effectors to limit tumor growth, prompting therapies that capitalize upon this antineoplastic property (immune checkpoint inhibition; ICI). Unfortunately, ICI treatments have been largely ineffective for high-grade brain tumors (gliomas; HGGs). Leveraging several single-cell RNA sequencing datasets, we report greater CD8

Host Dna Depletion On Frozen Human Respiratory Samples Enables Successful Metagenomic Sequencing For Microbiome Studies, Minsik Kim, Raymond C Parrish, Michael J Tisza, Viral S Shah, Thi Tran, Matthew Ross, Juwan Cormier, Aribah Baig, Ching-Ying Huang, Laura Brenner, Isabel Neuringer, Katrine Whiteson, J Kirk Harris, Amy D Willis, Peggy S Lai

Faculty, Staff and Students Publications

Most respiratory microbiome studies use amplicon sequencing due to high host DNA. Metagenomics sequencing offers finer taxonomic resolution, phage assessment, and functional characterization. We evaluated five host DNA depletion methods on frozen nasal swabs from healthy adults, sputum from people with cystic fibrosis (pwCF), and bronchoalveolar lavage (BAL) from critically ill patients. Median sequencing depth was 76.4 million reads per sample. Untreated nasal, sputum, and BAL had 94.1%, 99.2%, and 99.7% host reads, respectively. Host depletion effects varied by sample type, generally increasing microbial reads, species and functional richness; this was mediated by higher effective sequencing depth. Rarefaction curves showed …

Clinical Effects Of Dexamethasone Among Patients With Sickle Cell Disease Hospitalized With Covid-19: Outcomes From A Single Academic Health System, William M. Garneau, Matthew J. Lankiewicz, Catherine R. Lesko, Ashley P. Lauriello, Kelly A. Gebo, Sophie M. Lanzkron

Department of Medicine Faculty Papers

BACKGROUND: Dexamethasone is a steroid used in the treatment of hospitalized patients with severe COVID-19. However, the effect of dexamethasone in patients with SCD remains unclear given that steroids may precipitate vaso-occlusive crisis (VOC) in patients with SCD.

METHODS AND FINDINGS: We performed a retrospective analysis of patients with SCD who were hospitalized at Johns Hopkins Health System between June 1, 2020 and June 26, 2022. We reviewed individual charts to assess severity of illness and eligibility for dexamethasone treatment. The exposure of interest was treatment with dexamethasone. Outcomes of interest included incident VTE, length of hospital stay, ICU admission, …

Characterising The Anxiogenic Network From Functional Connectivity Analysis Of The Co2 Challenge Model, Daniel Graham, Santra Mathew, Jonathan Marsden, Alastair D Smith, Gary Smerdon, Stephen D Hall

School of Psychology

The CO2 challenge model (CCM) is a gas inhalation paradigm that provides precisely controlled anxiety induction in experimental settings. Despite its potential as an experimental model of anxiety, our understanding of the neural effects of the CCM is incomplete. This study employs resting-state functional magnetic resonance imaging (rs-fMRI) to explore functional connectivity (FC) changes underlying the CCM. Following a preliminary CO2 tolerance assessment, participants completed an MRI session that included three rs-fMRI scans: during inhalation of control air (pre and post), and during a 6% CCM exposure. Here, we confirm that 6% CCM is a tolerable anxiogenic model in the …

Magrolimab Plus Rituximab In Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: 3-Year Follow-Up Of A Phase 1/2 Trial, Amitkumar Mehta, Leslie Popplewell, Graham P Collins, Sonali M Smith, Ian W Flinn, Nancy L Bartlett, Nilanjan Ghosh, Gal Hacohen-Kleiman, Yanan Huo, Linda Su-Feher, Camille Renard, Ranjana Advani, Mark Roschewski

