Digital Commons Network^™

Spatial Colocalization And Molecular Crosstalk Of Myofibroblastic Cafs And Tumor Cells Shape Lymph Node Metastasis In Oral Squamous Cell Carcinoma, Ken Furudate, Shuya Kasai, Tadashi Yoshizawa, Yuya Sasaki, Kohei Fujikura, Shintaro Goto, Ryohei Ito, Koki Takagi, Tomoyuki Tanaka, Hiroshi Kijima, Kosei Kubota, Ken Itoh, Wataru Kobayashi, Koichi Takahashi

Faculty, Staff and Student Publications

Lymph node metastasis (LNM) is a critical prognostic factor for patients with oral squamous cell carcinoma (OSCC). Previous research has implicated the partial epithelial-to-mesenchymal transition of tumor cells and myofibroblastic cancer-associated fibroblasts (myCAFs) in the LNM process. However, the underlying molecular mechanisms remain poorly understood. Here, we conducted a comprehensive molecular analysis integrating original and publicly available OSCC data from bulk genome and transcriptome, single-cell transcriptome, and spatial transcriptome analyses. We found that myCAFs were quantitatively and functionally activated in LNM-positive samples and spatially colocalized with OSCC cells within the invasive tumor front (ITF), providing a niche that may facilitate …

Dna Methylation Cooperates With Genomic Alterations During Non-Small Cell Lung Cancer Evolution, Francisco Gimeno-Valiente, Carla Castignani, Elizabeth Larose Cadieux, Nana E Mensah, Xiaohong Liu, Kezhong Chen, Olga Chervova, Takahiro Karasaki, Clare E Weeden, Corentin Richard, Siqi Lai, Carlos Martínez-Ruiz, Emilia L Lim, Alexander M Frankell, Thomas B K Watkins, Georgia Stavrou, Ieva Usaite, Wei-Ting Lu, Daniele Marinelli, Sadegh Saghafinia, Gareth A Wilson, Pawan Dhami, Heli Vaikkinen, Jonathan Steif, Selvaraju Veeriah, Robert E Hynds, Martin Hirst, Crispin Hiley, Andrew Feber, Özgen Deniz, Mariam Jamal-Hanjani, Nicholas Mcgranahan, Tracerx Consortium, Stephan Beck, Jonas Demeulemeester, Miljana Tanić, Charles Swanton, Peter Van Loo, Nnennaya Kanu

Faculty, Staff and Student Publications

Aberrant DNA methylation has been described in nearly all human cancers, yet its interplay with genomic alterations during tumor evolution is poorly understood. To explore this, we performed reduced representation bisulfite sequencing on 217 tumor and matched normal regions from 59 patients with non-small cell lung cancer from the TRACERx study to deconvolve tumor methylation. We developed two metrics for integrative evolutionary analysis with DNA and RNA sequencing data. Intratumoral methylation distance quantifies intratumor DNA methylation heterogeneity. MR/MN classifies genes based on the rate of hypermethylation at regulatory (MR) versus nonregulatory (MN) CpGs to identify driver genes exhibiting recurrent functional …

The Brescia International Multidisciplinary Consensus Guidelines On The Optimal Pathology Assessment And Multidisciplinary Pathways Of Non-Pancreatic Neoplasms In And Around The Ampulla Of Vater (Peripan), Mohammad Abu Hilal, Bas A Uijterwijk, Daniël H L Lemmers, Boris V Janssen, Marc G Besselink, Denise Bianchi, Arantza Fariña, Noriyoshi Fukushima, Anthony J Gill, Seung-Mo Hong, Alyssa Krasinskas, Claudio Luchini, Laura Melocchi, Giulio Rossi, Aldo Scarpa, Olca Basturk, Deyali Chatterjee, Angela Chou, Irene Esposito, Roger Feakins, Bas Groot Koerkamp, Ralph H Hruban, Stefano La Rosa, Chanjuan Shi, Aatur Singhi, Joanne Verheij, Huamin Wang, Sergio Alfieri, Fabio Ausania, Adnan Alseidi, Marco J Bruno, Ugo Boggi, Claudio Bnà, Christos Dervenis, Massimo Falconi, Michele Ghidini, Jakob W Kist, Giovanni Marchegiani, Michele Milella, Roberto Salvia, Ajith Siriwardena, Hanneke Wilmink, Alberto Zaniboni, Shaimaa Al-Janabi, Maia Blomhoff Holm, Eva Roos, Naoki Sano, In Hye Song, Zeynep Tarcan, Gianpaolo Balzano, Isabella Frigerio, Alfredo Guglielmi, Giuseppe Malleo, Horacio Asbun, Volkan Adsay, Caroline Verbeke

Faculty, Staff and Student Publications

IMPORTANCE: The lack of multidisciplinary workflow guidelines and clear definitions and classifications for neoplasms in and around the ampulla of Vater results in inconsistencies affecting patient care and research.

