Digital Commons Network^™

Critical Care Of The Adult With Congenital Heart Disease, Christopher W Valle, Amanda C Garfinkel, Jonathan Buber, Anitra W Romfh, Andrea M Elliott, Jonathan N Menachem, Jennifer Nelson, Peter C Laussen, Jane Heggie, Cameron Dezfulian, David Morrow, Anne Marie Valente, American College Of Cardiology Critical Care Cardiology Section And Adult Congenital And Pediatric Cardiology Section

Faculty, Staff and Students Publications

Advances in the treatment of congenital heart disease (CHD) have led to dramatic improvements in survival for individuals with CHD. While adults with CHD represent a small percentage of admissions to the intensive care unit (ICU), the critical care needs of this population will grow as this population ages and develops increasingly complex cardiac and noncardiac conditions. Adults with CHD require special care in the ICU because of both their unique cardiovascular conditions and the multi-organ dysfunction that often accompanies their cardiac pathophysiology. This review aims to summarize the current epidemiology of critical care for adults with CHD, describe key …

Pfas Exposure And Postoperative Weight Regain In Adolescents After Bariatric Surgery: Findings From The Teen-Labs Study, Brittney O Baumert, Elizabeth Costello, Zhenjiang Li, Justin R Ryder, Thomas Inge, Todd Jenkins, Stephanie Sisley, Stavra A Xanthakos, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Objective: Weight regain following bariatric surgery remains a clinical challenge, with limited understanding of contributing environmental factors. Per- and polyfluoroalkyl substances (PFAS), persistent chemicals linked to metabolic dysfunction, may influence long-term weight trajectories. This study aimed to evaluate associations between PFAS exposure and changes in BMI, percent weight loss, and waist circumference among adolescents after bariatric surgery.

Methods: We included 186 adolescents (mean age: 17.1 years; 76.3% female; 72.0% White) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort who underwent surgery between 2007 and 2012. Anthropometric measurements were collected at baseline and 6, 12, 36, and 60 months post …

Fructose And Glucose From Sugary Drinks Enhance Colorectal Cancer Metastasis Via Sord, Tianshi Feng, Qin Luo, Yanlin Liu, Zeyu Jin, David Skwarchuk, Rumi Lee, Miso Nam, John M Asara, Daya R Adye, Philip L Lorenzi, Lin Tan, Guangsheng Pei, Zhongming Zhao, Neda Zarrin-Khameh, Adriana Paulucci-Holthauzen, Brian W Simons, Ju-Seog Lee, Scott Kopetz, Jihye Yun

Faculty, Staff and Students Publications

The consumption of sugar-sweetened beverages (SSBs), which contain high levels of fructose and glucose, has been causally and mechanistically linked to an increased risk of colorectal cancer (CRC). However, the effects of SSB consumption on advanced stages of disease progression, including metastasis, remain poorly understood. Here we show that exposure of CRC cells to a glucose and fructose formulation-reflecting the composition of both high-fructose corn syrup and sucrose found in SSBs-enhances cellular motility and metastatic potential compared to glucose alone. Given that CRC cells grow poorly in fructose alone, and cells in vivo are not physiologically exposed to fructose without …

Dissecting The Effects Of 223radium On The Bone Microenvironment, Sergio Barrios, Elisa Serafini, Ludovica La Posta, D Nicole Meyers, Nicholas J Dunbar, Paul G Corn, Florent Elefteriou, Catherine G Ambrose, Stefano Casarin, Antonios G Mikos, Eleonora Dondossola

Faculty, Staff and Students Publications

Radium-223 (223Ra) is a bone-seeking, alpha-particle-emitting radionuclide that is approved for the treatment of patients with metastatic prostate cancer and is currently being tested in clinical trials for primary and metastatic cancers to the bone. 223Ra accumulates in mineralized bone areas with high bone turnover, where its effects are confined within 100 μm of the bone–marrow interface due to the short tissue penetrance of the alpha particles. A recent clinical study has shown a significantly increased fracture rate associated with the administration of 223Ra, mostly in tumor-free bones. Importantly, the biological mechanisms underlying this bone fragility remain unclear. In this …

