Medical Specialties Commons^™

Synthetic Zfta Fusions Pinpoint Disordered Protein Domain Acquisition As A Mechanism Of Brain Tumorigenesis, A Arabzade, H K Shirnekhi, S Varadharajan, S M Ippagunta, A H Phillips, N Laboe, D W Baggett, Wahiduzzaman, M Jo, T Zheng, R Pathak, D Gee, D Bhimsaria, H Wu, X Gao, J Liu, E Emanus, A Bland, A Kardian, A Hancock, B Holcomb, T Wright, T Bugbee, H Sun, M Zhai, E Caesar, M Park, S Tripathi, A Shirinifard, K Lowe, A Khalighifar, R A Petersen, S King, D Stabley, A Pitre, G E Campbell, C-G Park, W T Freyaldenhoven, B Chandra, Y Xia, E Bonten, A Achari, S Kandikonda, A Carisey, S B Pounds, J Xu, D W Ellison, B Deneen, K C Bertrand, R W Kriwacki, S C Mack

Children’s Nutrition Research Center Staff Publications

Over 95% of ependymomas that arise in the cortex are driven by a gene fusion involving the zinc finger translocation-associated (ZFTA) protein. Here, using super-resolution and lattice light-sheet microscopy, we demonstrate that the most frequent fusion variant, ZFTA-RELA (ZR), forms dynamic nuclear condensates that are required for oncogene expression and tumorigenesis. Mutagenesis studies of ZR reveal a key intrinsically disordered region (IDR) in RELA that governs condensate formation. Condensate-modulating IDR mutations introduced into ZR impaired its genomic occupancy at oncogenic loci and inhibited the recruitment of transcriptional effector proteins, such as MED1, BRD4 and RNA polymerase II. Using nuclear magnetic …

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 …

Randomized Trial: Peppermint Oil (Menthol) Pharmacokinetics In Children And Effects On Gut Motility In Children With Functional Abdominal Pain: 540 Mg Vs. 900 Mg Dose Comparison, Robert J Shulman, Bruno P Chumpitazi, Daniel Gonzalez, Uttam Garg, Salma Musaad, Jiali Wen, Gregory L Kearns

Children’s Nutrition Research Center Staff Publications

Aims: There is a paucity of information on the pharmacokinetics (PK) and pharmacodynamics (PD) of menthol, the active ingredient in peppermint oil (PMO). We studied the PK of menthol (540 and 900 mg) in children and measured their effects on gut transit/contractility.

Methods: Children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. One week later, they were randomized to 540 mg or 900 mg of oral enteric-coated PMO. Blood was sampled over 24 h to determine menthol PK. The WMC test was repeated while they took their respective dose (180 mg thrice or 180 …

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 …

The Potential Of 4-Methylumbelliferone To Be Repurposed For Treating Liver Fibrosis, Xi Chen, Huiqiao Li, Yanru Deng, Jieyi Meng, Shangang Zhao, Clavia Ruth Wooton-Kee, Xia Gao, Bingning Dong, Dongyin Guan, Chaodong Wu, Philipp E Scherer, Yi Zhu

Faculty, Staff and Students Publications

4-Methylumbelliferone (4-MU) is the active component of hymecromone, a choleretic and antispasmodic drug with an excellent safety profile. In rodent studies, high doses of 4-MU are also used to inhibit the production of hyaluronan (HA), a biomarker of liver fibrosis. Further, 4-MU shows excellent efficacy in inhibiting liver fibrosis of different etiologies in animal studies, eliciting interest in its repurposing for this condition. However, 4-MU's mechanism of action, and whether it inhibits liver fibrosis by impeding HA synthesis remains unclear. Using several transgenic mouse models with HA overproduction or degradation in different types of liver cells, we found that both …

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 …

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 …

Atherosclerotic Cardiovascular Disease In Gulf War Veterans In Relation To Deployment Exposures, Sarah T Ahmed, Ruosha Li, Lea Steele, Peter Richardson, Kellie Sims, Rachel Quaden, Kelly M Harrington, Vijay Nambi, John M Gaziano, Robert Morgan, George L Delclos, Drew A Helmer

