Digital Commons Network^™

Identifying Sorafenib Benefit Among Patients With Hepatocellular Carcinoma: A Transcriptomic And Genomic Approach, Sun Young Yim, Hayeon Kim, Tae Hyung Kim, Sang-Hee Kang, Youngwoo Lee, Eunho Choi, Yang Jae Yoo, Seong Hee Kang, Young-Sun Lee, Young Kul Jung, Yeon Seok Seo, Hyung Joon Yim, Jong Eun Yeon, Kyung Suk Yang, Yitao Tang, Bowha Sohn, Yun Seong Jeong, Hyewon Park, Han Liang, Ju-Seog Lee, Ji Hoon Kim

Faculty, Staff and Student Publications

Background & aims: Sorafenib has been a cornerstone of hepatocellular carcinoma (HCC) therapy; however, its efficacy is limited, and identifying patients who will benefit from sorafenib is challenging. We aimed to identify predictive biomarkers of sorafenib benefit in patients with HCC.

Methods: Gene expression data from 33 HCC tumors treated with sorafenib were analyzed to construct a prediction model aimed at identifying patients with greater benefit from sorafenib treatment. The robustness of the predictor was validated using gene expression data from two phase III clinical trials, IMbrave150 and STORM.

Results: The analysis of transcriptome data revealed a 50-gene signature, the …

Platelets Cause Microvascular Occlusion And Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice., Ari Dienel, Sung-Ha Hong, Kiara Torres, Kanako Matsumura, Jose Guzman, Peeyush Thankamani Pandit, Bibek Samal, Harveen Kaur, Samitha Nemirajaiah, Angelica Bernal, H Alex Choi, Louise D Mccullough, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

After subarachnoid hemorrhage (SAH), some patients develop delayed neurological deficits (DND). Microthrombi are considered a contributing factor to DND, but clinical trials of antiplatelets had mixed results. Existing research suggests that platelets play a role in the etiology of DND, but no comprehensive study has tested causality between platelets and DND after SAH. Here we hypothesize that after SAH, platelet activation promotes microthrombi formation, occlusion of the brain microvasculature and contributes to DND, and that inhibiting platelet aggregation is a therapeutic strategy. Mice experiencing SAH were administered various interventions. The animals were subjected to stimulation of platelets, platelet depletion, or …

Eating For Healthy Eyes: The Role Of Nutrition In Ocular Health, Brianna Stroh

Honors Program: Senior Projects (Public)

The central research question of this thesis asks: How does nutrition influence ocular health overall and the impact of nutrition on the development or progression of common eye diseases? Building upon existing research in optometry/ophthalmology, nutrition science, and public health, this project examines the physiological mechanisms linking diet to eye health and evaluates how specific nutrients and dietary patterns contribute to disease prevention and visual function. This thesis employs a comprehensive review of peer-reviewed literature to evaluate the relationship between nutrition and ocular disease. Key areas of focus include the role of oxidative stress in eye disease development, the protective …

Single-Center Experience Using Endologix Anatomically Fixated Endograft Device For Treatment Of Aortoiliac Occlusive Disease, Isabella Muti, Gaurang Joshi, Dawn M. Salvatore, Michael J. Nooromid, Paul J. Dimuzio, Babak Abai

Department of Surgery Faculty Papers

OBJECTIVE: The covered endovascular reconstruction of the aortic bifurcation (CERAB) technique was developed in recent years as a novel surgical intervention for aortoiliac occlusive disease (AIOD). One tool frequently used in such procedures is the anatomically fixated endograft (AFX), manufactured by Endologix. The present study aimed to review the outcomes of patients with AIOD after CERAB procedure using the Endologix AFX device.

