Medical Specialties Commons^™

Safety And Efficacy Of Ibrutinib In Combination With Rituximab And Lenalidomide In Previously Untreated Follicular And Marginal Zone Lymphoma: An Open Label, Phase 2 Study, Max J Gordon, Lei Feng, Paolo Strati, Hun Ju Lee, Fredrick B Hagemeister, Jason R Westin, Felipe Samaniego, Mario L Marques-Piubelli, Francisco Vega Vazquez, Edwin R Parra Cuentas, Luisa M Solis-Soto, Wencai Ma, Jing Wang, Linda Claret, Barbara Averill, Karina Ibanez, Luis E Fayad, Christopher R Flowers, Michael R Green, R Eric Davis, Sattva S Neelapu, Nathan H Fowler, Loretta J Nastoupil

Faculty, Staff and Student Publications

Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity-rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study.

Methods: The authors conducted an …

Effect Of Neutralizing Monoclonal Antibody Treatment On Early Trajectories Of Virologic And Immunologic Biomarkers In Patients Hospitalized With Covid-19, Tomas O Jensen, Greg A Grandits, Mamta K Jain, Thomas A Murray, Birgit Grund, Kathryn Shaw-Saliba, Michael A Matthay, Mahsa Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L Dewar, Anna L Goodman, Timothy J Hatlen, Helene C Highbarger, Mark Holodniy, Perrine Lallemand, Sylvain Laverdure, Bradley G Leshnower, David Looney, Charalampos D Moschopoulos, Henry Mugerwa, Daniel D Murray, Eleftherios Mylonakis, Stephanie Nagy-Agren, M Tauseef Rehman, Adam Rupert, Randy A Stevens, Stuart Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R Ko, Activ-3/Tico Study Group

Faculty, Staff and Student Publications

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.

METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.

RESULTS: Analysis included 2149 participants enrolled between …

Label-Aware Distance Mitigates Temporal And Spatial Variability For Clustering And Visualization Of Single-Cell Gene Expression Data, Shaoheng Liang, Jinzhuang Dou, Ramiz Iqbal, Ken Chen

Faculty, Staff and Student Publications

Clustering and visualization are essential parts of single-cell gene expression data analysis. The Euclidean distance used in most distance-based methods is not optimal. The batch effect, i.e., the variability among samples gathered from different times, tissues, and patients, introduces large between-group distance and obscures the true identities of cells. To solve this problem, we introduce Label-Aware Distance (LAD), a metric using temporal/spatial locality of the batch effect to control for such factors. We validate LAD on simulated data as well as apply it to a mouse retina development dataset and a lung dataset. We also found the utility of our …

Opportunities And Challenges For The Use Of Deep Brain Stimulation In The Treatment Of Refractory Major Depression, Prashin Unadkat, Joao Quevedo, Jair Soares, Albert Fenoy

Faculty, Staff and Student Publications

Major Depressive Disorder continues to remain one of the most prevalent psychiatric diseases globally. Despite multiple trials of conventional therapies, a subset of patients fail to have adequate benefit to treatment. Deep brain stimulation (DBS) is a promising treatment in this difficult to treat population and has shown strong antidepressant effects across multiple cohorts. Nearly two decades of work have provided insights into the potential for chronic focal stimulation in precise brain targets to modulate pathological brain circuits that are implicated in the pathogenesis of depression. In this paper we review the rationale that prompted the selection of various brain …

Viscosity Flow Curves Of Agar And The Bounded Ripening Growth Model Of The Gelation Onset, Vincenzo Villani

Faculty, Staff and Student Publications

The gelation kinetics of agar aqueous solutions were studied by means of the viscosity flow curves using a coaxial Couette cylinder viscometer. The viscosity curves show an unusual sigmoidal trend or an exponential decay to a viscous steady state. An original theory of gelation kinetics was developed considering the coarsening of increasingly larger and more stable clusters due to Ostwald ripening and the breakup of clusters that were too large due to the instability of rotating large particles induced by the shear rate. The developed

A Novel Spatiotemporal Graph Convolutional Network Framework For Functional Connectivity Biomarkers Identification Of Alzheimer’S Disease, Ying Zhang, Le Xue, Shuoyan Zhang, Jiacheng Yang, Qi Zhang, Min Wang, Luyao Wang, Mingkai Zhang, Jiehui Jiang, Yunxia Li

Faculty, Staff and Student Publications

BACKGROUND: Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer's disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-based class activation mapping (Grad-CAM) model (STGC-GCAM), to effectively identify FC biomarkers for AD.