Faculty, Staff and Students Publications

Many 1990-1991 Gulf War Veterans (GWVs) were exposed to toxicants and environmental hazards during deployment, including oil well fire smoke, chemical/biological agents, pyridostigmine bromide (PB) pills, and pesticides. Multiple constituents of smoke are associated with increased risk for atherosclerotic cardiovascular diseases (ASCVD), and other toxic exposures have been associated with autonomic and lipid dysfunction. We used data from the Gulf War Era Cohort and Biorepository Study of veterans deployed to Gulf War in 1990-1991 (n = 942). We evaluated the association of deployment exposures (no, yes (1-6 days), (7-30 days), (31 + days), and not sure) with clinical risk factors …

Focal Adhesion Kinase Drives Rho/Rock And Mtor Signaling To Protect And Augment Aortic Dissections, Zhen Zhou, Pujun Guan, Ripon Sarkar, Yang Yu, Alexis Richard, Dar Weiss, Yuki Kawamura, Chen Zhang, Yanming Li, Tomas Vaisar, Daniel R Martin, L Maximillian Buja, Zhouxuan Li, Kartik Venkatachalam, Ying H Shen, Scott A Lemaire, Jay D Humphrey, Dianna M Milewicz

Faculty, Staff and Students Publications

Dysfunctional mechanosensing via focal adhesions (FAs) significantly contributes to thoracic aortic dissection in the β-aminopropionitrile mouse model by triggering FA kinase activation and subsequent Rho/ROCK and mTOR signaling pathways. The present findings indicate that these signaling pathways play distinct roles in ascending vs descending dissections. Specifically, in the ascending aorta, smooth muscle cell FA kinase-Rho/ROCK signaling acts as a beneficial adaptive mechanism to prevent dissections, whereas mTOR signaling is pathogenic and contributes to dissections.

Determining Risk Factors And Rate Of Surgery After Collagenase Injections For Dupuytren Contracture, Ryan C. Cha, Juliet S. Chung, Sina Ramtin, Asif M. Ilyas

Department of Orthopaedic Surgery Faculty Papers

Purpose: Collagenase injections are a nonsurgical treatment for Dupuytren contracture, but their long-term effectiveness in preventing surgery remains unclear. This study aimed to evaluate the rate of surgical intervention following collagenase treatment and identify whether specific risk factors increase the likelihood of future surgical correction. Methods: This retrospective cohort study utilized the TriNetX US Collaborative network to identify patients diagnosed with Dupuytren contracture between January 2007 and September 2024. Patients initially treated with collagenase injections were identified using relevant current procedural terminology codes. Procedure-specific current procedural terminology codes were then used to determine which patients underwent a subsequent fasciectomy or …

Reliability And Spatial Consistency Of Mr Diffusion Tensor Imaging Measures Along The Cerebral Perivascular Space, Enchao Qiu, Joga Chaganti, Phillip Phan, M. Alizadeh, Devon Middleton, Kiran Talekar, Prabath Mondel, Scott H. Faro, Feroze Mohamed, Hsiangkuo Yuan

Department of Radiology Faculty Papers

BACKGROUND AND PURPOSE: Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has emerged as a promising noninvasive method for evaluating water motion that may reflect glymphatic system function. However, the reliability of DTI-ALPS measurements across different region-of-interest (ROI) selection methods remains underinvestigated. This study aimed to assess the interrater reliability among three neuroradiologists in native space and compare DTI-ALPS indices derived from ROIs placed in subjects' native space versus standardized Montreal Neurological Institute (MNI) space.

