Digital Commons Network^™

Loss Of Idh1 And Idh2 Mutations During The Evolution Of Metastatic Chondrosarcoma, William Cross, Iben Lyskjær, Christopher Davies, Abigail Bunkum, Ana Maia Rocha, Tom Lesluyes, Fernanda Amary, Roberto Tirabosco, Cristina Naceur-Lombardelli, Mariam Jamal-Hanjani, Charles Swanton, Nischalan Pillay, Simone Zaccaria, Adrienne M Flanagan, Peter Van Loo

Faculty, Staff and Student Publications

Driver mutations in IDH1 and IDH2 are initiating events in the evolution of chondrosarcoma and several other cancer types. Here, we present evidence that mutant IDH1 is recurrently lost in metastatic central chondrosarcoma. This may reflect either relaxed positive selection for the mutant IDH1 locus, or negative selection for the hypermethylation phenotype later in tumor evolution. This finding highlights the challenge for therapeutic intervention by mutant IDH1 inhibitors in chondrosarcoma.

Predicting The Response Of Triple Negative Breast Cancer To Neoadjuvant Systemic Therapy Via Biology-Based Modeling And Habitat Analysis, Casey E Stowers, Chengyue Wu, Clinton Yam, Jingfei Ma, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Despite being the standard-of-care treatment, neoadjuvant therapy (NAT) attains a complete response only in approximately half of the patients with triple negative breast cancer. Thus, methods to predict and optimize patient response to NAT are needed. Previously, we employed patient-specific MRI data to calibrate a biology-based mathematical model that describes cell movement, proliferation, and death due to drug at the tumor level and cell proliferation at an image voxel level. We now extend our approach by using MRI data to group voxels into "habitats" whereby tumor cells of a habitat share the same proliferation. With this approach, we now calibrate …

Current Status And Future Directions For The Use Of Artificial Intelligence In Pediatric Critical Care Nephrology, Sameer Thadani, Christopher M Horvat, Christin Silos, Bronwyn Sutherland, Kristin Dolan, Jin Chen, Ayse Akcan-Arikan, Javier A Neyra

Library Staff Publications

Artificial intelligence (AI) has the potential to significantly improve the practice of medicine. However, its application in pediatric critical care nephrology remains underdeveloped. This scoping review investigates the current state of AI/machine learning (ML) algorithms developed and implemented in the field of pediatric critical care nephrology over more than two decades (2000-2024). We identified 24 articles related to commonly encountered pathologies including acute kidney injury (AKI), electrolyte and acid-base imbalances, fluid management, and dialysis. Twenty (80%) of these articles focused on AKI (prediction and/or detection) and only two articles (4%) investigated the impact of implemented AI/ML models on clinical care …

Leaping Between Branches: Hybridisation And The Tangled Evolutionary History Of True Lemurs, Giacomo Mercuri, Giovanni Merici, Kyle Kai-How Farh, Lukas F K Kuderna, Jeffrey Rogers, Tomàs Marques-Bonet, Giuseppe Donati, Riccardo Percudani, Cristian Capelli

Faculty, Staff and Students Publications

The true lemurs (genus Eulemur) are a genetically diverse and spatially widespread group of species inhabiting most of Madagascar's forests. Including 12 recognized species, the genus can be divided into four major evolutionary groups: E. rubriventer, E. mongoz, the Brown Lemur Species Complex (BLSC), and the coronatus-macaco-flavifrons complex (CMFC), although monophyly for the CMFC is not always supported. Recent genome-based studies highlighted topological and chronological differences between nuclear and mitochondrial phylogenies of true lemurs, which could be explained by events of hybridisation. In order to reconstruct the evolutionary history of the genus, we test for gene-flow between Eulemur clades using …

Advances In Artificial Intelligence For Glioblastoma Radiotherapy Planning And Treatment, Reid Master, Nesha Rubin, James Sampson, Kamlesh K Yadav, Shruti Pandita, Aria Sabbagh, Anika Krishnan, Patrick J Silva, Kenneth S Ramos, Vincent Gregoire, Nikos Paragios, Sunil Krishnan, Tej K Pandita

