Digital Commons Network^™

Risk Factors For Complication And Reoperation In The Treatment Of Discoid Lateral Meniscus In Children And Adolescents: A Multicenter Study, Suzanna Ohlsen, Jeffrey J Nepple, Et Al.

2020-Current year OA Pubs

BACKGROUND: The discoid lateral meniscus (DLM) is a common congenital abnormality of the meniscus. Tears are common, and initial treatment is often not definitive, leading to a spectrum of complications, including persistent symptoms, meniscal insufficiency, osteochondral defects, and recurrent tears potentially requiring reoperation.

PURPOSE: To determine demographic, injury, and perioperative risk factors that increase the likelihood of complications and reoperation after treatment in patients with DLM.

STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: Patients surgically treated for DLM from 9 institutions between 2000 and 2020 were reviewed. Data on demographics, presenting symptoms and signs, surgical findings and treatments, …

Supporting Emergency Department Patients Experiencing Homelessness, Antony Hsu, Michael A Light, Callan Fockele, Samantha Hay, Stephen Y Liang, Wendy Macias-Konstantopoulos, Carla B Brim, William Weber

2020-Current year OA Pubs

Homelessness is a growing public health crisis across the United States. Emergency physicians are uniquely positioned to address immediate medical concerns and the underlying social drivers of health for patients experiencing homelessness. Initiating coordination of care in the emergency department addresses their hierarchy of needs and can help support patient movement through the department. Practice adaptations described include early engagement; trauma-informed care approach; addressing unmet nonmedical needs; establishing safe dispositions; documenting homelessness, substance use disorder, and linkages to care; clinical practice adaptations; and palliative care approaches. Programs and initiatives outside of the emergency department described include street medicine and government …

Harmonizing Neuropsychological Test Data Across Prospective Studies, Rosita Shishegar, James D. Doecke, Yen Ying Lim, Pierrick Bourgeat, Vincent Dore, Bhargav Tallapragada, Simon M. Laws, Tenielle Porter, Samantha Burnham, Azadeh Feizpour, Ashley Gillman, Michael Weiner, Jason Hassenstab, Christopher C. Rowe, Victor L. Villemagne, Colin L. Masters, Jurgen Fripp, Hamid Sohrabi, Paul Maruff

Research outputs 2022 to 2026

Introduction: Alzheimer's disease (AD) research relies on large datasets and advanced statistical models. However, individual population studies often lack sufficient sample size for conclusive results. Harmonizing cognitive test data across studies can address this gap, despite differences in testing protocols. This study harmonizes cognitive data from three major AD cohorts to support robust clinical–pathological modelling. Methods: Information from the Alzheimer's Disease Neuroimaging Initiative (N = 1446); Australian Imaging, Biomarkers and Lifestyle (N = 1764); and Open Access Series of Imaging Studies-3 (N = 440) were integrated, including cognitive scores, demographics, genetics, and clinical and neuroimaging data. Neuropsychological tests relevant to …

Novel Small-Molecule Analogues Of Iu1 Ameliorate Amyloid-Β Mediated Toxicity In Alzheimer’S Disease Cell And Worm Models, Ajish Ariyath, Fraulein Denise Arigo, Izhar Wallach, W. M.A.D.Binosha Fernando, Ralph N. Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Dysregulation of the deubiquitinating enzyme Ubiquitin-specific peptidase 14 (USP14) is implicated in several neurodegenerative diseases, and IU1, an allosteric inhibitor, has shown neuroprotective effects by reducing protein aggregate toxicity. This study aimed to develop new IU1 analogues and evaluate their ability to mitigate amyloid-β (Aβ) accumulation and toxicity in Alzheimer’s disease (AD) cell and Caenorhabditis elegans worm models. IU1 and 71 newly designed analogues identified using the AtomNet^® virtual screening platform were assessed in an amyloid precursor protein-C terminal fragment/amyloid-β (APP-C99/Aβ)-producing AD cell model using a high-throughput toxicity assay. Lead compounds were further evaluated for their effects on neurodegeneration, …

