Medicine and Health Sciences Commons^™

Examination Of Fully Automated Mammographic Density Measures Using Libra And Breast Cancer Risk In A Cohort Of 21,000 Non-Hispanic White Women, Laurel A Habel, Aimilia Gastounioti, Et Al.

2020-Current year OA Pubs

BACKGROUND: Breast density is strongly associated with breast cancer risk. Fully automated quantitative density assessment methods have recently been developed that could facilitate large-scale studies, although data on associations with long-term breast cancer risk are limited. We examined LIBRA assessments and breast cancer risk and compared results to prior assessments using Cumulus, an established computer-assisted method requiring manual thresholding.

METHODS: We conducted a cohort study among 21,150 non-Hispanic white female participants of the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California who were 40-74 years at enrollment, followed for up to 10 years, and had archived …

Er-Mitochondria Contacts And Cholesterol Metabolism Are Disrupted By Disease-Associated Tau Protein, Leonora Szabo, Nadia Cummins, Paolo Paganetti, Alex Odermatt, Andreas Papassotiropoulos, Celeste Karch, Jürgen Götz, Anne Eckert, Amandine Grimm

2020-Current year OA Pubs

Abnormal tau protein impairs mitochondrial function, including transport, dynamics, and bioenergetics. Mitochondria interact with the endoplasmic reticulum (ER) via mitochondria-associated ER membranes (MAMs), which coordinate and modulate many cellular functions, including mitochondrial cholesterol metabolism. Here, we show that abnormal tau loosens the association between the ER and mitochondria in vivo and in vitro. Especially, ER-mitochondria interactions via vesicle-associated membrane protein-associated protein (VAPB)-protein tyrosine phosphatase-interacting protein 51 (PTPIP51) are decreased in the presence of abnormal tau. Disruption of MAMs in cells with abnormal tau alters the levels of mitochondrial cholesterol and pregnenolone, indicating that conversion of cholesterol into pregnenolone is impaired. …

Indwelling Catheter Vs Intermittent Catheterization: Is There A Difference In Uti Susceptibility?, Vera Neumeier, Fabian P Stangl, Joëlle Borer, Collene E Anderson, Veronika Birkhäuser, Oksana Chemych, Oliver Gross, Miriam Koschorke, Jonas Marschall, Shawna Mccallin, Ulrich Mehnert, Helen Sadri, Lara Stächele, Thomas M Kessler, Lorenz Leitner

2020-Current year OA Pubs

BACKGROUND: Patients with neurogenic lower urinary tract dysfunction (NLUTD) often rely on some type of catheterization for bladder emptying. Intermittent catheterization (IC) is considered the gold standard and is preferred over continuous catheterization, since it is considered to cause fewer urinary tract infections (UTIs) than indwelling catheterization. The main objective of our study was to describe UTI prevalence (at visit) and incidence (within the last 12 months) and urine culture characteristics between patients using an indwelling catheter versus (vs) those performing IC.

METHODS: In this cross-sectional study, we prospectively evaluated from 02/2020 to 01/2021 patients with NLUTD undergoing urine cultures …

Exploring Caregiver Interest In And Preferences For Interventions For Children With Risk Of Asthma Exacerbation: Web-Based Survey, Gabrielle Pogge, David A Fedele, Erika A Waters, Julia Maki, Jean M Hunleth, Sreekala Prabhakaran, Deborah J Bowen, James A Shepperd

2020-Current year OA Pubs

BACKGROUND: Maintaining control of asthma symptoms is the cornerstone of asthma treatment guidelines in the United States. However, suboptimal asthma control and asthma exacerbations among young people are common and are associated with many negative outcomes. Interventions to improve asthma control are needed. For such interventions to be successful, it is necessary to understand the types of interventions that are appealing to caregivers of children with different levels of risk of exacerbation.

OBJECTIVE: This study aimed to evaluate whether caregivers of children with high (vs low) risk of asthma exacerbation show different levels of interest in and preferences for potential …

Genetic Insights Into Resting Heart Rate And Its Role In Cardiovascular Disease, Yordi J Van De Vegte, Lihua Wang, Dabeeru C Rao, Et Al.

2020-Current year OA Pubs

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample …

Alcohol Consumption Among Adults With A Cancer Diagnosis In The All Of Us Research Program, Mengyao Shi, Chongliang Luo, Oluseye K Oduyale, Xiaoyu Zong, Noelle K Loconte, Yin Cao

2020-Current year OA Pubs

IMPORTANCE: Alcohol consumption is associated with adverse oncologic and treatment outcomes among individuals with a diagnosis of cancer. As a key modifiable behavioral factor, alcohol consumption patterns among cancer survivors, especially during treatment, remain underexplored in the United States.