METHODS: This is an institutional review board-approved retrospective study investigating the experience of a single center in using Endologix's AFX device as CERAB for AIOD from September 2018 to June 2024. Data were obtained from the medical records …

Initial Site Of Metastasis Influences Prognosis In Pancreatic Ductal Adenocarcinoma, Eleanor Mancheski, David Baek, Wilbur Bowne, Harish Lavu, Charles Yeo, Avinoam Nevler

Department of Surgery Faculty Papers

INTRODUCTION: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a highly aggressive malignancy. Prior studies suggest that the initial site of metastasis may impact prognosis. This study investigates whether overall survival in mPDAC patients differs between patients first presenting with lung metastases versus those presenting with liver metastases.

METHODS: This retrospective analysis utilized the multi-institutional TriNetX database, identifying patients with histologically diagnosed PDAC who initially presented with either liver or lung metastases. Demographic, histologic, and outcome data were collected and analyzed. Patients were matched 1:1 using a nearest neighbor propensity score (PS) algorithm, and Kaplan-Meier survival analyses were performed. Cox regression was …

Concerns Regarding The Efficacy Of Utilizing The Vibrational Response Of Aminocyanine Molecules To Near Infrared Light For Cancer Cell Destruction, Parsa Faghani-Eskandarkolaei, James Welsh, Seyed Ali Reza Mortazavi, Parmis Taghizadeh, Mobina Baramaki, Fatemeh Shams, Mohammed Nasir Abubakari, Seyed Mohammad Javad Mortazavi, Lembit Sihver

Informatics and Engineering Systems Faculty Publications

Recent advancements in cancer treatment have introduced the use of aminocyanine molecules, activated by near-infrared (NIR) light, to induce vibrational responses that can selectively destroy cancer cells. This commentary critically examines a study that reports a 99% efficacy of this method against human melanoma cells in vitro, and significant tumor reduction in murine models. While the findings are promising, our analysis highlights crucial oversights in the study’s implications for clinical applications. Specifically, the persistence of even a small fraction of cancer cells post-treatment poses significant risks for tumor regrowth and acquired resistance. Additionally, the study’s approach neglects the heterogeneity of …

Axillary Management After Neoadjuvant Endocrine Therapy (Net), Laura Leonard, Min Yi, Emma Wingate, Puneet Singh, Abigail Caudle, Rosa F Hwang, Isabelle Bedrosian, Vicente Valero, Jennifer Litton, Nuhad Ibrahim, Kelly K Hunt

Faculty, Staff and Student Publications

BACKGROUND: In patients with hormone receptor-positive (HR

PATIENTS AND METHODS: We performed a retrospective review of patients with clinical stage I-III, HR

RESULTS: A total of 230 patients were included; 120 (52.2%) were clinically node-negative (cN0), while 110 (47.8%) were clinically node-positive (cN+). In the cN+ group, 7.3% (8/110) had a nodal pathologic complete response (pCR). In total, 76.4% (84/110) in the cN+ group underwent axillary lymph node dissection (ALND) as the initial axillary procedure, and 90.9% (100/110) underwent ALND overall. In total, 98.3% (118/120) with cN0 disease underwent sentinel lymph node dissection (SLND), and 28 (23.7%) had positive nodes. …

Same Day Discharge Can Be Performed Safely After Atrial Fibrillation Catheter Ablation Using A Wide-Footprint Lattice-Tip Dual-Energy System., Tyler L Taigen, Devi G Nair, Dinesh Sharma, Erich L Kiehl, Jose Osorio, Petr Neuzil, Josef Kautzner, Stavros E Mountantonakis, Andrea Natale, John D Hummel, Shephal K Doshi, Anish K Amin, Usman R Siddiqui, Kelly A Van Bragt, Jeffrey Cerkvenik, Khaldoun G Tarakji, Vivek Y Reddy, Moussa Mansour, Elad Anter

Heart and Vascular Articles

BACKGROUND: Same-day discharge (SDD) after atrial fibrillation (AF) ablation is generally considered safe, since most complications are identified during (or immediately) after the procedure.

OBJECTIVE: This study aimed to evaluate SDD in the SPHERE Persistent-Atrial Fibrillation trial.