2020-Current year OA Pubs

Relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) is generally considered incurable with current treatment options. Previous phase 1b/2 results showed combining magrolimab (anti-cluster-of-differentiation [CD] 47 antibody) with the anti-CD20 antibody rituximab (M+R) has antitumor activity against R/R iNHL. We report 3-year follow-up data from this phase 1b/2 study assessing long-term safety and efficacy of M+R in R/R iNHL. After magrolimab priming, 4 patient groups in phase 1b M+R received 10 to 45-mg/kg magrolimab doses with 375 mg/m2 rituximab. Phase 2 explored 30 and 45 mg/kg magrolimab. Primary end points were treatment-emergent adverse events (TEAEs) and objective response rate (ORR). Secondary end …

Real-World Impact Of Emicizumab And Immunosuppression On Acquired Hemophilia A: A Multicenter Us Cohort, Jacqueline N Poston, Cassandra Bryan, Annette Von Drygalski, Kadhim Al Banaa, Jenny Y Zhou, Aric Parnes, Evan C Chen, Osman Khan, Patrick Ellsworth, Lorraine Cafuir, Christopher Walsh, Miguel A Escobar, James F Wu, Lynn M Malec, Craig M Kessler, Maissaa Janbain, Rebecca Kruse-Jarres

Faculty, Staff and Student Publications

Acquired hemophilia A (AHA) is an autoimmune bleeding disorder that is caused by factor VIII (FVIII) autoantibodies with high morbidity and mortality due to bleeding and complications from immunosuppression (IST). To address the real-world implications of the FVIII mimetic antibody, emicizumab, and the role of IST, we retrospectively collected de-identified data on 62 patients with AHA who were treated off-label with emicizumab for a median of 10 weeks at 12 US-based hemophilia treatment centers. Most patients (95.2%) had acute bleeding at diagnosis, and 62.9% had partial or no control of bleeds despite the use of hemostatic agents at the time …

Metabolite Signatures Of Chronological Age, Aging, Survival, And Longevity, Paola Sebastiani, Mary F Feitosa, Mary K Wojczynski, Gary J Patti, Et Al.

2020-Current year OA Pubs

Metabolites that mark aging are not fully known. We analyze 408 plasma metabolites in Long Life Family Study participants to characterize markers of age, aging, extreme longevity, and mortality. We identify 308 metabolites associated with age, 258 metabolites that change over time, 230 metabolites associated with extreme longevity, and 152 metabolites associated with mortality risk. We replicate many associations in independent studies. By summarizing the results into 19 signatures, we differentiate between metabolites that may mark aging-associated compensatory mechanisms from metabolites that mark cumulative damage of aging and from metabolites that characterize extreme longevity. We generate and validate a metabolomic …

Association Of Type 2 Diabetes Mellitus With Sensorineural Hearing Loss - A Population-Based Analysis, Marwin Li, Natalie Perlov, Jena Patel, Dev Amin, Ayan Kumar, Zachary D. Urdang, Thomas O. Willcox, Rebecca C. Chiffer

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: To test the hypothesis that patients with poorly controlled type 2 diabetes mellitus are more likely to develop sensorineural hearing loss (SNHL) than non-diabetic patients.

STUDY DESIGN: Retrospective cohort study.

SETTING: TriNetX US Collaborative Network (2003-2022).

METHODS: Electronic medical record data from the TriNetX US Collaborative Network was queried for subjects without prior hearing loss, defined using medical billing codes (ICD-10, CPT, etc.), who were diagnosed with type 2 diabetes mellitus after January 2003. Patients were stratified by most recent HbA1c (8.0-13.9% or ≥14.0%) and by age at diagnosis (21-30, 31-40, 41-50, 51-60, 61-70, ≥71 years). Primary outcome was …

Mitochondrial Heteroplasmy Improves Risk Prediction For Myeloid Neoplasms, Yun Soo Hong, Sergiu Pasca, Wen Shi, Daniela Puiu, Nicole J Lake, Monkol Lek, Meng Ru, Megan L Grove, Anna Prizment, Corinne E Joshu, Elizabeth A Platz, Eliseo Guallar, Dan E Arking, Lukasz P Gondek