The Brown Foundation: Institute of Molecular Medicine

Glioblastoma is an aggressive central nervous system tumor characterized by diffuse infiltration. Despite substantial advances in oncology, survival outcomes have shown little improvement over the past three decades. Radiotherapy remains a cornerstone of treatment; however, it faces several challenges, including considerable inter-observer variability in clinical target volume delineation, dose constraints associated with adjacent organs at risk, and the persistently poor prognosis of affected patients. Recent advances in artificial intelligence, particularly deep learning, have shown promise in automating radiation therapy mapping to improve consistency, accuracy, and efficiency. This narrative review explores current auto segmentation frameworks, dose mapping, and biologically informed radiotherapy …

Botulinum Toxin Combined With Robot-Assisted Therapy For Post-Stroke Spasticity: A Systematic Review, Salvatore Facciorusso, Stefania Spina, Mirko Filippetti, Rajiv Reebye, Gerard E Francisco, Andrea Santamato

Faculty, Staff and Student Publications

Background: Post-stroke spasticity limits motor recovery and independence. Combining botulinum toxin type-A (BoNT-A) injection with intensive, task-specific robot-assisted therapy (RAT) might enhance neuroplasticity and functional gains, but its additive effect and optimal timing are uncertain. (

Methods: We systematically searched major medical databases and trial registries up to April 2025 for randomized controlled trials in adults with post-stroke spasticity comparing botulinum toxin type-A injection plus RAT with toxin injection plus conventional therapy, or RAT alone with RAT combined with toxin injection. Risk of bias was assessed using the RoB 2 tool, and findings were synthesized narratively.

Results: Seven trials ( …

Targeting The Hepatic Circadian Clock Concomitant With Tyrosine Kinase Inhibition Reverses Late-Stage Hepatocellular Carcinoma, Baharan Fekry, Savera Aggarwal, Rachel Van Drunen, Rafael Bravo, Andy Escalante, Constance Atkins, Sheng Pan, Zheng Chen, Kai Sun, David R Hall, Mamoun Younes, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Most patients present at advanced stages, and the effectiveness of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors is constrained by limited patient response. A subset of HCC shows elevated expression of the promoter 2 ("P2")-driven hepatocyte nuclear factor 4 alpha (HNF4α) isoform, which directly transcriptionally represses the circadian brain and muscle ARNT-like protein 1 (BMAL1) transcription factor. This subtype of HCC is robustly inhibited by the plant-based flavonoid nobiletin (NOB), a circadian-fortifying compound. Using patient-matched human HCC and serum, we show that BMAL1-deficient HCC shows exaggerated carnitine palmitoyl transferase …

Hemolysis Detection Using The Gem 7000 At The Point Of Care In A Pediatric Hospital Setting: Does It Affect Outcomes?, Ridwan B Ibrahim, Nazmin Bithi, Charlene Hernandez, Hanna Uhrova, Brandy D Recio, Sridevi Devaraj

Faculty, Staff and Students Publications

No abstract provided.

An Analysis Of Diagnostic Metabolomic Profiles Associated With Hepatotoxicity During Childhood All Induction Therapy, Emily J Mason, Anna M Crain, Michael E Scheurer, Philip J Lupo, Karen R Rabin, Olga A Taylor, Marley Roberts, John P Woodhouse, Ashley Chavana, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, M Monica Gramatges, Joanna S Yi, Sandi L Pruitt, M Brooke Bernhardt, Hong Zhu, Steven D Mittelman, Van Huynh, Etan Orgel, Jeremy M Schraw, Austin L Brown