OBJECTIVE: To comprehensively characterize alcohol consumption patterns among US cancer survivors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from May 6, 2018, to January 1, 2022, from the National Institutes of Health All of Us Research Program, a diverse US cohort with electronic health record (EHR) linkage, and included 15 199 participants who reported a cancer diagnosis and 1839 …

An Experimental Model Of Chronic Severe Mitral Regurgitation, Martha M O Mcgilvray, Tari-Ann E Yates, Lynn Pauls, Meghan O Kelly, Nicholas Razo, Stacie Mcelligott, Glenn J Foster, Jie Zheng, Jonathan K Zoller, Christian Zemlin, Ralph J Damiano Jr

2020-Current year OA Pubs

OBJECTIVE: To develop a minimally invasive, reproducible model of chronic severe mitral regurgitation (MR) that replicates the clinical phenotype of left atrial (LA) and left ventricular dilation and susceptibility to atrial fibrillation.

METHODS: Under transesophageal echocardiographic guidance, chordae tendinae were avulsed using endovascular forceps until the ratio of regurgitant jet area to LA area was ≥70%. Animals survived for an average of 8.6 ± 1.6 months (standard deviation) and imaged with monthly transthoracic echocardiography (TTE). Animals underwent baseline and preterminal magnetic resonance imaging. Terminal studies included TTE, transesophageal echocardiography, and rapid atrial pacing to test inducibility of atrial tachyarrhythmias.

RESULTS: …

Refractory Mogamulizumab-Associated Rash Responding To An Oral Janus Kinase Inhibitor, Carine M Lama, Miguel A Hernandez-Rovira, Neha Mehta-Shah, Aaron Russell, Amy C M Musiek

2020-Current year OA Pubs

No abstract provided.

Decision-Making For Pediatric Cervical Spine Imaging After Blunt Trauma: Investigating Team Dynamics In The Emergency Department, Megan E Gregory, Annie Truelove, Fahd Ahmad, Daniel Corwin, Leah Tzimenatos, Scott J Oglesbee, Martin J Herman, Julie C Leonard

2020-Current year OA Pubs

OBJECTIVE: Cervical spine imaging decision-making for pediatric traumas is complex and multidisciplinary. Implementing a risk assessment tool has the potential to reduce variation in these decisions and unnecessary radiation exposure for pediatric patients. We sought to determine how emergency department-trauma team dynamics may affect implementation of such a tool.

METHODS: We interviewed (pediatric and general emergency physicians, trauma surgeons, neurosurgeons, orthopedic surgeons and ED nurses at 21 hospitals to ascertain how team dynamics affect the pediatric cervical spine imaging decision-making process. Data were coded following a framework-driven deductive coding process and thematic analysis was used.

RESULTS: Forty-eight physicians, advanced practice …

Induction Of Cancer Neoantigens Facilitates Development Of Clinically Relevant Models For The Study Of Pancreatic Cancer Immunobiology, Usman Y Panni, Michael Y Chen, Felicia Zhang, Darren R Cullinan, Lijin Li, C Alston James, Xiuli Zhang, S Rogers, A Alarcon, John M Baer, Daoxiang Zhang, Feng Gao, Christopher A Miller, Qingqing Gong, Kian-Huat Lim, David G Denardo, S Peter Goedegebuure, William E Gillanders, William G Hawkins

2020-Current year OA Pubs

Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC. KP2 was treated with oxaliplatin and olaparib (OXPARPi), and a resistant cell line was subsequently cloned to generate multiple genetically distinct cell lines (KP2-OXPARPi clones). Clones A and E are sensitive to immune checkpoint …

Prescribing Patterns For Sodium-Glucose Cotransporter 2 Inhibitors: A Survey Of Nephrologists, Tripti Singh, Tingting Li, Didier Mandelbrot, Brad C Astor, Ali Poyan Mehr

2020-Current year OA Pubs

No abstract provided.

Management Of Acetaminophen Poisoning In The Us And Canada: A Consensus Statement, Richard C Dart, Michael E Mullins, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management.

OBJECTIVE: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada.