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential is the primary pathogenic risk factor for myeloid neoplasms, while heteroplasmy (mutations in a subset of cellular mitochondrial DNA) is another marker of clonal expansion associated with hematological malignancies. We explore how these two markers relate and influence myeloid neoplasms incidence, and their role in risk stratification. We find that heteroplasmy is more common in individuals with clonal hematopoiesis of indeterminate potential, particularly those with higher variant allele fractions, multiple mutations, or spliceosome machinery mutations. Individuals with both markers have a higher risk of myeloid neoplasms than those with either alone. Furthermore, heteroplasmic variants with …

Clc-Kb Pore Mutation Disrupts Glycosylation And Triggers Distal Tubular Remodeling, Yogita Sharma, Robin Lo, Viktor N Tomilin, Kotdaji Ha, Holly Deremo, Aishwarya V Pareek, Wuxing Dong, Xiaohui Liao, Svetlana Lebedeva, Vivek Charu, Neeraja Kambham, Kerim Mutig, Oleh Pochynyuk, Vivek Bhalla

Faculty, Staff and Student Publications

Mutations in the CLCNKB gene (1p36), encoding the basolateral chloride channel ClC-Kb, cause type 3 Bartter syndrome. We identified a family with a mixed Bartter/Gitelman phenotype and early-onset kidney failure and by employing a candidate gene approach, identified what we believe is a novel homozygous mutation (CLCNKB c.499G>T [p.Gly167Cys]) in exon 6 of CLCNKB in the index patient. We then validated these results with Sanger and whole-exome sequencing. Compared with wild-type ClC-Kb, the Gly167Cys mutant conducted less current and exhibited impaired complex N-linked glycosylation in vitro. We demonstrated that loss of Gly-167, rather than gain of a mutant Cys, …

A Proteogenomic Analysis Of Cervical Cancer Reveals Therapeutic And Biological Insights, Jing Yu, Xiuqi Gui, Yunhao Zou, Qian Liu, Zhicheng Yang, Jusheng An, Xuan Guo, Kaihua Wang, Jiaming Guo, Manni Huang, Shuhan Zhou, Jing Zuo, Yimin Chen, Lu Deng, Guangwen Yuan, Ning Li, Yan Song, Jia Jia, Jia Zeng, Yuxi Zhao, Xianming Liu, Xiaoxian Du, Yansheng Liu, Pei Wang, Bing Zhang, Li Ding, Ana I Robles, Henry Rodriguez, Hu Zhou, Zhen Shao, Lingying Wu, Daming Gao

Faculty, Staff and Students Publications

Although the incidence of cervical cancer (CC) has been reduced in high-income countries due to human papillomavirus (HPV) vaccination and screening strategies, it remains a significant public health issue that poses a threat to women's health in low-income countries. Here, we perform a comprehensive proteogenomic profiling of CC tumors obtained from 139 Chinese women. Integrated proteogenomic analysis links genetic aberrations to downstream pathogenesis-related pathways and reveals the landscape of HPV-associated multi-omic changes. EP300 is found to enhance the acetylation of FOSL2-K222, consequently accelerating the malignant proliferation of CC cells. Proteomic stratification identifies three patient subgroups with distinct features in prognosis, …

A Proteogenomic Analysis Of Cervical Cancer Reveals Therapeutic And Biological Insights, Jing Yu, Li Ding, Et Al.

2020-Current year OA Pubs

Although the incidence of cervical cancer (CC) has been reduced in high-income countries due to human papillomavirus (HPV) vaccination and screening strategies, it remains a significant public health issue that poses a threat to women's health in low-income countries. Here, we perform a comprehensive proteogenomic profiling of CC tumors obtained from 139 Chinese women. Integrated proteogenomic analysis links genetic aberrations to downstream pathogenesis-related pathways and reveals the landscape of HPV-associated multi-omic changes. EP300 is found to enhance the acetylation of FOSL2-K222, consequently accelerating the malignant proliferation of CC cells. Proteomic stratification identifies three patient subgroups with distinct features in prognosis, …

