Medicine and Health Sciences Commons^™

Multidimensional Biomarker Predicts Disease Control In Response To Immunotherapy In Recurrent Or Metastatic Head And Neck Squamous-Cell Carcinoma, Kevin C Flanagan, Jessica Ley, Douglas R Adkins, Eric J Duncavage, Et Al.

2020-Current year OA Pubs

PURPOSE: Anti-PD-1 therapy provides clinical benefit in 40-50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity.

METHODS: Clinical treatment and outcomes data for 103 RM-HNSCC patients were paired with RNA-sequencing data from formalin-fixed patient samples. Using logistic regression methods, we developed a novel biomarker classifier based on expression patterns in the tumor immune …

Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 At 2 Children's Hospitals, Eric E Engstrom, Alexander S Plattner, J Chase Mcneil, Kristina G Hulten, Patrick J Reich, Mary G Boyle, James J Dunn, Stephanie A Fritz, Sheldon L Kaplan

2020-Current year OA Pubs

BACKGROUND: Invasive infections caused by

METHODS: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures from July 2018 through December 2022. Admission data were used to estimate frequency. For comparison, rates of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2 were estimated by the number of positive viral test results at each institution.

RESULTS: I-CO-SA infections showed little variation in the study period. Rates of iGAS infection and IPD decreased by 46% and 44%, respectively, from 2019 to 2020, coinciding with a substantial decrease in RSV and influenza. In …

Regional Vulnerability Indices In Youth With Persistent And Distressing Psychoticlike Experiences, Nicole R Karcher, Hailey Modi, Peter Kochunov, Si Gao, Deanna M Barch

2020-Current year OA Pubs

IMPORTANCE: Distressing and persistent psychoticlike experiences (PLEs) in youth are associated with greater odds of developing psychiatric conditions in adulthood. Despite this risk, it is unclear whether early PLEs show similar brain patterns compared with adults with psychiatric and neurologic conditions.

OBJECTIVE: To examine the degree to which persistent and distressing PLEs exhibit neural metrics that show similarity to adults with chronic psychiatric and neurologic conditions.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Adolescent Brain Cognitive Development (ABCD) Study examining the persistence and distress associated with PLEs across the first 3 waves of data with baseline structural magnetic resonance …

A Not-So-Sweet Syndrome: A Case Report Of A Male Presenting With Acute Febrile Neutrophilic Dermatosis, Kim-Long R. Nguyen, Aaron J. Lacy, Suelin Hilbert, Rosanne S. Naunheim

2020-Current year OA Pubs

Physicians often encounter patients who present with a chief complaint of skin changes or lesions in both acute and primary care settings. Early initiation of appropriate treatment and pharmacotherapy in patients who present with rash is crucial to prevent decompensation, morbidity, and further downstream utilization of hospital resources. Acute febrile neutrophilic dermatosis, more commonly known as Sweet syndrome, is a rare and highly symptomatic inflammatory skin condition. Early recognition of Sweet syndrome is important as it requires specific treatment considerations and often can be a sign of an underlying pro-inflammatory condition, malignancy, or reaction to new medication that must be …

Both Horatio And Polonius: Innate Lymphoid Cells In Tissue Homeostasis And Repair, Intelly S Lee, Steven J Van Dyken

2020-Current year OA Pubs

Innate lymphoid cells (ILCs) have emerged as critical tissue-resident lymphocytes that coordinate responses to environmental stress and injury. Traditionally, their function was thought to mirror adaptive lymphocytes that respond to specific pathogens. However, recent work has uncovered a more central role for ILCs in maintaining homeostasis even in the absence of infection. ILCs are now better conceptualized as an environmental rheostat that helps maintain the local tissue setpoint during environmental challenge by integrating sensory stimuli to direct homeostatic barrier and repair programs. In this article, we trace the developmental origins of ILCs, relate how ILCs sense danger signals, and describe …