Traumatic Brain Injury In Pregnancy: A Single Level I Trauma Center Experience, Hector Fuentes Plata, Nisha K Dabhi, Shankar P Gopinath, Spyridoula Tsetsou

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) is less common in pregnancy than in the general population; however, it poses significant challenges in diagnosis and management. These include the potential teratogenicity of medications, radiation exposure from imaging modalities, physiological changes associated with pregnancy, and obstetric complications that may arise. Although there are general guidelines for trauma in the obstetric patient, they are not specific to TBI, and most recommendations are based on low-level evidence or institutional experiences.

We conducted a retrospective review of the hospital trauma registry over a 10-year period. We included all the patients admitted to our neurosurgical intensive care unit …

Tigit Affects Car Nk-Cell Effector Function In The Solid Tumor Microenvironment By Modulating Immune Synapse Strength, Ishwar Navin, Matthew Dysthe, Prashant S Menon, Corrine Baumgartner, Tim Sauer, Navin Varadarajan, Robin Parihar

Faculty, Staff and Students Publications

Therapies using NK cells that express chimeric antigen receptors (CAR-NK) have been successfully employed against hematologic malignancies. However, solid tumors resist CAR-NKs partly by enriching tumor microenvironments with ligands for NK cell inhibitory receptors. Although the NK inhibitory receptor T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) has been implicated in impaired antitumor activity of endogenous NK cells, the consequences of TIGIT expression on engineered CAR-NKs have not been explored. To address this gap, we compared TIGIT-expressing and TIGIT-deleted human CAR-NKs targeting the GD2 solid tumor antigen in tumor immune microenvironment co-cultures and in vivo tumor immune …

Protein Kinase Rock1 Activates Mitochondrial Fission Linking To Oxidative Stress And Muscle Atrophy, Meijun Si, Jihong Chen, Rizhen Yu, Hongchun Lin, Feng Li, Sungyun Jung, Sandhya S Thomas, Farhard R Danesh, Yanlin Wang, Hui Peng, Zhaoyong Hu

Faculty, Staff and Students Publications

Introduction: Chronic kidney disease (CKD) is associated with protein-energy wasting, characterized by a reduction in muscle mass and strength. Although mitochondrial dysfunction and oxidative stress are implicated in the pathogenesis of muscle wasting, underlying mechanisms remain unclear.

Methods: Here, we used transcriptomic analysis, metabolomics analyses, and mouse gene manipulation to investigate the effects of mitochondrial plasticity and oxidative stress on muscle wasting the subtotal nephrectomy mouse models of CKD. The mice with CKD were age- and sex-matched to sham-operated controls.

Results: Through these approaches, Rho-associated kinase ROCK1 emerged as a key molecule responsible for the observed mitochondrial fission and oxidative …

Correction: Ron Signalling Promotes Therapeutic Resistance In Esr1 Mutant Breast Cancer, Derek Dustin, Guowei Gu, Amanda R Beyer, Sarah K Herzog, David G Edwards, Hangqing Lin, Thomas L Gonzalez, Sandra L Grimm, Cristian Coarfa, Doug W Chan, Beom-Jun Kim, Jean-Paul De La O, Matthew J Ellis, Dan Liu, Shunqiang Li, Alana L Welm, Suzanne A W Fuqua

Faculty, Staff and Students Publications

No abstract provided.

Molecular And Genetic Landscapes Of Retina And Brain Microglia In Neurodegenerative Diseases, Khang Ma, Rinki Ratnapriya

Faculty, Staff and Students Publications

Microglia-driven dysregulation has emerged as a significant underlying mechanism in many neurodegenerative diseases, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Although both brain and retinal microglia originate from the yolk sac, it is uncertain whether they share molecular similarities or genetic and molecular foundations related to neurodegenerative diseases. In this study, we examine the transcriptomic and epigenetic profiles of retina and brain microglia through integrative analyses of single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq) from 97 independent human samples across 11 different studies. Our findings reveal that retina and brain microglia share similar expression and …