OBJECTIVE: The PERIPAN international multidisciplinary consensus group aimed to standardize the multidisciplinary diagnostic workflow and achieve consensus on definitions and classifications in order to ensure proper classification and optimal diagnostic assessment and consequently to improve patient care and future research.

DESIGN: An international team of 43 experts (pathologists, surgeons, radiologists, gastroenterologists, oncologists) from 12 countries identified knowledge gaps, reviewed 37061 articles, and proposed recommendations using the Scottish Intercollegiate Guidelines Network methodology …

Lifecycles Of Cochrane Systematic Reviews (2003-2024): A Bibliographic Study, Shiyin Li, Chong Wu, Zichen Zhang, Mengli Xiao, Mohammad Hassan Murad, Lifeng Lin

Faculty, Staff and Student Publications

Background and objectives: The relevance of Cochrane systematic reviews depends on timely completion and updates. This study aimed to empirically assess the lifecycles of Cochrane reviews published from 2003 to 2024, including transitions from protocol to review, update patterns, and withdrawals.

Methods: We extracted data from Cochrane Library publications between 2003 and 2024. Each review topic was identified using a unique six-digit DOI-based ID. We recorded protocol publication, review publication, updates, and withdrawals (i.e., removed from the Cochrane Library for editorial or procedural reasons), calculating time intervals between stages and conducting subgroup analyses by review type.

Results: Of 8137 protocols, …

High-Resolution Peripheral Quantitative Computed Tomography Reliability And Accuracy Of Bone Density And Morphology Properties In Children, Roman J Shypailo, Chadi Calarge, Punam K Saha, Xiaoliu Zhang, Xiaojie Chen, Stephanie Dinh, Xiaofan Huang, Babette S Zemel, Fida Bacha

Faculty, Staff and Students Publications

Volumetric bone density, microarchitecture, and strength measures using HR-pQCT are valuable measures of bone health in pediatrics. Our cross-sectional study evaluated bone measure reproducibility in pediatric participants using repeat HR-pQCT (XtremeCT II, Scanco Medical) scans of non-dominant distal tibia and radius of 30 healthy children and adolescents (7-17 yr, 47% female) by 2 technicians. Additionally, we examined HR-pQCT and micro-CT of 26 cadaveric distal tibia specimens to evaluate agreement between the modalities. All HR-pQCT scans were analyzed using manufacturer-provided software (Image Processing Language, Scanco Medical) and a fully automated, previously validated, in-house algorithm, offering measures of bone microstructure (eg, trabecular …

Folliculin Deletion In The Mouse Kidney Results In Cystogenesis Of The Loops Of Henle Via Aberrant Tfeb Activation, Ola Shalaby, Tomoko Ohmori, Koichiro Miike, Shunsuke Tanigawa, Luh Ade Wilan Krisna, Alessia Calcagnì, Andrea Ballabio, Yoshiaki Kubota, Laura S Schmidt, W Marston Linehan, Takaaki Ito, Masaya Baba, Ryuichi Nishinakamura

Duncan NRI Faculty and Staff Publications

The mammalian kidney contains numerous nephrons connected to the collecting ducts, and each nephron consists of a glomerulus, a proximal tubule, the loop of Henle (LoH), and a distal tubule. Folliculin (FLCN) is a causative gene for Birt-Hogg-Dubé syndrome, which is characterized by a variety of manifestations, including renal cysts and cancer. Although deletion of Flcn in the mouse collecting duct and distal nephron leads to cyst formation, its precise role in the entire nephron remains unclear. Herein, nephron-specific Flcn knockout mice exhibited cystogenesis along the entire nephron segments, most prominent in the LoH, preceded by an irregularly shaped lumen …

Excision And Regional Flap Reconstruction With Radiation Therapy Of Granuloma Annulare Of The Digit: A Case Report, Austin Y Jiang, Linda K Green, David Netscher