METHODS: Patients with persistent AF were randomized to the dual-energy lattice-tip mapping and ablation catheter (investigational) vs a conventional contact-force radiofrequency ablation system (control). SDD and timing of 30-day procedure- or device-related serious adverse events (SAEs) were assessed in the full cohort. In a subset of centers that performed SDD in the trial, predictors of SDD, 30-day readmissions, and mortality rates were assessed. …

When Birth Control Turns Biliary: A Rare Case Of Profound Hyperbilirubinemia From Oral Contraceptives, Taiwo Ajani, Aura Calderon, Jose J. Loayza Pintado, Nayiri Derian, Catherine Matos, Ivan Mogollon, Andres Suarez Parraga

School of Medicine Publications

Oral contraceptives (OCs) are extensively utilized and generally considered safe (reference); nonetheless, infrequent hepatobiliary complications such as cholestasis and hyperbilirubinemia have been documented, particularly among individuals with a genetic predisposition. We present a case involving a 19-year-old female who exhibited significant conjugated hyperbilirubinemia shortly after the commencement of OC therapy. Comprehensive investigations ruled out alternative causes, and the findings from liver biopsy, in conjunction with the clinical context, indicated an estrogen-induced cholestatic injury, likely revealing an underlying Dubin–Johnson syndrome. This case underscores the critical necessity of acknowledging hepatic adverse effects associated with estrogen as well as the influence of genetic …

Trends In Meningioma-Related Mortality Among U.S. Adults: A Cdc Wonder Analysis From 2000 To 2023, Tirath Patel, Rai Muhammad Umar Khan, Fatima Hussain, Meer Murtaza, Muhammad Shayan Tariq, Abuzar Khan, Sara Aleem, Maryam Athar, Sharoz Shahid, Nikhilesh Anand

School of Medicine Publications

Background: Meningiomas are the most common primary intracranial tumors in the United States, comprising nearly 41% of central nervous system tumors. While the majority are benign, atypical (World Health Organization Grade II) and malignant (Grade III) subtypes are clinically significant due to their aggressive biology, higher recurrence, and increased mortality risk. Despite their burden, national mortality trends and demographic disparities in meningioma-related deaths remain underexplored.

Methods: We conducted a population-based analysis of meningioma-related mortality among U.S. adults aged ≥65 years from 1999 to 2023 using the centers for disease control and prevention (CDC) wide-ranging online data for epidemiologic research (WONDER) …

Secondary Syphilis Mimicking Marginal Zone B-Cell Lymphoma In A 70-Year-Old Man., Hannah Gier, Shannon Trotter

Ambulatory and Primary Care Articles

No abstract provided.

Umbilical Cord Milking Versus Early Cord Clamping In Late Preterm And Term Neonates Who Are Non-Vigorous At Birth: A Cluster-Randomized Controlled Trial (Cordmilk Trial), Zubair H. Aghai, Sangappa M. Dhaded, S Yogeshkumar, Sunil S. Virnekar, Benjamin L. Leiby, Vinita Jain, Yvonne E. Vaucher, Nitin Chouthai, Meenakshi Girish, Seema Parvekar

Conference Presentation Abstracts

No abstract provided.

Exploring Single Celled Rna Biomarkers Using Deconvolution Analysis For Severe Retinopathy Of Prematurity In Extremely Premature Newborns, Vighnesh Ghatpande, Saachi A. Bodas, Nitin Chouthai

Conference Presentation Abstracts

Background: Timely, precise diagnosis of Retinopathy of Prematurity (ROP) is key to implementing appropriate treatment, as distinctions between mild-ROP and severe-ROP are the primary factors in its characterization. Deconvolution analysis of bulk RNA sequencing is an indirect method to identify static and dynamic molecular and physiological associations.

Objective: The objective of this this study was to evaluate if deconvolution analysis can be used to identify cellular biomarkers of ROP.