Genetic Risk Classification For Adults With Aml Receiving Less-Intensive Therapies: The 2024 Eln Recommendations, Hartmut Döhner, Courtney D Dinardo, Frederick R Appelbaum, Charles Craddock, Hervé Dombret, Benjamin L Ebert, Pierre Fenaux, Lucy A Godley, Robert P Hasserjian, Richard A Larson, Ross L Levine, Yasushi Miyazaki, Dietger Niederwieser, Gert Ossenkoppele, Christoph Röllig, Jorge Sierra, Eytan M Stein, Martin S Tallman, Hwei-Fang Tien, Jianxiang Wang, Agnieszka Wierzbowska, Andrew H Wei, Bob Löwenberg

Faculty, Staff and Student Publications

The European LeukemiaNet (ELN) genetic risk classifications were developed based on data from younger adults receiving intensive chemotherapy. Emerging analyses from patients receiving less-intensive therapies prompted a proposal for an ELN genetic risk classification specifically for this patient population.

Firearm Access, Carriage And Use In An Ethnically Diverse Sample Of Young Adults In Texas, Usa, Yu Lu, Elizabeth Baumler, Annalyn Saludares Demello, Leila Wood, Hillary Mcguire, Jeff R Temple

Faculty, Staff and Student Publications

Background Despite the high rates of firearm ownership and firearm-related injuries and mortalities in Southern US states, understandings on the factors contributing to these are lacking.

Methods Using wave 10 (2021) data from a longitudinal study, we examined firearm-related experiences among 636 ethnically diverse young adults (mean age=26 years; 62% female) in Texas, USA.

Results Just over half of participants had ready access to firearms, with 22.3% having carried a firearm outside of their home, 4.9% having been threatened with a firearm by a romantic partner and 4.4% by a non-romantic partner. More firearm access and carriage were reported in …

Genetic Risk Stratification And Outcomes Among Treatment-Naive Patients With Aml Treated With Venetoclax And Azacitidine, Hartmut Döhner, Keith W Pratz, Courtney D Dinardo, Andrew H Wei, Brian A Jonas, Vinod A Pullarkat, Michael J Thirman, Christian Récher, Andre C Schuh, Sunil Babu, Xiaotong Li, Grace Ku, Zihuan Liu, Yan Sun, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A Pollyea

Faculty, Staff and Student Publications

The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most …

Insights Into Human Norovirus Cultivation In Human Intestinal Enteroids, Khalil Ettayebi, Gurpreet Kaur, Ketki Patil, Janam Dave, B Vijayalakshmi Ayyar, Victoria R Tenge, Frederick H Neill, Xi-Lei Zeng, Allison L Speer, Sara C Di Rienzi, Robert A Britton, Sarah E Blutt, Sue E Crawford, Sasirekha Ramani, Robert L Atmar, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are a significant cause of epidemic and sporadic acute gastroenteritis worldwide. The lack of a reproducible culture system hindered the study of HuNoV replication and pathogenesis for almost a half-century. This barrier was overcome with our successful cultivation of multiple HuNoV strains in human intestinal enteroids (HIEs), which has significantly advanced HuNoV research. We optimized culture media conditions and generated genetically modified HIE cultures to enhance HuNoV replication in HIEs. Building upon these achievements, we now present new insights into this culture system, which involve testing different media, unique HIE lines, and additional virus strains. HuNoV infectivity …

Genotype-Specific Effects Of Elamipretide In Patients With Primary Mitochondrial Myopathy: A Post Hoc Analysis Of The Mmpower-3 Trial, Amel Karaa, Enrico Bertini, Valerio Carelli, Bruce Cohen, Gregory M Ennes, Marni J Falk, Amy Goldstein, Gráinne Gorman, Richard Haas, Michio Hirano, Thomas Klopstock, Mary Kay Koenig, Cornelia Kornblum, Costanza Lamperti, Anna Lehman, Nicola Longo, Maria Judit Molnar, Sumit Parikh, Han Phan, Robert D S Pitceathly, Russekk Saneto, Fernando Scaglia, Serenella Servidei, Mark Tarnopolsky, Antonio Toscano, Johan L K Van Hove, John Vissing, Jerry Vockley, Jeffrey S Finman, Anthony Abbruscato, David A Brown, Alana Sullivan, James A Shiffer, Michelango Mancuso, Mmpower-3 Trial Investigators

