Neurosciences Commons^™

Sex Differences In Inter-Temporal Decision Making And Cortical Thickness Of The Orbitofrontal And Insula In Young Adult Cannabis Users: Evidence From 1111 Subjects, Alan N. Francis, Joan A. Camprodon, Francesca Filbey

School of Medicine Publications

To test for sex differences in the impact of cannabis use on decision-making and brain correlates, we employed cortical thickness (CT) analysis of brain regions involved in intertemporal decision-making namely bilateral orbitofrontal cortex(OFC) and insula in young adult nondependent cannabis-users(CU) and non-users(NU) and their scores on delay discounting task. Neuroimaging analyzes of previously collected data were performed on 608CU and 503NU. CT analysis was performed on MRI images. OFC and insula thickness, scores on the delay discounting test were compared between groups and correlated. Controlling alcohol-use and intra-cranial-volume, CU exhibited sex differences in CT. The bilateral insula was significantly thinner …

Blood Biomarker Profiles In Young-Onset Neurocognitive Disorders: A Cohort Study, Oneil G. Bhalala, Jessica Beamish, Dhamidhu Eratne, Patrick Summerell, Tenielle Porter, Simon M. Laws, Matthew J.Y. Kang, Aamira J. Huq, Wei Hsuan Chiu, Claire Cadwallader, Mark Walterfang, Sarah Farrand, Andrew H. Evans, Wendy Kelso, Leonid Churilov, Rosie Watson, Nawaf Yassi, Dennis Velakoulis, Samantha M. Loi

Research outputs 2022 to 2026

Introduction: Young-onset neurocognitive symptoms result from a heterogeneous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the Biomarkers in Younger-Onset Neurocognitive Disorders cohort, a study of individuals < 65 years old presenting with neurocognitive symptoms for a diagnosis and who have undergone cognitive and biomarker analyses. Methods: Sixty-five participants (median age at assessment of 56 years, 45% female) were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia, and categorized as either early-onset Alzheimer’s disease (n = 18), non-Alzheimer’s disease neurodegeneration (n = 23) or primary psychiatric disorders (n = 24). Levels of neurofilament light chain, glial fibrillary acidic protein …

Effects Of Perinatal Exposure To Lipopolysaccharide And Acetaminophen On Learning In Adult Long-Evans Rats, Lucy A. Sivils

College of Graduate Studies: Theses & Dissertations

The present study investigated the individual and combined effects of elevated perinatal inflammation, oxidative stress caused by acetaminophen (APAP) exposure, or elevated inflammation and oxidative stress on adult learning behaviors in Long-Evans rats. While prior studies have examined these factors independently, the combined effects of inflammation and oxidative stress via APAP exposure during early development on learning-related behaviors remain unexplored. The present research aimed to address this gap by the analysis of potential long-term neurodevelopmental consequences of lipopolysaccharide (LPS)-induced inflammation and APAP-induced oxidative stress. LPS, APAP, or LPS + APAP was administered during the perinatal period: postnatal days (PD) 9, …

Circulating Medium- And Long-Chain Acylcarnitines Are Associated With Plasma P-Tau181 In Cognitively Normal Older Adults, Tahmida Sharmin, Pratishtha Chatterjee, James D. Doecke, Nicholas J. Ashton, Kevin Huynh, Steve Pedrini, Hamid R. Sohrabi, Benjamin Heng, Shaun Eslick, Henrik Zetterberg, Kaj Blennow, Manohar Garg, Ralph N. Martins

Research outputs 2022 to 2026

Alzheimer's disease (AD) pathogenesis involves dysregulation in diverse biochemical processes. Nevertheless, plasma tau phosphorylated at threonine 181 (P-tau181), a recognised AD biomarker, has been described to reflect early-stage cortical amyloid-β (Aβ) deposition in cognitively normal (CN) adults. Therefore, identifying changes in plasma metabolites associated with plasma P-tau181 at the pre-clinical stage may provide insights into underlying biochemical mechanisms to better understand initial AD pathogenesis. In the current study, plasma P-tau181, quantified via single molecule array (Simoa) technology, and plasma metabolites, quantified via targeted-mass spectrometry, were investigated for associations in CN older adults and upon stratification by positron emission tomography (PET)-Aβ …