Faculty, Staff and Students Publications

Hepatotoxicity is a well-documented complication of induction chemotherapy for acute lymphoblastic leukemia (ALL), but our understanding of its biological mechanisms is limited. We identified 314 patients with ALL (aged 1-19 years) treated at Texas Children’s Hospital (2008-2019) with diagnostic bone marrow plasma available for metabolomic profiling: 234 for discovery and 80 for replication. Hepatotoxicity during induction was defined as follows: (1) transaminitis: grade ≥3 aspartate aminotransferase or alanine aminotransferase or (2) conjugated hyperbilirubinemia: conjugated bilirubin (c.bili) >3 mg/dL. Untargeted profiling detected 519 metabolites. Adjusted odds ratios (aORs) for each metabolite were calculated with logistic regression, accounting for sex, age, body …

Nivolumab Plus Ipilimumab Induce Hyper-Progression In Renal Medullary Carcinoma: Results Of A Phase Ii Trial And Preclinical Evidence, Melinda Soeung, Xinmiao Yan, Ciro Zanca, Jing Qian, Menuka Karki, Fei Duan, Hania Khan, Li Zhang, David H Peng, Mariah Williams, Rong He, Ziheng Chen, Luigi Perelli, Jianfeng Chen, Rebecca S Tidwell, Pankaj K Chauhan, Courtney N Le, Truong N A Lam, Nirjar Bhattacharya, Rutvi Shah, I-Lin Ho, Jason P Gay, Caroline C Carrillo, Ningping Feng, Kang Le, Guang Gao, Teresa L Perry, Faika Mseeh, Yongying Jiang, Quanyun A Xu, Niki Marie Zacharias, Rahul A Sheth, Tharakeswara K Bathala, Priya Rao, Najat C Daw, Durga N Tripathi, Cheryl L Walker, Mohammad M Mohammad, Jianhua Zhang, Guangchun Han, Yanshuo Chu, Ruiping Wang, Minghao Dang, Enyu Dai, Fuduan Peng, Yunhe Liu, Akshaya Jadhav, Wenhua Lang, Claudio A Arrechedera, Leticia Campos Clemente, Edwin R Parra, Hsinyi Lu, Cara L Haymaker, Ignacio I Wistuba, Andrew Futreal, Andrea Viale, Michael J Soth, Philip Jones, Joseph R Marszalek, Timothy Heffernan, Giulio F Draetta, Nizar M Tannir, Jianjun Gao, Linghua Wang, Giannicola Genovese, Pavlos Msaouel

Faculty, Staff and Students Publications

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here we report the results of a phase II clinical trial (NCT03274258) of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in patients with RMC, with objective response rate as primary outcome. Enrollment was halted for futility at a prespecified interim analysis as all 10 treated patients experienced rapid disease progression. 5/10 met radiological criteria for hyperprogression and median progression-free survival (secondary outcome) was 1.38 months (95% confidence interval: 1.28, 1.60). In a post-hoc single-cell RNA sequencing analysis, data from patients with RMC before and after nivolumab plus ipilimumab treatment indicated that …

Turning Patients' Open-Ended Narratives Of Chronic Pain Into Quantitative Measures: Natural Language Processing Study, Raquel Norel, Jennifer Gewandter, Zhengwu Zhang, Anika Tahsin, Chadi G Abdallah, John Markman, Zhiyao Duan, Guillermo Cecchi, Paul Geha

Faculty, Staff and Students Publications

Background: Subjective report of pain remains the gold standard for assessing symptoms in patients with chronic pain and their response to analgesics. This subjectivity underscores the importance of understanding patients' personal narratives, as they offer an accurate representation of the illness experience.

Objective: In this pilot study involving 20 patients with chronic low back pain (CLBP), we applied emerging tools from natural language processing (NLP) to derive quantitative measures that captured patients' pain narratives.

Methods: Patients' narratives were collected during recorded semistructured interviews in which they spoke about their lives in general and their experiences with CLBP. Given that NLP …

Hemorrhage-Related Maternal Morbidity Of Secondary Compared To Primary Postpartum Hemorrhage, Matthew R Carroll, Sarah Tounsi, Jessica L Gerard, Susan M Leong-Kee, Laurie S Swaim, Mark A Turrentine

Faculty, Staff and Students Publications

Objectives: To compare a composite hemorrhage-related maternal morbidity in individuals with secondary to primary postpartum hemorrhage and treatment interventions utilized.