Faculty, Staff and Students Publications

Granuloma annulare (GA) is a benign, often self-limited granulomatous skin condition that typically resolves spontaneously. Treatment is often not required, but topical and injectional corticosteroids are the most common interventions. Excision is effective for diagnosis and temporary treatment, but usually not considered curative. This case report describes the unconventional treatment of a recurrent biopsy-proven GA of the index finger. Due to the combination of the recalcitrant nodules interfering with function and patient preference, the nodules were excised multiple times. Ultimately requiring reconstruction with a pedicled radial forearm flap, the patient thereafter received radiation therapy to prevent recurrence, the combination of …

2d Speckle Tracking Strain Echocardiography In Multisystem Inflammatory Syndrome In Children: A Multicenter Analysis From The Music Study, Francesca Sperotto, Valiantsina Kazlova, Felicia L Trachtenberg, Dongngan T Truong, Sanjeev Aggarwal, Joseph R Block, Tamara T Bradford, Sujatha Buddhe, Audrey Dionne, Andreea Dragulescu, Kanwal M Farooqi, Daniel E Forsha, Therese M Giglia, Ian F Golding, Keren Hasbani, Pei-Ni Jone, Anita Krishnan, Sean M Lang, Carol A Mcfarland, Elizabeth C Mitchell, Elias Moussi Saad, Todd T Nowlen, Ricardo H Pignatelli, Scott Pletzer, Ryan Serrano, Divya Shakti, Shubhika Srivastava, Thor Thorsson, Jodie K Votava-Smith, Hunter C Wilson, Jane W Newburger, Kevin G Friedman

Faculty, Staff and Students Publications

Background: 2D-speckle tracking echocardiography may help detect subclinical ventricular dysfunction, but data in multisystem inflammatory syndrome in children (MIS-C) are scarce. We investigated left ventricular (LV) strain parameters in MIS-C and their association with outcomes.

Methods: We performed an ambi-directional, 32-center cohort study on hospitalized patients with MIS-C (March 2020-November 2021) with at least 1 echocardiogram read by the Core Lab. Generalized estimating equation modeling was used to test associations between LV strain and a composite in-hospital adverse cardiovascular outcome (vasoactive support, arrhythmias, cardiac arrest, extracorporeal support, death, or heart transplant).

Results: Of 349 patients (median age, 8.7 years [interquartile …

Changes In Child Placement After Child Abuse Pediatrics Consultation For Suspected Physical Abuse, Kristine A Campbell, Antoinette L Laskey, Daniel M Lindberg, M Katherine Henry, Porcia Vaughn, James D Anderst, Megan M Letson, Angela N Bachim, Nancy S Harper, Carmen M Coombs, Lori D Frasier, Joanne N Wood

Faculty, Staff and Students Publications

Background: The association between child abuse pediatric (CAP) assessments and child welfare outcomes is unknown.

Objective: To determine the association between a CAP determination of the likelihood of physical abuse and change in child placement. We hypothesized that child race would be associated with CAP determination of abuse likelihood and child welfare outcomes.

Participants and setting: Children under age ten years with in-person CAP consultation and referral to child protective services for suspected physical abuse at a U.S. pediatric referral center participating in CAPNET, a CAP research network, from 02/2021 to 01/2023.

Methods: We created a series of generalized estimating …

A Phase 2 Randomized Trial Of Nbi-1065846 (Tak-041) In Patients With Anhedonia Associated With Major Depressive Disorder: Results Of The Terpsis Study, Shannon R Benedetto, Adrian Ionescu, Tingting Ge, Maura Furey, Swan Lin, Manish K Jha, Andrew Krystal, Asim A Shah, David P Walling, Neel Shah, Sakina J Rizvi, Sidney Kennedy, Antonio Laurenza, Venkatesha Murthy, Eiry Roberts, Jaskaran B Singh

Faculty, Staff and Students Publications

Background: Anhedonia is a core symptom of major depressive disorder (MDD) that may result from aberrant lateral habenula hyperactivity. Targeting G-protein coupled receptor 139 (GPR139) may improve anhedonia by modulating lateral habenula activity. NBI-1065846 is an investigational GPR139 agonist that improved anhedonia, anxiety, and depression in rodent models.