METHODS: This multi-center cross-racial retrospective study involved 2,272 participants, including 1,105 cognitively normal (CN) subjects, 790 mild cognitive impairment (MCI) individuals, and 377 AD patients. All participants underwent functional magnetic resonance imaging (fMRI) and T1-weighted MRI scans. In this study, …

Effect Of Neutralizing Monoclonal Antibody Treatment On Early Trajectories Of Virologic And Immunologic Biomarkers In Patients Hospitalized With Covid-19, Tomas O Jensen, Greg A Grandits, Mamta K Jain, Thomas A Murray, Birgit Grund, Kathryn Shaw-Saliba, Michael A Matthay, Mahsa Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L Dewar, Anna L Goodman, Timothy J Hatlen, Helene C Highbarger, Mark Holodniy, Perrine Lallemand, Sylvain Laverdure, Bradley G Leshnower, David Looney, Charalampos D Moschopoulos, Henry Mugerwa, Daniel D Murray, Eleftherios Mylonakis, Stephanie Nagy-Agren, M Tauseef Rehman, Adam Rupert, Randy A Stevens, Stuart Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R Ko

Faculty, Staff and Student Publications

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.

METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.

RESULTS: Analysis included 2149 participants enrolled between …

A Road Map Of Relapse In Mds After Allo-Hsct, Juan Jose Rodriguez-Sevilla, Simona Colla

Faculty, Staff and Student Publications

No abstract provided.

Btn1a1 Is A Novel Immune Checkpoint Mutually Exclusive To Pd-L1, Young-Seung Kim, Seung-Hoon Lee, Andrew H Park, Chunai Wu, Bong-Ki Hong, Hyunjin Jung, Steven H Lin, Stephen S Yoo

Faculty, Staff and Student Publications

BACKGROUND: While Programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockade is a potent antitumor treatment strategy, it is effective in only limited subsets of patients with cancer, emphasizing the need for the identification of additional immune checkpoints. Butyrophilin 1A1 (BTN1A1) has been reported to exhibit potential immunoregulatory activity, but its ability to function as an immune checkpoint remains to be systematically assessed, and the mechanisms underlying such activity have yet to be characterized.

METHODS: BTN1A1 expression was evaluated in primary tumor tissue samples, and its ability to suppress T-cell activation and T cell-dependent tumor clearance was examined. …

Lifestyle Medicine For The Prevention And Treatment Of Pancreatitis And Pancreatic Cancer, Sruthi Kapliyil Subramanian, Bhaumik Brahmbhatt, Jennifer M Bailey-Lundberg, Nirav C Thosani, Pritesh Mutha

Faculty, Staff and Student Publications

The incidence of pancreatitis and pancreatic cancer is on the upswing in the USA. These conditions often lead to higher healthcare costs due to the complex nature of diagnosis and the need for specialized medical interventions, surgical procedures, and prolonged medical management. The economic ramification encompasses direct healthcare expenses and indirect costs related to productivity losses, disability, and potential long-term care requirements. Increasing evidence underscores the importance of a healthy lifestyle in preventing and managing these conditions. Lifestyle medicine employs evidence-based interventions to promote health through six key pillars: embracing a whole-food, plant-predominant dietary pattern; regular physical activity; ensuring restorative …