Design/Methods: This is a prospective study (IRB#086113MP2E) with a convenience sample size of 8 neonates with no ROP, 6 neonates with mild to moderate ROP (M-ROP), and 7 neonates with severe …

Complement Anaphylatoxin C5a-Induced Mouse Lymphatic Functions Modulate Interactions Between Endothelial Cells And T Lymphocytes, Haydn E Rich, Yi-Dong Li, Kathryn D Hok, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Anthony Shadid, Rajarajan A Thandavarayan, Hari Krishna Yalamanchili, Marie-Francoise Doursout, Tingting Weng-Mills, Faraz Bishehsari, Nirmal K Banda, Kristin L Eckel-Mahan, Marcos I Restrepo, Pooja Shivshankar

Faculty, Staff and Students Publications

The lymphatic system is a highly branched endothelial tubular network that facilitates the migration of immune cells from the peripheral tissues to lymph nodes (LNs) and other lymphoid organs. Complement factors are essential for innate and adaptive immune functions. Complement anaphylatoxin C5a is crucial in vascular endothelial cell activation and lymphocyte polarization. Understanding the impact of C5a and its cognate receptor C5ar1 signaling on lymphatic function could provide new insights into the mechanisms of immune dysregulation observed in chronic inflammatory diseases. We demonstrate that acute C5a challenge in wildtype C57B6/J mice significantly reduced lymph propulsion compared to their C5ar1-deficient counterparts. …

Fronto-Cerebellar Features Associate With Cognitive Dysfunction In Childhood-Onset Systemic Lupus Erythematosus, Hanne Van Der Heijden, Gabrielle Alonzi, Amanda Cao, Raquel Van Gool, Merve Koç Yekedüz, Lise Vrolix, Itamar Ronen, Vanessa Rameh, Kyle Mcbrearty, Aditi Deokar, Robert P Sundel, Eyal Muscal, Joseph Gonzalez-Heydrich, Andrea Knight, Joyce C Chang, Jaymin Upadhyay

Faculty, Staff and Students Publications

Objective: Cognitive dysfunction (CD) is a prevalent symptom in childhood-onset systemic lupus erythematosus (cSLE). This study aimed to investigate the neurobehavioral basis of CD in cSLE.

Methods: Patients with cSLE (N=20) and age- and sex-matched healthy controls (HCs, N=20) completed questionnaires and multiple neurocognitive tests. The Systemic Lupus Erythematosus Disease Activity Index 2000 and laboratory markers were used to monitor patients' clinical status. Neuroimaging assessments included functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and structural MRI.

Results: cSLE patients demonstrated moderate disease activity with high inflammation and immune dysregulation, alongside low medication adherence. Relative to HCs, cSLE patients …

Trauma-Related Compulsions In Obsessive-Compulsive Disorder: Functional Insights From Factor Analysis, Caitlin M Pinciotti, Max Thorsson, Gregor Horvath, Matti Cervin

Faculty, Staff and Students Publications

Resisting obsessive-compulsive disorder (OCD) compulsions is a key predictor of exposure and response prevention (ERP) effectiveness, yet trauma-exposed individuals with OCD endorse more severe compulsions and are more likely to be labelled 'treatment resistant.' Among trauma-exposed individuals, compulsions are theorised to function to prevent future trauma and cope with trauma-related responses. Recent findings suggest that certain compulsions in the context of trauma exposure differentially impact treatment outcomes, yet missing from extant literature is a larger empirically derived conceptualisation for how trauma may impact the underlying function of compulsions. In a sample of 662 adult patients enroled in intensive OCD treatment …

Black Equality In Ocd Neurogenomics (Belong): Study Protocol, Iasha J Williams, Dalia Y Marquez, Kara E Lopez-Lengowski, Malini Bommiasamy, Ogechi Cynthia Onyeka, Slayton J Underwood, Juliana E Avery, Jacob Gluckman, Thariana Pichardo, Rhea Chandler, Yulu Brown, Katie Mangen, Emma Grace Choplin, Black Equality In Ocd Neurogenomics (Belong) Study Team, Sonyia C Richardson, Joseph D Buxbaum, Eric A Storch, James J Crowley, Sidney H Hankerson, Dorothy E Grice