Methods: TERPSIS was a phase 2, proof-of-concept clinical study. Adults with MDD experiencing a major depressive episode with anhedonia were randomized 1:1 to NBI-1065846 or placebo for 8 weeks. The primary endpoint was the change in the Dimensional Anhedonia Rating Scale (DARS) score. Secondary endpoints were change in total Montgomery Åsberg Depression …

Comparative Effectiveness Of En-Bloc Vs Conventional Transurethral Resection For Non-Muscle-Invasive Bladder Cancer A Systematic Review And Meta-Analysis, David E Hinojosa-Gonzalez, Gal Saffati, Troy La, Jackson Cathey, Juan C Angulo-Lozano, Gustavo Salgado-Garza, Jonathan Walsh, Bailey Slawin, Shane Kronstedt, Kate Lowrey, Jeremy R Slawin

Faculty, Staff and Students Publications

Introduction: Transurethral en-bloc resection of bladder tumor (ERBT) has emerged as an alternate technique to conventional transurethral resection of bladder tumor (cTURBT). While theoretically advantageous, the comparative effectiveness of ERBT across various technical approaches remains unclear. We performed an updated systematic review and meta-analysis to evaluate perioperative, pathologic, and oncologic outcomes of ERBT vs. cTURBT.

Methods: We systematically searched PubMed, EMBASE, Scopus, and Google Scholar for randomized controlled trials (RCTs) comparing ERBT and cTURBT. The primary outcome was recurrence-free survival (RFS). Secondary outcomes were operative time, complication rates, detrusor muscle presence, and need for repeated resection. Meta-analyses were performed, with …

Optical Coherence Tomography Enables The Depth-Resolved Measurement Of Cilia Beat Frequency In Ex Vivo Human Fallopian Tubes, Dilara J Long, Tian Xia, Photini F Rice, Deirdre M Scully, Makayla Johnson, Ryan Mistifer, Andrea Aguirre, John M Heusinkveld, Irina V Larina, Jennifer K Barton

Faculty, Staff and Students Publications

Objectives: The movement of cilia in the fallopian tubes (FTs) facilitates important processes involved in fertility, and abnormalities in cilia function are linked with diseases including endometriosis and pelvic inflammatory disease. For the first time, we demonstrate the use of optical coherence tomography (OCT) to create depth-resolved mapping of motile cilia locations and quantify cilia beat frequency (CBF) in human FT samples ex vivo.

Methods: Segments of the FT ampulla were acquired from five patients following salpingectomy under an IRB approved protocol. The samples were longitudinally opened to expose the luminal surface for imaging. A sequence of at least 500 …

Pancrelipase Treatment Of Exocrine Pancreatic Insufficiency Due To Chronic Pancreatitis: Rationale And Methodology Of A Real-World, Prospective, Observational Study, Mohamed O Othman, Jens J Kort, Tamas A Gonda, Guru Trikudanathan, Darshan J Kothari, Walter Park, Luis F Lara, Moming Li, Diala Harb

Faculty, Staff and Students Publications

No abstract provided.

Bone Quality Response To Lifestyle Intervention In Older Adults With Obesity (Limb-Q Trial): A Randomised Controlled Trial, Giulia Gregori, Sanjay Mediwala, Michael Liebschner, Daeseung Kim, Mon S Bryant, Nina Klonis, Reina Armamento-Villareal, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

Background: Lifestyle interventions for weight loss might exacerbate age-related bone loss and osteoporosis. However, there is limited knowledge about their effects on bone quality. We examined whether lifestyle intervention can preserve or enhance bone quality, despite reductions in bone mineral density.

Methods: The Lifestyle Intervention to Improve Bone Quality (LIMB-Q) study was a randomised controlled trial conducted at Baylor College of Medicine and the Michael E DeBakey VA Medical Center (Houston, TX, USA) including older adults (aged 65-85 years) with obesity (BMI ≥30 kg/m2). Participants were randomly assigned to receive either an intensive lifestyle intervention (intensive lifestyle group, consisting of …

Optimal Head-Of-Bed Positioning Before Thrombectomy In Large Vessel Occlusion Stroke: A Randomized Clinical Trial, Anne W Alexandrov, Anne J Shearin, Pitchaiah Mandava, Gabriel Torrealba-Acosta, Cheran Elangovan, Balaji Krishnaiah, Katherine Nearing, Elizabeth Robinson, Cara Guthrie-Chu, Matthew Holzmann, Bryan Fill, Dharti R Trivedi, Alicia Richardson, Sandy Middleton, Barbara B Brewer, David S Liebeskind, Nitin Goyal, James C Grotta, Andrei V Alexandrov

Faculty, Staff and Students Publications

Importance: Small studies show that 0° head positioning of patients with large vessel occlusion (LVO) stroke improves penumbral blood flow and clinical stability. Understanding whether 0° head position maintains clinical stability would allow for optimal patient positioning before thrombectomy.