Genomic Evolution Shapes Prostate Cancer Disease Type, Dan J Woodcock, Atef Sahli, Ruxandra Teslo, Vinayak Bhandari, Andreas J Gruber, Aleksandra Ziubroniewicz, Gunes Gundem, Yaobo Xu, Adam Butler, Ezequiel Anokian, Bernard J Pope, Chol-Hee Jung, Maxime Tarabichi, Stefan C Dentro, J Henry R Farmery, Cruk Icgc Prostate Group, Peter Van Loo, Anne Y Warren, Vincent Gnanapragasam, Freddie C Hamdy, G Steven Bova, Christopher S Foster, David E Neal, Yong-Jie Lu, Zsofia Kote-Jarai, Michael Fraser, Robert G Bristow, Paul C Boutros, Anthony J Costello, Niall M Corcoran, Christopher M Hovens, Charlie E Massie, Andy G Lynch, Daniel S Brewer, Rosalind A Eeles, Colin S Cooper, David C Wedge

Faculty, Staff and Student Publications

The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype …

Safety And Efficacy Of Dynamic Catheter-Directed Cerebral Digital Subtraction Angiography For Diagnosis Of Bowhunter Syndrome Spectrum Disorders: A Systematic Review Of The Literature, Joo Won Choi, Yang Qiao, Tej I Mehta, Jessica N Wilson, Trevor H Torigoe, Samuel Tsappidi, Y Jonathan Zhang, Stacy C Brown, Ferdinand K Hui, Todd Abruzzo

Faculty, Staff and Student Publications

Introduction: Dynamic catheter-directed cerebral digital subtraction angiography (dcDSA) is the gold standard for diagnosing dynamic vascular occlusion syndromes such as bowhunter syndrome (BHS). Nonetheless, concerns about its safety exist and no standardized protocols have been published to date.

Methods: We describe our methodology and insights regarding the use of dcDSA in patients with BHS. We also perform a systematic literature review to identify cases of typical and atypical presentations of BHS wherein dcDSA was utilized and report on any procedural complications related to dcDSA.

Results: Our study included 104 cases wherein dcDSA was used for the diagnosis of BHS. There …

Cytoplasmic Genome Contributions To Domestication And Improvement Of Modern Maize, Shuai Cao, Huanhuan Zhang, Yang Liu, Yi Sun, Z Jeffrey Chen

Faculty, Staff and Student Publications

Background: Studies on maize evolution and domestication are largely limited to the nuclear genomes, and the contribution of cytoplasmic genomes to selection and domestication of modern maize remains elusive. Maize cytoplasmic genomes have been classified into fertile (NA and NB) and cytoplasmic-nuclear male-sterility (CMS-S, CMS-C, and CMS-T) groups, but their contributions to modern maize breeding have not been systematically investigated.

Results: Here we report co-selection and convergent evolution between nuclear and cytoplasmic genomes by analyzing whole genome sequencing data of 630 maize accessions modern maize and its relatives, including 24 fully assembled mitochondrial and chloroplast genomes. We show that the …

Detection Of Acute Brain Injury In Intensive Care Unit Patients On Ecmo Support Using Ultra-Low-Field Portable Mri: A Retrospective Analysis Compared To Head Ct, Sung-Min Cho, Shivalika Khanduja, Jiah Kim, Jin Kook Kang, Jessica Briscoe, Lori R Arlinghaus, Kha Dinh, Bo Soo Kim, Haris I Sair, Audrey-Carelle N Wandji, Elena Moreno, Glenda Torres, Jose Gavito-Higuera, Huimahn A Choi, John Pitts, Aaron M Gusdon, Glenn J Whitman

Faculty, Staff and Student Publications

Early detection of acute brain injury (ABI) is critical to intensive care unit (ICU) patient management and intervention to decrease major complications. Head CT (HCT) is the standard of care for the assessment of ABI in ICU patients; however, it has limited sensitivity compared to MRI. We retrospectively compared the ability of ultra-low-field portable MR (ULF-pMR) and head HCT, acquired within 24 h of each other, to detect ABI in ICU patients supported on extracorporeal membrane oxygenation (ECMO). A total of 17 adult patients (median age 55 years; 47% male) were included in the analysis. Of the 17 patients assessed, …

