Digital Commons Network^™

Semi-Parametric Testing For Ordinal Treatment Effects In Time-To-Event Data Via Dynamic Dirichlet Process Mixtures Of The Inverse-Gaussian Distribution., Jonathan A Race, Amy S Ruppert, Yvonne Efebera, Michael L Pennell

Ambulatory and Primary Care Articles

Time-to-event data often violate the proportional hazards assumption under which the log-rank test is optimal. Such violations are especially common in the sphere of biological and medical data where heterogeneity due to unmeasured covariates or time varying effects are common. A variety of parametric survival models have been proposed in the literature which make more appropriate assumptions on the hazard function, at least for certain applications. One such model is derived from the first hitting time paradigm which assumes that a subject's event time is determined by a latent stochastic process reaching a threshold value. Several random effects specifications of …

Dysregulation Of Mirna Expression And Excitation In Mef2c Autism Patient Hipsc-Neurons And Cerebral Organoids, Dorit Trudler, Swagata Ghatak, Michael Bula, James Parker, Maria Talantova, Melissa Luevanos, Sergio Labra, Titas Grabauskas, Sarah Moore Noveral, Mayu Teranaka, Emily Schahrer, Nima Dolatabadi, Clare Bakker, Kevin Lopez, Abdullah Sultan, Parth Patel, Agnes Chan, Yongwook Choi, Riki Kawaguchi, Pawel Stankiewicz, Ivan Garcia-Bassets, Piotr Kozbial, Michael G Rosenfeld, Nobuki Nakanishi, Daniel H Geschwind, Shing Fai Chan, Wei Lin, Nicholas J Schork, Rajesh Ambasudhan, Stuart A Lipton

Faculty, Staff and Students Publications

MEF2C is a critical transcription factor in neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Despite prior animal studies of MEF2C heterozygosity to mimic MHS, MHS-specific mutations have not been investigated previously, particularly in a human context as hiPSCs afford. Here, for the first time, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits. Unexpectedly, we found that decreased neurogenesis was accompanied by activation of a micro-(mi)RNA-mediated gliogenesis pathway. We also demonstrate network-level hyperexcitability in MHS neurons, as evidenced by excessive synaptic …

Ethics Of Learning Surgical Autonomy In Safety-Net Hospital Systems With Patients Who Are Incarcerated, Kala T Pham, Rachel W Davis

Faculty, Staff and Students Publications

Safety-net hospitals care for patients who are incarcerated and are key environments in which surgical trainees learn to wield their professional autonomy. This article explores ethical questions raised by surgical trainees' participation in carceral care and canvasses possible responses to those questions.

Klf4 Enhances Transplantation-Induced Hematopoiesis By Inhibiting Tlrs And Noncanonical Nfκb Signaling At A Steady State, Chun Shik Park, Cory S Bridges, Andrew H Lewis, Taylor J Chen, Saptarsi Shai, Wa Du, Monica Puppi, Barry Zorman, Sumazin Pavel, H Daniel Lacorazza

Faculty, Staff and Students Publications

The transcription factor Krüppel-like factor 4 (KLF4) acts as a transcriptional activator and repressor. KLF4 plays a role in various cellular processes, including the dedifferentiation of somatic cells into induced pluripotent stem cells. Although it has been shown to enhance self-renewal in embryonic and leukemia stem cells, its role in adult hematopoietic stem cells (HSCs) remains underexplored. We demonstrate that conditional deletion of the Klf4 gene in hematopoietic cells led to an increased frequency of immunophenotypic HSCs in the bone marrow, along with a normal distribution of lymphoid and myeloid progenitor cells. Noncompetitive bone marrow transplants showed normal engraftment and …

Differentiation Stage Predicts Radiosensitivity In Mesenchymal-Like Pancreatic Cancer, Tingshi Su, Xinjian Yu, Mojtaba Hoseini-Ghahfarokhi, David B Flint, Scott J Bright, Joana I D S Antunes, David K J Martinus, Mandira Manandhar, Mariam Ben Kacem, Poliana C Marinello, Eurico J G Pereira, Hua-Sheng Chiu, Uwe Titt, David R Grosshans, Jan Schuemann, Henning Willers, Harald Paganetti, Pavel Sumazin, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Purpose: To derive a genomic classifier to predict radiosensitivity of pancreatic cancer cell lines and patients with pancreatic cancer to allow genomic-guided radiation therapy.