Faculty, Staff and Students Publications

BACKGROUND: As previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing nuclear DNA (nDNA) pathogenic variants receiving elamipretide experienced an improvement in the six-minute walk test (6MWT), while the cohort of subjects with mitochondrial DNA (mtDNA) pathogenic variants showed no difference versus placebo. These published findings prompted additional genotype-specific post hoc analyses of the MMPOWER-3 trial. Here, we present these analyses to further investigate the findings and to seek trends and commonalities among those …

Does Muscle Pain Induce Alterations In The Pelvic Floor Motor Unit Activity Properties In Interstitial Cystitis/Bladder Pain Syndrome? A High-Density Semg-Based Study, Monica Albaladejo-Belmonte, Michael Houston, Nicholas Dias, Theresa Spitznagle, Henry Lai, Yingchun Zhang, Javier Garcia-Casado

2020-Current year OA Pubs

Several studies have shown interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic condition that poses challenges in both diagnosis and treatment, is associated with painful pelvic floor muscles (PFM) and altered neural drive to these muscles. However, its pathophysiology could also involve other alterations in the electrical activity of PFM motor units (MUs). Studying these alterations could provide novel insights into IC/BPS and help its clinical management. This study aimed to characterize PFM activity at the MU level in women with IC/BPS and pelvic floor myalgia using high-density surface electromyography (HD-sEMG). Signals were recorded from 15 patients and 15 healthy controls …

Analyzing Longitudinal Trait Trajectories Using Gwas Identifies Genetic Variants For Kidney Function Decline, Simon Wiegrebe, Mathias Gorski, Janina M Herold, Klaus J Stark, Barbara Thorand, Christian Gieger, Carsten A Böger, Johannes Schödel, Florian Hartig, Han Chen, Thomas W Winkler, Helmut Küchenhoff, Iris M Heid

Faculty, Staff and Student Publications

Understanding the genetics of kidney function decline, or trait change in general, is hampered by scarce longitudinal data for GWAS (longGWAS) and uncertainty about how to analyze such data. We use longitudinal UK Biobank data for creatinine-based estimated glomerular filtration rate from 348,275 individuals to search for genetic variants associated with eGFR-decline. This search was performed both among 595 variants previously associated with eGFR in cross-sectional GWAS and genome-wide. We use seven statistical approaches to analyze the UK Biobank data and simulated data, finding that a linear mixed model is a powerful approach with unbiased effect estimates which is viable …

Phase I Dose Escalation Study Of Io-108, An Anti-Lilrb2 Antibody, In Patients With Advanced Solid Tumors, Matthew H Taylor, Aung Naing, John Powderly, Paul Woodard, Luke Chung, Wen Hong Lin, Hongyu Tian, Nathan Siemers, Hong Xiang, Rong Deng, Kyu Hong, Donna Valencia, Tao Huang, Ying Zhu, X Charlene Liao, Xiao Min Schebye, Manish R Patel

Faculty, Staff and Student Publications

Purpose: In this first-in-human dose escalation study, the safety and efficacy of IO-108, a fully human monoclonal antibody targeting leukocyte immunoglobulin-like receptor B2 (LILRB2), was investigated in patients with advanced solid tumors as monotherapy and in combination with pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody.

Methods: The study included patients with histologically or cytologically confirmed advanced and relapsed solid tumors, with measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1. Patients were treated with escalating doses of IO-108 every 3 weeks (Q3W) as monotherapy and in combination with pembrolizumab. Safety and tolerability were the primary objectives. …

Spatiotemporal Mapping Of Auditory Onsets During Speech Production, Garret Lynn Kurteff, Alyssa M Field, Saman Asghar, Elizabeth C Tyler-Kabara, Dave Clarke, Howard L Weiner, Anne E Anderson, Andrew J Watrous, Robert J Buchanan, Pradeep N Modur, Liberty S Hamilton

Faculty, Staff and Students Publications

The human auditory cortex is organized according to the timing and spectral characteristics of speech sounds during speech perception. During listening, the posterior superior temporal gyrus is organized according to onset responses, which segment acoustic boundaries in speech, and sustained responses, which further process phonological content. When we speak, the auditory system is actively processing the sound of our own voice to detect and correct speech errors in real time. This manifests in neural recordings as suppression of auditory responses during speech production compared with perception, but whether this differentially affects the onset and sustained temporal profiles is not known. …

Electrical Impedance Tomography Monitoring In Adult Icu Patients: State-Of-The-Art, Recommendations For Standardized Acquisition, Processing, And Clinical Use, And Future Directions, Gaetano Scaramuzzo, Bhushan H Katira, Et Al.