Landscape Of Pharmacogenetic Variants Associated With Non-Insulin Antidiabetic Drugs In The Indian Population, Ambily Sivadas, S Sahana, Bani Jolly, Rahul C Bhoyar, Abhinav Jain, Disha Sharma, Mohamed Imran, Vigneshwar Senthivel, Mohit Kumar Divakar, Anushree Mishra, Arpita Mukhopadhyay, Greg Gibson, Km Venkat Narayan, Sridhar Sivasubbu, Vinod Scaria, Anura V Kurpad

Faculty, Staff and Student Publications

INTRODUCTION: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants.

RESEARCH DESIGN AND METHODS: We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with …

Distributed Neural Representations Of Conditioned Threat In The Human Brain, Zhenfu Wen, Edward F Pace-Schott, Sara W Lazar, Jörgen Rosén, Fredrik Åhs, Elizabeth A Phelps, Joseph E Ledoux, Mohammed R Milad

Faculty, Staff and Student Publications

Detecting and responding to threat engages several neural nodes including the amygdala, hippocampus, insular cortex, and medial prefrontal cortices. Recent propositions call for the integration of more distributed neural nodes that process sensory and cognitive facets related to threat. Integrative, sensitive, and reproducible distributed neural decoders for the detection and response to threat and safety have yet to be established. We combine functional MRI data across varying threat conditioning and negative affect paradigms from 1465 participants with multivariate pattern analysis to investigate distributed neural representations of threat and safety. The trained decoders sensitively and specifically distinguish between threat and safety …

Author Correction: Hypomorphic Brca2 And Rad51c Double Mutant Mice Display Fanconi Anemia, Cancer And Polygenic Replication Stress, Karl-Heinz Tomaszowski, Sunetra Roy, Carolina Guerrero, Poojan Shukla, Caezaan Keshvani, Yue Chen, Martina Ott, Xiaogang Wu, Jianhua Zhang, Courtney D Dinardo, Detlev Schindler, Katharina Schlacher

Faculty, Staff and Student Publications

No abstract provided.

Incidence And Risk Factors Of Early Onset Vod/Sos Differ In Younger Vs Older Adults After Stem Cell Transplantation, Curtis Marcoux, Rima M Saliba, Whitney Wallis, Sajad Khazal, Dristhi Ragoonanan, Gabriela Rondon, Priti Tewari, Uday Popat, Betul Oran, Amanda Olson, Qaiser Bashir, Muzaffar Qazilbash, Amin Alousi, Chitra Hosing, Yago Nieto, Gheath Alatrash, David Marin, Katayoun Rezvani, Issa Khouri, Samer Srour, Richard Champlin, Elizabeth Shpall, Partow Kebriaei

Faculty, Staff and Student Publications

Veno-occlusive disease (VOD) is a rare but potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Although increasing awareness and modern transplant techniques have mitigated risk, the interaction of historic risk factors in the current era with posttransplant cyclophosphamide (PTCy) is unknown. We performed a retrospective single-center analysis of adult patients aged ≥18 years undergoing allo-SCT (N = 1561) using predominately PTCy as graft-versus-host disease (GVHD) prophylaxis (72%). We found a higher rate of VOD at 16.8% (20 of 119) in those aged ≤25 years compared with 3.8% (55 of 1442) in those aged >25 years, with unique predictors …

A Biogeographical Appraisal Of The Threatened South East Africa Montane Archipelago Ecoregion, Julian Bayliss, Gabriela B Bittencourt-Silva, William R Branch, Carl Bruessow, Steve Collins, T Colin E Congdon, Werner Conradie, Michael Curran, Savel R Daniels, Iain Darbyshire, Harith Farooq, Lincoln Fishpool, Geoffrey Grantham, Zacharia Magombo, Hermenegildo Matimele, Ara Monadjem, Jose Monteiro, Jo Osborne, Justin Saunders, Paul Smith, Claire N Spottiswoode, Peter J Taylor, Jonathan Timberlake, Krystal A Tolley, Érica Tovela, Philip J Platts