METHODS: DTI-ALPS indices from 16 healthy subjects were calculated from both left and right hemispheres using two ROI placement approaches: (1) native space ROIs …

Patients´ Characteristics And Six-Month Outcomes Of Patients With Atrial Fibrillation In Kenya: A Retrospective Observational Cohort Study From The National Cardiovascular Registry, Salim Abdallah, Jasmit Shah, Anders Barasa, Felix Barasa, Benard Gitura, Mzee Ngunga

Internal Medicine, East Africa

Introduction: atrial fibrillation is increasingly diagnosed in Kenya due to the persistence of rheumatic heart disease and the rising burden of cardiovascular risk factors. We aim to describe the baseline, clinical, treatment characteristics, and six-month outcomes of patients diagnosed with atrial fibrillation in Kenya.

Methods: a retrospective observational cohort study design was employed. Data were obtained from three Kenyan referral hospitals, including public and private institutions. Baseline and six-month data were collected. Depending on the type of variable, data were summarized descriptively.

Results: two hundred forty participants were enrolled, with a median age of 59.0 (IQR: 42.0-75.8). …

Left Bundle Area Pacing Outcomes Among Patients With Very Wide Qrs – Insights From An African Registry, Willy Mucyo, Mzee Ngunga, Miriam Msunza, Jeilan Mohamed, Marcus Ngantcha, Brian Vezi

Internal Medicine, East Africa

Background: Left Bundle Area Pacing (LBAP) is a promising alternative to conventional cardiac resynchronization therapy. There is a high prevalence of dilated cardiomyopathy in Africa, which is often associated with very wide QRS. However, data on LBAP outcomes in Africa are limited. Objective To evaluate the procedural and clinical outcomes of LBAP among African patients with very wide QRS durations.

Methods: The Multicenter African Cardiac Outcomes in Pacing (MACOP) registry enrolled 311 patients in Kenya and South Africa who underwent LBAP between 2021 and 2024. We evaluated procedural and clinical outcomes. Patients were stratified by baseline QRSd (normal …

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 …

Parent Needs, Recommendations, And Systemic Challenges Affecting Pediatric Hypertension Detection, Abbas H. Zaidi, Erica D. Sood, Sarah De Ferranti, Samuel Gidding, Varsha Zadokar, Jonathan M. Miller, Anne E Kazak

Department of Pediatrics Faculty Papers

Pediatric hypertension (HTN) affects 3%-5% of children in the United States, yet only 25% are diagnosed and 60% lack recommended follow-up care. Skepticism about elevated blood pressure (BP) readings and reluctance to use antihypertensive medications by parents and clinicians highlight the need for stakeholder-informed strategies to address these challenges. This study examined parents' perceived needs, their recommended strategies to improve HTN detection, and contextual health system challenges. Parents and clinicians from 10 pediatric primary care clinics participated in semi-structured qualitative interviews. Only parents of children with documented stage 2 BP readings and a HTN diagnosis, but with gaps in care …

Triage Tools To Inform The Prioritisation Of Physical Health Services Following A Diagnosis Of Cancer: A Scoping Review, Georgia L. White, Lauren C. Capozzi, Corey Linton, Adrian Wright, Tamara Jones, Hattie H. Wright, Kate A. Bolam, Elizabeth A. Johnston, Briana K. Clifford, Keegan Bean, Stephanie Brown, Sarah Kolesaric, Mary A. Kennedy, Bryan A. Chan, Grace L. Rose

Research outputs 2022 to 2026

Purpose: Many people face multiple cancer- and treatment-related sequalae. Triage and referral to physical health services can manage such consequences, but a comprehensive understanding of available triage tools is lacking. This review (i) identifies tools used to triage to physical health services, (ii) maps tool characteristics and application outcomes and (iii) summarises existing gaps. Methods: A systematic search was conducted (three databases, April 2024). Articles were included if they used a tool to triage to physical health services. Tools were classified by triaged disciplines (i.e., diet, exercise, physical rehabilitation, multidisciplinary) and screened physical impairments (e.g., malnutrition). Tool characteristics (e.g., triage …

"My Child Needs A Chance And A Choice To Talk About Their Pain": Parents' Experiences And Perspectives Of Pain Communication In Paediatric Rheumatology., Rebecca R. Lee, Jade Edwards, Danielle C. Mountain, Janet E. Mcdonagh, Mark Connelly, Tonya Palermo, Sarah Peters

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To investigate parents' experiences and perspectives about pain communication with healthcare professionals in paediatric rheumatology.