Pathological Response Calculation Assessment Remains Accurate With Reduced Tumor Bed Examination After Neoadjuvant Immunotherapy In Clinically Detectable Stage Iii Melanoma, R. V. Rawson, N. G. Maher, A. M. Menzies, S. N. Lo, N. Mesbah Ardakani, L. A. Jackett, I. A. Vergara, T. E. Pennington, K. F. Shannon, S. Ch’Ng, M. Gonzalez, E. M. Burton, M. W. Lucas, I. L.M. Reijers, E. A. Rozeman, D. E. Gyorki, S. Sandhu, M. S. Carlino, J. Howle, M. Khattak, A. Van Der Westhuizen, M. C. Andrews, V. Atkinson, A. C.J. Van Akkooi, A. J. Spillane, R. P.M. Saw

Research outputs 2022 to 2026

Background: Neoadjuvant immunotherapy produces event-free survival advantage over adjuvant therapy for patients with surgically resectable macroscopic stage IIIB/C/D melanoma. Pathological response, determined as percentage residual viable tumor (% RVT), provides critical prognostic information and informs management decisions. Here, we assessed accuracy of %RVT calculation when reduced tumor bed (TB) was examined and leverage these results proposing streamlined protocols for pathological examination. Patients and methods: Comprehensive histopathological examination was carried out on 134 patient specimens after neoadjuvant immunotherapy with ipilimumab and nivolumab. Impact on %RVT when evaluating less TB than recommended by the initial International Neoadjuvant Melanoma Consortium (INMC) protocol was …

Plasma Biomarker Progression Across The Alzheimer's Disease Amyloid Beta And Tau Positron Emission Tomography Trajectories, Rodrigo Cánovas, Christopher J. Fowler, Azadeh Feizpour, Vincent Dóre, Pierrick Bourgeat, Ziad S. Saad, Gallen Triana-Baltzer, Hartmuth C. Kolb, Manu Vandijck, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Jurgen Fripp, Simon Laws, Anthony W. Bannon, Kaj Blennow, Henrik Zetterberg, Stephanie Rainey-Smith, Sulantha Mathotaarachchi, Christopher C. Rowe, Colin L. Masters, James D. Doecke

Research outputs 2022 to 2026

Introduction: With increased uptake in disease-modifying treatments for amyloid beta (Aβ) removal, it is important to measure performance of highly sensitive plasma biomarkers to detect the presence of Aβ and tau in cognitively impaired populations. Methods: In this study, we investigated a large set of plasma biomarkers for their capability to predict Aβ and tau positron emission tomography (PET) and their association with increasing Aβ and tau burden. RESULTS: From the biomarkers assessed, tau phosphorylated at threonine 217 (pTau217) showed the largest increases across the full range of Aβ and tau levels. Furthermore, pTau217/Aβ42 had the smallest proportion of participants …

Regulation Of Autophagy-Mediated Pathways By Diet, Physical Activity, And Sleep In Alzheimer's Disease, Ajish Ariyath, Zoe Mputhia, Christopher Dougherty, Bushra Kaleelur Rahuman, W. M.A.D.Binosha Fernando, Belinda Brown, Samantha L. Gardener, Stephanie R. Rainey-Smith, Ralph Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Alzheimer's disease (AD) is a progressive, age-related, neurodegenerative disorder marked by cognitive decline, memory loss, and accumulation of amyloid beta (Aβ) plaques and tau tangles. A key feature of AD is impaired protein homeostasis, often driven by autophagy dysfunction. Autophagy, a cellular degradation and recycling process, plays a vital role in maintaining neuronal health and is increasingly recognized as a therapeutic target in AD. Lifestyle factors such as diet, physical activity, and sleep can positively influence autophagy and support cognitive function. Intermittent fasting (IF) and calorie restriction (CR) activate autophagy and promote longevity; physical activity enhances cerebral blood flow and …