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is a chronic, serious psychiatric disorder that affects 2%-3% of the population and is associated with high personal and societal costs. Genetic factors are estimated to explain roughly half the risk of developing OCD, and genomic studies are just beginning to identify common and rare genetic variants mediating this risk. A major goal of genomic studies is to yield insights into the etiology of OCD and identify molecular targets for the development of novel therapeutics. However, the overwhelming majority of subjects in existing genetic studies are of European ancestry, limiting the generalizability of these findings. To address …

Body Mass Index And Survival In Children Receiving Extracorporeal Membrane Oxygenation, Pilar Anton-Martin, Keith Baxelbaum, Shilpa Vellore, Erika O'Neil, Vinai Modem, Sameer Thadani

Faculty, Staff and Students Publications

Importance: Underweight and obesity represent opposite ends of the nutritional risk spectrum that negatively affect children's health worldwide. Both conditions have been associated with increased mortality in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) support.

Objective: To investigate the association of underweight and obesity status with pediatric ECMO outcomes using body mass index (BMI) z scores.

Design, setting, and participants: This retrospective cohort analysis used data from the Extracorporeal Life Support Organization (ELSO) database from January 1, 2019, to December 31, 2023. Participants included all pediatric patients from international ECMO centers aged 29 days to 18 years who received ECMO …

Androgen Activity In The Male Embryonic Hindbrain Drives Lethal Pfa Ependymoma, Jiao Zhang, Winnie Ong, Alexandra Rasnitsyn, Ricardo Daniel Gonzalez, Rodrigo Lopez Gutierrez, Polina Balin, Amr Saadeldin, Xiaochong Wu, Maria C Vladoiu, Vicente Santa-Maria Lopez, Fernando Gonzalez-Salinas, Navneesh Yadav, Dinesh Mohanakrishnan, Kannan Boosi Narayana Rao, Raja Gopal Reddy Mooli, Hinda Najem, Sebastian Pacheco, Kaitlin Kharas, Cory Richman, David Przelicki, Evan Y Wang, Haipeng Su, Rachel Naomi Curry, Runze Yang, Michelle Masayo Kameda-Smith, Bryn Livingston, David Scott, Zaili Luo, Mingyang Xia, Namal Abeysundara, Anders W Erickson, Ncedile Mankahla, Lucas Zhongming Hu, Chu Pan, Raul Suarez, Ning Huang, Yihao Wu, Hao Wang, Tajana Douglas, Jonelle Pallota, Steven Hébert, Karen Ng, Krystin Mantione, Heather Whetstone, Hassaan Maan, Hussein Lakkis, Juyeun Lee, Sadeesh K Ramakrishnan, Yanxin Pei, Yujie Tang, Frank Y Lin, Guillermo Aldave, Marco Gallo, Robert M Friedlander, Faiyaz Notta, Laura K Donovan, Murali Chintagumpala, Bo Wang, Yun Li, Daniel D De Carvalho, Zhaolei Zhang, Ying Mao, Wei Hua, Charles Eberhart, Calixto-Hope G Lucas, Sriram Venneti, Poul H Sorensen, Alberto Delaidelli, Hao Li, Wenhao Zhou, Jason Kirk, Dean G Tang, Tao Jiang, Hailong Liu, Justin D Lathia, Hiromichi Suzuki, Jeremy N Rich, Lincoln D Stein, Nada Jabado, Vijay Ramaswamy, Q Richard Lu, Amy B Heimberger, Craig Daniels, Kulandaimanuvel Antony Michealraj, Claudia L Kleinman, Michael D Taylor

Faculty, Staff and Students Publications

Posterior fossa type A (PFA) ependymoma is an unusual infantile brain tumour with few known somatic mutations, thought to be driven by epigenetic mechanisms1. PFA ependymoma has a markedly higher incidence and worse prognosis in male children than in female children2. The mechanisms that underlie these sex differences are at present unknown. Here we show that the cellular hierarchy of PFA ependymoma is less differentiated in male individuals than it is in female individuals. In the normal developing mouse hindbrain, male gliogenic progenitors are less differentiated than matched female sibling controls. To further parse the effects …