Obstetrics And Gynecology Clerkship Directors' Experiences Advising Residency Applicants, Helen K Morgan, Laura Baecher-Lind, Rashmi Bhargava, Susan Cox, Elise Everett, Angela Fleming, Scott Graziano, Chris Morosky, Celeste Royce, Tammy Sonn, Jill Sutton, Shireen Madani Sims

2020-Current year OA Pubs

BACKGROUND: The evolving landscape of application processes for obstetrics and gynecology residency applicants poses many challenges for applicants and advisors. The lack of data coordination among national groups creates crucial gaps in information for stakeholder groups.

OBJECTIVE: This study aimed to identify the current state of the advising milieu for obstetrics and gynecology residency applicants and their career advisors, the annual Association of Professors of Gynecology and Obstetrics survey focused on US clerkship directors' experiences advising students through these processes.

STUDY DESIGN: A 23-item anonymous survey was developed that asked respondents about demographics and outcomes for the students that they …

Increasing Hub Disruption Parallels Dementia Severity In Autosomal Dominant Alzheimer Disease, Jiaxin Cindy Tu, Peter R Millar, Jeremy F Strain, Andrew Eck, Babatunde Adeyemo, Alisha Daniels, Celeste Karch, Eric Mcdade, Jason Hassenstab, John Morris, Jorge J Llibre-Guerra, Laura Ibanez, Randell J Bateman, Richard J Perrin, Tammie Benzinger, Beau M Ances, Adam T Eggebrecht, Brian A Gordon, Muriah D Wheelock, Et Al.

2020-Current year OA Pubs

Hub regions in the brain, recognized for their roles in ensuring efficient information transfer, are vulnerable to pathological alterations in neurodegenerative conditions, including Alzheimer Disease (AD). Given their essential role in neural communication, disruptions to these hubs have profound implications for overall brain network integrity and functionality. Hub disruption, or targeted impairment of functional connectivity at the hubs, is recognized in AD patients. Computational models paired with evidence from animal experiments hint at a mechanistic explanation, suggesting that these hubs may be preferentially targeted in neurodegeneration, due to their high neuronal activity levels-a phenomenon termed "activity-dependent degeneration". Yet, two critical …

The Preserving Kidney Function In Children With Ckd (Preserve) Study: Rationale, Design, And Methods, Michelle R Denburg, Vikas Dharnidharka, Et Al.

2020-Current year OA Pubs

RATIONALE & OBJECTIVE: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management.

STUDY DESIGN: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]).

SETTING & PARTICIPANTS: PRESERVE will include …

Steatosis Drives Monocyte-Derived Macrophage Accumulation In Human Metabolic Dysfunction-Associated Fatty Liver Disease, Mandy M Chan, Joseph W Beals, Marina Terekhova, Christina F Fu, Li He, Arick C Park, Gordon I Smith, Kathleen Byrnes, Wandy L Beatty, Shaina R Eckhouse, J Christopher Eagon, Daniel Ferguson, Brian N Finck, Samuel Klein, Maxim N Artyomov, Joel D Schilling, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common complication of obesity with a hallmark feature of hepatic steatosis. Recent data from animal models of MAFLD have demonstrated substantial changes in macrophage composition in the fatty liver. In humans, the relationship between liver macrophage heterogeneity and liver steatosis is less clear.

METHODS: Liver tissue from 21 participants was collected at time of bariatric surgery and analysed using flow cytometry, immunofluorescence, and H&E microscopy. Single-cell RNA sequencing was also conducted on a subset of samples (n = 3). Intrahepatic triglyceride content was assessed via MRI and tissue histology. …

Pemphigoid Gestationis Treated With Dupilumab, Rita E Chen, Christine C Yokoyama, Milan J Anadkat

2020-Current year OA Pubs

No abstract provided.