Methods: A retrospective case-control study of deliveries complicated by secondary postpartum hemorrhage was performed at a tertiary care center. To estimate a clinically relevant increase of 50 % in the composite maternal hemorrhage-related maternal morbidity (35-53 % absolute increase) in individuals with secondary postpartum hemorrhage, a correlation coefficient of 0.2, at an 80 % power with a p < 0.05 with a two-sided test would require 95 individuals with secondary postpartum hemorrhage be matched to 95 individuals with a primary postpartum hemorrhage. Logistic regression analysis was used to evaluate the outcome of the composite of hemorrhage-related maternal morbidity.

Results: From January 2018 through December 2022, 33,026 deliveries occurred, and 94 individuals were identified that were admitted with secondary postpartum hemorrhage, …

Optimizing Lower Intensity Triplet Therapy In Acute Myeloid Leukemia: A Practical Guide, Wei-Ying Jen, Curtis A Lachowiez, Jennifer Marvin-Peek, Jessica K Altman, Musa Yilmaz, Jacqueline S Garcia, Yasmin Abaza, Nicholas J Short, Joshua F Zeidner, Naval G Daver, Andrew H Wei, Ghayas C Issa, Courtney D Dinardo

Faculty, Staff and Student Publications

Venetoclax-based doublets with azacitidine or low dose cytarabine are the standard of care for the treatment of acute myeloid leukemia (AML) in older patients or those unfit for intensive chemotherapy. However, some patients do not attain complete remission, and over time, most patients relapse. Frontline triplet therapy incorporating a targeted therapy (FLT3, IDH or menin inhibitor) is an emerging treatment concept under investigation for this population. Initial triplet regimens have yielded encouraging composite complete remission and measurable residual disease negativity rates, enabling the transition to allogeneic stem cell transplantation for eligible patients. While effective, triplets are associated with myelosuppression and …

Patient-Reported Outcomes After Ipsilateral Radiation Therapy For N2b Tonsillar Squamous Cell Carcinoma, Chike O Abana, Adam S Garden, G Brandon Gunn, Gregory M Chronowski, Abdallah S R Mohamed, Andrew J Frankart, Natalie Geier, Houda Bahig, Carly E A Barbon, Kate Hutcheson, Vinita Takiar, Clifton D Fuller, Steven J Frank, David I Rosenthal, Jack Phan

Faculty, Staff and Student Publications

Background: Previous studies have reported excellent disease control and survival in patients with well-lateralized, American Joint Committee on Cancer (AJCC)-7 T1-2N2b tonsillar squamous cell carcinoma (SCC). The reduced treatment volume is associated with lower rates of physician-assessed toxicity. Patient-reported outcomes (PROs) have been proposed as a similarly reliable measure, but the body of literature is limited for unilaterally treated patients. Our goal was to review PROs of such patients who had reduced treatment volumes.

Methods: We reviewed PROs of patients with AJCC-7 T1-2N2b disease treated with ipsilateral radiation therapy (RT), with or without surgery or chemotherapy before RT. PROs were …

Coordinated Transfer Of Dna Between Pol Θ And Pol Δ Resets Microhomology Choice During Double-Strand Break Repair, Yuzhen Li, Mark Returan, Adele T Guerin, April M Averill, Dorcas Oladapo, Sylvie Doublié, Richard D Wood

Faculty, Staff and Student Publications

DNA polymerase theta (Pol θ)-mediated end joining (TMEJ) initiates DNA double-strand break repair by using short homologies (microhomologies) between single-stranded DNA tails. This repair process is particularly important in cancer cells defective in homologous recombination. The exonuclease function of DNA polymerase delta (Pol δ) has been identified as an essential component for TMEJ, functioning to remove unpaired bases flanking a microhomology (MH). It is not known if the exonuclease removes all unpaired bases at once and how this removal might affect subsequent MH selection. Here, we reconstituted a functional TMEJ repair process using purified human Pol θ and Pol δ. …