EVIDENCE REVIEW: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical …

Changing Faces: Factors Associated With The Intention To Pursue Plastic Surgery And Practice In Underserved Areas, Mytien Nguyen, Annette Kaminaka, Nicholas N. Brutus, Luis A. Gonzalez, Amit Ratanpal, Michael Alperovich, Donna B. Jeffe, Ashar Ata, Hyacinth R. C. Mason, Paris D. Butler

2020-Current year OA Pubs

UNLABELLED: Improving the number of plastic and reconstructive surgeons who provide care to patients in underserved communities is critical to achieving health equity. We aimed to identify factors associated with graduating medical students' intentions to pursue plastic surgery and practice in underserved areas.

METHODS: De-identified data for US medical school graduates were obtained from the Association of American Medical Colleges for students who matriculated in academic years 2007-2008 and 2011-2012. Data collected included self-reported demographic and future practice intentions. Multivariate analysis was conducted to determine indicators of students' interest in plastic surgery, and their intention to practice in underserved areas. …

Loop-And-Let-Go Technique For The Management Of Symptomatic Large Colonic Lipoma, Syedreza Haider, Matthew Peller, Vladimir Lamm, Ahmad Najdat Bazarbashi

2020-Current year OA Pubs

Video 1We depict (1) identification of a large lipoma in the sigmoid colon; (2) radial echo endoscopy confirming diagnosis; (3) removal with the loop-and-let-go technique; (4) ex vivo demonstration of the technique; and (5) an interval follow-up demonstrating healing of the lesion.

Resolvin D1 Prevents Injurious Neutrophil Swarming In Transplanted Lungs, Wenjun Li, Hailey M Shepherd, Yuriko Terada, Ashley E Shay, Amit I Bery, Andrew E Gelman, Kory J Lavine, Charles N Serhan, Daniel Kreisel

2020-Current year OA Pubs

Neutrophils are the primary cell type involved in lung ischemia-reperfusion injury (IRI), which remains a frequent and morbid complication after organ transplantation. Endogenous lipid mediators that become activated during acute inflammation-resolution have gained increasing recognition for their protective role(s) in promoting the restoration of homeostasis, but their influence on early immune responses following transplantation remains to be uncovered. Resolvin D1, 7

Impact Of Prior Therapies And Subsequent Transplantation On Outcomes In Adult Patients With Relapsed Or Refractory B-Cell Acute Lymphoblastic Leukemia Treated With Brexucabtagene Autoleucel In Zuma-3, Bijal D Shah, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) …

Cation Leak Through The Atp1a3 Pump Causes Spasticity And Intellectual Disability, Daniel G Calame, Marwan Shinawi, Et Al.

2020-Current year OA Pubs

ATP1A3 encodes the α3 subunit of the sodium-potassium ATPase, one of two isoforms responsible for powering electrochemical gradients in neurons. Heterozygous pathogenic ATP1A3 variants produce several distinct neurological syndromes, yet the molecular basis for phenotypic variability is unclear. We report a novel recurrent variant, ATP1A3(NM_152296.5):c.2324C>T; p.(Pro775Leu), in nine individuals associated with the primary clinical features of progressive or non-progressive spasticity and developmental delay/intellectual disability. No patients fulfil diagnostic criteria for ATP1A3-associated syndromes, including alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism or cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss (CAPOS), and none were suspected of having an ATP1A3-related disorder. Uniquely among known …

Delayed-Onset Angioedema Following A Snakebite In A Patient On Ace Inhibitors: A Case Report, Christopher Scott Sampson, Evan Schwarz

2020-Current year OA Pubs

INTRODUCTION: Angiotensin converting enzyme inhibitors (ACEI) are a common class of medications prescribed to patients for hypertension. Anti-hypertensive use is not normally considered an important factor when treating patients with crotalid envenomations; however, in combination with the venom in this patient, it may have resulted in angioedema.

CASE REPORT: A 65-year-old male on ACEI presented to his community emergency department following a snake envenomation to his thumb. Six vials of Crotalidae polyvalent immune fab were administered, and he was transferred to a referral center. Approximately 18 hours after the envenomation, the patient complained of tongue swelling and difficulty speaking. There …

Hgf/C-Met Pathway Inhibition Combined With Chemotherapy Increases Cytotoxic T-Cell Infiltration And Inhibits Pancreatic Tumour Growth And Metastasis, Alpha Raj Mekapogu, Zhihong Xu, Srinivasa Pothula, Chamini Perera, Tony Pang, S M Zahid Hosen, Vishnu Damalanka, James Janetka, David Goldstein, Romano Pirola, Jeremy Wilson, Minoti Apte