Comparative Analysis Of Aav Serotypes For Transduction Of Olfactory Sensory Neurons, Benjamin D W Belfort, Johnathan D Jia, Alexandra R Garza, Anthony M Insalaco, J P Mcginnis, Brandon T Pekarek, Joshua Ortiz-Guzman, Burak Tepe, Hu Chen, Ascent-Pd Investigators, Zhandong Liu, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Olfactory sensory neurons within the nasal epithelium detect volatile odorants and relay odor information to the central nervous system. Unlike other sensory inputs, olfactory sensory neurons interface with the external environment and project their axons directly into the central nervous system. The use of adeno-associated viruses to target these neurons has garnered interest for applications in gene therapy, probing olfactory sensory neuron biology, and modeling disease. To date, there is no consensus on the optimal AAV serotype for efficient and selective transduction of olfactory sensory neurons

Dual Inhibitor Of Mdm2 And Nfat1 For Experimental Therapy Of Breast Cancer: In Vitro And In Vivo Anticancer Activities And Newly Discovered Effects On Cancer Metabolic Pathways, Wei Wang, Marlene Aguilar, Sayantap Datta, Abigail Alley, Meheret Tadesse, Xinshi Wang, Xia Gao, Ruiwen Zhang

Faculty, Staff and Students Publications

INTRODUCTION: The oncogene MDM2 has garnered attention not only for its role in cancer as a negative regulator of the tumor suppressor p53 but also for its p53-independent oncogenic activities. MDM2 also involves metabolic reprogramming, such as serine metabolism, respiration, mitochondrial functions, the folate cycle, and redox balance. Traditional MDM2 inhibitors blocking the protein-protein binding between MDM2 and p53 have shown limited clinical success in various stages of clinical trials, most likely due to low efficacy, drug toxicity, and drug resistance, highlighting the need for a novel, p53-independent strategy to inhibit MDM2. The present study investigated the antitumor effects of …

Real-World Experiences With Vmat2 Inhibitors In Pediatric Hyperkinetic Movement Disorders, Sujal Manohar, Jennifer Jacobe, Rebecca Berger, Joseph Jankovic, Mariam Hull

Faculty, Staff and Students Publications

Background: Vesicular monoamine transporter 2 (VMAT2) inhibitors are often prescribed for the treatment of hyperkinetic movement disorders such as tics, stereotypy, tardive dyskinesia and chorea. These dopamine depleters have been FDA approved in adults for the treatment of chorea in Huntington's disease and tardive dyskinesia. Use of VMAT2 inhibitors in pediatric hyperkinetic movement disorders, however, is limited due to lack of pediatric FDA approval. We review the real-world prescribing practices and patient experiences with VMAT2 inhibitors in children.

Methods: We performed a retrospective chart review of patients treated with VMAT2 inhibitors at a pediatric movement disorders clinic from 2011 to …

Improving Interprofessional Neurology Training Using Tele-Education, Fariha Jamal, Amtul Farheen, Christine Rizk

Faculty, Staff and Students Publications

Background: Neurological disorders are a leading cause of disability and death worldwide. Their burden on the health care system has substantially increased in the past 25 years, due to more effective treatments and longer life expectancies. The Veterans Health Administration has seen increases in neurology referrals and patients with neurologic disorders.

Observations: Collaborative efforts among primary care, geriatrics, neurology, psychiatry, physical medicine and rehabilitation, social work, and other disciplines are needed to properly care for veterans with neurologic disorders. Neurology education is an important tool for clinicians to better care for veterans with neurologic disorders. The use of technology and …

Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables The Detection Of Erroneous Self-Reported Energy Intake, Rania Bajunaid, Chaoqun Niu, Catherine Hambly, Zongfang Liu, Yosuke Yamada, Heliodoro Aleman-Mateo, Liam J Anderson, Lenore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Carlijn V C Bouten, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Regina Casper, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Prasangi Dabare, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Asmaa El Hamdouchi, Hinke H Haisma, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, William R Leonard, Nader Lessan, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, James C Morehen, James P Morton, Aviva Must, Marian L Neuhouser, Theresa A Nicklas, Christine D Nyström, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca Reynolds, Susan B Roberts, Dulani Samaranayakem, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Marina Stamatiou, Eric Stice, Samuel S Urlacher, Ludo M Van Etten, Edgar G A H Van Mil, George Wilson, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Srishti Sinha, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Faculty, Staff and Students Publications