Stiefel Md Anderson Oropharynx Cancer (Mda-Opc) Cohort: A Single-Institution, Prospective Longitudinal Outcomes Study, Amy Moreno, Ariana J Sahli, Faye Johnson, Xiaowen Sun, Carly Barbon, Waree Rinsurongkawong, Wenye Song, Flavie M Luciani, Han Liang, Jun Li, Wei Liu, J Jack Lee, S J Frank, Stephen Lai, Clifton Fuller, Katherine Hutcheson

Faculty, Staff and Student Publications

Purpose: The MD Anderson Oropharynx Cancer (MDA-OPC) cohort is a unique single-institution, prospective longitudinal cancer cohort. The cohort aims to enhance the therapeutic index of OPC management by supporting data needs for independent investigators to conduct rigorous observational studies examining exposures and factors associated with acute and late toxicities, cancer progression, recurrence, new malignancies and quality of life in OPC survivors.

Participants: A total of 1811 patients with OPC with a minimum follow-up of 6 months have been consented to our prospective registry between 18 March 2015 and 29 December 2023. Clinical and treatment (Tx) data are available on all …

Study On The Mechanical Characteristics Of A Natural Fiber-Based Hybrid Polymer Composite, Mohan Kumar Anand Raj, P Manoj Kumar, Praveensabari Palanisamy, Sanjay Dharmaraju, Sureshkumar Periyasamy, Murugesan Palaniappan, Dawit Tafesse Gebreyohannes

Faculty, Staff and Students Publications

In this work, the hybrid fiber-based epoxy composite samples have been prepared with the application of three unlike organic natural fibers viz., Sisal (S), Ramie (R), and Flax (F) and epoxy as the matrix, with a weight ratio of 70:30 for epoxy and fibers. Six different stacking sequences of fibers, pure fibers and pure matrix were used for specimen preparation, namely S/F/F/F/S, F/S/S/S/F, F/R/R/R/F, R/F/F/F/R, R/S/S/S/R, S/R/R/R/S, PS, PR, PF, and Pure matrix. The composite specimen was prepared by manually and uniform thickness was obtained by the compression moulding process. The mechanical trials such as, tensile, impact, hardness, and flexural …

A Contemporary Review On Heart Failure With Improved Ejection Fraction, Allison Weiss, Ambre Flowers, Scott D Eisenberg, Lingling Wu, Mario Rodriguez, Muzamil Khawaja, Errol Moras, Carl J Lavie, Gregg C Fonarow, W H Wilson Tang, Biykem Bozkurt, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Heart failure is a complex condition caused by various etiologies that reduce cardiac output or increase cardiac pressures. It is classified by left ventricular ejection fraction, a key prognostic factor. New therapies, devices, and better management of secondary causes have improved outcomes. A recently identified group-those with heart failure and improved ejection fraction-shows better prognosis. This review explores its definition, causes, clinical significance, and management strategies.

Live-Cell Quantitative Monitoring Reveals Distinct, High-Affinity Gβγ Regulations Of Girk2 And Girk1/2 Channels, Reem Handklo-Jamal, Tal Keren Raifman, Boris Shalomov, Patrick Hofer, Uri Kahanovitch, Theres Friesacher, Galit Tabak, Vladimir Tsemakhovich, Haritha P Reddy, Orna Chomsky-Hecht, Debi Ranjan Tripathy, Kerstin Zuhlke, Carmen W Dessauer, Enno Klussmann, Yoni Haitin, Joel A Hirsch, Anna Stary-Weinzinger, Daniel Yakubovich, Nathan Dascal

Faculty, Staff and Student Publications

Gi/o protein-coupled receptors (GPCRs) inhibit cardiac and neuronal excitability via G protein-activated K+ channels (GIRK), assembled by combinations of GIRK1 - GIRK4 subunits. GIRKs are activated by direct binding of the Gβγ dimer of inhibitory Gi/o proteins. However, key aspects of this textbook signaling pathway remain debated. Recent studies suggested no Gi/o-GIRK pre-coupling and low (>250 µM) Gβγ-GIRK interaction affinity, contradicting earlier sub-µM estimates and implying low signaling efficiency. We show that Gγ prenylation, which mediates Gβγ membrane attachment required for GIRK activation, also contributes to the Gβγ-GIRK interaction, explaining the poor affinity obtained with non-prenylated Gβγ. Using quantitative …