Methods and materials: We collected a comprehensive data set of full clonogenic cell survival curves of 45 pancreatic cancer cell lines irradiated with clinical photon and proton beams. We derived classifiers based on data from human embryonic and fetal pancreas single-cell RNA-sequencing to distinguish between epithelial and mesenchymal cells and to predict pancreas cell-line differentiation stage. Independent testing was done with an embryonic mouse pancreas single-cell RNA-sequencing data set. We then used bulk RNA-seq profiles from …

Significant Increase Of Firework Induced Eye Injuries In Germany And The Netherlands- Are We Doing Enough To Protect Minors And Bystanders?, Ameli Gabel-Pfisterer, Stefan Johann Lang, Daniel Boehringer, Hansjürgen Agostini, Lotte C De Geus, Jan Tjeerd De Faber

Faculty, Staff and Students Publications

Background: After 2 years of pandemic sales ban, on New Year`s Eve 2022/23 consumer firework articles were officially available again in Germany and the Netherlands.

Methods: In the Netherlands we prospectively and anonymously collected data on patients treated for firework induced eye injuries from 2009 on, in Germany since 2016.

Results: Around New Year ́s Eve 2022/23 the number of patients with firework inflicted eye injuries increased in the Netherlands to 133 and in Germany to 838. In both countries the participation of eye departments was 90%. The incidence of firework induced eye injuries in the Netherlands was 0,8 /100 …

Calcium-Sensing Receptor As A Novel Target For The Treatment Of Idiopathic Pulmonary Fibrosis, Kasope Wolffs, Renjiao Li, Bethan Mansfield, Daniel A Pass, Richard T Bruce, Ping Huang, Rachel Paes De Araújo, Bahareh Sadat Haddadi, Luis A J Mur, Jordanna Dally, Ryan Moseley, Rupert Ecker, Harry Karmouty-Quintana, Keir E Lewis, A John Simpson, Jeremy P T Ward, Christopher J Corrigan, Renata Z Jurkowska, Benjamin D Hope-Gill, Daniela Riccardi, Polina L Yarova

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and no curative therapies. Fibroblast activation by transforming growth factor β1 (TGFβ1) and disrupted metabolic pathways, including the arginine-polyamine pathway, play crucial roles in IPF development. Polyamines are agonists of the calcium/cation-sensing receptor (CaSR), activation of which is detrimental for asthma and pulmonary hypertension, but its role in IPF is unknown. To address this question, we evaluated polyamine abundance using metabolomic analysis of IPF patient saliva. Furthermore, we examined CaSR functional expression in human lung fibroblasts (HLFs), assessed the anti-fibrotic effects of a CaSR antagonist, NPS2143, in TGFβ1-activated normal …

Resting Energy Expenditure And Metabolic Features In Children With Septo-Optic Dysplasia, David J. Cullingford, Jacqueline A. Curran, Mary B. Abraham, Aris Siafarikas, A. Marie Blackmore, Jenny Downs, Catherine S.Y. Choong

Research outputs 2022 to 2026

Context: Septo-optic dysplasia (SOD) is a major cause of congenital hypopituitarism and is known to be associated with overweight and obesity in up to 44% of children. Given the role of the hypothalamus in hormonal regulation, we sought to assess the association of resting energy expenditure (REE), appetite and physical activity with SOD. Objective: To characterize REE and other metabolic features in patients with SOD and evaluate relationships with elevated body mass index (BMI). Methods: Children with SOD above 5 years of age attending Perth Children's Hospital participated. A CosMED Q-NRG indirect calorimeter was used to calculate mean measure REE …