Objective: To determine superiority of 0° over 30° head positioning at maintaining clinical stability in patients with LVO before thrombectomy.

Design, setting, and participants: This was a prospective randomized clinical trial with blinding to study enrollment/end points conducted from May 2018 to November 2023. There were 3 planned interim analyses, and the study was conducted at certified thrombectomy hospitals in the …

Cognitive Performance In Early Neuronal Synuclein Disease With Hyposmia But Without Motor Disability: Association With Dopamine Deficiency And Isolated Rapid Eye Movement Sleep Behavior Disorder, Daniel Weintraub, Anuprita R Nair, Ryan Kurth, Michael C Brumm, Christine Kohnen, Michele K York, Roseanne D Dobkin, Kenneth Marek, Caroline Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana M Chahine, Christopher Coffey, Kalpana Merchant, Kathleen L Poston, Tatiana Foroud, Brit Mollenhauer, Ethan G Brown, Karl Kieburtz, Mark Frasier, Sohini Chowdhury, Roy N Alcalay, Aleksandar Videnovic, Parkinson's Progression Markers Initiative

Faculty, Staff and Students Publications

Objective: To determine the impact of dopamine deficiency and isolated rapid eye movement (REM) sleep behavior disorder (iRBD) on cognitive performance in early neuronal α-synuclein disease (NSD) with hyposmia but without motor disability.

Methods: Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) derived from robust healthy control (HC) norms. Performance was examined for participants with hyposmia in early NSD-Integrated Staging System (NSD-ISS), either stage 2A (cerebrospinal fluid α-synuclein seed amplification assay [SAA]+, dopamine transporter scan [DaTscan]-) or 2B (SAA+, DaTscan+).

Results: Participants were stage 2A (n = 101), stage 2B (N …

A Prospective, Randomized, Controlled Clinical Trial Of High-Frequency Electromagnetic Coupling Powered Permanent Peripheral Nerve Stimulator For The Treatment Of Chronic Craniofacial Pain, Salim M Hayek, Nameer Haider, Ashwin Viswanathan, Mehul Desai, Jeffrey Rosenberg, Niek E Vanquathem

Faculty, Staff and Students Publications

than one-fifth of the US population. While various medications and conservative treatment modalities are available for this condition, many patients have refractory symptoms. These patients suffer from social impairment, reduced quality of life, and increased financial burdens.

Objective: The objective of this study was to examine the clinical outcomes of patients receiving a permanent, high-frequency electromagnetic coupling (HF-EMC) powered peripheral nerve stimulator (PNS) system for the treatment of chronic craniofacial neuropathic pain.

Study design: This study was a multicenter, randomized, controlled clinical trial conducted under an investigational device exemption (IDE).

Setting: This study was conducted in 7 clinical sites in …

Microbiome Signatures And Inflammatory Biomarkers In Culture-Negative Neonatal Sepsis, Morcos Hanna, Shixia Huang, Matthew Ross, Anaid Reyes, Dimuthu Perera, Anil Surathu, Sara Javornik Cregeen, Joseph Hagan, Mohan Pammi

Faculty and Staff Publications

Overuse of antibiotics is a concern in 'culture-negative sepsis' but it is unclear whether this is due to infection with viruses, fungi or other microbes that are not easily cultured, or whether it results from inflammatory processes. In a prospective study, we enrolled 50 preterm neonates with culture-positive sepsis (CP), culture-negative sepsis (CN), and asymptomatic preterm controls (CO). The microbiome of stool, skin, and blood, including bacterial, viral and fungal components and serum cytokine profiles were evaluated. The microbiome alpha or beta diversity did not differ between CN and CO groups. A MaAsLin analysis revealed increased relative abundances of specific …