Analysis Of A Deeply-Phenotyped Familial Hypercholesterolemia Cohort From Mexico Shows A Role For Both Rare And Common Alleles Across Known Dyslipidemia Genes And Reveals Structural Variation In A Novel Locus, Nicholas Katsanis, Niki Mourtzi, Consuelo D Quinto-Cortés, Alexandro J Martagon, Alexander G Ioannidis, Francisco M De La Vega, Jeff Gulcher, Ming Ta Michael Lee, Mohammad A Faghihi, Arturo Lopez-Pineda, Sonia Moreno-Grau, Daniel Mas Montserrat, Míriam Barrabés, David Bonet, Pavel Salazar Fernandez, Jeff Wall, Babak Moatamed, Roopa Mehta, Gabriela A Galan-Ramirez, Rafael Zubirán, Daniel Elias-Lopez, Teresa Tusié-Luna, Carlos A Aguilar-Salinas, Carlos D Bustamante

Faculty, Staff and Student Publications

Familial hypercholesterolemia (FH) is a genetic disorder driven in part by mutations in three genes that encode components of the cholesterol pathway: LDLR, APOB, and PCSK9. However, the majority of FH genetics has been performed in individuals of European descent. Here, we leveraged a cohort of 300 patients from the Mexican FH registry to understand how rare, high liability alleles and common variants might contribute to shaping individual risk. Using a combination of whole exome and of short- and long-read whole genome sequencing, we report three key findings. First, we observed that rare pathogenic point mutations and structural variants in …

Mycobacterium Chelonae Outbreak Investigation At A Quaternary Pediatric Hospital Following The Opening Of A Leed-Certified Critical Care Tower: Where Does Water Sustainability Intersect With Infection Control?, Andrea L Ankrum, Silvia M Caceres, Michael Torsell, Elaine Epperson, Vinicius Calado Nogueira De Moura, Jennifer J Gilick, Michael Strong, Qingyun Liu, Matthew J Strand, Rachel N Wilsey, Jennifer R Honda, Jane E Gross, Felicia A Scaggs-Huang

Faculty, Staff and Student Publications

Objective: Investigate the increased incidence of Mycobacterium chelonae positive respiratory cultures in hospitalized patients.

Design: Apply the Healthcare-Associated Links in Transmission of Nontuberculous Mycobacteria (HALT NTM) toolkit to an outbreak investigation of M. chelonae.

Setting: Quaternary-care pediatric hospital and medical center in the United States with a recently opened LEED-certified critical care tower.

Patients: Adult and pediatric patients with M. chelonae positive respiratory cultures between June 2022 and January 2024.

Methods: An epidemiological investigation involving clinical and laboratory practices, water management, building construction and renovation projects. Environmental sampling of air vents, water sources and endoscope reprocessing equipment was performed. M. …

Naphthalimide-Based Type-I Nano-Photosensitizers For Enhanced Antitumor Photodynamic Therapy: H2s Synergistically Regulates Pet And Self-Assembly, Huiyu Niu, Songnan Wang, Yang Liu, Nana Ma, Shuaiwei Cheng, Beidou Feng, Hyunsun Jeong, Yonggang Yang, Ge Wang, Tony D James, Juyoung Yoon, Jonathan L Sessler, Hua Zhang

Faculty, Staff and Student Publications

Photodynamic therapy (PDT) relies on a combination of light and photosensitizers (PSs) to achieve local control over cancerous lesions. However, it is subject to limitations, including tumor hypoxia, low tumor targeting, off‐target phototoxicity, and always‐on fluorescence. Here, we propose a design strategy for activated nano‐PSs (N‐PSs) to simultaneously overcome the limitations of PDT, wherein photoinduced electron transfer (PeT) is coupled with an endogenous H2S‐regulated self‐association process to promote Type‐I photochemical reactions. Using theoretical calculations, spectral analysis, and microscopic imaging, we verified the generation of self‐assembly and occurrence of PeT. And it was also shown that H2S could synergistically inhibit the …