Fostering Cognitive Complexity In Behavioral Health Providers: Perspectives From Supervisors In Integrated Primary Care, Katherina Nako

Counseling & Human Services Theses & Dissertations

The integration of behavioral health into primary care settings, known as Integrated Primary Care (IPC), offers a holistic approach to addressing both physical and mental health needs (Ramanuj et al., 2019). Efforts to expand access to mental healthcare have contributed to the growing presence of IPC settings (Martin 2017), with mental health providers, such as mental health counselors, joining these teams as Behavioral Health Providers (BHPs; Blount, 2017). However, the unique complexities of IPC often leave BHPs feeling underprepared, largely due to the traditional training frameworks emphasized in many graduate counseling programs. The need for BHPs to adapt to the …

Circulating Short-Chain And Branched Short-Chain Fatty Acids And The Risk Of Incident Type 2 Diabetes: Findings From The 4c Study, Shuangyuan Wang, Hong Lin, Xiaojing Jia, Yiting Lin, Chunyan Hu, Mian Li, Yu Xu, Min Xu, Jie Zheng, Xinjie Zhao, Yanli Li, Lulu Chen, Tianshu Zeng, Ruying Hu, Zhen Ye, Lixin Shi, Qing Su, Yuhong Chen, Xuefeng Yu, Li Yan, Tiange Wang, Zhiyun Zhao, Guijun Qin, Qin Wan, Gang Chen, Meng Dai, Di Zhang, Bihan Qiu, Xiaoyan Zhu, Ruixin Liu, Xiao Wang, Xulei Tang, Zhengnan Gao, Feixia Shen, Xuejiang Gu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Guixia Wang, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Yiming Mu, Guowang Xu, Shenghan Lai, Donghui Li, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu

Faculty, Staff and Student Publications

Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus (T2DM) …

Insulin-Like Growth Factor 2 As A Driving Force For Exponential Expansion And Differentiation Of The Neonatal Thymus, Seung Woo Kang, Bryan R Helm, Yu Wang, Shiyun Xiao, Wen Zhang, Anusha Vasudev, Ken S Lau, Qi Liu, Ellen R Richie, Laura P Hale, Nancy R Manley

Faculty, Staff and Student Publications

Like all organs, the thymus grows in size and function rapidly during development, but this growth comes to a halt after birth. However, the molecular mechanisms behind such a transition in the thymus remain obscure. Using single-cell RNA sequencing (scRNA-seq) of the murine thymic stroma, we identified that major transcriptomic changes occur in the endothelium and mesenchyme across the transition to homeostasis. Differentially expressed gene and intercellular network analyses of temporally resolved scRNA-seq data revealed fibroblast-derived insulin-like growth factor 2 (IGF2) as a candidate driving neonatal thymic expansion. We demonstrated that IGF2 activity promotes a cortical thymic epithelial cell-specific proliferation …

Uncertainty-Guided Pancreatic Tumor Auto-Segmentation With Tversky Ensemble, Cenji Yu, Skylar S Gay, Aashish C Gupta, Rachael M Martin-Paulpeter, Ethan B Ludmir, Yao Zhao, Jack Duryea, Xinru Chen, Carlos E Cardenas, Jinzhong Yang, Albert C Koong, Tucker J Netherton, Dong Joo Rhee, Laurence E Court

Faculty, Staff and Student Publications

Background and purpose: Pancreatic gross tumor volume (GTV) delineation is challenging due to their variable morphology and uncertain ground truth. Previous deep learning-based auto-segmentation methods have struggled to handle tasks with uncertain ground truth and have not accommodated stylistic customizations. We aim to develop a human-in-the-loop pancreatic GTV segmentation tool using Tversky ensembles by leveraging uncertainty estimation techniques.