METHODS: Data were collected using semi-structured telephone interviews with parents of children/adolescents recruited from three UK tertiary paediatric rheumatology centres. A framework analysis was used to characterise parents' experiences and perspectives.

RESULTS: Eighteen parents participated. Their children had a median age of 13 years (SD= 3.16 years, Range= 6-16 years, 55 % male), with diagnoses of chronic primary pain (e.g. Ehlers Danlos syndrome/Hypermobility) and chronic secondary pain (e.g. Juvenile Idiopathic Arthritis). Data were organised into four themes: 1) Parents' active role in pain communication, …

Contemporary Characteristics And Outcomes Of Pediatric Oncology Patients Participating In Early Phase Clinical Trials., Avina Rami, Kira Bona, Suzanne Shusterman, Karen Wright, Andrew E. Place, Puja J. Umaretiya, Ketki Bhushan, Steven G. Dubois, Kevin Campbell

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Phase 1 or phase 1/2 trials are a first step in pediatric cancer drug development. Currently, there is a paucity of information regarding contemporary outcomes for pediatric patients enrolled in these trials. We describe characteristics and outcomes of patients enrolled in pediatric phase 1 clinical trials over a 9-year period at a single institution.

METHODS: We queried our clinical trials management system to generate a list of patients enrolled and treated on pediatric phase 1 or phase 1/2 trials from 2011 to 2019. We collected baseline demographics, clinical data, efficacy, and safety endpoints post-enrollment including: time to death, objective …

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 Anderst, Megan M. Letson, Angela N. Bachim, Nancy S. Harper, Carmen M. Coombs, Lori D. Frasier, Joanne N. Wood

Manuscripts, Articles, Book Chapters and Other Papers

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 …

Association Between Chd And Cerebral Abscess: Insights From A National Database., Keats Ewing, Rohit Seath Loomba, Saul Flores, Enrique G. Villarreal, Juan S. Farias, Matthew Taylor Coghill

Manuscripts, Articles, Book Chapters and Other Papers

CHD has been historically associated with the development of cerebral abscess. This retrospective cohort study examines the association of CHD with the occurrence of cerebral abscess in an inpatient paediatric population. We analysed data from the Pediatric Health Information System database, an administrative database that captures data from participating children's hospitals in the United States. We included all patients admitted to participating paediatric ICUs between 2016 and 2021 for a total of 426,029 admissions. Including all admissions, 1,387 (0.3%) patients experienced a cerebral abscess, and of 80,927 (19%) patients with CHD, only 88 (0.1%) experienced a cerebral abscess (odds ratio …

Fractures In Parkinson's Disease: Pathophysiology, Prevention, And Orthopedic Outcomes., Ali Osman, Tala Maya, Rayyan Bhutta, Natasha Doshi, Maryam Khan, Sara Shah, Paslene Periceles, Janae Rasmussen

Surgery Articles

Fractures are an important comorbidity in Parkinson's disease (PD), which can result in disability, mortality, and high healthcare costs. Impaired mobility, postural instability, bradykinesia, muscle rigidity, and decreased bone mineral density (BMD) contribute to the increased risk of falls, which often result in hip and upper extremity fractures. Hip fractures in patients with PD are associated with an increased hospital length of stay and a decline in functional independence. Multimodal fall prevention in PD is well established, but prevention of fractures is often underutilized, despite evidence-based interventions. Information on fall-related fracture outcomes after exercise interventions is an area warranting further …

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 …

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 …

Current Controversies In Prenatal Diagnosis 2: Conventional Postmortem Examination Remains The Gold Standard For The Anatomical Examination Of Fetal Loss, J Ciaran Hutchinson, Lorraine Potocki, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