Taurine Supplementation And Human Heat Tolerance: Mechanisms, Evidence, And Integration With Heat Acclimation, Cooling, And Hydration, Siavash Naddafha, Jeffrey R. Stout, Cassandra Evans

Research outputs 2022 to 2026

Heat exposure during strenuous exercise increases core temperature and cardiovascular strain, impairing performance and elevating the risk of heat illness. Standard countermeasures include heat acclimation, cooling, and hydration/electrolyte planning. Taurine is a sulfur-containing amino acid present in excitable tissues and widely used as an oral supplement; emerging human trials suggest it can augment thermoregulation, primarily by enhancing eccrine sweating and evaporative heat loss. This narrative review synthesizes mechanistic and applied evidence on taurine during exercise in hot environments and evaluates potential interactions with acclimation, cooling strategies (pre- and per-cooling), and hydration practices. Across a small number of randomized, mostly double-blind …

Early Neonatal Admissions With Feeding Difficulties To Acute Paediatric Services At A Tertiary Paediatric Hospital In England: Sequential Audits Pre-Covid-19 And During The Covid-19 Pandemic, Kalvin Lee, Thomas Frederick Dunne, Mary Masoud, Hayley Gleig, Heidi Stott, Helen Nabwera, Halina Kamarova

Centre of Excellence in Women and Child Health

Introduction: Our objective was to describe the population of infants < 7 days of age admitted to the acute general paediatric services at Alder Hey Children’s Hospital and ascertain the proportion with feeding difficulties amenable to community-based support.

Methods: Sequential retrospective audits of all infants < 7 days of age admitted to acute paediatrics at Alder Hey Children’s Hospital, Liverpool, England, from March to September 2019 (pre-COVID-19) and March to September 2020 (during COVID-19). All the infants were born and discharged from maternity units in Merseyside, Northwest England. Anonymised data were extracted from the electronic clinical records by three members of the clinical team.

Results: Pre-COVID-19, 38.6% (93) of the 241 admissions to acute general paediatric services had feeding difficulties. 31.2% (29) presented solely with feeding difficulties and 31.2% (29) were exclusively breastfed. However, during COVID-19, although there were fewer admissions (104), more than half (51%, 54) had feeding difficulties and for 54% (29), this was the only reason for admission. Over half (53.7%, 29) were exclusively breastfed.

Conclusion: Our audits showed that at least a third of infants < 7 days of age admitted with feeding difficulties did not have any other features of severe illness. These admissions unnecessarily expose infants to hospital-acquired infections while disrupting the opportunity for families to build close and loving relationships that enhance the establishment of breastfeeding. Co-designing infant feeding strategies with the mothers and stakeholders will be a crucial next step to enhance infant feeding support, particularly in impoverished communities in the region.

Sit, Stay, And Teach: Exploring Teachers' Perceptions Of Facility Dogs' Impact On Stress And Retention, Dennis Powers

Graduate Student Dissertations, Theses, Capstones, and Portfolios

The teaching profession remains at a high level of workplace stress, a factor contributing to teacher burnout and turnover. The study examines how teachers in K-12 public education perceived that facility dogs might reduce stress, increase job satisfaction, and aid in teacher retention in public schools of a southeastern state. The study employed a qualitative, cross-sectional survey that was emailed to 112,546 educators from a LISTSERV request. A total of 1,242 individuals provided informed consent and completed the survey, which consisted of Likert-scale measurement items, open-ended questions, and an informational video inserted to achieve a common understanding of the facility …