Da Vinci Single-Port Transvaginal Natural Orifice Transluminal Endoscopic Surgery (Vnotes) Sacrocolpopexy: A Case Report And Literature Review, Xiaoming Guan, Chunhua Zhang, Qiannan Yang, Shunjia Hong, Wai Ieng Fong

Faculty, Staff and Students Publications

Pelvic organ prolapse remains a common condition requiring durable surgical correction, with sacrocolpopexy considered the gold standard. Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) has emerged as a scarless minimally invasive approach, while the integration of robotic single-port technology may further enhance surgical precision and ergonomics. However, data on robotic-assisted single-port vNOTES (RSP-vNOTES) sacrocolpopexy remains limited. We report a case of a 58-year-old Asian woman with symptomatic apical pelvic organ prolapse. The pelvic organ prolapse quantification (POP-Q) assessment demonstrated stage II uterine prolapse. She underwent robotic-assisted single-port vNOTES (RSP-vNOTES) sacrocolpopexy using the da Vinci single-port (SP) platform. The procedure was …

Comprehensive Profiling Of The Human Tear Fluid Mirnome Using Small Rna Sequencing, Garrett Jones, Drew Mayernik, Saleh Ahmed, Eliza Williams, Jeremy Altman, Tae Jin Lee, Amy Estes, Cintia S De Paiva, Pamela Martin, Shruti Sharma, Ashok Sharma

Faculty, Staff and Students Publications

Purpose: To generate a comprehensive profile of microRNAs (miRNAs) present in human tear fluid using next-generation sequencing (NGS), establish a reference miRNome for healthy human tear fluid, and investigate whether miRNA expression varies by sex, race, or age.

Methods: Tear samples were collected from 32 adults using Schirmer strips. RNA was isolated using the miRNeasy Serum/Plasma Kit, and cDNA libraries were prepared using the QIAseq miRNA Library Kit. Barcoded libraries were sequenced on the NovaSeq 6000 platform. Bioinformatic analyses included adapter trimming, alignment to miRBase, normalization with DESeq2, and functional annotation using multiMiR and clusterProfiler. Differential expression analysis was performed …

Rexinoid Net-3ib Promotes Resident Macrophage Gene Expression And Mitigates Desiccation-Induced Ocular Surface Disease, Jehan Alam, Yangluowa Qu, Jianming Shao, Ebru Yaman, Karen Zheng, Hiroki Kakuta, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To evaluate the effects of rexinoid NEt-3IB on desiccating stress-induced dry eye, as well as monocyte/macrophage gene expression and cellular trajectory.

Methods: Eyes were topically treated with rexinoid NEt-3IB (5 µM) or vehicle three times a day for 5 days of desiccating stress-induced dry eye. Single-cell RNA sequencing (RNA-seq) profiled gene expression in conjunctival immune cells. RNA-seq was also used to evaluate gene expression in lipopolysaccharide (LPS)-stimulated, dexamethasone-treated (Dex, 1 µM), or NEt-3IB-treated (1-1000 nM) cultured monocytes. Cellular state trajectory and latent time were inferred with scVelo, and latent-time-associated genes were identified using Monocle 3. Permeability to Oregon Green-labeled …

Results Of A Randomized, Double-Masked, Placebo-Controlled Phase 1/2 Study Of A Trpv1 Antagonist Sjp-0132 In Participants With Dry Eye Disease, Tomoyuki Wada, Kazunori Omatsu, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To investigate the safety, tolerability, pharmacokinetic profile, and efficacy of SJP-0132 in participants with dry eye disease (DED).

Design: Phase 1/2, randomized, double-masked, single-center, placebo-controlled single and multiple ascending dose study.