A comprehensive postmortem examination is an essential component of a work-up after stillbirth. Its findings can support accurate counseling of parents about causes and risk of recurrence. It also supports providers' decisions about most appropriate testing and management plans for future pregnancy to prevent recurrence. Informing parents about fetal autopsy and obtaining their consent is challenging, and conducting a fetal autopsy requires expertise that is, not universally available. Newer non-invasive or minimally invasive methods such as postmortem MRI and targeted biopsies can replace or supplement autopsies, but one must recognize that expertise in these methods is likewise not broadly available. …

Prenatal Genetic Consultation And Testing, Sarah Araji, Lauren Westerfield, Roni Zemet, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

The evolution of prenatal genetic testing has transformed prenatal diagnosis into a more precise and individualized approach. Advanced tools such as chromosomal microarray analysis and exome sequencing have enabled the prenatal diagnosis of more genetic conditions, including anomalies and disorders eligible for fetal therapy. When in utero therapy is considered, accurate genetic diagnosis is essential for guiding providers' and patients' decisions regarding management and outcomes. This chapter reviews available prenatal genetic screens and tests, their indications, and counseling strategies. It also explores genetic abnormalities associated with fetal structural anomalies and their implications for decision-making in fetal interventions.

Knowledge, Attitude And Practice Of Artificial Intelligence Among Healthcare Professionals: An Online Cross-Sectional Survey, Nikhil R, Divya K L, Mahabaleshwar Mamadapur, Harshwardhan S Patil, Shashirekha B, Hema Sameera Pinnam, Purna Bansal

Digital Journal of Clinical Medicine

Background: Deep learning-powered Artificial Intelligence-driven assistance offers enormous potential to improve healthcare by facilitating administrative work, diagnosis, and the treatment of chronic diseases. The gap between clinical values and the day-to-day realities of primary care practice might widen if AI is not successfully incorporated.

Methods: A cross-sectional design was used to evaluate healthcare professionals' perceptions and understanding of AI within a clinical setting. The study was conducted among 456 Health care Workers from May to November 2024.

Results: Among 456 participants, 55.7% were MBBS students/interns, and 37.9% were postgraduates/professionals. More than 50% supported AI integration, and 62.3% of MBBS …

Cardiogenic Shock With Acute Myocardial Infarction Among Older Adults In The United States, Taha Mansoor, Ali Bin Jabbar, Mahmoud Ismayl, Dylan Yu, Kartik Gupta, Sachin Parikh, Austin Brubaker, Abdul Minhas, Dmitry Abramov, Salim S. Virani

Population Health, East Africa

Background: Characteristics and outcomes associated with cardiogenic shock (CS) with acute myocardial infarction (AMI) in older patients have not been well characterized.

Objectives: The purpose of this study was to investigate characteristics and outcomes of older patients admitted with CS with AMI.

Methods: We used the National Inpatient Sample database to evaluate clinical characteristics of hospitalizations, clinical outcomes, and health care utilization of hospitalizations of older patients ≥80 years with CS and AMI from 2003 to 2021. We also compared data from older patients with a reference relatively younger patient population (18-79 years).

Results: During the study period, …

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) …

Predicting Clinical Success Of Ct-Based Functional Drained Liver Volume Assessment In Malignant Biliary Obstruction, Ethan Y Lin, Bruno C Odisio, Koustav Pal, Iwan Paolucci, Ryan P Kempen, Nicolas Cardenas, Paige Reed, Ketan Y Shah, Ahmed Awad, Rahul A Sheth, David Fuentes, Alda Tam

Faculty, Staff and Student Publications

Purpose

To compare the predictive accuracy of subjective versus objective assessment of three-dimensional functional drained liver volume (fDLV) for clinical success after percutaneous transhepatic biliary drainage (PTBD).

Materials and Methods

This retrospective study included patients with malignant biliary obstruction and hyperbilirubinemia who underwent de novo PTBD between January 2016 and February 2017. Clinical success was defined as achieving total bilirubin level less than 1.8 mg/dL (30.8 μmol/L) within 30 days after PTBD. Seven interventional radiologists independently categorized subjective fDLV into four groups: less than 30%, 30%–50%, 51%–75%, and greater than 75% of the total liver volume. Objective fDLV was calculated …