2020-Current year OA Pubs

Pancreatic cancer (PC) is a deadly cancer with a high mortality rate. The unique characteristics of PC, including desmoplasia and immunosuppression, have made it difficult to develop effective treatment strategies. Pancreatic stellate cells (PSCs) play a crucial role in the progression of the disease by interacting with cancer cells. One of the key mediators of PSC - cancer cell interactions is the hepatocyte growth factor (HGF)/c-MET pathway. Using an immunocompetent in vivo model of PC as well as in vitro experiments, this study has shown that a combined approach using HGF/c-MET inhibitors to target stromal-tumour interactions and chemotherapy (gemcitabine) to …

Shephard: A Modular And Extensible Software Architecture For Analyzing And Annotating Large Protein Datasets, Garrett M Ginell, Aidan J Flynn, Alex S Holehouse

2020-Current year OA Pubs

MOTIVATION: The emergence of high-throughput experiments and high-resolution computational predictions has led to an explosion in the quality and volume of protein sequence annotations at proteomic scales. Unfortunately, sanity checking, integrating, and analyzing complex sequence annotations remains logistically challenging and introduces a major barrier to entry for even superficial integrative bioinformatics.

RESULTS: To address this technical burden, we have developed SHEPHARD, a Python framework that trivializes large-scale integrative protein bioinformatics. SHEPHARD combines an object-oriented hierarchical data structure with database-like features, enabling programmatic annotation, integration, and analysis of complex datatypes. Importantly SHEPHARD is easy to use and enables a Pythonic interrogation …

Increased Incidence And Risk Of Septicemia And Urinary Tract Infection After Clostridioides Difficile Infection, Margaret A Olsen, Matthew R Keller, Dustin Stwalley, Holly Yu, Erik R Dubberke

2020-Current year OA Pubs

BACKGROUND: Although increased occurrence of septicemia in persons with

METHODS: The first episode of CDI was identified using 2011-2017 MarketScan and CMS Medicare data and CDI cases categorized by standard surveillance definitions. Uninfected persons were frequency matched 4:1 to cases by the CDI case surveillance definition. Multivariable Cox proportional hazards models were used to identify risk factors for septicemia and UTI within 90 days of CDI onset, accounting for the competing risk of death in the Medicare population.

RESULTS: The incidence of septicemia was highest after hospital-onset CDI in the Medicare, younger commercial, and younger Medicaid populations (25.5%, 15.7%, and …

Csf Mtbr-Tau243 Is A Specific Biomarker Of Tau Tangle Pathology In Alzheimer's Disease, Kanta Horie, Nicolas R Barthélemy, Yan Li, Yingxin He, Benjamin Saef, Charles D Chen, Hong Jiang, Chihiro Sato, Brian A Gordon, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Aggregated insoluble tau is one of two defining features of Alzheimer's disease. Because clinical symptoms are strongly correlated with tau aggregates, drug development and clinical diagnosis need cost-effective and accessible specific fluid biomarkers of tau aggregates; however, recent studies suggest that the fluid biomarkers currently available cannot specifically track tau aggregates. We show that the microtubule-binding region (MTBR) of tau containing the residue 243 (MTBR-tau243) is a new cerebrospinal fluid (CSF) biomarker specific for insoluble tau aggregates and compared it to multiple other phosphorylated tau measures (p-tau181, p-tau205, p-tau217 and p-tau231) in two independent cohorts (BioFINDER-2, n = 448; and …

Cerebrospinal Fluid Proteomics Define The Natural History Of Autosomal Dominant Alzheimer's Disease, Erik C B Johnson, Brian A Gordon, Eric Mcdade, Nicolas R Barthélemy, Celeste M Karch, Chengjie Xiong, Carlos Cruchaga, Richard J Perrin, John C Morris, Tammie L S Benzinger, Randall J Bateman, Anne M Fagan, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes-aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)-are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of Aβ plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning …

Use Of A Mixed Reality System For Navigational Mapping During Cardiac Electrophysiological Testing Does Not Prolong Case Duration: A Subanalysis From The Cardiac Augmented Reality Study, David Bloom, David Catherall, Nathan Miller, Michael K Southworth, Andrew C Glatz, Jonathan R Silva, Jennifer N Avari Silva

2020-Current year OA Pubs

BACKGROUND: CommandEP™ is a mixed reality (MXR) system for cardiac electrophysiological (EP) procedures that provides a real-time 3-dimensional digital image of cardiac geometry and catheter locations. In a previous study, physicians using the system demonstrated improved navigational accuracy. This study investigated the impact of the CommandEP system on EP procedural times compared to the standard-of-care electroanatomic mapping system (EAMS) display.