Profiling Tumour-Infiltrating Immune Cells In A Large Paediatric Medulloblastoma Cohort: A Retrospective Analysis, Mingze Chen, Xiangjun Shi, Yi Wang, Jiao Zhang, Jirong Guo, Xiuchen Guan, Yu Sun, Wenhao Wu, Chunde Li, Yongji Tian, Yunwei Ou, Tian Li, Kai Jiang, Michael D Taylor, Xuebin Liao, Liwei Zhang, Tao Sun

Faculty, Staff and Students Publications

Background: Tumour-infiltrating immune cells exert both pro-tumour and anti-tumour effects on intracranial tumours. In this study, we investigated the prognostic value of various infiltrating immune cells in medulloblastoma (MB) within a large cohort.

Methods: We employed multiplex immunofluorescent (mIF) staining of tissue microarrays to assess the densities of T cells, B cells, NK cells, macrophages, and immune checkpoints in tumour samples from 249 primary paediatric patients with primary MB. Overall survival (OS) analysis, progression-free survival (PFS), and Cox regression analyses were utilised to explore potential relationships between immune cell densities and survival outcomes. Subsequently, multivariate Cox regression was validated using …

Divergent Prefrontal Cortex Circuits Regulate Cued Food Seeking Under Distinct Metabolic Or Emotional States, Xu O Zhang, Guillermo Aquino-Miranda, Claire E Cho, Yongzhe Wang, Duy Hoang Ha, Nikita Elinson-Watson, Allen Dong, Caleb Kemere, Fabricio H Do-Monte

Faculty, Staff and Student Publications

Flexibly adjusting food-seeking behaviour in response to food-associated cues and internal states is crucial for animals' survival. However, the neural mechanisms that modulate cued food-seeking behaviour during varying metabolic (i.e., hungry vs. satiated) and emotional (i.e., safe vs. threatened) states remain elusive. Here, we show that the encoding of metabolic or threat states in projection-defined neurons in the prelimbic cortex (PL) mediates cued food-seeking responses in rats. Using microendoscopic imaging, we demonstrate that neural population dynamics in PL consistently represent food cues, task-relevant behaviours, and internal state changes by recruiting distinct subsets of cue-responsive neurons at each state. Single-unit recording …

Bilateral Concomitant Infection Of Cytomegalovirus And Varicella-Zoster Virus Retinitis In An Immunocompromised Adult, Henry C Skrehot, Amer Alsoudi, Daniel Olson, Nhon Le, Asad Loya, Tahira Scholle

Faculty, Staff and Students Publications

Purpose: To report a novel case of bilateral concomitant cytomegalovirus (CMV) retinitis and acute retinal necrosis (ARN) due to varicella-zoster virus (VZV) in an immunocompromised adult.

Methods: A case report was evaluated.

Results: A 36-year-old immunocompromised man presented with acute painful vision loss in the left eye. On initial presentation, uncorrected distance visual acuity was 20/20 in the right eye and counting fingers at 3 feet (≈1 m), which deteriorated to no light perception (NLP) in the left eye. Fundus examination showed necrotizing retinitis in both eyes, with features of both CMV retinitis and ARN. One week after initiation of …

Analysis And Interpretation Of Somatic Nmd-Escaping Variants In Oncogenes And Dual-Function Genes Across Adult And Pediatric Cancer Cohorts, Mohammad K Eldomery, Karissa M Dieseldorff Jones, Maria Namwanje, Runjun D Kumar, Jiaming Li, Mark R Wilkinson, Lu Wang, Jeffery M Klco, Li Tang, Jennifer L Neary, Sharon E Plon, Patrick R Blackburn