A Consensus Guide To Preclinical Indirect Calorimetry Experiments, Alexander S Banks, David B Allison, Thierry Alquier, Ansarullah, Steven N Austad, Johan Auwerx, Julio E Ayala, Joseph A Baur, Stefania Carobbio, Gary A Churchill, Morten Dall, Rafael De Cabo, Jose Donato, Nathalia R V Dragano, Carol F Elias, Anthony W Ferrante, Brian N Finck, Jose E Galgani, Zachary Gerhart-Hines, Laurie J Goodyear, Justin L Grobe, Rana K Gupta, Kirk M Habegger, Sean M Hartig, Andrea L Hevener, Steven B Heymsfield, Corey D Holman, Martin Hrabě De Angelis, David E James, Lawrence Kazak, Jae Bum Kim, Martin Klingenspor, Xingxing Kong, Sander Kooijman, Louise Lantier, K C Kent Lloyd, James C Lo, Irfan J Lodhi, Paul S Maclean, Owen P Mcguinness, Gema Medina-Gómez, Raghavendra G Mirmira, Christopher D Morrison, Gregory J Morton, Timo D Müller, Yoshihiro Ogawa, David Pajuelo-Reguera, Matthew J Potthoff, Nathan Qi, Marc L Reitman, Patrick C N Rensen, Jan Rozman, Jennifer M Rutkowsky, Kei Sakamoto, Philipp E Scherer, Gary J Schwartz, Radislav Sedlacek, Mohammed Selloum, Saame Raza Shaikh, Shuai Chen, Gerald I Shulman, Vojtěch Škop, Alexander A Soukas, John R Speakman, Bruce M Spiegelman, Gregory R Steinberg, Katrin J Svensson, John P Thyfault, Tony Tiganis, Paul M Titchenell, Nigel Turner, Licio A Velloso, Antonio Vidal-Puig, Christopher S Ward, Ashley S Williams, Christian Wolfrum, Allison W Xu, Ying Xu, Juleen R Zierath, International Indirect Calorimetry Consensus Committee (Iiccc)

Children’s Nutrition Research Center Staff Publications

Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data …

A Metabolomics Study Of Cardiac Dysfunction In Hyperglycemia: Findings From The Atherosclerosis Risk In Communities (Aric) Study And The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Yilin Yoshida, Ngoc Quynh Nguyen, Eun Hye Moon, Casey Rebholz, Hicham Skali, Victoria Arthur, Justin B Echouffo-Tcheugui, Christie Ballantyne, Elizabeth Selvin, Amil Shah, Robert Kaplan, Carlos J Rodriguez, Qibin Qi, Susan Cheng, Bing Yu

Faculty, Staff and Student Publications

Objective: Hyperglycemic states (prediabetes and diabetes) are associated with heart failure (HF) risk. We aimed to identify distinct metabolites for subclinical cardiac dysfunction, a precursor of HF, in hyperglycemic or euglycemic individuals.

Research design and methods: We conducted cross-sectional and prospective analyses of 2,492 HF-free participants from the Atherosclerosis Risk in Communities (ARIC) study visit 5, 2011-2013. A total of 1,297 participants were hyperglycemic (assessed on the basis of hemoglobin A1c >5.7%, fasting glucose >100 mg/dL, use of diabetes medication, or diagnosis), and 1,195 were euglycemic. We used logistic regression for analysis of association between 790 metabolites and cardiac dysfunction, …

From Imaging To Impact: A Multi-Disciplinary T32 Program Framework And Initial Insights For Training In Image-Guided Cancer Therapy, Kari J Brewer Savannah, Stephen Y Lai, Clifton D Fuller, Kristy K Brock

Faculty, Staff and Student Publications

As multi-disciplinary image-guided assessment and therapies become increasingly important for precision oncology, the need for comprehensive training opportunities that effectively prepare the next generation of clinician-scientists and scientists is evident. We present an innovative, evidence-based research training framework that integrates the following critical features: 1) intentional and personalized mentoring and career development, 2) immersive research in image-guided cancer therapy, 3) strategic mentored clinical exposure, 4) structured didactic learning and professional development opportunities, and 5) mentored grant writing. Designed to foster scientific rigor, translational thinking, and multi-disciplinary collaboration, the Image-Guided Cancer Therapy T32 Training Program (IGCT-T32) aims to prepare postdoctoral fellows …