Participants: Generally healthy adults aged ≥18 years with a patient-reported history of DED for ≥6 months, eye dryness visual analog scale (VAS: 0-100) ≥40 mm, 5-item dry eye questionnaire (DEQ-5) ≥6, and central corneal fluorescein staining (CFS) of 2 to 4 (Baylor scale: 0-5 for each of five zones).

Methods: This study consisted of Part A and Part B, containing four single- and two multiple-ascending dose cohorts, respectively. …

Atopic Dermatitis, Children's Mercy Kansas City

Clinical Pathways

No abstract provided.

Association Of Higher Body Mass Index With Imaging Escalation And Operative Complexity In Pediatric Appendicitis, Ryan T. Davis, Sahithi Pemmasani, Margaret Menoch

Conference Presentation Abstracts

Background: Obesity may complicate clinical assessment and ultrasound (US) evaluation in children with appendicitis, potentially increasing reliance on computed tomography (CT). At the same time, national pediatric quality-improvement initiatives and ALARA-driven imaging pathways emphasize reducing CT use and promoting US-first approaches. Data examining how body mass index (BMI) influences diagnostic pathways within these modern low-radiation protocols are limited.

Objective: To determine whether higher BMI is associated with greater CT utilization, escalation from US to CT, nondiagnostic US examinations, emergency department (ED) length of stay (ED-LOS), and operative duration in children with appendicitis.

Design/Methods: This retrospective cohort study included patients < 18 years with surgically confirmed appendicitis presenting to a tertiary pediatric ED from January 1, 2010, to December 31, 2023. Consistent with prior dataset methodology, encounters were identified through structured EHR query using ICD-10 and CPT codes and restricted to unique first visits. A total of 2,275 children were included; BMI was available for 2,012 (88%). BMI was analyzed in quartiles. Imaging modality (US-only, CT-only, or CT after US) and operative duration (proxy for case complexity) were evaluated. χ² and Wilcoxon tests and odds ratios (OR) with 95% CI were used. IRB approval was obtained (Corewell Health IRB No. 2024-128).

Results: …

Author Correction: Phenome-Wide Analysis Of Copy Number Variants In 470,727 Uk Biobank Genomes, Xueqing Zoe Zou, Fengyuan Hu, Haiyi Lou, Oliver S Burren, Xiaoyin Li, Karyn Megy, Eleanor Wheeler, Qiang Wu, Santosh S Atanur, Marcin Karpinski, Douglas Loesch, Zammy Fairhurst-Hunter, Sri V V Deevi, Erin Oerton, Sean Wen, Xiao Jiang, Cecilia Salvoro, Jonathan Mitchell, Abhishek Nag, Ben Hollis, Amanda O'Neill, Astrazeneca Genomics Initiative, Jen Harrow, Stewart Macarthur, Sebastian Wasilewski, Sean O'Dell, Lifeng Tian, Katherine R Smith, Guillermo Del Angel, Margarete Fabre, Ryan S Dhindsa, Quanli Wang, Slavé Petrovski, Keren Carss

Duncan NRI Faculty and Staff Publications

No abstract provided.

Weaning Drives Microbiome-Mediated Epigenetic Regulation To Shape Immune Memory In Mice, Li Yang, Robert C Peery, Shirui Zhou, Xiaomin Chen, Leah M Farmer, Fabiola Gutierrez, Stephanie Fowler, Lanjing Zhang, Julia M Salamat, Karen Riggins, Jiejun Shi, Lanlan Shen

Children’s Nutrition Research Center Staff Publications

During weaning, the transition to solid food diversifies the gut microbiome, triggering a programmed immune response critical for long-lasting mucosal immunity. Previous work showed that the gut microbiome mediates epigenetic development in intestinal stem cells (ISCs) during suckling, but what happens during weaning is unclear. Here, genome-wide profiling revealed that weaning-driven microbiome changes shape the DNA methylome and transcriptome of murine ISCs in an IFNγ-dependent manner. Specifically, we observe demethylation of enhancer elements essential for MHC class II genes, which results in a transcriptional memory that persists through differentiation into adulthood. IFNγ blockade, or low-dose penicillin to target Gram-positive bacteria, …