Faculty, Staff and Students Publications

Interpreting protein-truncating variants predicted to escape nonsense-mediated decay (NMDe) based on the 50-bp rule is challenging due to their variable consequences. The Clinical Genome Resource, Cancer Genomics Consortium, and Variant Interpretation for Cancer Consortium recommendations focus on tumor suppressor genes where NMDe variants may result in loss-of-function. However, guidance for interpreting NMDe variants in oncogenes and dual-function genes remains limited. To address this gap, we screened the Catalogue of Somatic Mutations in Cancer, focusing on oncogenes and dual-function genes with ≥10 NMDe variants supported by published functional studies. This analysis prioritized 15 genes exhibiting two distinct NMDe patterns resulting in …

Retraction Note: Runt-Related Transcription Factor 1 Promotes Apoptosis And Inhibits Neuroblastoma Progression In Vitro And In Vivo, Mei Hong, Jing He, Duo Li, Yuanyuan Chu, Jiarui Pu, Qiangsong Tong, Harish C Joshi, Shaotao Tang, Shiwang Li

Faculty, Staff and Students Publications

No abstract provided.

The Time-Dependent Association Between Irritable Bowel Syndrome And All-Cause And Cause-Specific Mortality In The Nih-Aarp Cohort Study, Daniela S Gutiérrez-Torres, Fangyu Li, Linda M Liao, Carrie R Daniel, Shreela V Sharma, Ruosha Li, Eric L Brown, Qing Lan, Maki Inoue-Choi, Baharak Moshiree, Paul Albert, Rashmi Sinha, Emily Vogtmann

Faculty, Staff and Student Publications

Introduction: Evidence on the association between irritable bowel syndrome (IBS) and mortality is conflicting. In this study, we estimated the association between IBS and all-cause and cause-specific mortality in the NIH-AARP Diet and Health Study.

Methods: IBS diagnoses between 1994 and 2008 were identified from Medicare claims data, and mortality outcomes through 2019 were obtained through linkage to the National Death Index. Using multivariable Cox proportional hazards regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality within partitioned follow-up time categories (>2-5, >5-8, >8-11, >11-14, >14-17, and >17 years) with adjustment …

Impact Of Peek Implant Surface Design On Postoperative Complications In Cranioplasty: A Retrospective Review, Carmen A Zavala, Laura Zima, Subhiksha Srinivasan, Sanjay V Neerukonda, Mark J Dannenbaum

Faculty, Staff and Student Publications

Background: The aim of this study was to evaluate and compare complication rates and clinical outcomes associated with smooth and perforated polyetheretherketone (PEEK) implants used in cranioplasty.

Methods: A retrospective analysis of 94 patients who underwent cranioplasty with either smooth (n = 45) or perforated (n = 49) PEEK implants over a five-year period was conducted. Patient demographics, comorbidities, reasons for initial craniectomy, time interval between craniectomy and cranioplasty, postoperative complications, hospital stays, and rates of revision surgeries were analyzed. Multivariate logistic regression was used to control for confounding factors.

Results: No statistically significant differences were observed in demographic characteristics, …

Alteration Of Gut Microbial Ecology By The Direct Activation Of The Brain: Inverse Gut-Microbiome-Brain Dynamics, I-Ching Wang, Jessica L Swanson, Jillian L Waters, Mikhail Y Kochukov, Shelly A Buffington, Sean W Dooling, Benjamin R Arenkiel, Mauro Costa-Mattioli

Faculty, Staff and Students Publications

The gut-microbiome-brain axis is a bidirectional communication system influencing host physiology and overall fitness. While "bottom-up" effects-where gut microbes influence brain function and behavior-are well established, direct evidence for "top-down" modulation-where the brain shapes the gut microbial ecology-remains elusive. Here, we show that the selective expression of the bacterial ion channel mNaChBac in glutamatergic lateral habenula (LHb) neurons increases their bursting activity and leads to endophentypes associated with depression. Importantly, this chronic activation leads to changes in the gut microbiome composition over time, as reflected by shifts in alpha-diversity and alterations in specific microbial taxa. These findings provide direct evidence …