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years. The resultant regression equation predicts expected TEE from easily acquired variables, such as body weight, age and sex, with 95% predictive limits that can be used …

Technical Considerations In The Tcd Evaluation Of Cerebral Circulatory Arrest In Death By Neurological Criteria, Alexandra S Reynolds, Jimmy Suh, Ahmedyar Hasan, Parth Upadhyaya, Venkatakrishna Rajajee, Mohammad I Hirzallah, David M Greer, Aarti Sarwal

Faculty, Staff and Students Publications

Background and purpose: Ancillary testing is essential for diagnosing brain death/death by neurologic criteria (BD/DNC) when clinical determination (neurologic exam and apnea testing) cannot be fully or safely performed. Transcranial Doppler ultrasound (TCD) has been recommended as an ancillary test; however, the technical descriptions have been heterogeneous. We aimed to consolidate the technical considerations related to the use of TCD as an ancillary test in the evaluation of BD/DNC.

Methods: We performed a scoping review of the available literature from inception to December 2024. Articles describing TCD as an ancillary test for BD/DNC were included using appropriate Medical Subject Headings …

Optic Nerve Sheath Diameter: Which Axis Should Be Measured?, Jakob Pansell, Tina Thomsson, Emelie Eng, Andreas Wallin, Mohammad Hirzallah

Faculty, Staff and Students Publications

Background and purpose: Optic nerve sheath diameter (ONSD) measured by point-of-care ultrasound (POCUS) is a commonly used non-invasive estimate of intracranial pressure (ICP). However, methodological variations limit standardization of this promising technique. Different imaging axes are identified as one such source of ONSD POCUS methodological variation. This study aimed to evaluate the agreement and diagnostic accuracy for elevated ICP between transverse and sagittal ONSD measurements.

Methods: We conducted a post-hoc analysis of 213 intensive care patients from three prior studies. ONSD was measured in both transverse and sagittal planes, externally (ONSDext) and internally (ONSDint) of the dura mater. Agreement was …

Purely Cystic Intraosseous Meningioma Of The Skull: A Radiologic Conundrum And Histologic Challenge, Diego Rojas, Arman Kavoussi, Ashley Rose Ricciardelli, Alex Flores, Sricharan Gopakumar, Luis Carrete, Hsiang-Chih Lu, Alex W Brenner, Akash J Patel

Faculty, Staff and Students Publications

Background: Intraosseous meningiomas and cystic meningiomas are two rare subtypes of meningiomas. Meningiomas can develop with characteristics encompassing both cystic and intraosseous, termed intraosseous cystic meningiomas, that pose a diagnostic challenge.

Case description: We report the case of a 41-year-old woman with a history of hearing loss presented with a left frontal mass that had been present for 12 years. Her history of hearing loss was in the setting of ear infections bilaterally since she was a teenager and was being evaluated by ear, nose, and throat specialists at the time. Initial cranial computed tomography (CT) identified a skull lesion …

Fractalkine Inhibition Improves Survival And Reduces Tumor Immune Cell Infiltration In Orthotopic Murine Glioma Models, Eric A Goethe, Malcolm Mcdonald, Ashley Puentes, Karina Moreno, Yuhui Yang, Khatri Latha, Ganesh Rao

Faculty, Staff and Students Publications

No abstract provided.

Opsoclonus In Alternating Hemiplegia Of Childhood Secondary To Atp1a3 Pgly803arg, Alyssa D Runco, Jesse M Levine, Cristina Trandafir, Rod Foroozan, Mered Parnes, Daniel G Calame

Faculty, Staff and Students Publications

No abstract provided.