Circulating Fatty Acid Binding Protein 4 (Fabp-4) Concentrations And Mortality In Individuals With Colorectal Cancer In The European Prospective Investigation Into Cancer And Nutrition Study, Thu Thi Pham, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Veronika Fedirko, Anja Olsen, Anne Tjønneland, Claire Cadeau, Gianluca Severi, Matthias B Schulze, Renée Turzanski Fortner, Verena Katzke, Claudia Agnoli, Carlotta Sacerdote, Rosario Tumino, Simona Signoriello, Camino Trobajo-Sanmartín, Jesús-Humberto Gómez, María-Dolores Chirlaque, Maria-Jose Sánchez, Marta Crous-Bou, Anne May, Alicia Heath, Dagfinn Aune, Elisabete Weiderpass, Tobias Pischon

Faculty, Staff and Student Publications

Human fatty acid binding protein‐4 (FABP‐4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity–mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC‐specific, non‐CRC‐specific, and all‐cause mortality by FABP‐4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC …

Hypoglossal Neuropathy In The Pathogenesis Of Fibrosis-Related Late-Radiation Associated Dysphagia: A Correlative Analysis Utilizing Electromyography To Explore The Frequency Of Clinical And Subclinical Neuropathy In A Pilot Dysphagia Trial, Holly Mcmillan, Christine Okoro, Sheila Buoy, Karin Woodman, Nicolaas Anderson, Clifton Fuller, Stephen Y Lai, Katherine Hutcheson

Faculty, Staff and Student Publications

Background: Late radiation-associated dysphagia (late-RAD) commonly presents in patients with signs of hypoglossal neuropathy, with hallmark clinical features including lingual atrophy, deviation, and fasciculation. Gold-standard electromyography (EMG) has not been used to explore the frequency of hypoglossal neuropathy in patients with late-RAD.

Methods: Exploratory post hoc secondary analysis of MANTLE trial (NCT03612531) was completed. The presence of cranial nerve XII (CN XII) neuropathy was classified by (1) features of clinical assessment as well as (2) intramuscular genioglossus EMG pre-MANTLE intervention in disease-free HNC survivors ≥ 2 years post-radiotherapy (RT) with grade ≥ 2 fibrosis and dysphagia.

Results: All …

Impact Of Treatment Interruption On Outcomes In Head And Neck Cancer: Nrg/Rtog Secondary Analysis, Laila A Gharzai, Emily Morris, Matthew J Schipper, Kelley M Kidwell, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Richard C Jordan, Adam S Garden, Shlomo A Koyfman, Jimmy J Caudell, Dukagjin M Blakaj, Neal E Dunlap, Greg A Krempl, John M Longo, Christopher U Jones, Michael F Gensheimer, Thomas J Galloway, Lyudmila Demora, Quynh-Thu Le, Jennifer L Shah, Krithika Suresh, Michelle Mierzwa

Faculty, Staff and Student Publications

Importance: Historical evidence demonstrated that delays or interruptions in radiotherapy (RT) are associated with poorer oncologic outcomes in head and neck squamous cell carcinoma (HNSCC). Substantial concerns arose during the COVID-19 pandemic, when treatment schedules were frequently disrupted.

Objective: To determine the association of RT interruptions with locoregional failure (LRF) and overall survival (OS).

Design, setting, and participants: This retrospective review and secondary analysis of 3 randomized clinical trials (NRG/RTOG 0129, 0522, and 1016) included patients enrolled in the trials who were treated with RT. Patients with HNSCC were grouped as (1) p16-positive oropharynx (p16+ OPSCC) and (2) p16-negative oropharynx …

Identification Of Raptor And Gli1 As Usp37 Substrates Highlight Its Context-Specific Function In Medulloblastoma Cells, Ashutosh Singh, Donghang Cheng, Amanda R Haltom, Yanwen Yang, Tara Dobson, Rashieda Hatcher, Veena Rajaram, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