Faculty, Staff and Student Publications

Recent biological surveys of ancient inselbergs in southern Malawi and northern Mozambique have led to the discovery and description of many species new to science, and overlapping centres of endemism across multiple taxa. Combining these endemic taxa with data on geology and climate, we propose the 'South East Africa Montane Archipelago' (SEAMA) as a distinct ecoregion of global biological importance. The ecoregion encompasses 30 granitic inselbergs reaching > 1000 m above sea level, hosting the largest (Mt Mabu) and smallest (Mt Lico) mid-elevation rainforests in southern Africa, as well as biologically unique montane grasslands. Endemic taxa include 127 plants, 45 vertebrates …

Evaluation Of Treatment Parameters For Focused-Extracorporeal Shock Wave Therapy In Knee Osteoarthritis Patients With Bone Marrow Lesions: A Pilot Study, Hani Al-Abbad, Jacqueline E Reznik, Erik Biros, Bruce Paulik, Rob Will, Samuel Gane, Penny Moss, Anthony Wright

Faculty, Staff and Student Publications

OBJECTIVES: To evaluate the effect of different dosage parameters of focused-extracorporeal shock wave therapy on pain and physical function in knee osteoarthritis patients with bone marrow lesions. In addition, to investigate pathophysiological changes based on imaging and biomarker measures.

METHODS: Using a single-case experimental design, a total of 12 participants were randomly allocated in 4 equal groups of 3 to receive different dosages of focused-extracorporeal shock wave therapy. Each group received either 4 or 6 sessions of 1500 or 3000 shocks over 4 or 6 weekly sessions. Participants underwent repeated measurements during the baseline, intervention, and post-intervention phases for Western …

Draft Genome Sequences Of Pseudomonas Strains Zfem001–005 Isolated From The Intestine Of Larval Zebrafish Danio Rerio, Sabona B Simbassa, Justin Clark, Keiko Salazar, Anthony Maresso, Anne-Marie Krachler

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Here, we report the draft genome sequences of Pseudomonas strains zfem001–005, five isolates from the intestinal microbiota of healthy larval zebrafish Danio rerio at a developmental age of 7 days post fertilization. The isolates have been identified as Pseudomonas sediminis, Pseudomonas japonica, Pseudomonas otitidis, Pseudomonas sichuanensis, and Pseudomonas tohonis, respectively.

Automating Data Analysis For Hydrogen/Deuterium Exchange Mass Spectrometry Using Data-Independent Acquisition Methodology, Frantisek Filandr, Vladimir Sarpe, Shaunak Raval, D Alex Crowder, Morgan F Khan, Pauline Douglas, Stephen Coales, Rosa Viner, Aleem Syed, John A Tainer, Susan P Lees-Miller, David C Schriemer

Faculty, Staff and Student Publications

We present a hydrogen/deuterium exchange workflow coupled to tandem mass spectrometry (HX-MS2) that supports the acquisition of peptide fragment ions alongside their peptide precursors. The approach enables true auto-curation of HX data by mining a rich set of deuterated fragments, generated by collisional-induced dissociation (CID), to simultaneously confirm the peptide ID and authenticate MS1-based deuteration calculations. The high redundancy provided by the fragments supports a confidence assessment of deuterium calculations using a combinatorial strategy. The approach requires data-independent acquisition (DIA) methods that are available on most MS platforms, making the switch to HX-MS2 straightforward. Importantly, we find that HX-DIA enables …