Tfeb Degradation Is Regulated By An Ikk/Β-Trcp2 Phosphorylation-Ubiquitination Cascade, Yan Xiong, Jaiprakash Sharma, Meggie N Young, Wen Xiong, Ali Jazayeri, Karl F Poncha, Ma Xenia G Ilagan, Qing Wang, Bei Gao, Hui Zheng, Nicolas L Young, Marco Sardiello

Center on Aging Staff Publications

Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and cellular clearance pathways. TFEB activity is tightly controlled by multiple post-translational mechanisms, but the exact molecular mechanism controlling its stability has remained elusive. Here, we identify the IκB kinase (IKK) complex as a key regulator of TFEB protein stability through a phosphorylation-ubiquitination cascade. A high-content kinase inhibitor screen reveals that IKK inhibition increases TFEB protein levels, and genetic ablation of IKK components increases TFEB stability, upregulates lysosomal genes, and enhances lysosomal biogenesis and degradative capacity. Mechanistically, we show that IKK phosphorylates TFEB on a cluster of serine residues …

Phenome-Wide Analysis Of Copy Number Variants In 470,727 Uk Biobank Genomes, Xueqing Zoe Zou, Fengyuan Hu, Haiyi Lou, Oliver S Burren, Xiaoyin Li, Karyn Megy, Eleanor Wheeler, Qiang Wu, Santosh S Atanur, Marcin Karpinski, Douglas Loesch, Zammy Fairhurst-Hunter, Sri V V Deevi, Erin Oerton, Sean Wen, Xiao Jiang, Cecilia Salvoro, Jonathan Mitchell, Abhishek Nag, Ben Hollis, Amanda O'Neill, Jen Harrow, Stewart Macarthur, Sebastian Wasilewski, Sean O'Dell, Lifeng Tian, Katherine R Smith, Guillermo Del Angel, Margarete Fabre, Ryan S Dhindsa, Quanli Wang, Slavé Petrovski, Keren Carss

Duncan NRI Faculty and Staff Publications

Copy number variants (CNVs) are key drivers of human diversity and disease risk1. Here we evaluate the role of CNVs across a broad range of human phenotypes and diseases by analysing CNVs from 470,727 UK Biobank whole-genome sequences and conducting a variant- and gene-level phenome-wide association study (PheWAS) with 2,941 plasma protein abundance measurements, 13,336 binary clinical phenotypes and 1,911 quantitative traits. Proteomic analyses validated functional associations of CNVs with nearby genes (cis-protein quantitative trait loci; cis-pQTLs)—with deletions and duplications typically associated with reduced and increased protein levels, respectively—and uncovered previously unknown protein–protein interactions …

X-Linked Cancer-Associated Polypeptide (Xcp) From Lncrna1456 Modulates Phf8 Histone Demethylase Activity To Regulate The Epigenome, Gene Expression, And Cellular Pathways In Breast Cancer, Shrikanth S. Gadad, Cristel V. Camacho, Xuan Gong, Micah Thornton, Venkat S. Malladi, Anusha Nagari, Aishwarya Sundaresan, Tulip Nandu, Sneh Koul, Yan Peng, W. Lee Kraus

School of Medicine Publications

Recent studies have demonstrated that a subset of long “noncoding” RNAs (lncRNAs) produce functional polypeptides and proteins. In this study, we discovered a 132 amino acid protein in human breast cancer cells named XCP (X-linked Cancer-associated Polypeptide), which is encoded by lncRNA1456 (a.k.a. RHOXF1P3), a transcript previously thought to be noncoding. lncRNA1456 is a pancreas- and testis-specific RNA whose gene is located on chromosome X. We found that the expression of lncRNA1456 and XCP is highly upregulated in the luminal A, luminal B, and HER2 molecular subtypes of breast cancer. XCP modulates both estrogen-dependent and estrogen-independent growth of breast …