Material and methods: In this study, we utilized a total of 282 patients from the pancreas task of the Medical Segmentation Decathlon. Thirty patients were randomly selected to form an independent test set, while the remaining 252 patients were divided into an …

Concurrent Bone Marrow Acute Undifferentiated Leukemia And Mediastinal T‐Lymphoblastic Lymphoma With Identical Set::Nup214 Fusion And Phf6 And Ezh2 Mutations, Qing Wei, Fatima Z Jelloul, Sa A Wang, Guilin Tang, Shaoying Li, Pei Lin, Sanam Loghavi, Huan-You Wang, L Jeffrey Medeiros, Jie Xu

Faculty, Staff and Student Publications

Acute undifferentiated leukemia (AUL) is a rare hematologic malignancy lacking lineage‐specific markers. Concurrent, clonally related AUL and T‐lymphoblastic lymphoma (T‐LBL) has not been reported previously. Here we describe a patient who was diagnosed with AUL in the bone marrow and T‐LBL in the mediastinum after a thorough immunophenotyping by flow cytometry and immunohistochemistry. Despite their immunophenotypic differences, the AUL and T‐LBL showed identical genetic alterations: SET::NUP214 fusion, PHF6, and EZH2 mutations. The patient achieved and remained in complete remission after chemotherapy and stem cell transplantation. This case underscores the value of comprehensive immunophenotyping and genetic analysis in rare hematologic …

Correction To: Selinexor In Combination With Carboplatin And Paclitaxel In Patients With Advanced Solid Tumors: Results Of A Single-Center, Multi-Arm Phase Ib Study, Kyaw Z Thein, Daniel D Karp, Apostolia Tsimberidou, Jing Gong, Selma Sulovic, Jatin Shah, Denái R Milton, David S Hong, Filip Janku, Lacey Mcquinn, Bettzy A Stephen, Rivka Colen, Brett W Carter, Timothy A Yap, Sarina A Piha-Paul, Siqing Fu, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

No abstract provided.

The Effect Of Alzheimer's Disease Genetic Factors On Limbic White Matter Microstructure, Anna Lorenz, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Michael E Kim, Chenyu Gao, Nancy R Newlin, Karthik Ramadass, Praitayini Kanakaraj, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Niranjana Shashikumar, Kimberly R Pechman, Trevor Bryan Jackson, Abigail W Workmeister, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Mohamad Habes, Di Wang, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Barbara Bendlin, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer

Faculty, Staff and Student Publications

Introduction: White matter (WM) microstructure is essential for brain function but deteriorates with age and in neurodegenerative conditions such as Alzheimer's disease (AD). Diffusion MRI, enhanced by advanced bi-tensor models accounting for free water (FW), enables in vivo quantification of WM microstructural differences.

Methods: To evaluate how AD genetic risk factors affect limbic WM microstructure - crucial for memory and early impacted in disease - we conducted linear regression analyses in a cohort of 2,614 non-Hispanic White aging adults (aged 50.12 to 100.85 years). The study evaluated 36 AD risk variants across 26 genes, the association between AD polygenic scores …

Vitamin D-Related Genetic Variants And Prostate Cancer Risk In Black Men, Tracy M Layne, Joseph H Rothstein, Xiaoyu Song, Shaneda Warren Andersen, Emma K T Benn, Weiva Sieh, Robert J Klein

Faculty, Staff and Student Publications

Background: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men.

Methods: We assessed a total of 73 candidate variants in genes (namely GC, CYP27A1, CYP27B1, CYP24A1, VDR, and RXRA) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide …

A Plain Language Summary Of The Ascertain Trial: Oral Decitabine And Cedazuridine Versus Intravenous Decitabine For Mds Or Cmml, Guillermo Garcia-Manero, James Mccloskey, Elizabeth A Griffiths, Karen W L Yee, Amer M Zeidan, Aref Al-Kali, H Joachim Deeg, Mitchell Sabloff, Mary-Margaret Keating, Nancy Zhu, Nashat Y Gabrail, Salman Fazal, Joseph Maly, Olatoyosi Odenike, Amy E Dezern, Casey L O'Connell, Gail J Roboz, Lambert Busque, Rena Buckstein, Harshad Amin, Brian Leber, Aditi Shastri, Aram Oganesian, Harold N Keer, Mohammad Azab, Michael R Savona