The USP37 gene encodes a deubiquitylase (DUB), which catalyzes the proteolytic removal of ubiquitin moieties from proteins to modulate their stability, cellular localization or activity. Its expression is downregulated in a subgroup of medulloblastomas driven by constitutive activation of sonic hedgehog (SHH) signaling. Patients with SHH-driven medulloblastomas with elevated expression of the RE1 silencing transcription factor (REST) and reduced expression of USP37 have poor outcomes. In previous studies, we showed sustained proliferation of SHH-medulloblastoma cells due to blockade of terminal cell cycle exit and neuronal differentiation stemming from a failure in USP37-dependent stabilization of its target, the cyclin-dependent kinase inhibitor …

Introducing A New Frontier In The Journal Of Pediatric Rehabilitation Medicine: An Interdisciplinary Approach Throughout The Lifespan: The Pediatric Brain Injury Section, Michael Green, Glendaliz Bosques, Kimberly Davis, Brenda Eagan-Johnson, Carty Husted

Faculty, Staff and Student Publications

No abstract provided.

Melody: Mediation Analysis In Logistic Regression For High-Dimensional Mediators And A Binary Outcome, Sunyi Chi, Xingyu Li, Peng Wei, Xuelin Huang

Faculty, Staff and Student Publications

Mediation analysis is a pivotal tool for elucidating the indirect effect of an environmental factor or treatment on disease through potentially high‐dimensional omics data, such as gene expression profiles. However, traditional mediation analysis methods tailored for binary outcomes often rely on the rare disease assumption in logistic regression and provide inadequate measures of total mediation effect when multiple mediators have effects in different directions. In this paper, we develop a MEdiation analysis framework in LOgistic regression for high‐Dimensional mediators and a binarY outcome (MELODY). It leverages a second‐moment‐based measure analogous to the ��2 for linear models to quantify the total …

Tumour-Brain Crosstalk Restrains Cancer Immunity Via A Sensory-Sympathetic Axis, Haohan K Wei, Chuyue D Yu, Bo Hu, Xing Zeng, Hiroshi Ichise, Liang Li, Yu Wang, Ruiqi L Wang, Ronald N Germain, Rui B Chang, Chengcheng Jin

Faculty, Staff and Student Publications

Body–brain communication has emerged as a key regulator of tissue homeostasis1–5. Solid tumours are innervated by different branches of the peripheral nervous system and increased tumour innervation is associated with poor cancer outcomes6–8. However, it remains unclear how the brain senses and responds to tumours in peripheral organs, and how tumour–brain communication influences cancer immunity. Here we identify a tumour–brain axis that promotes oncogenesis by establishing an immune-suppressive tumour microenvironment. Combining genetically engineered mouse models with neural tracing, tissue imaging and single-cell transcriptomics, we demonstrate that lung adenocarcinoma induces innervation and functional …

The Pandemic Effect: Secondary Impact On The Diagnosis Of Clinically Significant Congenital Heart Disease And Role Of Deprivation Index, Cassandra Campbell, Kristin Wyckoff, Ronak Naik, Nithya Swaminathan, Salima Ahmed Bhimani, Jason Johnson, Vijaya Joshi, Ranjit Philip

Faculty, Staff and Student Publications

We sought to determine the impact of the COVID-19 on prenatal diagnosis (PND) of clinically significant congenital heart disease (CHD) and the role of socioeconomic status (SES), complexity of diagnosis, and proximity to advance testing. This single-center retrospective study evaluated 2 eras of infants (COVID (born July 1, 2020–July 31, 2023) and pre-COVID (born June 1, 2017–July 1, 2020) who had cardiac surgery in the first year of life. 512 infants, 292 in pre-COVID era and 220 in COVID era with no significant difference in the rate of prenatal care (PNC) or PND in the COVID era (88%/42%) versus pre-COVID …

Cardiometabolic Indicators Of Cognitive Impairment In The Cameron County Hispanic Cohort, Fadi I Musfee, Seema Agarwal, Vahed Maroufy, Chelsea Liu, Joseph B Mccormick, Susan Fisher-Hoch, Sean I Savitz