Molecular Diagnostic Yield Of Exome Sequencing In Patients With Congenital Hydrocephalus: A Systematic Review And Meta-Analysis, Ana B W Greenberg, Neel H Mehta, Garrett Allington, Sheng Chih Jin, Andrés Moreno-De-Luca, Kristopher T Kahle

2020-Current year OA Pubs

IMPORTANCE: Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH).

OBJECTIVE: To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH.

DATA SOURCES: PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023. The following search terms were used to identify studies: congenital hydrocephalus, …

The Structure Of Nad+ Consuming Protein Acinetobacter Baumannii Tir Domain Shows Unique Kinetics And Conformations, Erik Klontz, Kow Essuman, Jeffrey Milbrandt, Aaron Diantonio, Et Al.

2020-Current year OA Pubs

Toll-like and interleukin-1/18 receptor/resistance (TIR) domain-containing proteins function as important signaling and immune regulatory molecules. TIR domain-containing proteins identified in eukaryotic and prokaryotic species also exhibit NAD+ hydrolase activity in select bacteria, plants, and mammalian cells. We report the crystal structure of the Acinetobacter baumannii TIR domain protein (AbTir-TIR) with confirmed NAD

Humoral Immune Response To Covid-19 Mrna Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Ofatumumab, Amit Bar-Or, Rany Aburashed, Angel R Chinea, Barry A Hendin, Elisabeth Lucassen, Xiangyi Meng, James Stankiewicz, Mark J Tullman, Anne H Cross

2020-Current year OA Pubs

BACKGROUND: There are limited data available regarding the impact of ofatumumab, an anti-CD20 B-cell-depleting monoclonal antibody for relapsing multiple sclerosis (RMS), on vaccination response. The study objective was to assess humoral immune response (HIR) to non-live coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination in patients with RMS treated with ofatumumab.

METHODS: This was an open-label, single-arm, multicenter, prospective pilot study of patients with RMS aged 18-55 years who received 2 or 3 doses of a COVID-19 mRNA vaccine after ≥1 month of subcutaneous ofatumumab (20 mg/month) treatment. The primary endpoint was the proportion of patients achieving HIR, as defined …

Advances In Screening For Radiation-Associated Cardiotoxicity In Cancer Patients, Walter Schiffer, Lauren N Pedersen, Matthew Lui, Carmen Bergom, Joshua D Mitchell

2020-Current year OA Pubs

PURPOSE OF REVIEW: Radiation is foundational to the treatment of cancer and improves overall survival. Yet, it is important to recognize the potential cardiovascular effects of radiation therapy and how to best minimize or manage them. Screening-both through imaging and with biomarkers-can potentially identify cardiovascular effects early, allowing for prompt initiation of treatment to mitigate late effects.

RECENT FINDINGS: Cardiac echocardiography, magnetic resonance imaging (MRI), computed tomography, and measurements of troponin and natriuretic peptides serve as the initial screening tests of choice for RICD. Novel imaging applications, including positron emission tomography and specific MRI parameters, and biomarker testing, including myeloperoxidase, …

Repeated Measures Of Mammographic Density And Texture To Evaluate Prediction And Risk Of Breast Cancer: A Systematic Review Of The Methods Used In The Literature, Akila Anandarajah, Yongzhen Chen, Carolyn Stoll, Angela Hardi, Shu Jiang, Graham A Colditz

2020-Current year OA Pubs

PURPOSE: It may be important for women to have mammograms at different points in time to track changes in breast density, as fluctuations in breast density can affect breast cancer risk. This systematic review aimed to assess methods used to relate repeated mammographic images to breast cancer risk.

METHODS: The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021. Eligibility criteria included published articles in English describing the relationship of change in mammographic features with risk of breast cancer. Risk of bias was assessed using the …

T Cell Control Of Inflammaging, Irina Shchukina, Pavla Bohacova, Maxim N Artyomov

2020-Current year OA Pubs

T cells are a critical component of the immune system, found in abundance in blood, secondary lymphoid organs, and peripheral tissues. As individuals age, T cells are particularly susceptible to changes, making them one of the most affected immune subsets. These changes can have significant implications for age-related dysregulations, including the development of low-grade inflammation - a hallmark of aging known as inflammaging. In this review, we first present age-related changes in the functionality of the T cell compartment, including dysregulation of cytokine and chemokine production and cytotoxicity. Next, we discuss how these changes can contribute to the development and …

Perineal Hernia As A Sequela Of Anal Reconstruction Surgeries In Perianal Crohn's Disease, Favour O Garuba, Josh M Mcphie, Rachel A Anolik, Parakkal Deepak, David H Ballard, Radhika K Smith

2020-Current year OA Pubs

Perineal hernia is a rare complication of pelvic surgeries that can occur in patients with perianal Crohn's disease (pCD) as a long-term outcome of surgeries for complex fistula treatment. We present a case of a symptomatic pCD male patient with multiple perianal surgeries who presents with anal pain, diarrhea, and discharge. Magnetic resonance imaging showed a perineal hernia in the ischioanal fossa violating the convergence of the left external sphincter complex. The hernia was treated with an open primary hernia repair via the perineal approach. It recurred after 3 months, and the patient underwent secondary hernia repair with gracilis muscle …

Parenchymal Border Macrophages Regulate Tau Pathology And Tau-Mediated Neurodegeneration, Antoine Drieu, Siling Du, Michal Kipnis, Megan E Bosch, Jasmin Herz, Choonghee Lee, Hong Jiang, Melissa Manis, Jason D Ulrich, Jonathan Kipnis, David M Holtzman, Maud Gratuze

2020-Current year OA Pubs

Parenchymal border macrophages (PBMs) reside close to the central nervous system parenchyma and regulate CSF flow dynamics. We recently demonstrated that PBMs provide a clearance pathway for amyloid-β peptide, which accumulates in the brain in Alzheimer's disease (AD). Given the emerging role for PBMs in AD, we explored how tau pathology affects the CSF flow and the PBM populations in the PS19 mouse model of tau pathology. We demonstrated a reduction of CSF flow, and an increase in an MHCII

The Association Between Reasons For First Using Cannabis, Later Pattern Of Use, And Risk Of First-Episode Psychosis: The Eu-Gei Case-Control Study, Edoardo Spinazzola, Emma C Johnson, Et Al.

2020-Current year OA Pubs

BACKGROUND: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.

METHODS: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case-control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case-control status.

RESULTS: Controls (86.1%) …

Protective Effects Of Epigallocatechin-3-Gallate Counteracting The Chronic Hypobaric Hypoxia-Induced Myocardial Injury In Plain-Grown Rats At High Altitude, Haotian Chen, Chen Chen, Yuhui Qin, Lei Wang, Jie Zheng, Fabao Gao

2020-Current year OA Pubs

Exposure to hypobaric hypoxia (HH) environment causes stress to the body, especially the oxygen-consuming organs. Chronic HH conditions have adverse effects on the myocardium. Thus, we conducted this experiment and aim to evaluate such adverse effects and explore the therapeutic role of epigallocatechin-3-gallate (EGCG) in rats' heart under chronic HH conditions. For that purpose, we transported rats from plain to a real HH environment at high altitude for establishing the HH model. At high altitude, animals were treated with EGCG while the salidroside was used as the positive control. General physiological data were collected, and routine blood test results were …

Modeling The Normal:Abnormal Spectrum Of Early Childhood Internalizing Behaviors: A Clinical-Developmental Approach For The Multidimensional Assessment Profiles Internalizing Dimensions, Lauren S Wakschlag, Phillip Sherlock, Courtney K Blackwell, James L Burns, Sheila Krogh-Jespersen, Richard C Gershon, David Cella, Kristin A Buss, Joan L Luby

2020-Current year OA Pubs

BACKGROUND: We expanded the Multidimensional Assessment Profiles (MAPS) Scales developmental specification model to characterize the normal:abnormal spectrum of internalizing (anxious and depressive) behaviors in early childhood via the MAPS-Internalizing (MAPS-INT) scale.

METHODS: The MAPS-INT item pool was generated based on clinical expertise and prior research. Analyses were conducted on a sub-sample of families (n = 183) from the diverse When to Worry early childhood sample.

RESULTS: Normal:abnormal descriptive patterns for both anxious and depressive behaviors were consistent with prior work: (1) extremes of normative variation are abnormal when very frequent; and (2) pathognomonic indicators that most children do not engage …

Clinical Course And Management Of Children With Iga Vasculitis With Nephritis, Hillarey K Stone, Vikas R Dharnidharka, Et Al.

2020-Current year OA Pubs

BACKGROUND: IgA vasculitis is the most common vasculitis in children and is often complicated by acute nephritis (IgAVN). Risk of chronic kidney disease (CKD) among children with IgAVN remains unknown. This study aimed to describe the clinical management and kidney outcomes in a large cohort of children with IgAVN.

METHODS: This observational cohort study used the PEDSnet database to identify children diagnosed with IgAV between January 1, 2009, and February 29, 2020. Demographic and clinical characteristics were compared among children with and without kidney involvement. For children followed by nephrology, clinical course, and management patterns were described. Patients were divided …

Cux1-Related Neurodevelopmental Disorder: Deep Insights Into Phenotype-Genotype Spectrum And Underlying Pathology, Henry Oppermann, Christina A Gurnett, Et Al.

2020-Current year OA Pubs

Heterozygous, pathogenic CUX1 variants are associated with global developmental delay or intellectual disability. This study delineates the clinical presentation in an extended cohort and investigates the molecular mechanism underlying the disorder in a Cux1

Long Non-Coding Rna Snhg8 Drives Stress Granule Formation In Tauopathies, Reshma Bhagat, Miguel A Minaya, Arun Renganathan, Muneshwar Mehra, Jacob Marsh, Rita Martinez, Abdallah M Eteleeb, Alissa L Nana, Salvatore Spina, William W Seeley, Lea T Grinberg, Celeste M Karch

2020-Current year OA Pubs

Tauopathies are a heterogenous group of neurodegenerative disorders characterized by tau aggregation in the brain. In a subset of tauopathies, rare mutations in the MAPT gene, which encodes the tau protein, are sufficient to cause disease; however, the events downstream of MAPT mutations are poorly understood. Here, we investigate the role of long non-coding RNAs (lncRNAs), transcripts >200 nucleotides with low/no coding potential that regulate transcription and translation, and their role in tauopathy. Using stem cell derived neurons from patients carrying a MAPT p.P301L, IVS10 + 16, or p.R406W mutation and CRISPR-corrected isogenic controls, we identified transcriptomic changes that occur …

Pigo-Cdg: A Case Study With A New Genotype, Expansion Of The Phenotype, Literature Review, And Nosological Considerations, Rodrigo Tzovenos Starosta, Nino Kerashvili, Cassandra Pruitt, Matthew J. Schultz, Suzanne W Boyer, Eva Morava, Maria Laura Duque Lasio, Dorothy K Grange

2020-Current year OA Pubs

The phosphatidylinositol glycan anchor biosynthesis class O protein (PIGO) enzyme is an important step in the biosynthesis of glycosylphosphatidylinositol (GPI), which is essential for the membrane anchoring of several proteins. Bi-allelic pathogenic variants in

Tet3 Plays A Critical Role In White Adipose Development And Diet-Induced Remodeling, Byung Chul Jung, Dongjoo You, Ikjun Lee, Daofeng Li, Rebecca L Schill, Katherine Ma, Anna Pi, Zehan Song, Wei-Chieh Mu, Ting Wang, Ormond A Macdougald, Alexander S Banks, Sona Kang

2020-Current year OA Pubs

Maintaining healthy adipose tissue is crucial for metabolic health, requiring a deeper understanding of adipocyte development and response to high-calorie diets. This study highlights the importance of TET3 during white adipose tissue (WAT) development and expansion. Selective depletion of Tet3 in adipose precursor cells (APCs) reduces adipogenesis, protects against diet-induced adipose expansion, and enhances whole-body metabolism. Transcriptomic analysis of wild-type and Tet3 knockout (KO) APCs unveiled TET3 target genes, including Pparg and several genes linked to the extracellular matrix, pivotal for adipogenesis and remodeling. DNA methylation profiling and functional studies underscore the importance of DNA demethylation in gene regulation. Remarkably, …

The Trna Methyltransferase Trmb Is Critical For Acinetobacter Baumannii Stress Responses And Pulmonary Infection, Jenna C Mcguffey, Clay D Jackson-Litteken, Gisela Di Venanzio, Aubree A Zimmer, Jessica M Lewis, Jesus S Distel, Kyusik Q Kim, Hani S Zaher, Juan Alfonzo, Nichollas E Scott, Mario F Feldman

2020-Current year OA Pubs

As deficiencies in tRNA modifications have been linked to human diseases such as cancer and diabetes, much research has focused on the modifications' impacts on translational regulation in eukaryotes. However, the significance of tRNA modifications in bacterial physiology remains largely unexplored. In this paper, we demonstrate that the m

Mycobacterium Tuberculosis Carrying The Rifampicin Drug-Resistance-Conferring Rpob Mutation H445y Is Associated With Suppressed Immunity Through Type I Interferons, Suhas Bobba, Nicole C Howard, Shibali Das, Mushtaq Ahmed, Linrui Tang, Shyamala Thirunavukkarasu, Michelle H Larsen, Barun Mathema, Maziar Divangahi, Shabaana A Khader

2020-Current year OA Pubs

This study highlights the impact of specific rifampicin-resistance-conferring mutations on the host immune response to

Application Of The Expert Recommendations For Implementing Change (Eric) Compilation Of Strategies To Health Intervention Implementation In Low- And Middle-Income Countries: A Systematic Review, Kathryn L Lovero, Christopher G Kemp, Bradley H Wagenaar, Ali Giusto, M Claire Greene, Byron J Powell, Enola K Proctor

2020-Current year OA Pubs

BACKGROUND: The Expert Recommendations for Implementing Change (ERIC) project developed a compilation of implementation strategies that are intended to standardize reporting and evaluation. Little is known about the application of ERIC in low- and middle-income countries (LMICs). We systematically reviewed the literature on the use and specification of ERIC strategies for health intervention implementation in LMICs to identify gaps and inform future research.

METHODS: We searched peer-reviewed articles published through March 2023 in any language that (1) were conducted in an LMIC and (2) cited seminal ERIC articles or (3) mentioned ERIC in the title or abstract. Two co-authors independently …

Functional Connectivity Between The Amygdala And Prefrontal Cortex Underlies Processing Of Emotion Ambiguity, Sai Sun, Hongbo Yu, Rongjun Yu, Shuo Wang

2020-Current year OA Pubs

Processing facial expressions of emotion draws on a distributed brain network. In particular, judging ambiguous facial emotions involves coordination between multiple brain areas. Here, we applied multimodal functional connectivity analysis to achieve network-level understanding of the neural mechanisms underlying perceptual ambiguity in facial expressions. We found directional effective connectivity between the amygdala, dorsomedial prefrontal cortex (dmPFC), and ventromedial PFC, supporting both bottom-up affective processes for ambiguity representation/perception and top-down cognitive processes for ambiguity resolution/decision. Direct recordings from the human neurosurgical patients showed that the responses of amygdala and dmPFC neurons were modulated by the level of emotion ambiguity, and amygdala …