Prostaglandin E2 As A Mechanistic Biomarker Of Chronic Pancreatitis, Jami L Saloman, Bahiyyah Jefferson, Samuel Han, William E Fisher, Evan L Fogel, Phil A Hart, Liang Li, Walter G Park, Santhi Swaroop Vege, Dhiraj Yadav, Mark D Topazian, Darwin L Conwell

Faculty, Staff and Students Publications

Introduction: Chronic pancreatitis (CP) is a disease associated with chronic inflammation, fibrosis, and pain. There is a lack of tools available that facilitate early diagnosis, when intervention could prevent irreversible damage. Pilot data suggested prostaglandin E2 (PGE2) as a candidate biomarker for early CP. PGE2 activates signaling pathways that promote inflammation, pain, and fibrosis.

Methods: We assessed PGE2, metabolites, and downstream targets in pancreatic fluid collected endoscopically 0-10 (n = 110) and 10-20 (n = 111) minutes after intravenous secretin administration. PGE2 and metabolites were measured in plasma (n = 75) and urine (n = 71) from the same subjects. …

Classifying A Distinct Form Of Diabetes In Lean Individuals With A History Of Undernutrition: An International Consensus Statement, Pradnyashree Wadivkar, Felix Jebasingh, Nihal Thomas, Chittaranjan S Yajnik, Allan Arthur Vaag, Davis Kibirige, Silver Bahendeka, Mandeep Bajaj, Michael S Boyne, Charlotte Bavuma, Jacko Abodo, Sarah Wild, Ullas Kolthur-Seetharam, Satinath Mukhopadhyay, Noel P Somasundaram, Peter Schwarz, Dirk L Christensen, Faruque Pathan, Angus G Jones, Sandeep Mathur, Sylvia Kehlenbrink, Meredith Hawkins, Vellore Declaration Signatories

Faculty, Staff and Students Publications

Since 1955, a form of diabetes in lean, young (BMI < 18·5 kg/m2, age < 30 years) individuals with a history suggestive of undernutrition from before birth and throughout childhood has been described in the literature. In 1985, WHO formally classified it as malnutrition-related diabetes, but subsequently removed the classification in 1999 over a disagreement as to whether undernutrition was a sufficient risk factor to cause this type of diabetes. Emerging evidence now strongly supports the distinct classification of this unique diabetes phenotype, which is characterised by substantial impairment of pancreatic insulin secretion, with normal hepatic and peripheral insulin sensitivity, an absence of ketoacidosis, and no islet cell autoantibodies. In this consensus statement, we synthesise this evidence to produce a set of common features of the disease, proposed pathogenetic mechanisms, and suggested management and prevention strategies. During a consensus meeting in Vellore, India, in January, 2025, type 5 diabetes was proposed as the nomenclature for this distinct form of diabetes, subsequently formalised at the International Diabetes Federation (IDF) World Diabetes Congress in April, 2025. We call upon the international diabetes community to recognise this distinct form of the disease, and to support the IDF's Type 5 Diabetes Working Group and its goals to promote more research into its phenotype, pathophysiology, and treatment, which will benefit millions of patients worldwide, particularly in low-income and middle-income countries.

Item Selection For The Development And Validation Of A Revised Classification Criteria For Adult And Juvenile Idiopathic Inflammatory Myopathies: Myoroc Project, Didem Saygin, Rachel Zeng, Stefanie Glaubitz, Matteo Bottai, Anthony A Amato, Lorenzo Cavagna, Sonye K Danoff, Marianne De Visser, Mazen M Dimachkie, Manabu Fujimoto, Masataka Kuwana, Pedro M Machado, Merrilee Needham, Clarissa Pilkington, Liza Rajasekhar, Lisa G Rider, Yasser Salem, Samuel Katsuyuki Shinjo, Jasvinder A Singh, Mohammed Tikly, Guochun Wang, Victoria P Werth, Rohit Aggarwal, Ingrid E Lundberg

Faculty, Staff and Students Publications

Objective: A revision of the 2017 EULAR-ACR myositis classification criteria, namely EULAR-ACR funded Myositis Revision of Classification (MyoROC) project, is currently underway involving a large international group of experts. In the first phase of this project, we identified additional items to be tested in the criteria.