2020-Current year OA Pubs

Electrical impedance tomography (EIT) is an emerging technology for the non-invasive monitoring of regional distribution of ventilation and perfusion, offering real-time and continuous data that can greatly enhance our understanding and management of various respiratory conditions and lung perfusion. Its application may be especially beneficial for critically ill mechanically ventilated patients. Despite its potential, clear evidence of clinical benefits is still lacking, in part due to a lack of standardization and transparent reporting, which is essential for ensuring reproducible research and enhancing the use of EIT for personalized mechanical ventilation. This report is the result of a four-day expert meeting …

Association Of Binge Alcohol Use With Functional Outcomes Among Individuals With Covid-19 Infection, Sebastian T. Tong, Michael Gottlieb, Imtiaz Ebna Mannan, Zihan Zheng, Manisha Sinha, Michelle Santangelo, Kristyn Gatling, Efrat Kean, Phillip Watts, Ralph Wang, Juan Carlos Montoy, Ahamed Idris, Samuel Macdonald, Ryan Huebinger, Mandy Hill, Kelli N O'Laughlin, Nicole L. Gentile, Jocelyn Dorney, Caitlin Malicki, Joann G. Elmore, Kate Diaz Roldan, Gary Chan, Zhenqiu Lin, Robert A. Weinstein, Kari A. Stephens

Department of Medicine Faculty Papers

AIMS: Alcohol consumption along with negative sequelae from excess alcohol intake increased during the COVID-19 pandemic. We evaluated the association between binge alcohol use and long-term functional outcomes among COVID-19-positive individuals.

METHODS: Using a prospective, longitudinal, multisite cohort study design, we evaluated the association between binge alcohol use and mental and physical functional outcomes using Patient-Reported Outcomes Measurement Information System (PROMIS)-29 scores three and six months postinfection. Eligible patients were those who presented with COVID-19-like symptoms, tested positive for COVID-19, and completed a three-month survey. Binge drinking was identified at the time of infection using the Tobacco, Alcohol, Prescription medication …

Comparative Neurofilament Light Chain Trajectories In Csf And Plasma In Autosomal Dominant Alzheimer's Disease, Anna Hofmann, Jorge J Llibre-Guerra, Richard J Perrin, Laura Ibanez, Randall J Bateman, Eric Mcdade, Brian A Gordon, Et Al.

2020-Current year OA Pubs

Disease-modifying therapies for Alzheimer's disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum. CSF and plasma trajectories were similar at presymptomatic stages, discriminating …

Identifying Barriers To Hepatitis B And Delta Screening, Prevention, And Linkage To Care Among People Who Use Drugs In Philadelphia, Pennsylvania, Usa, Beatrice Zovich, Catherine Freeland, Holly Moore, Kara Sapp, Anousha Qureshi, Amy Jessop, Rachel Holbert, Fiona Borondy-Jenkins, Quinn Plunkett, Chari Cohen

Student Papers, Posters & Projects

BACKGROUND: People who use drugs (PWUD) are at increased risk for blood-borne viruses, including hepatitis B (HBV) and delta (HDV). Despite the public health threats both viruses present, awareness remains low among at-risk communities and providers who serve them. This study assessed barriers to HBV and HDV prevention, diagnosis, and linkage to care, evaluated existing levels of knowledge, and identified educational needs and preferences among both PWUD and service providers.

METHODS: For this mixed-methods study, data were collected through an anonymous online provider-focused survey, and interviews with PWUD, non-medical staff, and healthcare providers at a harm reduction organization in Philadelphia, …