Isolated Calvarial Lesion As The Initial Presentation Of Metastatic Hepatocellular Carcinoma: A Case Report And Review Of The Literature, Jeffrey Wu Chen, Nisha Giridharan, Arman A Kavoussi, Dawn Van Arsdale, Shervin Hosseingholi Nouri, Vijay Nitturi, Trevor Trudeau, Jacob J Mandel, Hsiang-Chih Lu, Akash J Patel

Faculty, Staff and Students Publications

Background: Hepatocellular carcinoma (HCC) contributes significantly to global cancer-related mortality, often because patients present at advanced stages of the disease. HCC commonly metastasizes to the lung, abdominal lymph nodes, and bone. However, even among bony metastases, calvarial lesions are exceptionally rare, especially in the initial presentation.

Case description: We describe a unique case of a 65-year-old African American woman who presented with a rapidly growing skull lesion as her first clinical sign of metastatic HCC. Imaging revealed an extensive soft-tissue mass involving the left calvaria and partially obstructing the superior sagittal sinus. We suspected that the lesion was a meningioma …

A Model To Address Healthcare Gaps And Poor Research Participation In Hispanic Patients With Parkinson’S Disease, M Felice Ghilardi, Alessandro Di Rocco, Jennifer Fearday, Donna Sperlakis, Maria Lima, Nora Vanegas-Arroyave, Elisa Tatti, Marcelo Arroyave, Evelyn Stevens, Denise Hernandez, Paulina Latapi-Gonzalez, Meri-Margaret Deoudes, Christiana Evers

Faculty, Staff and Students Publications

Parkinson's disease (PD), a progressive neurodegenerative disorder, manifests with motor and non-motor symptoms. Despite similar incidence, in the US, disease management of Hispanic patients with PD is poorer than that of White non-Hispanics, and their participation in clinical trials does not reflect expected values (well below 5% vs. expected values around 20%). Together with other evidence, these observations are expressions of poor healthcare in Hispanic patients with PD, suggesting underutilization of proper healthcare, social and economic disadvantage, and other factors. The scant participation of Hispanic patients in clinical trials further exacerbates care inadequacy. In this paper, after reviewing evidence of …

Validation Of The Polish Version Of The Movement Disorder Society Non-Motor Rating Scale (Mds-Nms), Joanna Siuda, Mateusz Toś, Tomasz Chmiela, Andrzej Bogucki, Barbara Borodziuk, Sławomir Budrewicz, Marek Dąbrowski, Marceli Gacan, Agata Gajos, Justyna Gawryluk, Piotr Janik, Justyna Kaczyńska, Ewa Koziorowska-Gawron, Jakub Malkiewicz, Ewa Papuć, Paulina Kaczmarska, Monika Rudzińska-Bar, Jarosław Sławek, Magdalena Wójcik-Pędziwiatr, Luowen Yu, Sheng Luo, Christopher Goetz, Glenn Stebbins, Pablo Martinez-Martin, Tiago Mestre, Alvaro Sanchez-Ferro, Monika Kurtis, Michelle Hyczy De Siqueira Tosin, Roberta Balestrino, Chi-Ying Roy Lin, Carmen Gasca-Salas

Faculty, Staff and Students Publications

Aim of the study: We aimed to translate and validate the Polish version of the MDS-NMS and compare it with the original English version.

Clinical rationale for the study: Non-motor symptoms (NMS) affect a significant portion of the Parkinson's disease (PD) patient population and may negatively impact their quality of life. Non-motor symptoms may contribute to an increased sense of illness among patients and to a greater burden upon their caregivers. It is therefore advisable to develop a Polish validation of a reference scale for diagnosing and assessing the severity of NMS.

Material and methods: The MDS-NMS was translated into …

Pregnancy In Dystonia Or Tourette's Patients With Dbs Fourteen News Cases And A Review Of The Literature, Raja Mehanna, Arjun Tarakad, Lisa Yutong Taneff, Erin Furr Stimming

Faculty, Staff and Students Publications

Background: Deep Brain Stimulation (DBS) has been demonstrated to improve quality of life in patients with refractory dystonia and Tourette's syndrome (TS). Because of the young age at onset of these disorders, and the marked benefit from DBS, pregnancy in patients who have received DBS is becoming a more frequent clinical occurrence, although clear management guidelines are lacking.