Methods: We distributed an electronic survey to International Myositis Assessment and Clinical Studies (IMACS) members to identify new items. The identified items were discussed within the Steering Committee and a multi-step Delphi consensus process consisting of an open discussion and three rounds of e-voting were conducted to reach the final item list.

Results: The …

Exploring Patients' Perceptions Of An Advance Care Planning Intervention In The Emergency Department: A Qualitative Study, Youkie Shiozawa, Saaya Morton, Nanako Shirai, Hannah Oelschlager, Lucy Kiernat, Anita N Chary, Anna C Revette, Adrian Haimovich, Smit Desai, Kai-Wei Chang, Shan W Liu, Maura Kennedy, Mara A Schonberg, Kei Ouchi

Faculty, Staff and Students Publications

Objectives: Emergency department (ED) visits offer opportunities for seriously ill patients to formulate future medical care goals, yet ED clinicians lack practical strategies for these conversations. ED GOAL, a behavioral intervention, engages seriously ill yet clinically stable older adults in the ED to address advance care planning (ACP) with their outpatient clinicians. In a randomized trial, goals-of-care documentation was significantly higher in the intervention group compared to controls after three (24.3% vs. 9.9%, p = 0.03) and 6 months (31.4% vs. 12.7%, p < 0.01). This study is a sub-analysis to learn about intervention arm participants' perceived benefits and obstacles of the intervention.

Methods: We conducted semi-structured interviews between October 2022 and August 2024 (N = 52) with intervention-arm patients …

Adeno-Associated Virus-Mediated Silencing Of Sox4 Leads To Long-Term Amelioration Of Liver Phenotypes In Mouse Models Of Alagille Syndrome, Duncan Fox, Jun Xie, Jennifer L Burwinkel, Josh M Adams, Kashish Chetal, Marzieh Keivandarian, Yaniv Faingelernt, Sanjay Subramanian, Mario F Lopez, Anna L Peters, Nathan Salomonis, Neda Zarrin-Khameh, Guangping Gao, Stacey S Huppert, Hamed Jafar-Nejad

Faculty, Staff and Students Publications

Background & aims: In patients with Alagille syndrome (ALGS), bile duct paucity often leads to severe cholestatic phenotypes for which liver transplantation remains the only definitive treatment. No Food and Drug Administration-approved mechanism-based strategies exist to enhance biliary development in ALGS or other diseases with bile duct paucity. We aimed to identify a therapeutic target to address this unmet need.

Methods: Preclinical ALGS mouse models lacking 1 copy of Jag1 with or without conditional deletion of 1 or both copies of Sox9 were used. Sox4 levels were reduced genetically or with adeno-associated virus 8 (AAV8) vectors driving a Sox4-silencing sequence. …

Picalm Alzheimer’S Risk Allele Causes Aberrant Lipid Droplets In Microglia, Alena Kozlova, Siwei Zhang, Ari Sudwarts, Hanwen Zhang, Stanislau Smirnou, Seul Kee Byeon, Christina Thapa, Xiaotong Sun, Kimberley Stephenson, Xiaojie Zhao, Brendan Jamison, Moorthi Ponnusamy, Xin He, Julie A Schneider, Akhilesh Pandey, David A Bennett, Zhiping P Pang, Alan R Sanders, Hugo J Bellen, Gopal Thinakaran, Jubao Duan

Faculty, Staff and Students Publications

Despite genome-wide association studies (GWAS) of late-onset Alzheimer’s disease (LOAD) having identified many genetic risk loci1–3, the underlying disease mechanisms remain largely unclear. Determining causal disease variants and their LOAD-relevant cellular phenotypes has been a challenge. Here, using our approach for identifying functional GWAS risk variants showing allele-specific open chromatin, we systematically identified putative causal LOAD-risk variants in human induced pluripotent stem (iPS)-cell-derived neurons, astrocytes and microglia, and linked a PICALM LOAD-risk allele to a microglial-specific role of PICALM in lipid droplet (LD) accumulation. Allele-specific open-chromatin mapping revealed functional risk variants for 26 LOAD-risk loci, mostly …