Faculty, Staff and Student Publications

What is this summary about?This summary describes results from a phase 3 clinical trial called ASCERTAIN.Researchers compared two treatments in people with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML), either of which can develop into acute myeloid leukemia (AML). One group was treated with oral decitabine and cedazuridine (oral DEC-C) and the other with intravenous decitabine.Treatment was given in a series of cycles. In the first cycle, people were randomly assigned to receive oral DEC-C or intravenous decitabine and then switched to the other treatment in the second cycle. After the first two cycles, everyone …

Correction To: Selinexor In Combination With Carboplatin And Paclitaxel In Patients With Advanced Solid Tumors: Results Of A Single-Center, Multi-Arm Phase Ib Study, Kyaw Z Thein, Daniel D Karp, Apostolia Tsimberidou, Jing Gong, Selma Sulovic, Jatin Shah, Denái R Milton, David S Hong, Filip Janku, Lacey Mcquinn, Bettzy A Stephen, Rivka Colen, Brett W Carter, Timothy A Yap, Sarina A Piha-Paul, Siqing Fu, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

No abstract provided.

Characterization Of A Time-Resolved, Real-Time Scintillation Dosimetry System For Ultra-High Dose-Rate Radiation Therapy Applications, Alexander Baikalov, Daline Tho, Kevin Liu, Stefan Bartzsch, Sam Beddar, Emil Schüler

Faculty, Staff and Student Publications

Purpose: Scintillation dosimetry has promising qualities for ultra-high-dose-rate (UHDR) radiation therapy (RT), but no system has shown compatibility with mean dose rates (DR¯) above 100 Gy/s and doses per pulse (Dp) exceeding 1.5 Gy typical of UHDR (FLASH)-RT. The aim of this study was to characterize a novel scintillation dosimetry system with the potential of accommodating UHDRs.

Methods and materials: We undertook a thorough dosimetric characterization of the system on an UHDR electron beamline. The system's response as a function of dose, DR¯, Dp, and the pulse dose-rate (DRp) was investigated, as was the system's dose sensitivity (signal per unit …

Evaluation Of A Comprehensive Set Of Normal Tissue Complication Probability Models For Patients With Head And Neck Cancer In An International Cohort, Suzanne P M De Vette, Maria I Van Rijn-Dekker, Lisa Van Den Bosch, Kylie Keijzer, Hendrike Neh, Hung Chu, Yan Li, Mark L Frederiks, Hans Paul Van Der Laan, Jolien Heukelom, Peter Van Luijk, Arjen Van Der Schaaf, Roel J H M Steenbakkers, Nanna M Sijtsema, Katherine A Hutcheson, Clifton D Fuller, Johannes A Langendijk, Amy C Moreno, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Background/purpose: Normal tissue complication probability (NTCP) models can be used to guide radiation therapy (RT) decisions by estimating side-effect risks pretreatment to minimize (late) side-effects. Recently, a comprehensive individual toxicity risk (CITOR) profile of NTCP models addressing common side-effects in head and neck cancer (HNC) patients was developed. This study investigates the generalizability of these models in an international setting, with different treatment approaches and side-effect assessments, promoting their integration into more widespread clinical practice.

Materials/methods: From a prospective registry study, 407 HNC patients were included who were treated with definitive RT with or without systemic therapy between 2015 and …

External Validation Of An Algorithm To Detect Vertebral Level Mislabeling And Autocontouring Errors, Tucker J Netherton, Didier Duprez, Tina Patel, Gizem Cifter, Laurence E Court, Christoph Trauernicht, Ajay Aggarwal

Faculty, Staff and Student Publications

Background and purpose: This work performs external validation of a previously developed vertebral body autocontouring tool and investigates a post-processing method to increase performance to clinically acceptable levels.