Cases: We report 14 new pregnancies in patients with dystonia or TS and DBS.

Literature review: Upon review of the literature, 23 pregnancies in patients with dystonia or TS were previously reported in seven articles.

Conclusion: Based on the available data from …

Early Cerebrospinal Fluid Elevations Of Ptau-217 In Severe Traumatic Brain Injury Subjects, Hamad Yadikar, Firas H Kobeissy, Claudia Robertson, Spyridoula Tsetsou, John B Williamson, Damon G Lamb, Amy K Wagner, Todd Kibaugh, Shih-Han Kao, Zhifeng Kou, Robert D Welch, Jose-Miguel Yamal, Luis Leon-Novelo, Richard Rubenstein, Kevin K W Wang

Faculty, Staff and Students Publications

Introduction: Tauopathies, including Alzheimer's disease (AD), feature abnormal accumulations of hyperphosphorylated Tau protein; however, their biomarker potential in traumatic brain injury (TBI) is not well-defined. This study investigated whether cerebrospinal fluid (CSF) phosphorylated Tau at threonine-217 (pTau-217) could serve as an early biomarker for severe TBI (sTBI).

Methods: CSF samples from 26 sTBI patients, collected between 6 and 240 h post-injury, and 19 healthy controls were analyzed using an optimized direct enzyme-linked immunosorbent assay (ELISA; sensitivity < 4.7 pg/mL) for pTau-217 detection, complemented by Western blot validation. Temporal analysis, ROC curves, and trajectory clustering were used for interpretation.

Results: CSF pTau-217 levels were significantly elevated in sTBI patients at 6, 12, 18, 24, and 48 h post-injury compared to controls (p …

Inferred Developmental Origins Of Brain Tumors From Single-Cell Rna-Sequencing Data, Su Wang, Rachel Naomi Curry, Malcolm F Mcdonald, Hyun Yong Koh, Anders W Erickson, Claudia L Kleinman, Michael D Taylor, Ganesh Rao, Benjamin Deneen, Arif O Harmanci, Akdes Serin Harmanci

Faculty, Staff and Students Publications

Background: The reactivation of neurodevelopmental programs in cancer highlights parallel biological processes that occur in both normal development and brain tumors. Achieving a deeper understanding of how dysregulated developmental factors play a role in the progression of brain tumors is therefore crucial for identifying potential targets for therapeutic interventions. Single-cell RNA-sequencing (scRNA-Seq) provides an opportunity to understand how developmental programs are dysregulated and reinitiated in brain tumors at single-cell resolution. The aim of this study is to identify the developmental origins of brain tumors using scRNA-Seq data.

Methods: Here, we introduce COORS (Cell Of ORigin like CellS), a computational tool …

Vascularized Iliac Crest Bone Graft For The Reconstruction Of Anterior Vertebral Corpus Defects: A Literature Review And Cadaveric Feasibility Study, Jonathan L Jeger, Casey J Martinez, Maria Shvedova, Alec Simoni, Alanna Rebecca, Sebastian Winocour, Alexander E Ropper, Michael Bohl, William J Casey, Maziyar Kalani, Edward M Reece

Faculty, Staff and Students Publications

BACKGROUND: Vertebral body defects pose a significant challenge in spinal reconstructive surgery. Compression fractures of the vertebral corpus are typically treated with vertebral augmentation procedures. There are significant risks associated with the introduction of foreign material in the spine, including infection and pseudarthrosis. Vascularized bone grafts (VBGs) have become a popular alternative for spinal reconstruction in the last decade thanks to their robust blood supply and autologous nature. VBGs have been described predominantly for the reconstruction of posterior vertebral defects. The objective of this study is to describe a novel procedure for the reconstruction of vertebral corpus defects in the …

Aerodigestive Sequelae And Triple Endoscopy After Congenital Tracheoesophageal Fistula Repair In Children, Whitney Jin, Eric H Chiou, Shailendra Das, Kathleen E Hosek, Elton M Lambert

Faculty, Staff and Students Publications

Children post-tracheoesophageal fistula (TEF) repair may present with chronic respiratory and gastrointestinal symptoms that can affect quality of life.