Is Bedtime Use Of Kratom (Mitragyna Speciosa) A Sleep Aid Or Disruptor? Examining Its Daily Effects And Individual Differences, Chung Jung Mun, Patricia Timmons, Leigh V Panlilio, Christopher D Verrico, Ynhi T Thomas, C Austin Zamarripa, David H Epstein, Kirsten E Smith

Faculty, Staff and Students Publications

Kratom (Mitragyna speciosa) is a psychoactive botanical native to Southeast Asia increasingly used in the U.S. for various self-reported benefits, including sleep improvement. However, empirical evidence concerning kratom’s effects on sleep is limited. Here, we examined the association between bedtime kratom use and self-reported sleep outcomes in naturalistic settings across consecutive days, while also exploring sex and chronic pain status as potential moderators. A secondary analysis was conducted using the data from a 15-day ecological momentary assessment (EMA) study of 357 U.S. adults who reported regularly using kratom. Participants made daily reports of their bedtime kratom use and …

Liver-Specific Expression Of Hiv-1 Viral Protein R Causes Hepatic Steatosis And Glucose Intolerance In Male Mice, Neeti Agarwal, Pradip Saha, Claudia E Ramirez Bustamante, Sean M Hartig, Mark A Herman, Ashok Balasubramanyam, Jordan E Lake

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in people with HIV (PWH), with both HIV and antiretroviral therapy contributing to liver damage and glucose intolerance. However, the role of viral proteins derived from reservoirs in this process remains unclear.

Methods: Adeno-associated virus (AAV) constructs encoding a control protein or HIV-1 viral protein R (Vpr) driven by the thyroxine-binding globulin promoter were administered to male mice (n = 5 per group) fed regular chow or a high-fat diet (HFD). Young adult mice underwent intraperitoneal glucose tolerance testing and magnetic resonance imaging, followed by euthanasia. Liver and adipose tissues …

Inhibition Of Ros1 Activity With Lorlatinib Reversibly Suppresses Fertility In Male Mice, Yuki Oyama, Kentaro Shimada, Haruhiko Miyata, Rie Iida-Norita, Chihiro Emori, Maki Kamoshita, Seiya Oura, Ryohei Katayama, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Background: Inhibition of sperm maturation in the epididymis is a promising post-testicular strategy for short-acting male contraceptives. It has been shown that ROS1, a receptor tyrosine kinase expressed in the epididymis, is essential for epididymal differentiation, sperm maturation, and male fertility in mice. However, it is unknown if inhibition of ROS1 suppresses male fertility reversibly.

Objectives: Our study aimed to investigate the effects of ROS1 inhibitor administration in male mice on sperm function and fertility.

Materials and methods: We used lorlatinib, an anti-cancer drug that inhibits ROS1. We treated 10-week-old sexually mature male mice with lorlatinib for 3 weeks and …

Germline Cancer Predisposition Results From The National Cancer Institute-Children's Oncology Group Pediatric Match Trial, Sarah Scollon, Sharon E Plon, Steven Joffe, Jaclyn A Biegel, Shashikant Kulkarni, George Miles, David R Patton, Brent Coffey, Cynthia L Winter, Gregory J Tsongalis, Mark J Routbort, Nilsa C Ramirez, Lauren Saguilig, Jin Piao, Todd A Alonzo, Stacey L Berg, Elizabeth Fox, Brenda Weigel, Douglas S Hawkins, Jeffrey S Abrams, Margaret Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, D Williams Parsons

Faculty, Staff and Students Publications

Purpose: Precision oncology trials have generally focused on tumor testing to identify actionable alterations. The National Cancer Institute-Children's Oncology Group Pediatric MATCH trial incorporated return of germline results to assess feasibility of reporting in a cooperative group setting and characterize germline cancer predisposition in patients with refractory cancers.