Faculty, Staff and Student Publications

Background

Objective

Methods

Venous Thromboembolism In Aggressive B-Cell Lymphoma Patients Treated With Cd19 Car-T Therapy: Single-Institution Study, Neha Venkatesh, Kevin Milligan, Julia Parrish, Yun Qing, Ryan Sun, Paolo Strati, Jeremy Ramdial, Amy Ayers, Sairah Ahmed, Cristhiam Rojas Hernandez

Faculty, Staff and Student Publications

Background: Large B-cell lymphomas (LBCLs) are a common subtype of non-Hodgkin lymphomas. CD19 chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized LBCL treatment, with high remission rates but also significant toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Venous thromboembolism (VTE) in CAR-T therapy patients is understudied.

Objective: This study aims to determine the incidence and characteristics of acute VTE in LBCL patients treated with CAR-T therapy and identify baseline clinical features associated with VTE. Methods: We retrospectively reviewed 172 adult LBCL patients treated with CAR-T therapy from January 2018 to November 2019 at MD …

A Guide To Transcriptomic Deconvolution In Cancer, Yaoyi Dai, Shuai Guo, Yidan Pan, Carla Castignani, Matthew D Montierth, Peter Van Loo, Wenyi Wang

Faculty, Staff and Student Publications

Cancer tissues are heterogeneous mixtures of tumour, stromal and immune cells, where each component comprises multiple distinct cell types and/or states. Mapping this heterogeneity and understanding the unique contributions of each cell type to the tumour transcriptome is crucial for advancing cancer biology, yet high-throughput expression profiles from tumour tissues only represent combined signals from all cellular sources. Computational deconvolution of these mixed signals has emerged as a powerful approach to dissect both cellular composition and cell-type-specific expression patterns. Here, we provide a comprehensive guide to transcriptomic deconvolution, specifically tailored for cancer researchers, presenting a systematic framework for selecting and …

Leveraging Large Language Models For Heuristic Usability Assessment Of Medical Software: Insights With The Radiation Planning Assistant, Laurence E Court, Jacobus Smit, Lourens Strauss, William Shaw, Andrea Marais, Christoph Trauernicht, Nanette Joubert, Elaine Smith, Shona Badre, Graeme L Lazarus, Thekiso Khotle, Lauren Netherton, Wanda Van Heerden, Carlos Cardenas, Monica Serban, Jan Seuntjens, Christine V Chung, Pavel Govyadinov, Meena Khan, Saurabh Nair, Tucker Netherton, Lifei Zhang

Faculty, Staff and Student Publications

Background: Usability engineering is essential for ensuring the safety and effectiveness of medical software, as design-related issues are a leading cause of use errors in clinical settings. Heuristic evaluation provides a practical approach to identifying usability problems, but its outcomes depend heavily on expert interpretation. Large Language Models (LLMs), such as ChatGPT, offer a potential means to augment heuristic evaluation by generating structured, context-aware usability feedback. This study explored the use of ChatGPT to support heuristic assessment of the Radiation Planning Assistant (RPA), a web-based radiotherapy planning tool designed to support clinical teams in low- and middle-income countries.

Methods: ChatGPT …

The American College Of Radiology Diagnostic Fluoroscopy Dose Index Registry Pilot: Dosimetric Performance And Benchmarking Challenges, Steve D Mann, Donald L Miller, Grant Fong, Allen R Goode, Emily L Marshall, Thomas Nishino, Pavlina Boxx, Liqiang Ren, Celalettin Topbas, Alan H Schoenfeld, Vivek Singh, Jie Zhang

Faculty, Staff and Student Publications

Background: The ACR Diagnostic Fluoroscopy Dose Index Registry (DIR-Fluoro) is expanding to include diagnostic fluoroscopy. Variations in dose reference points and overhead radiography events may introduce unique challenges for benchmarking.

Purpose: To survey the technological status and dosimetric performance of fluoroscopes participating in the DIR-Fluoro pilot project, focusing on longitudinal stability and variability of fluoroscopic dose reporting accuracy across multiple institutions and vendors.