OBJECTIVE: To identify factors associated with positive findings on triple endoscopy following neonatal TEF repair.

STUDY DESIGN: Case series with retrospective review of patients.

SETTING: Tertiary care center aerodigestive program.

METHODS: Children with neonatally repaired congenital TEF who had a triple endoscopy between 2011 and 2022 were reviewed. The presence of chronic cough, recurrent pulmonary infections, lipid-laden macrophages (LLM), and airway and esophageal anomalies were among the variables analyzed. Chi-square and Kruskal-Wallis univariate analysis was performed.

RESULTS: The mean age was …

Glutamatergic Lateral Habenula Neurons Modulate Consolidation Of Associative Memories, Snigdha Srivastava, I-Ching Wang, Mikhail Y Kochukov, Jessica L Swanson, Mauro Costa-Mattioli, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

INTRODUCTION: Despite the rise in psychiatric disorders worldwide, the underlying brain circuits responsible for these devastating conditions remain elusive. The lateral habenula (LHb) has emerged as a key brain structure in depression studies due to its hyperactive state in both patients and animal models. While this aligns with known roles in driving aversive states and regulating serotonin release, it is still unclear how acute and transient activity changes in the LHb can influence higher order cognitive processes such as learning, memory, and behavioral adaptation. Given the importance of these processes to psychiatric conditions, understanding how LHb activity impacts cognitive function …

Resort Enhances Reference-Based Cell Type Deconvolution For Spatial Transcriptomics Through Regional Information Integration, Linhua Wang, Ling Wu, Guantong Qi, Chaozhong Liu, Wanli Wang, Xiang H-F Zhang, Zhandong Liu

Duncan NRI Faculty and Staff Publications

Motivation: Spatial transcriptomics (ST) captures positional gene expression within tissues but lacks single-cell resolution. Reference-based cell type deconvolution methods were developed to understand cell type distributions for ST. However, batch/platform discrepancies between references and ST impact their accuracy.

Results: We present Region-based Cell Sorting (ReSort), which utilizes ST's region-level data to lessen reliance on reference data and alleviate these technical issues. In simulation studies, ReSort enhances reference-based deconvolution methods. Applying ReSort to a mouse breast cancer model highlights macrophages M0 and M2 enrichment in the epithelial clone, revealing insights into epithelial-mesenchymal transition and immune infiltration.

Availability and implementation: Source codes …

Recurrent Carotid Paragangliomas In A Syndromic Patient With A Heterozygous Missense Variant In Dna Methyltransferase 3 Alpha, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Lisa Saba, Robin Fletcher, Matthew L Tedder, Bekim Sadikovic, Jennifer Kerkhof, Michael Wangler, Carlos A Bacino

Duncan NRI Faculty and Staff Publications

We report a 40-year-old African American female with a novel variant in exon 8 of DNA methyltransferase 3 alpha (DNMT3A), (NM_022552.4: c.905G>C, p.G302A) who presented with a history of recurrent carotid paragangliomas, mediastinal mass, intellectual disability, dysarthria, cholelithiasis, diabetes mellitus, hypertension, and dysmorphic features. We interpret this novel variant as likely pathogenic and causative for the patient's syndromic features of Heyn-Sproul-Jackson syndrome. Heyn-Sproul-Jackson syndrome is a condition caused by gain-of-function genetic changes in DNMT3A. Paragangliomas have also been observed in non-syndromic patients with genetic alterations in DNMT3A. We describe a patient with clinical features of Heyn-Sproul-Jackson syndrome such as …

Analysis Of 1,25-Dihydroxyvitamin D Genomic Action In Human Enteroids And Colonoids Reveals Multiple Regulatory Effects Of Vitamin D In Human Intestinal Physiology, Zachary K Criss, Kali Deans-Fielder, James C Fleet, Sylvia Christakos, Noah Shroyer

Faculty, Staff and Students Publications

Introduction: The intestine has molecular and functional diversity across the proximal-distal and the crypt-villus axes, so it is imperative to determine the common and compartment-specific molecular actions of vitamin D. However, very little work on vitamin D mediated gene regulation has been done in normal human intestine. Here, we examined the impact of 1,25-dihydroxyvitamin D (1,25(OH)2D3) on cultures of human intestinal epithelium derived from duodenum (Dd) and distal colon (Co) biopsies of 6 subjects per tissue.