Materials and methods: Vertebral bodies within CT scans from two separate institutions (40 from institution A and 41 from institution B) were automatically 1) localized and enumerated, 2) contoured, and 3) screened as a means of quality assurance (QA) for errors. Identification rate, contour acceptability rate, and QA accuracy were calculated to assess the tool's performance. These metrics were compared to those calculated on CTs from the model's original training dataset, and …

Opioid Prescribing Patterns And The Effect Of Chronic Kidney Disease In Pediatric Urology Population: A Retrospective Cohort Analysis., Kristen M. Meier, Darren Ha, Carter Sevick, Eliza D. Blanchette, Megan A. Brockel, Vijaya M. Vemulakonda, Kyle O. Rove

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Significant efforts have been undertaken to decrease opioid prescribing, but there is little research into patient-specific factors presenting as barriers in the pediatric surgical population. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be a safe and effective alternative to opioids for pain control, however, concerns about their impact on renal function limit their use in patients with chronic kidney disease (CKD). Data is limited on the interplay of CKD on opioid prescribing.

OBJECTIVE: We hypothesized that opioid reduction efforts were successful, but patients with CKD would be more likely to receive an opioid prescription than those without CKD. …

Imaging Considerations For Patients With Chronic Low Back Pain: A Case Report, Kennedy Kirkpatrick, Jay D Shah, Krishna Shah

Faculty, Staff and Students Publications

Background: The incidence of low back pain, a leading cause of global disability, has increased significantly. Spinal cord stimulation (SCS) is US Food and Drug Administration-approved for treating intractable back pain, particularly in patients with prior surgical interventions.

Case report: A 43-year-old woman was referred for SCS implantation following 3 prior lumbar spinal surgeries with continued, right-sided radicular back pain. Additional diagnostic imaging was obtained, and a magnetic resonance imaging with and without contrast revealed a recurrent disc despite 3 lumbar microdiscectomies. The patient was then referred for lumbar spinal fusion, specifically anterior lumbar interbody fusion.

Conclusions: This case underscores …

Mapping The Transcriptional And Epigenetic Landscape Of Organotypic Endothelial Diversity In The Developing And Adult Mouse, Manuel E Cantu Gutierrez, Matthew C Hill, Gabrielle E Largoza, William B Gillespie, James F Martin, Joshua D Wythe

Faculty, Staff and Students Publications

The vascular endothelium features unique molecular and functional properties across different vessel types, such as between arteries, veins and capillaries, as well as between different organs, such as the leaky sinusoidal endothelium of the liver versus the impermeable vessels of the brain. However, the transcriptional networks governing endothelial organ specialization remain unclear. Here we profile the accessible chromatin and transcriptional landscapes of the endothelium from the mouse liver, lung, heart, kidney, brain and retina, across developmental time, to identify potential transcriptional regulators of endothelial heterogeneity. We then determine which of these putative regulators are conserved in human brain endothelial cells, …

Atrial Cardiomyocyte-Restricted Cleavage Of Gasdermin D Promotes Atrial Arrhythmogenesis, Yue Yuan, Pascal Martsch, Xiaohui Chen, Enrique Martinez, Luge Li, Jia Song, Theresa Poppenborg, Florian Bruns, Jong Hwan Kim, Markus Kamler, James F Martin, Issam Abu-Taha, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

Background and aims: Enhanced inflammatory signalling causally contributes to atrial fibrillation (AF) development. Gasdermin D (GSDMD) is an important downstream effector of several inflammasome pathways. However, the role of GSDMD, particularly the cleaved N-terminal (NT)-GSDMD, in non-immune cells remains elusive. This study aimed to elucidate the function of NT-GSDMD in atrial cardiomyocytes (ACMs) and determine its contribution to atrial arrhythmogenesis.

Methods: Human atrial appendages were used to assess the protein levels and localization. A modified adeno-associated virus 9 was employed to establish ACM-restricted overexpression of NT-GSDMD in mice.