Methods: Sixty-six fluoroscopic systems from nine institutions (24 facilities) were surveyed for facility type, fluoroscope type, image receptor type, age, dose reporting capabilities, and other key features. Of these, 56 were evaluable. Semi-annual measurements assessed reference air …

Convolutional Neural Networks For Automatic Tuber Segmentation And Quantification Of Tuber Burden In Tuberous Sclerosis Complex, Iván Sánchez Fernández, Matheus D Soldatelli, Gillian N Miller, Catharina F Gout, Ellen C Broekhuizen, Iris C J Den Hertog, Daan A Pijs, Errol Apostolopoulos, Prabhjot Kaur, Abdelhakim Ouaalam, Martina E Bebin, Hope Northrup, Darcy A Krueger, Joyce Y Wu, Alexander L Cohen, Mustafa Sahin, Davood Karimi, Simon K Warfield, Jurriaan M Peters

Faculty, Staff and Student Publications

Objective: This study was undertaken to develop a fully automated algorithm for tuber segmentation and quantification of tuber volume that performs similarly to the gold standard human neuroradiologist.

Methods: We used brain magnetic resonance imaging (MRI) from patients with tuberous sclerosis complex (TSC) to train and validate a convolutional neural network (CNN), which was evaluated on segmentation with the Dice-Sørensen similarity coefficient (DSSC) and on tuber burden quantification with Spearman correlation coefficient against a neuroradiologist's gold standard in the test set.

Results: We collected 263 MRIs from 196 patients (57% males) with median (25th percentile-75th percentile) age of 4.3 (3.0-10.1) …

Retrospective Analysis Of Cutaneous Immune-Related Adverse Events Following Checkpoint Inhibitor Therapy In Melanoma Patients Reveals Increased Risk Associated With The Hla-B*51:01 Allele, Mckenzie Dileo, Samantha Oglesby, Cheuk Hong Leung, Kristen E Pauken, Sahira Farooq, Lauren E Haydu, Shelby L Kubicki, Rebeca Martinez, Macartney Welborn, Sana Zahiruddin, Jun Zou, Kai Cao, Anisha B Patel

Faculty, Staff and Student Publications

Background: While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.

Methods: A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as …

Presenilin L166p Mutation, A Model Of Familial Alzheimer's Disease, Leads To Early Onset Bone Loss, Vidyani Suryadevara, Connor J Krehbial, Anuradha K Valiya, Melinda Vang, Julian Balanta-Melo, Pierre P Eleniste, Sumana Posritong, Jung Min Hong, Katie Chester, Gabriel M Pagnotti, Teresita Bellido, Monte S Willis, Angela Bruzzaniti

Faculty, Staff and Student Publications

Accelerated bone loss has been reported in the early stages of Alzheimer's disease (AD) as indicated by reduced bone mineral density and increased fracture risk in these patients, compared to healthy individuals. In the present study, we investigated bone loss in mouse models of familial Alzheimer's disease harboring the Presenilin 1 (L166P) knock-in mutation (PSEN1 KI), with or without the human amyloid precursor protein transgene (hAPP Tg+) known to induce brain amyloid pathology by 6 months. Female and not male 12-month PSEN1/hAPP Tg+ mice exhibited reduced whole-body bone mineral density and bone mineral content, compared to sex-matched controls. Consistent with …

Can Patients With Recurrent Or Primary Squamous Cell Carcinoma Of The Anus In A Previously Irradiated Pelvis Receive Definitive Reirradiation, Jordan Mcdonald, Ethan P Damron, Prajnan Das, Eugene J Koay, Ethan B Ludmir, Bruce D Minsky, Sonal S Noticewala, Grace L Smith, Craig Messick, Van K Morris, Emma B Holliday

Faculty, Staff and Student Publications

Purpose: Although salvage surgery is the standard of care for locoregionally recurrent anal cancer, few local options exist for inoperable pelvic recurrences. Newly diagnosed anal cancer arising in a previously irradiated field also provides a unique treatment challenge, as delivery of standard doses would result in unsafe cumulative dose to pelvic structures. We aimed to evaluate efficacy and toxicity of a hyperfractionated accelerated reirradiation (reRT) regimen for such patients.