Methods: Human enteroids and colonoids were cultured for 3 days to promote a stem cell phenotype (undifferentiated, Un) or to induce differentiation (Diff) and …

Pattern Integration And Differentiation: Dual Process Model Of Episodic Memory, Hallvard Røe Evensmoen, Lars M. Rimol, Henning Stople Rise, Tor Ivar Hansen, Hamed Nili, Anderson M. Winkler, Asta K. Håberg

Human Genetics Publications

The role of precise timing in episodic memory remains obscure. We showed 139 participants episodes consisting of objects, and tested subsequent memory for the precise timing and order of the objects and episodes. Temporal compression of the episode enhanced memory for relative but not absolute timing of the objects’ presentation and their order. Conversely, temporal expansion between neighboring episodes was associated with successful memory for episode order. fMRI in 36 participants revealed that temporal compression of the episode was associated with more similar activation patterns within episodes in several brain regions including the posterior hippocampus. However, the activation pattern in …

Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables The Detection Of Erroneous Self-Reported Energy Intake, Rania Bajunaid, Chaoqun Niu, Catherine Hambly, Zongfang Liu, Yosuke Yamada, Heliodoro Aleman-Mateo, Liam J Anderson, Lenore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Carlijn V C Bouten, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Regina Casper, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Prasangi Dabare, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Asmaa El Hamdouchi, Hinke H Haisma, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, William R Leonard, Nader Lessan, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, James C Morehen, James P Morton, Aviva Must, Marian L Neuhouser, Theresa A Nicklas, Christine D Nyström, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca Reynolds, Susan B Roberts, Dulani Samaranayakem, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Marina Stamatiou, Eric Stice, Samuel S Urlacher, Ludo M Van Etten, Edgar G A H Van Mil, George Wilson, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Srishti Sinha, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Faculty, Staff and Students Publications

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years. The resultant regression equation predicts expected TEE from easily acquired variables, such as body weight, age and sex, with 95% predictive limits that can be used …

Survey And Improvement Strategies For Gene Prioritization With Large Language Models, Matthew B Neeley, Guantong Qi, Guanchu Wang, Ruixiang Tang, Dongxue Mao, Chaozhong Liu, Sasidhar Pasupuleti, Bo Yuan, Fan Xia, Pengfei Liu, Zhandong Liu, Xia Hu

Duncan NRI Faculty and Staff Publications

Motivation: Rare diseases remain difficult to diagnose due to limited patient data and genetic diversity, with many cases remaining undiagnosed despite advances in variant prioritization tools. While large language models have shown promise in medical applications, their optimal application for trustworthy and accurate gene prioritization downstream of modern prioritization tools has not been systematically evaluated.

Results: We benchmarked various language models for gene prioritization using multi-agent and Human Phenotype Ontology classification approaches to categorize patient cases by phenotype-based solvability levels. To address language model limitations in ranking large gene sets, we implemented a divide-and-conquer strategy with mini-batching and token limiting …

Drosophila Models Uncover Substrate Channeling Effects On Phospholipids And Sphingolipids In Peroxisomal Biogenesis Disorders, Michael F Wangler, Yu-Hsin Chao, Mary Roth, Ruth Welti, James A Mcnew

Duncan NRI Faculty and Staff Publications

Peroxisomal Biogenesis Disorders Zellweger Spectrum (PBD-ZSD) disorders are a group of autosomal recessive defects in peroxisome formation that produce a multi-systemic disease presenting at birth or in childhood. Well documented clinical biomarkers such as elevated very long chain fatty acids (VLCFA) are key biochemical diagnostic findings in these conditions. Additional, secondary biochemical alterations such as elevated very long chain lysophosphatidylcholines are allowing newborn screening for peroxisomal disease. In addition, a more widespread impact on metabolism and lipids is increasingly being documented by metabolomic and lipidomic studies. Here we utilize Drosophila models of pex2 and pex16 as well as human plasma …