Immune Heterogeneity In Small-Cell Lung Cancer And Vulnerability To Immune Checkpoint Blockade, Barzin Y Nabet, Habib Hamidi, Myung Chang Lee, Romain Banchereau, Stefanie Morris, Leah Adler, Velimir Gayevskiy, Ahmed M Elhossiny, Minu K Srivastava, Namrata S Patil, Kiandra A Smith, Rajiv Jesudason, Caleb Chan, Patrick S Chang, Matthew Fernandez, Sandra Rost, Lisa M Mcginnis, Hartmut Koeppen, Carl M Gay, John D Minna, John V Heymach, Joseph M Chan, Charles M Rudin, Lauren A Byers, Stephen V Liu, Martin Reck, David S Shames

Faculty, Staff and Student Publications

Atezolizumab (anti-PD-L1), combined with carboplatin and etoposide (CE), is now a standard of care for extensive-stage small-cell lung cancer (ES-SCLC). A clearer understanding of therapeutically relevant SCLC subsets could identify rational combination strategies and improve outcomes. We conduct transcriptomic analyses and non-negative matrix factorization on 271 pre-treatment patient tumor samples from IMpower133 and identify four subsets with general concordance to previously reported SCLC subtypes (SCLC-A, -N, -P, and -I). Deeper investigation into the immune heterogeneity uncovers two subsets with differing neuroendocrine (NE) versus non-neuroendocrine (non-NE) phenotypes, demonstrating immune cell infiltration hallmarks. The NE tumors with low tumor-associated macrophage (TAM) but …

Learning From The Implementation Of A Surgical Opioid Reduction Initiative In An Integrated Health System: A Qualitative Study Among Providers And Patients, Willemijn L A Schäfer, Julie K Johnson, Meagan S Ager, Cassandra B Iroz, Reiping Huang, Salva N Balbale, Jonah J Stulberg

Faculty, Staff and Student Publications

BACKGROUND: Surgical opioid overprescribing can result in long-term use or misuse. Between July 2018 and March 2019, the multicomponent intervention, Minimizing Opioid Prescribing in Surgery (MOPiS) was implemented in the general surgery clinics of five hospitals and successfully reduced opioid prescribing. To date, various studies have shown a positive outcome of similar reduction initiatives. However, in addition to evaluating the impact on clinical outcomes, it is important to understand the implementation process of an intervention to extend sustainability of interventions and allow for dissemination of the intervention into other contexts. This study aims to evaluate the contextual factors impacting intervention …

Metabolomic Profiles In Jamaican Children With And Without Autism Spectrum Disorder, Akram Yazdani, Maureen Samms-Vaughan, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Amirali Tahanan, Megan L Grove, Tanja Gangnus, Vasanta Putluri, Abu Hena Mostafa Kamal, Nagireddy Putluri, Katherine A Loveland, Mohammad H Rahbar

Faculty, Staff and Student Publications

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, the underlying metabolic perturbations associated with ASD which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls.

OBJECTIVE: To elucidate potential metabolomic signatures associated with ASD in children and identify specific metabolites that may serve as biomarkers for the disorder. …

Nanofibrous Multidomain Peptide Hydrogels Provide T Cells A 3d, Cytocompatible Environment For Cell Expansion And Antigen-Specific Killing, Viridiana Leyva-Aranda, Shailbala Singh, Maria J Telesforo, Simon Young, Cassian Yee, Jeffrey D Hartgerink

Faculty, Staff and Student Publications

T cells have the ability to recognize and kill specific target cells, giving therapies based on their potential for treating infection, diabetes, cancer, and other diseases. However, the advancement of T cell-based treatments has been hindered by difficulties in their ex vivo activation and expansion, the number of cells required for sustained in vivo levels, and preferential localization following systemic delivery. Biomaterials may help to overcome many of these challenges by providing a combined means of proliferation, antigen presentation, and cell localization upon delivery. In this work, we studied self-assembling Multidomain Peptides (MDPs) as scaffolds for T cell culture, activation, …

Methodological Advances In Patient-Centered Rare Disease Research: The Uthealth Houston Turner Syndrome Society Of The United States Research Registry, Sara Mansoorshahi, Cindy Scurlock, Scientific Advisory Board Of The Turner Syndrome Society Of The United States Research Registry, Siddharth K Prakash