Patients and methods: Tumor and blood DNA from patients 1-21 years of age with treatment-refractory solid tumors, non-Hodgkin lymphomas, or histiocytic disorders underwent cancer gene panel sequencing. Clinical germline reports returned to 151 study sites included pathogenic/likely pathogenic (P/LP) germline variants found in 38 cancer predisposition genes (CPGs). European Society of Medical …

Bi-Allelic Loss-Of-Function Variants In Poc5 Cause A Syndromic Retinal, Endocrine, And Neuromuscular Ciliopathy, Anneke T Vulto-Van Silfhout, Ingrid M Jazet, Suzanne Yzer, Jeroen Pas, Serwet Demirdas, Elisabeth F C Van Rossum, Alberta A H J Thiadens, Ronald Van Beek, Lonneke Haer-Wigman, Daniela Q C M Barge-Schaapveld, Charlotte Brasch-Andersen, Simon Frost, Miriam Bauwens, Elfride De Baere, Irina Balikova, Filip Van Den Broeck, Monika Weisz-Hubshman, Pascal Joset, Peter Miny, Isabel Filges, Susanne Kohl, Pietro De Angeli, Laura Kühlewein, Jan-Philipp Bodenbender, Tobias Haack, Karin Poths, Lidia Fernandez-Caballero, Marta Corton, Fiona Blanco Kelly, Carmen Ayuso, Peggy Martínez-Esteban, John Vissing, Jordi Díaz-Manera, Volker Straub, Ana Töpf, Siying Lin, Gavin Arno, William L Macken, Jennifer Spillane, Radha Ramachandran, Erik De Vrieze, Tjakko Van Ham, Susanne Roosing, Machteld M Oud

Faculty, Staff and Students Publications

Purpose: A homozygous loss-of-function (LoF) variant in POC5 was previously described in an individual with retinitis pigmentosa. We identified POC5 variants in 12 probands with a syndromic phenotype. We aim to define the phenotype spectrum and molecular mechanism associated with biallelic POC5 LoF variants.

Methods: We studied a cohort of 12 families with bi-allelic LoF POC5 variants and performed detailed phenotype analysis. POC5 localization studies were performed in 3 proband-derived fibroblast cell lines.

Results: Detailed phenotyping of probands with POC5 variants expands the phenotype spectrum beyond ocular manifestations. This syndrome causes not only rod-cone dystrophy but also diabetes mellitus with …

Single Cell Sequencing Analysis Of Respiratory Syncytial Virus-Infected Pediatric And Adult Human Nose Organoids Reveals Age Differences, Proliferative Diversity And Identifies Novel Cellular Tropism, Anubama Rajan, Divya Nagaraj, Carolyn Bomidi, Gina M Aloisio, Ashley M Murray, Emily M Schultz, Amal Kambal, Mary K Estes, Erin Nicholson, Vasanthi Avadhanula, Sarah E Blutt, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is a leading cause of infant death across the globe. Age is a significant factor that contributes to the severity of infection in young children. RSV primarily infects the ciliated cells of the airway epithelium, induces mucus hypersecretion, and impaired mucociliary clearance. Better understanding of RSV infection at the cellular level is needed for the development of effective therapeutic interventions. To investigate the age difference and comprehensively understand gene signatures associated with RSV infection, we performed single-cell transcriptomic analysis of adult and pediatric human nose organoids (HNOs) infected with RSV. Our analysis revealed a significant difference …

Exploring The Transformative Effects Of Calorie Restriction On The Lacrimal Gland In Adult Mice, Olivier Mauduit, Prashant Kumar, Kaitlin K Scholand, Emre Aksan, Laura Schaefer, Anmar Abu-Romman, Vanessa Delcroix, Zhiyuan Yu, Aude I Sindikubwabo, Ron Korstanje, Helen P Makarenkova, Cintia S De Paiva