Results: The cleavage of GSDMD was enhanced in ACMs of AF patients. …

Intestinal Epithelial Serotonin As A Novel Target For Treating Disorders Of Gut-Brain Interaction And Mood, Lin Y Hung, Nuno D Alves, Andrew Del Colle, Ardesheer Talati, Sarah A Najjar, Virginie Bouchard, Virginie Gillet, Yan Tong, Zixing Huang, Kirsteen N Browning, Jialiang Hua, Ying Liu, James O Woodruff, Daniel Juarez, Melissa Medina, Jonathan Posner, Raquel Tonello, Nazli Yalcinkaya, Narek Israelyan, Roey Ringel, Letao Yang, Kam W Leong, Mu Yang, Ji Ying Sze, Tor Savidge, Jay Gingrich, Robert J Shulman, Michael D Gershon, Annie Ouellet, Larissa Takser, Mark S Ansorge, Kara Gross Margolis

Faculty, Staff and Students Publications

Background & aims: Mood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons. Yet, the compartments that mediate the therapeutic and adverse effects of SSRIs are unknown, as is whether gestational SSRI exposure directly …

A Multipronged Effort To Incorporate Professionalism Into Campuswide Programming Through A Center For Professionalism, Kyler M Godwin, Asma Ali, Larry Laufman, Ellen M Friedman

Faculty, Staff and Students Publications

Background Professionalism, a core competency for graduate medical education accreditation, has a clear educational mandate. However, the pathway to successful incorporation of professionalism within organizational culture has not been established. Integration of professionalism within the learning environment requires intentional design and formal education. Objective To describe the integration of professionalism in the learning environment through formal education and programming and report feasibility and acceptability data.

Methods The Center for Professionalism (Center) was developed in 2013 to align with the learning and clinical environments of our academic medical center. Primary drivers of a culture of professionalism were identified through input from …

Citation Issues In The American Academy Of Pediatrics Policy Statement On Transgender And Gender-Diverse Children And Adolescents (Rafferty, 2018), Kathleen Mcdeavitt

Faculty, Staff and Students Publications

No abstract provided.

Correction To: Active Versus Passive Learning In Large-Group Sessions In Medical School: A Randomized Cross-Over Trial Investigating Effects On Learning And The Feeling Of Learning, Peter Boedeker, Tobias Schlingmann, Joshua Kailin, Ajith Nair, Cara Foldes, David Rowley, Katherine Salciccioli, Ronald Maag, Nancy Moreno, Nadia Ismail

Faculty, Staff and Students Publications

This corrects the article "Active Versus Passive Learning in Large-Group Sessions in Medical School: A Randomized Cross-Over Trial Investigating Effects on Learning and the Feeling of Learning" on page 459.

Suppression Of Hypothalamic Oestrogenic Signal Sustains Hyperprolactinemia And Metabolic Adaptation In Lactating Mice, Meng Yu, Bing Feng, Jonathan C Bean, Qianru Zhao, Yongjie Yang, Hailan Liu, Yongxiang Li, Benjamin P Eappen, Hesong Liu, Longlong Tu, Kristine M Conde, Mengjie Wang, Xi Chen, Na Yin, Darah Ave Threat, Nathan Xu, Junying Han, Peiyu Gao, Yi Zhu, Darryl L Hadsell, Yang He, Pingwen Xu, Yanlin He, Chunmei Wang

Faculty, Staff and Students Publications

17β-oestradiol (E2) inhibits overeating and promotes brown adipose tissue (BAT) thermogenesis, whereas prolactin (PRL) does the opposite. During lactation, the simultaneous decline in E2 and surge in PRL contribute to maternal metabolic adaptations, including hyperphagia and suppressed BAT thermogenesis. However, the underlying neuroendocrine mechanisms remain unclear. Here, we find that oestrogen receptor alpha (ERα)-expressing neurons in the medial basal hypothalamus (MBH), specifically the arcuate nucleus of the hypothalamus and the ventrolateral subdivision of the ventromedial hypothalamus (vlVMH), are suppressed during lactation. Deletion of ERα from MBH neurons in virgin female mice induces metabolic phenotypes characteristic of lactation, including hyperprolactinemia, hyperphagia …