Faculty, Staff and Student Publications

BACKGROUND: Many different clinical specialists provide care to patients with Turner syndrome (TS), who have highly variable clinical manifestations. Therefore, a national TS registry is essential to inform a cohesive approach to healthcare and research. In 2015, the Turner Syndrome Society of the United States (TSSUS) created the Turner Syndrome Research Registry (TSRR) to engage directly with community participants who voluntarily provide longitudinal data about their experiences with TS. TSRR projects are collaborative partnerships between people with TS, TSSUS, and researchers.

RESULTS: To ensure that registry workflows conform to the data privacy choices of participants, TSSUS collaborated with UTHealth Houston …

High Response Rate With Extended Dosing Of Cemiplimab In Advanced Cutaneous Squamous Cell Carcinoma, Danny Rischin, Brett G M Hughes, Nicole Basset-Séguin, Dirk Schadendorf, Samantha Bowyer, Sabiha Trabelsi Messai, Friedegund Meier, Thomas K Eigentler, Victoria Casado Echarren, Brian Stein, Marie Beylot-Barry, Sophie Dalac, Brigitte Dréno, Michael R Migden, Axel Hauschild, Chrysalyne D Schmults, Annette M Lim, Suk-Young Yoo, Anne J Paccaly, Apostolos Papachristos, Jenny-Hoa Nguyen, Emmanuel Okoye, Frank Seebach, Jocelyn Booth, Israel Lowy, Matthew G Fury, Alexander Guminski

Faculty, Staff and Student Publications

BACKGROUND: Cemiplimab (Libtayo

METHODS: In this open-label, phase II trial (ClinicalTrials.gov identifier NCT02760498), the cohort of patients ≥18 years old with advanced CSCC received cemiplimab 600 mg intravenously Q4W for up to 48 weeks. Tumor measurements were recorded every 8 weeks. The primary endpoint was objective response rate by independent central review.

RESULTS: Sixty-three patients with advanced CSCC were treated with cemiplimab. The median duration of follow-up was 22.4 months (range: 1.0-39.8). An objective response was observed in 39 patients (62%; 95% CI: 48.8% to 73.9%), with 22% of patients (n

CONCLUSIONS: Extended dosing of cemiplimab 600 mg intravenously Q4W …

Ape-Gen20: Expanding Rapid Class I Peptide-Major Histocompatibility Complex Modeling To Post-Translational Modifications And Noncanonical Peptide Geometries, Romanos Fasoulis, Mauricio M Rigo, Gregory Lizée, Dinler A Antunes, Lydia E Kavraki

Faculty, Staff and Student Publications

The recognition of peptides bound to class I major histocompatibility complex (MHC-I) receptors by T-cell receptors (TCRs) is a determinant of triggering the adaptive immune response. While the exact molecular features that drive the TCR recognition are still unknown, studies have suggested that the geometry of the joint peptide–MHC (pMHC) structure plays an important role. As such, there is a definite need for methods and tools that accurately predict the structure of the peptide bound to the MHC-I receptor. In the past few years, many pMHC structural modeling tools have emerged that provide high-quality modeled structures in the general case. …

Toward Generalizable Machine Learning Models In Speech, Language, And Hearing Sciences: Estimating Sample Size And Reducing Overfitting, Hamzeh Ghasemzadeh, Robert E Hillman, Daryush D Mehta

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PURPOSE: Many studies using machine learning (ML) in speech, language, and hearing sciences rely upon cross-validations with single data splitting. This study's first purpose is to provide quantitative evidence that would incentivize researchers to instead use the more robust data splitting method of nested

METHOD: First, the significant impact of different cross-validations on ML outcomes was demonstrated using real-world clinical data. Then, Monte Carlo simulations were used to quantify the interactions among the employed cross-validation method, the discriminative power of features, the dimensionality of the feature space, the dimensionality of the model, and the sample size. Four different cross-validation methods …