Faculty, Staff and Students Publications

Advanced age is one of the most recognizable risk factors for dry eye. Dry eye disease affects millions worldwide and can result from age-related lacrimal gland dysfunction, which correlates with a decline in lacrimal gland secretory cell function and chronic inflammation. This study investigated the potential of calorie restriction to maintain lacrimal gland and ocular surface health. Adult female C57BL/6 J mice were subjected to a 40% calorie restriction for 4 months, starting at 6-7 months and continuing until 10-11 months. These mice were compared to controls fed ad libitum. Bulk RNA sequencing of lacrimal glands, conjunctiva, and cornea subjected …

Author Correction: Clonal Dynamics And Somatic Evolution Of Haematopoiesis In Mouse, Chiraag D Kapadia, Nicholas Williams, Kevin J Dawson, Caroline Watson, Matthew J Yousefzadeh, Duy Le, Kudzai Nyamondo, Sreeya Kodavali, Alex Cagan, Sarah Waldvogel, Xiaoyan Zhang, Josephine De La Fuente, Daniel Leongamornlert, Emily Mitchell, Marcus A Florez, Krzysztof Sosnowski, Rogelio Aguilar, Alejandra Martell, Anna Guzman, David Harrison, Laura J Niedernhofer, Katherine Y King, Peter J Campbell, Jamie Blundell, Margaret A Goodell, Jyoti Nangalia

Faculty, Staff and Students Publications

No abstract provided.

Plasma Proteome Correlations With Liver Stiffness In Pediatric Cholestasis Implicate Epithelial To Mesenchymal Transition, Benjamin L Shneider, Rupa S Kanchi, Sandra L Grimm, Sridevi Devaraj, Juliet Emamaullee, Jeremy Schraw, Philip J Lupo, Jorge A Bezerra, Kathleen M Loomes, John C Magee, Ronald J Sokol, Kasper S Wang, Alyssa Kriegmeier, Evelyn Hsu, Jean P Molleston, Philip Rosenthal, Rohit Kohli, Saul J Karpen, Simon P Horslen, M Kyle Jensen, Arianna Barbetta, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Pediatric cholestatic liver diseases can be characterized by rapidly progressive fibrosis. A multicenter cross-sectional analysis of vibration-controlled elastography in biliary atresia (BA), alpha-1 antitrypsin deficiency (A1AT), and Alagille syndrome (ALGS) was leveraged to interrogate the plasma proteome relative to liver stiffness measurements (LSM).

Methods: Slow off-rate modified aptamer scanning profiling of >7000 proteins in plasma from 187 children with BA (n=93), A1AT (n=31), ALGS (n=46), and healthy pediatric controls (n=17) was performed, and correlations with LSM were undertaken.

Results: There was an abundance of LSM correlated proteins (BA n=2720, A1AT n=694, ALGS n=5968). Interestingly, a distinct plasma proteome was …

Carbonic Anhydrase Inhibition Sensitizes Group 3 Medulloblastoma To Radiotherapy, Cory M Richman, Alexandra Rasnitsyn, Borja L Holgado, Maria Vladoiu, Namal Abeysundara, Sandra Majo, Sara Chabi, Lucie J Taunay, Hiromichi Suzuki, Ichiyo Shibahara, Joonas Haapasalo, Jonelle G Pallotta, Tajana Douglas, Kaitlin Kharas, Kyle Juraschka, Oliver Ocsenas, Sachin A Kumar, Kristiina Nordfors, Ana Guerreiro Stücklin, Raul A Suarez, Jiao Zhang, Xiaochong Wu, Craig Daniels, Livia Garzia, Jüri Reimand, Olivier Saulnier, Thomas E Merchant, Celio Pouponnot, David R Raleigh, Michael D Taylor, Pasqualino De Antonellis

Faculty, Staff and Students Publications

Group 3 (G3) medulloblastoma constitutes the most aggressive molecular subgroup, and nearly all patients present with metastases upon recurrence. Treatment for newly diagnosed medulloblastoma relies on a combination of maximal safe surgical resection, followed by chemotherapy and ionizing radiation, and no therapies have been shown to confer a survival benefit at the time of recurrence. Given the limited therapeutic options available for patients with medulloblastoma, especially at recurrence, and the incomplete understanding of the molecular mechanisms underlying resistance to treatment, we sought to uncover actionable targets and biomarkers that could help refine patient selection and treatment of newly diagnosed medulloblastoma …