Time-Frequency Fingerprint Analysis In Seeg Source-Space To Identify The Epileptogenic Zone, Yash Shashank Vakilna, Deniz Atilgan, Johnson Hampson, Chinmay Chinara, Takfarinas Medani, Richard M Leahy, Nuria Lacuey, Samden D Lhatoo, Sandipan Pati, John C Mosher, Jay R Gavvala

Faculty, Staff and Student Publications

This case study highlights the application of seizure fingerprint analysis in the source-space of stereo-EEG (SEEG) data to accurately localize the epileptogenic zone (EZ) in patients with complex cortical malformations. A 25-year-old female with extensive bilateral perisylvian polymicrogyria (PMG) presented with intractable focal seizures. The source-level analysis performed in Brainstorm using the sLORETA imaging algorithm subsequently showed EZ fingerprint analysis. The patient underwent MR-guided laser interstitial thermal therapy (LITT), targeting the identified EZ, resulting in postoperative seizure freedom with minimal complications. Extending the analysis from the sensor-space to the source-space could further enhance surgical planning and improve outcomes in complex …

The Effect Of Tert Promoter Mutation On Predicting Meningioma Outcomes: A Multi-Institutional Cohort Analysis, Karenna J Groff, Ruchit V Patel, Yang Feng, Hia S Ghosh, Miguel A Millares Chavez, Joseph O'Brien, William C Chen, Vijay Nitturi, Akshay V Save, Mark W Youngblood, Craig M Horbinski, James P Chandler, Felix Ehret, Chloe Gui, Justin Z Wang, Kristen Park, Sonia Ajmera, Marc Rosenblum, Abigail K Suwala, Catena Kresbach, Christopher W Mount, Ulrich Schüller, Sandro Santagata, Felix Sahm, Tejus A Bale, Christina Jackson, Timothy E Richardson, Chunyu Cai, Farshad Nassiri, Gelareh Zadeh, David Kaul, David Capper, Stephen T Magill, John G Golfinos, Chandra Sen, Akash J Patel, David R Raleigh, Jennifer Moliterno, Donato Pacione, Matija Snuderl, Wenya Linda Bi

Duncan NRI Faculty and Staff Publications

Background: Molecular aberrations have been incorporated into tumour classification guidelines of meningioma. TERT-promoter (TERTp) mutation is associated with worse prognosis and is designated a WHO grade 3 biomarker. However, it remains unclear whether TERTp mutation is context-dependent, with other co-occurring genetic alterations potentially driving its association with prognosis. We sought to characterise the role of TERTp mutation in meningioma and guide TERTp sequencing.

Methods: We identified 1492 patients of all ages who had previously received surgery for meningioma across 14 medical centres in the USA, Canada, and Germany. Patients were eligible if they had post-surgical clinical or radiographical assessment of …

Plasma Lipidome Dysregulation In Frontotemporal Dementia Reveals Shared, Genotype-Specific, And Severity-Linked Alterations., Yohannes A Ambaw, Peter A Ljubenkov, Shubham Singh, Abdi Hamed, Sebastian Boland, Adam L Boxer, Tobias C Walther, Robert V Farese

Duncan NRI Faculty and Staff Publications

Introduction: Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.

Methods: We examined plasma lipidomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (GRN, C9orf72, MAPT) and non-carriers.

Results: FTD subjects exhibited increased plasma levels of gangliosides (GM3(d18:1_16:0), GM3(d18:1_24:1)), ceramide Cer(d18:1_23:0), and select polyunsaturated triacylglycerols. In contrast, phosphatidylethanolamine (PE(18:0_24:0) and sphingomyelin (SM(38:0) were reduced. Subtype-specific changes included elevated glucosylsphingosine (GlcSph(d18:1) …

Deepmvp: Deep Learning Models Trained On High-Quality Data Accurately Predict Ptm Sites And Variant-Induced Alterations, Bo Wen, Chenwei Wang, Kai Li, Ping Han, Matthew V Holt, Sara R Savage, Jonathan T Lei, Yongchao Dou, Zhiao Shi, Yi Li, Bing Zhang

Center on Aging Staff Publications

Post-translational modifications (PTMs) are critical regulators of protein function, and their disruption is a key mechanism by which missense variants contribute to disease. Accurate PTM site prediction using deep learning can help identify PTM-altering variants, but progress has been limited by the lack of large, high-quality training datasets. Here, we introduce PTMAtlas, a curated compendium of 397,524 PTM sites generated through systematic reprocessing of 241 public mass-spectrometry datasets, and DeepMVP, a deep learning framework trained on PTMAtlas to predict PTM sites for phosphorylation, acetylation, methylation, sumoylation, ubiquitination and N-glycosylation. DeepMVP substantially outperforms existing tools across all six PTM types. Its …