OBJECTIVE: The purpose of this retrospective case-controlled analysis was to evaluate the impact of a novel MXR interface on EP procedural times compared to a case-matched cohort.

METHODS: Cases from the Cardiac Augmented REality (CARE) study were matched for diagnosis …

Striatal Mglu5-Mediated Synaptic Plasticity Is Independently Regulated By Location-Specific Receptor Pools And Divergent Signaling Pathways, Yuh-Jiin I Jong, Yukitoshi Izumi, Steven K Harmon, Charles F Zorumski, Karen L Ómalley

2020-Current year OA Pubs

Metabotropic glutamate receptor 5 (mGlu

Epigenetic Age Acceleration Mediates The Relationship Between Neighborhood Deprivation And Pain Severity In Adults With Or At Risk For Knee Osteoarthritis Pain, Pamela Jackson, Burel R Goodin, Et Al.

2020-Current year OA Pubs

An estimated 250 million people worldwide suffer from knee osteoarthritis (KOA), with older adults having greater risk. Like other age-related diseases, residents of high-deprivation neighborhoods experience worse KOA pain outcomes compared to their more affluent neighbors. The purpose of this study was to examine the relationship between neighborhood deprivation and pain severity in KOA and the influence of epigenetic age acceleration (EpAA) on that relationship. The sample of 128 participants was mostly female (60.9%), approximately half non-Hispanic Black (49.2%), and had a mean age of 58 years. Spearman bivariate correlations revealed that pain severity positively correlated with EpAA (ρ = …

Prospective Role Of Cefiderocol In The Management Of Carbapenem-Resistant Acinetobacter Baumannii Infections: Review Of The Evidence, Marin Kollef, Herve Dupont, David E Greenberg, Pierluigi Viale, Roger Echols, Yoshinori Yamano, David P Nicolau

2020-Current year OA Pubs

Carbapenem-resistant Acinetobacter baumannii (CRAB) has been classified by the World Health Organization as being in the critical category of pathogens requiring urgent new antibiotic treatment options. Cefiderocol, the first approved siderophore cephalosporin, was designed for the treatment of carbapenem-resistant Gram-negative pathogens, particularly the non-fermenting species A. baumannii and Pseudomonas aeruginosa. Cefiderocol is mostly stable against hydrolysis by serine β-lactamases and metallo-β-lactamases, which are leading causes of carbapenem resistance. This review collates the available evidence on the in vitro activity, pharmacokinetics/pharmacodynamics, and efficacy and safety of cefiderocol, and outlines its current role in the management of CRAB infections. In vitro surveillance …

Framework For Quality Assurance Of Ultrahigh Dose Rate Clinical Trials Investigating Flash Effects And Current Technology Gaps, Wei Zou, Tianyu Zhao, Walter R Bosch, Et Al.

2020-Current year OA Pubs

FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology …

Symbiotic Bacteria, Immune-Like Sentinel Cells, And The Response To Pathogens In A Social Amoeba, Trey J. Scott, Tyler J. Larsen, Debra A. Brock, So Yeon Stacey Uhm, David C. Queller, Joan E. Strassmann

2020-Current year OA Pubs

Some endosymbionts living within a host must modulate their hosts' immune systems in order to infect and persist. We studied the effect of a bacterial endosymbiont on a facultatively multicellular social amoeba host. Aggregates of the amoeba

Mapping Cortical Activations Underlying Covert And Overt Language Production Using High-Density Diffuse Optical Tomography, Mariel L Schroeder, Arefeh Sherafati, Rachel L Ulbrich, Muriah D Wheelock, Alexandra M Svoboda, Emma D Klein, Tessa G George, Kalyan Tripathy, Joseph P Culver, Adam T Eggebrecht

2020-Current year OA Pubs

Gold standard neuroimaging modalities such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and more recently electrocorticography (ECoG) have provided profound insights regarding the neural mechanisms underlying the processing of language, but they are limited in applications involving naturalistic language production especially in developing brains, during face-to-face dialogues, or as a brain-computer interface. High-density diffuse optical tomography (HD-DOT) provides high-fidelity mapping of human brain function with comparable spatial resolution to that of fMRI but in a silent and open scanning environment similar to real-life social scenarios. Therefore, HD-DOT has potential to be used in naturalistic settings where other …