Analyzing The Learning Curve Of Vnotes Sacrocolpopexy By The Cumulative Summation Test: A Cohort Study, Wenyu Liu, Nannan Sun, Yuejiao Zhang, Yuyan Li, Weihao Lai, Youjun Zhou, Xiaoming Guan, Juan Liu

Faculty, Staff and Students Publications

Background: The learning curve of transvaginal natural orifice transluminal endoscopic sacrocolpopexy (vNOTES-SC) in the treat of pelvic organ prolapse (POP) is critical yet underexplored. Our objective is to describe the learning curve and surgical complications of vNOTES-SC, taking into account the factors that affect operative time and evaluate the long-term follow-up outcomes of this surgery.

Methods: We conducted a hospital-based cohort study involving patients who underwent vNOTES-SC from June 2017 to May 2024. All surgeries were performed by a single surgeon with over 20 years of surgical experience. This study employed cumulative summation test (CUSUM) analysis to quantify the learning …

Corneal Sensory Nerve Regulation Of Tear Production Through Stimulation Of Transient Receptor Potential Melastatin 8 (Trpm8) Channel: A Potential New Approach For Treating Dry Eye Disease, Juana Gallar, Stephen Pflugfelder, Anat Galor, Preeya K Gupta, Pedram Hamrah

Faculty, Staff and Students Publications

The lacrimal functional unit (LFU) tightly controls the secretion of all tear components, thus playing a critical role in maintaining ocular surface homeostasis. Forming an exquisitely sensitive neural network across the ocular surface, corneal sensory nerves detect environmental stimuli (e.g., temperature, chemicals, and mechanical pressure) through transient receptor potential (TRP) ion channels. Among these, TRP melastatin 8 (TRPM8) is a key regulator of basal tear production. Stimulated by the small temperature reductions and tear film osmolarity increases that arise due to evaporative cooling, TRPM8 activates the LFU, leading to increased basal tear production. Here, we focus on reviewing the topical …

Unravelling The Distinct Effects Of Vhl Mutations And Chromosome 3p Loss In Clear Cell Renal Cell Carcinoma: Implications For Prognosis And Treatment, Xiang Wang, Jian-Rong Li, Naail Raed Chowdhury, Lang Wu, Cheng Chao

Faculty, Staff and Students Publications

No abstract provided.

Nonprofit Hospital Ceo Compensation: Does Quality Matter?, Derek Jenkins, Marah Short, Vivian Ho

Faculty, Staff and Students Publications

Background: Past research has documented that increases in profits and health system size, as well as increases in the reward generosity for improving these metrics play an important role in explaining increases in nonprofit hospital CEO pay between 2012 and 2019.

Objectives: To test whether hospital quality measures play a supplemental role in determining CEO pay.

Research design: We estimated linear regressions for 2012 and 2019 of the log of CEO wages on system or independent hospital characteristics, including quality. The regressions were used to construct a Oaxaca decomposition of factors associated with CEO compensation.

Subjects: One thousand forty-seven nonprofit …

Transcript Diversity In Aging: Cryptic Transcription And Splicing, Brenna S Mccauley, Nicholas Nikoloutsos, Weiwei Dang

Faculty, Staff and Students Publications

Increased transcript diversity, which is caused in part by alternative splicing and cryptic transcription, is an underappreciated aspect of age-associated transcriptome remodeling. Recent work has revealed that structurally novel transcripts increase during aging in many tissues. Genes with cryptic and alternatively spliced transcripts with age are enriched for functional categories relevant to tissue function and aging, and have been implicated in cognitive decline, decreased muscle strength, reduced oocyte quality, immune aging, altered stem cell properties, and senescence. Indeed, there is emerging evidence that alternatively spliced transcripts and elevated cryptic transcription directly contribute to aging phenotypes in multiple tissues. The full …