Heightened Risk: Childhood Trauma And Anticipatory Grief Exacerbate The Impact Of Loneliness On Depressive Symptoms And Lps-Stimulated Cytokines In Dementia Caregivers, Kelly N Brice, Jensine Paoletti-Hatcher, E Lydia Wu-Chung, Vincent D Lai, Daniel L Argueta, Michelle A Chen, Itee Mahant, Bryan T Denny, Charles Green, Luis D Medina, Paul Schulz, Jennifer Stinson, Samantha K Henry, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Dementia spousal caregivers are at a disproportionate risk for adverse mental and physical health outcomes. Loneliness is associated with depressive symptoms and proinflammatory cytokine production among caregivers. Additionally, childhood trauma, anticipatory grief, and poor sleep quality are all associated with enhanced stress reactivity. This study used a cross-sectional design to investigate whether loneliness is associated with proinflammatory cytokine production and depressive symptoms in caregivers, and whether these relationships are strongest among caregivers who report high levels of childhood trauma, high amounts of anticipatory grief, or poor sleep quality. A sample of 111 dementia spousal caregivers provided blood samples and completed …

The Ethics Of Clinical Ethics, Matthew Shea

Center for Medical Ethics and Health Policy Staff Publications

The concept ethics defines health care ethics as a professional practice. Yet the meaning of "ethics" is often unclear in the theory and practice of clinical ethics. Clarity on this matter is crucial for understanding the nature of clinical ethics and for debates about the professional identity and proper role of ethicists, the sort of training and skills they should possess, and whether they have ethics expertise. This article examines two different ways the ethics of clinical ethics can be understood: Real Ethics, which consists of objective moral norms grounded in moral truth; and Conventional Ethics, which consists of conventional …

Coenzyme Q Headgroup Intermediates Can Ameliorate A Mitochondrial Encephalopathy, Guangbin Shi, Claire Miller, Sota Kuno, Alejandro G Rey Hipolito, Salsabiel El Nagar, Giulietta M Riboldi, Megan Korn, Wyatt C Tran, Zixuan Wang, Lia Ficaro, Tao Lin, Quentin Spillier, Begoña Gamallo-Lana, Drew R Jones, Matija Snuderl, Soomin C Song, Adam C Mar, Alexandra L Joyner, Roy V Sillitoe, Robert S Banh, Michael E Pacold

Duncan NRI Faculty and Staff Publications

Decreased brain levels of coenzyme Q10 (CoQ10), an endogenously synthesized lipophilic antioxidant1,2, underpin encephalopathy in primary CoQ10 deficiencies3,4 and are associated with common neurodegenerative diseases and the ageing process5,6. CoQ10 supplementation does not increase CoQ10 pools in the brain or in other tissues. The recent discovery of the mammalian CoQ10 headgroup synthesis pathway, in which 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) makes 4-hydroxymandelate (4-HMA) to synthesize the CoQ10 headgroup precursor 4-hydroxybenzoate (4-HB)7, offers an opportunity to pharmacologically restore CoQ10 synthesis and mechanistically treat CoQ10 deficiencies. To test whether 4-HMA …

Muscle Spectrin, Matthew N Rasband, Ahmet Hoke, Chuansheng Zhang, Ozlem Sert

Faculty, Staff and Students Publications

No abstract provided.

Experiences Of Emotional Support Among Parents Of Children And Adolescents With Type 1 Diabetes: A Qualitative Study, Sahar S Eshtehardi, Marissa N Baudino, Barbara J Anderson, Deborah I Thompson, David G Marrero, Marisa E Hilliard

Faculty, Staff and Students Publications

Objective: Parents of youth with type 1 diabetes (T1D) experience substantial disease-specific demands and distress, yet their perceptions about the emotional support they receive related to the challenges of caring for a child with diabetes have not been well described. This research aimed to characterize the types of emotional support parents of youth with T1D receive and how they experience emotional support.

Methods: As part of a larger qualitative study on diabetes health-related quality of life, 23 parents (96% mothers) of youth with T1D (M age = 10.9 ± 3.8 years; 35% female) completed semi-structured interviews about various aspects of …