Methods and materials: Patients treated with hyperfractionated accelerated reRT at a single institution between 2005 and 2024 for nonmetastatic inoperable locoregionally recurrent anal cancer or primary anal cancer in a previously …

Decellularized Extracellular Matrix Scaffolds To Engineer The Dormant Landscape Of Microscopic Colorectal Cancer Liver Metastasis, Sabrina N Vandenheuvel, Lucia L Nash, Abigail J Clevenger, Claudia A Collier, Oscar R Benavides, Sanjana Roy, Brinlee Goggans, Aelita Salikhova, Anvitha Tharakesh, Svasti Haricharan, Amber N Stratman, Scott Kopetz, Alex J Walsh, Shreya A Raghavan

Faculty, Staff and Student Publications

Recurrent liver-metastatic colorectal cancer contributes to high mortality. Recurrence occurs when dormant, microscopic residual disease survives initial treatment to escape dormancy. In their dormant, microscopic state within the liver, these metastatic lesions are undetectable by clinical diagnostic imaging until they form overt, chemoresistant metastases. Therefore, understanding the molecular mechanisms underlying dormancy in colorectal cancer liver metastases is a significant knowledge gap, motivating the engineering of nuanced in vitro models of disease. The current work presents an engineered model of liver-metastatic colorectal cancer dormancy. Decellularized extracellular matrix (dECM) scaffolds are used to provide microscopic colorectal cancer cell clusters with a biomimetic, …

Local Delivery Of Mir-27a* Using Ultrasound-Targeted Microbubble Cavitation Inhibits Squamous Cell Carcinoma Growth, Nikhil S Chari, Cheng Chen, Thiruganesh Ramasamy, Xucai Chen, Geetika Wadhwa, Anurag N Paranjape, Stephen Y Lai, Flordeliza S Villanueva

Faculty, Staff and Student Publications

Objective: Ultrasound-targeted microbubble (MB) cavitation (UTMC) is an image-guided therapeutic oligonucleotide delivery platform utilizing intravenously injected gas-filled ultrasound contrast agents, which carry the therapeutic on the MB shell. During transit of MBs in the microcirculation of target tissue, ultrasound causes MB oscillation, facilitating endocytosis-independent payload uptake within insonified cells. Here, we tested the hypothesis that UTMC-mediated miR-27a* delivery will reduce tumor growth rate and result in accumulation of miR-27a* within tumor cells and the tumor microenvironment.

Methods: We used UTMC to deliver miR-27a* to SCC-VII cells in vitro and in SCC-VII mouse tumor models. Pulsed ultrasound was delivered during intravenous …

Who Classification Of Skin Tumours: Key Updates In The Fifth Edition, Gabrielle Goldman-Lévy, Raymond Barnhill, Boris C Bastian, Werner Kempf, David Elder, Pedram Gerami, Wayne Grayson, Dmitry Kazakov, Daniela Massi, Jane Messina, Arnaud De La Fouchardière, Alexander J Lazar, Thomas Brenn, Brian Rous, Andrew Field, Anthony Gill, Jennelle C Hodge, Joseph D Khoury, Katia Leite, Shahin Sayed, Puay Hoon Tan, Rosalie Elenitsas, Eduardo Calonje, Lyn M Duncan, Liang Zhiyong, Holger Moch, Rajendra Singh, Harshima Wijesinghe, Ian Cree, Dilani Lokuhetty

Faculty, Staff and Student Publications

The 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: 'Tumours of the nail unit' and 'Metastases to skin', along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours.