Digital Commons Network^™

Pluripotency Of A Founding Field: Rebranding Developmental Biology, Crystal D Rogers, Chris Amemiya, Swathi Arur, Leslie Babonis, Michael Barresi, Madelaine Bartlett, Richard Behringer, Blair Benham-Pyle, Dominique Bergmann, Ben Blackman, C Titus Brown, Bill Browne, Jasmin Camacho, Chiswili Yves Chabu, Ida Chow, Ondine Cleaver, Jonah Cool, Megan Y Dennis, Alexandra Jazz Dickinson, Stefano Di Talia, Margaret Frank, Stewart Gillmor, Eric S Haag, Iswar Hariharan, Richard Harland, Aman Husbands, Loydie Jerome-Majewska, Kristen Koenig, Carole Labonne, Michael Layden, Chris Lowe, Madhav Mani, Megan Martik, Katelyn Mckown, Cecilia Moens, Christian Mosimann, Joyce Onyenedum, Robert Reed, Ajna Rivera, Dan Rokhsar, Loic Royer, Flora Rutaganira, Rachel Shahan, Neelima Sinha, Billie Swalla, Jaimie M Van Norman, Daniel E Wagner, Athula Wikramanayake, Sophia Zebell, Siobhán M Brady

Faculty, Staff and Student Publications

The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional …

Leptin Reduction As A Required Component For Weight Loss, Shangang Zhao, Na Li, Wei Xiong, Guannan Li, Sijia He, Zhuzhen Zhang, Qingzhang Zhu, Nisi Jiang, Christian Ikejiofor, Yi Zhu, May-Yun Wang, Xianlin Han, Ningyang Zhang, Carolina Solis-Herrera, Christine Kusminski, Zhiqiang An, Joel K Elmquist, Philipp E Scherer

Faculty, Staff and Students Publications

Partial leptin reduction can induce significant weight loss, while weight loss contributes to partial leptin reduction. The cause-and-effect relationship between leptin reduction and weight loss remains to be further elucidated. Here, we show that FGF21 and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide rapidly induced a reduction in leptin. This leptin reduction contributed to the beneficial effects of GLP-1R agonism in metabolic health, as transgenically maintaining leptin levels during treatment partially curtailed the beneficial effects seen with these agonists. Moreover, a higher degree of leptin reduction during treatment, induced by including a leptin neutralizing antibody with either FGF21 or …

Faster Discharge With Lactated Ringers Than Normal Saline In First 72 H Of Acute Pancreatitis: A Multicenter Randomized Trial, Peter R Farrell, Angelica W Despain, Peter Farmer, Leslie M Farrell, Bryan Greenfield, Michael E Rogers, Lindsey Hornung, Esther Kim, Ryan Pearman, Beemnet Neway, Tyler Thompson, James E Heubi, Sona Sehgal, Rana Amoury, Maisam Abu-El-Haija

Faculty, Staff and Students Publications

OBJECTIVES: Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS.

STUDY DESIGN: A multi-site randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.gov NCT03242473). Patients were randomized to exclusively LR or NS for the first 48 hours. Primary outcomes were C-Reactive Protein (CRP) values on admission, 24 and 48 hours. Secondary outcomes …

Circulating Immune Signatures Across Clinical Stages Of Chronic Pancreatitis: A Pilot Study, Rasmus Hagn-Meincke, Phil A Hart, Dana K Andersen, Santhi S Vege, Evan L Fogel, Jose Serrano, Melena D Bellin, Mark D Topazian, Darwin L Conwell, Liang Li, Stephen K Van Den Eeden, Asbjørn M Drewes, Stephen J Pandol, Chris E Forsmark, William E Fisher, Dhiraj Yadav, Søren S Olesen, Walter G Park, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Objective: This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP).

Methods: We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to …

Host Gastric Corpus Microenvironment Facilitates Ascaris Suum Larval Hatching And Infection In A Murine Model, Yifan Wu, Grace Adeniyi-Ipadeola, Mahliyah Adkins-Threats, Matthew Seasock, Charlie Suarez-Reyes, Ricardo Fujiwara, Maria Elena Bottazzi, Lizhen Song, Jason C Mills, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric …

Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer

Faculty, Staff and Students Publications

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia …

The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier

Faculty, Staff and Students Publications

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory …

Dynamic Prognosis Prediction For Patients On Dapt After Drug-Eluting Stent Implantation: Model Development And Validation, Fang Li, Laila Rasmy, Yang Xiang, Jingna Feng, Ahmed Abdelhameed, Xinyue Hu, Zenan Sun, David Aguilar, Abhijeet Dhoble, Jingcheng Du, Qing Wang, Shuteng Niu, Yifang Dang, Xinyuan Zhang, Ziqian Xie, Yi Nian, Jianping He, Yujia Zhou, Jianfu Li, Mattia Prosperi, Jiang Bian, Degui Zhi, Cui Tao

School of Medicine Faculty Publications

BACKGROUND: The rapid evolution of artificial intelligence (AI) in conjunction with recent updates in dual antiplatelet therapy (DAPT) management guidelines emphasizes the necessity for innovative models to predict ischemic or bleeding events after drug-eluting stent implantation. Leveraging AI for dynamic prediction has the potential to revolutionize risk stratification and provide personalized decision support for DAPT management. METHODS AND RESULTS: We developed and validated a new AI-based pipeline using retrospective data of drug-eluting stent-treated patients, sourced from the Cerner Health Facts data set (n=98 236) and Optum’s de-identified Clinformatics Data Mart Database (n=9978). The 36 months following drug-eluting stent implantation were …

The Urologist’S Role In Bowel Management Of Adult Spina Bifida: A Narrative Review, Malcolm Sundell, George E. Koch, Melissa Kaufman

School of Medicine Faculty Publications

Background and Objective: Urologists are central to the coordinated care of patients with spina bifida (SB), and efforts to optimize bladder management and protection of the upper tracts are well established. However, the urologist’s role in treating this population often extends to the management of bowel dysfunction which may be less defined. The methods available to the urologist for bowel management range from lifestyle modifications to medical and surgical therapy, with many patients requiring combinations of multiple strategies to combat conflicting symptoms of constipation and fecal incontinence (FI). This narrative review aims to compile a detailed algorithm of management options, …

Boarding Of Older Adults: A Concerning Trend In The Emergency Department, Julie Van Baardwijk, Eric Tharmathurai, Ariba Khan

Journal of Geriatric Emergency Medicine

Emergency department (ED) boarding (EDB) is the practice of holding admitted patients in the ED due to a lack of hospital beds. We identified one ED in our health system with a high rate of EDB. We sought to identify factors associated with EDB in this hospital by comparing it to a similar hospital in our health care system.

Methods: We conducted a retrospective study comparing two community hospitals in our healthcare system. Boarding was defined as a patient waiting ≥8 hours in ED for disposition. One hospital, located in a rural area with 55beds was chosen as it was …

Management Of Infliximab Refractory Immune Checkpoint Inhibitor Gastrointestinal Toxicity: A Multicenter Case Series, Catriona Harvey, Kazi J Nahar, Janet Mckeown, Serigne N Lo, Sheima Farag, Nadia Yousaf, Kate Young, Liselotte Tas, Aafke Meerveld-Eggink, Christian Blank, Austin Thomas, Jennifer Mcquade, Bastian Schilling, Douglas B Johnson, Roberto Martín Huertas, Ana Arance, Joanna Lee, Lisa Zimmer, Georgina V Long, Matteo S Carlino, Yinghong Wang, Alexander Maxwell Menzies

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor (ICI) gastrointestinal toxicity (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab, however best management of infliximab-refractory ICI gastrointestinal toxicity (IRIGItox) is unknown.

Methods: We conducted an international multicenter retrospective case series. IRIGItox was defined as failure of symptom resolution ≤grade 1 (Common Terminology Criteria for Adverse Events V.5.0) following ≥2 infliximab doses or failure of symptom resolution ≤grade 2 after one dose. Data were extracted regarding demographics, steroid use, response to treatment, and survival outcomes. Toxicity was graded at symptom onset and time of infliximab failure. …

A Case Of Occlusive Myocardial Infarction Caused By Nephrotic Syndrome In A 26-Year-Old Type 1 Diabetic, Kyle Admire, Charlotta Jornlid, Chelsea Ryan, Rebecca Pauly

Marshall Journal of Medicine

Nephrotic syndrome is a rare condition distinguished by proteinuria exceeding 3g per day. Other associated characteristics include hematuria, hypoalbuminemia, edema, and hyperlipidemia. There is an array of complications of this syndrome, which are primarily due to the profound losses of protein in the urine. One such complication is thromboembolism, with most documented cases in the form of venous thromboembolism of the extremities which is in part due to urinary loss of antithrombin III and increased synthesis of prothrombotic factors. There are limited available data regarding arterial thrombi and especially few reports about coronary thromboses, which can be life-threatening. In this …

Ultrasound – An Underutilized Diagnostic Tool For Ventricular Assist Device Driveline Infections, Kristina Krzelj, Tomislav Tokic, Tomislav Kopjar, Maja Cikes, Davor Milicic, Hrvoje Gasparovic

The VAD Journal

Patients with ventricular assist device (VAD) driveline infections (DLI) have reduced quality of life and increased risk of severe complications, such as sepsis, hemorrhagic or ischemic stroke, and wound infections. The management of VAD patients imposes a significant financial burden due to prolonged in-hospital stays, frequent re-admissions, expensive diagnostics, and the need for antibiotic therapy and/or surgical intervention. There is considerable room for improvement in DLI management, particularly in the early detection and treatment stages. Ultrasound, an easily applicable device available in almost every hospital, offers an unrecognized potential for the early detection of DLI. By increasing awareness about the …

Clinical Practice Guideline-Inconsistent Management Of Fever And Neutropenia In Pediatric Oncology: A Children's Oncology Group Study, L. Lee Dupuis, Brian T. Fisher, A. J. Sugalski, Allison Caren Grimes, Michelle Nuño, S. Ramakrishnan, M. P. Beauchemin, Paula D. Robinson, Nancy Santesso, Alexandra Walsh, A. R. Wrightson, Lolie Yu, Susan K. Parsons, Lillian Sung

School of Medicine Faculty Publications

Background: The primary objective was to measure the proportion of episodes where care delivery was inconsistent with selected recommendations of a clinical practice guideline (CPG) on fever and neutropenia (FN) management. The influence of site size on CPG-inconsistent care delivery, and association between patient outcomes and CPG-inconsistent care were described. Methods: This retrospective, multicenter study included patients less than 21 years old with cancer who were at high risk of poor FN outcomes and were previously enrolled to a Children's Oncology Group (COG) study at participating National Cancer Institute Community Oncology Research Program (NCORP) institutions from January 2014 through December …

Development Of A Culinary Medicine Toolkit To Improve Implementation Of Virtual Cooking Classes For Low-Income Adults With Type 2 Diabetes, David Ai, Natalia I Heredia, Vanessa Cruz, Diana C Guevara, Shreela V Sharma, Dolores Woods, Melisa Danho, John Wesley Mcwhorter

Faculty, Staff and Student Publications

Culinary medicine (CM) addresses diseases through nutrition and culinary education. To promote access to educational material for people with diabetes and engagement in virtual classes, we created a virtual culinary medicine toolkit (VCMT) sensitive to literacy levels and language preferences. The VCMT was developed to accompany existing virtual CM programs and help improve participant interaction and retention, offering educational materials for providers and participants. The provider VCMT offers level-setting education to reduce mixed nutrition messaging, including educational resources discussing inclusive nutrition and mindful eating topics. Each handout has a QR code and link to engaging, animated videos that provide further …

Myd88 In Myofibroblasts Enhances Nonalcoholic Fatty Liver Disease-Related Hepatocarcinogenesis Via Promoting Macrophage M2 Polarization, Yu Liu, Haiqiang Chen, Xuanxuan Yan, Jie Zhang, Zhenzhong Deng, Maosheng Huang, Jianchun Gu, Jinhua Zhang

Faculty, Staff and Student Publications

Background: Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver diseases and has emerged as the leading factor in the pathogenesis of hepatocellular carcinoma (HCC). MyD88 contributes to the development of HCC. However, the underlying mechanism by which MyD88 in myofibroblasts regulates NAFLD-associated liver cancer development remains unknown.

Results: Myofibroblast MyD88-deficient (SMAMyD88-/-) mice were protected from diet-induced obesity and developed fewer and smaller liver tumors. MyD88 deficiency in myofibroblasts attenuated macrophage M2 polarization and fat accumulation in HCC tissues. Mechanistically, MyD88 signaling in myofibroblasts enhanced CCL9 secretion, thereby promoting macrophage M2 polarization. This process may depend on …

It's Not That We Care Less: Insights Into Health Care Utilization For Comorbid Diabetes And Depression Among Latinos, Sharon Borja, Miriam G Valdovinos, Kenia M Rivera, Natalia Giraldo-Santiago, Robin E Gearing, Luis R Torres

Faculty, Staff and Student Publications

Despite robust knowledge regarding the socio-economic and cultural factors affecting Latino* access to healthcare, limited research has explored service utilization in the context of comorbid conditions like diabetes and depression. This qualitative study, embedded in a larger mixed-methods project, aimed to investigate perceptions held by Latinos and their social support systems (i.e., family members) regarding comorbid diabetes and depression and to identify barriers and facilitators to their help-seeking behaviors and treatment engagement. Bilingual and bicultural researchers conducted eight focus groups with 94 participants in a large U.S. metropolitan area and were primarily conducted in Spanish. The participants either had a …

Social And Psychosocial Determinants Of Racial And Ethnic Differences In Cardiovascular Health: The Masala And Mesa Studies, Nilay S. Shah, Xiaoning Huang, Lucia C. Petito, Michael P. Bancks, Alka M. Kanaya, Sameera Talegawkar, Saaniya Farhan, Mercedes R. Carnethon, Donald M. Lloyd-Jones, Norrina B. Allen, Namratha R. Kandula, Sadiya S. Khan

Student Papers, Posters & Projects

BACKGROUND: Social and psychosocial determinants are associated with cardiovascular health (CVH).

OBJECTIVES: To quantify the contributions of social and psychosocial factors to racial/ethnic differences in CVH.

METHODS: In the Multi-Ethnic Study of Atherosclerosis and Mediators of Atherosclerosis in South Asians Living in America cohorts, Kitagawa-Blinder-Oaxaca decomposition quantified the contributions of social and psychosocial factors to differences in mean CVH score (range 0-14) in Black, Chinese, Hispanic, or South Asian compared with White participants.

RESULTS: Among 7,978 adults (mean age 61 [SD 10] years, 52 % female), there were 1,892 Black (mean CVH score for decomposition analysis 7.96 [SD 2.1]), 804 …

Circulating Microrna Expression And Nonalcoholic Fatty Liver Disease In Adolescents With Severe Obesity, Yi-Jie Li, Brittney O Baumert, Nikos Stratakis, Jesse A Goodrich, Hao-Tian Wu, Jing-Xuan He, Yin-Qi Zhao, Max T Aung, Hong-Xu Wang, Sandrah P Eckel, Douglas I Walker, Damaskini Valvi, Michele A La Merrill, Justin R Ryder, Thomas H Inge, Todd Jenkins, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Andrea A Baccarelli, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.

AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.

METHODS: This …

Curcumin And Resveratrol: Nutraceuticals With So Much Potential For Pseudoachondroplasia And Other Er-Stress Conditions, Karen L Posey

Faculty, Staff and Student Publications

Natural products with health benefits, nutraceuticals, have shown considerable promise in many studies; however, this potential has yet to translate into widespread clinical use for any condition. Notably, many drugs currently on the market, including the first analgesic aspirin, are derived from plant extracts, emphasizing the historical significance of natural products in drug development. Curcumin and resveratrol, well-studied nutraceuticals, have excellent safety profiles with relatively mild side effects. Their long history of safe use and the natural origins of numerous drugs contrast with the unfavorable reputation associated with nutraceuticals. This review aims to explore the nutraceutical potential for treating pseudoachondroplasia, …

Health Equity And Policy Considerations For Pediatric And Adult Congenital Heart Disease Care Among Minoritized Populations In The United States., Keila N. Lopez, Kiona Y. Allen, Carissa M. Baker-Smith, Katia Bravo-Jaimes, Joseph Burns, Bianca Cherestal, Jason F. Deen, Brittany K. Hills, Jennifer H. Huang, Ramiro W. Lizano Santamaria, Carlos A. Lodeiro, Valentina Melo, Jasmine S. Moreno, Flora Nuñez Gallegos, Harris Onugha, Tony A. Pastor, Michelle C. Wallace, Deidra A. Ansah

Manuscripts, Articles, Book Chapters and Other Papers

Achieving health equity in populations with congenital heart disease (CHD) requires recognizing existing disparities throughout the lifespan that negatively and disproportionately impact specific groups of individuals. These disparities occur at individual, institutional, or system levels and often result in increased morbidity and mortality for marginalized or racially minoritized populations (population subgroups (e.g., ethnic, racial, social, religious) with differential power compared to those deemed to hold the majority power in the population). Creating actionable strategies and solutions to address these health disparities in patients with CHD requires critically examining multilevel factors and health policies that continue to drive health inequities, including …

Severe Dysphagia With Eosinophilic Esophagitis Pattern Of Injury Related To Pembrolizumab Therapy, James S Barnett, Kevin K Yu, Xavier Rivera Rivera, Asmeen Bhatt

Faculty, Staff and Student Publications

While immune checkpoint inhibitor (ICI) therapies are effective treatments for many cancers, ICI therapies are associated with immune-related adverse events. We present a 67-year-old man with non-small cell lung carcinoma, who developed severe dysphagia with biopsies from an esophagogastroduodenoscopy showing histopathology consistent with eosinophilic esophagitis while on ICI maintenance therapy with pembrolizumab. The patient's symptoms worsened despite standard therapy. However, he had complete resolution of dysphagia symptoms once pembrolizumab was discontinued. While immune-related adverse events affecting the gastrointestinal system are increasingly recognized, ICI-associated eosinophilic esophagitis is a rare entity.

Human Milk Polyunsaturated Fatty Acids Are Related To Neurodevelopmental, Anthropometric, And Allergic Outcomes In Early Life: A Systematic Review, Saori Mitguard, Olivia Doucette, John Miklavcic

Food Science Faculty Articles and Research

Polyunsaturated fatty acids are critically important for newborn nutrition and in the trajectory of growth and developmental processes throughout early life. This systematic review (PROSPERO ID: CRD42023400059) critically analyzes literature pertaining to how omega-3 and omega-6 fatty acids in human milk are related to health outcomes in early life. Literature selected for the review were published between 2005 and 2020 and included assessments in healthy term children between 0 and 5 years of age. The studies reported the relation between human milk fatty acids docosahexaenoic acid (C22:6n-3, DHA), eicosapentaenoic acid (C20:5n-3, EPA), alpha-linolenic acid (C18:3n-3, ALA), arachidonic acid (C20:4n-6, AA), …

Crispr Screening Identifies Bet And Mtor Inhibitor Synergy In Cholangiocarcinoma Through Serine Glycine One Carbon, Yan Zhu, Dengyong Zhang, Pooja Shukla, Young-Ho Jung, Prit Benny Malgulwar, Sharmeen Chagani, Medina Colic, Sarah Benjamin, John A Copland, Lin Tan, Philip L Lorenzi, Milind Javle, Jason T Huse, Jason Roszik, Traver Hart, Lawrence N Kwong

Faculty, Staff and Student Publications

Patients with cholangiocarcinoma have poor clinical outcomes due to late diagnoses, poor prognoses, and limited treatment strategies. To identify drug combinations for this disease, we have conducted a genome-wide CRISPR screen anchored on the bromodomain and extraterminal domain (BET) PROTAC degrader ARV825, from which we identified anticancer synergy when combined with genetic ablation of members of the mTOR pathway. This combination effect was validated using multiple pharmacological BET and mTOR inhibitors, accompanied by increased levels of apoptosis and cell cycle arrest. In a xenograft model, combined BET degradation and mTOR inhibition induced tumor regression. Mechanistically, the 2 inhibitor classes converged …

Multidisciplinary Prehabilitation To Improve Frailty And Functional Capacity In High-Risk Elective Surgical Patients: A Retrospective Pilot Study, Henry Man Kin Wong, Ding Qi, Bosco Hon Ming Ma, Pik Yi Hou, Calvin Ka Woon Kwong, Anna Lee, Prehab Study Group

Faculty, Staff and Student Publications

BACKGROUND: Frailty is associated with worse outcomes and higher healthcare costs. The long waiting time for surgery is a potential 'teachable' moment. We examined the feasibility and safety of a pilot prehabilitation programme on high-risk frail patients undergoing major elective surgery.

METHODS: A single-centre, retrospective pilot study (Dec 2020-Nov 2021) on a one-stop prehabilitation programme (structured exercise training, nutritional counselling/therapy, and psychological support) in collaboration with geriatricians and allied health professionals. At least 4 weeks before surgery, patients at high risk of frailty or malnutrition, or undergoing major hepatectomy, esophagectomy, pancreaticoduodenectomy, or radical cystectomy, were referred for prehabilitation (2-3 sessions/week). …

Role Of Polyunsaturated Fat In Modifying Cardiovascular Risk Associated With Family History Of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies, Federica Laguzzi, Agneta Åkesson, Matti Marklund, Frank Qian, Bruna Gigante, Traci M Bartz, Julie K Bassett, Anna Birukov, Hannia Campos, Yoichiro Hirakawa, Fumiaki Imamura, Susanne Jäger, Maria Lankinen, Rachel A Murphy, Mackenzie Senn, Toshiko Tanaka, Nathan Tintle, Jyrki K Virtanen, Kazumasa Yamagishi, Matthew Allison, Ingeborg A Brouwer, Ulf De Faire, Gudny Eiriksdottir, Luigi Ferrucci, Nita G Forouhi, Johanna M Geleijnse, Allison M Hodge, Hitomi Kimura, Markku Laakso, Ulf Risérus, Anniek C Van Westing, Stefania Bandinelli, Ana Baylin, Graham G Giles, Vilmundur Gudnason, Hiroyasu Iso, Rozenn N Lemaitre, Toshiharu Ninomiya, Wendy S Post, Bruce M Psaty, Jukka T Salonen, Matthias B Schulze, Michael Y Tsai, Matti Uusitupa, Nicholas J Wareham, Seung-Won Oh, Alexis C Wood, William S Harris, David Siscovick, Dariush Mozaffarian, Karin Leander, Fatty Acids And Outcomes Research Consortium (Force)

Faculty, Staff and Students Publications

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.

METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were …

Extreme Drought Impacts Have Been Underestimated In Grasslands And Shrublands Globally, Melinda D Smith, Kate D Wilkins, Martin C Holdrege, Peter Wilfahrt, Scott L Collins, Alan K Knapp, Osvaldo E Sala, Jeffrey S Dukes, Richard P Phillips, Laura Yahdjian, Laureano A Gherardi, Timothy Ohlert, Claus Beier, Lauchlan H Fraser, Anke Jentsch, Michael E Loik, Fernando T Maestre, Sally A Power, Qiang Yu, Andrew J Felton, Seth M Munson, Yiqi Luo, Hamed Abdoli, Mehdi Abedi, Concepción L Alados, Juan Alberti, Moshe Alon, Hui An, Brian Anacker, Maggie Anderson, Harald Auge, Seton Bachle, Khadijeh Bahalkeh, Michael Bahn, Amgaa Batbaatar, Taryn Bauerle, Karen H Beard, Kai Behn, Ilka Beil, Lucio Biancari, Irmgard Blindow, Viviana Florencia Bondaruk, Elizabeth T Borer, Edward W Bork, Carlos Martin Bruschetti, Kerry M Byrne, James F Cahill, Dianela A Calvo, Michele Carbognani, Augusto Cardoni, Cameron N Carlyle, Miguel Castillo-Garcia, Scott X Chang, Jeff Chieppa, Marcus V Cianciaruso, Ofer Cohen, Amanda L Cordeiro, Daniela F Cusack, Sven Dahlke, Pedro Daleo, Carla M D'Antonio, Lee H Dietterich, Tim S Doherty, Maren Dubbert, Anne Ebeling, Nico Eisenhauer, Felícia M Fischer, T'Ai G W Forte, Tobias Gebauer, Beatriz Gozalo, Aaron C Greenville, Karlo G Guidoni-Martins, Heather J Hannusch, Siri Vatsø Haugum, Yann Hautier, Mariet Hefting, Hugh A L Henry, Daniela Hoss, Johannes Ingrisch, Oscar Iribarne, Forest Isbell, Yari Johnson, Samuel Jordan, Eugene F Kelly, Kaitlin Kimmel, Juergen Kreyling, György Kröel-Dulay, Alicia Kröpfl, Angelika Kübert, Andrew Kulmatiski, Eric G Lamb, Klaus Steenberg Larsen, Julie Larson, Jason Lawson, Cintia V Leder, Anja Linstädter, Jielin Liu, Shirong Liu, Alexandra G Lodge, Grisel Longo, Alejandro Loydi, Junwei Luan, Frederick Curtis Lubbe, Craig Macfarlane, Kathleen Mackie-Haas, Andrey V Malyshev, Adrián Maturano-Ruiz, Thomas Merchant, Daniel B Metcalfe, Akira S Mori, Edwin Mudongo, Gregory S Newman, Uffe N Nielsen, Dale Nimmo, Yujie Niu, Paola Nobre, Rory C O'Connor, Romà Ogaya, Gastón R Oñatibia, Ildikó Orbán, Brooke Osborne, Rafael Otfinowski, Meelis Pärtel, Josep Penuelas, Pablo L Peri, Guadalupe Peter, Alessandro Petraglia, Catherine Picon-Cochard, Valério D Pillar, Juan Manuel Piñeiro-Guerra, Laura W Ploughe, Robert M Plowes, Cristy Portales-Reyes, Suzanne M Prober, Yolanda Pueyo, Sasha C Reed, Euan G Ritchie, Dana Aylén Rodríguez, William E Rogers, Christiane Roscher, Ana M Sánchez, Bráulio A Santos, María Cecilia Scarfó, Eric W Seabloom, Baoku Shi, Lara Souza, Andreas Stampfli, Rachel J Standish, Marcelo Sternberg, Wei Sun, Marie Sünnemann, Michelle Tedder, Pål Thorvaldsen, Dashuan Tian, Katja Tielbörger, Alejandro Valdecantos, Liesbeth Van Den Brink, Vigdis Vandvik, Mathew R Vankoughnett, Liv Guri Velle, Changhui Wang, Yi Wang, Glenda M Wardle, Christiane Werner, Cunzheng Wei, Georg Wiehl, Jennifer L Williams, Amelia A Wolf, Michaela Zeiter, Fawei Zhang, Juntao Zhu, Ning Zong, Xiaoan Zuo

Faculty, Staff and Students Publications

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on …

Characterization Of Variant Rnas Encapsidated During Bromovirus Infection By High-Throughput Sequencing, Sarah Dexheimer, Nipin Shrestha, Bandana Sharma Chapagain, Jozef J. Bujarski, Yanbin Yin

Food for Health: Publications

Previously, we described the RNA recombinants accumulating in tissues infected with the bromoviruses BMV (Brome mosaic virus) and CCMV (Cowpea chlorotic mottle virus). In this work, we characterize the recombinants encapsidated inside the purified virion particles of BMV and CCMV. By using a tool called the Viral Recombination Mapper (ViReMa) that detects recombination junctions, we analyzed a high number of high-throughput sequencing (HTS) short RNA sequence reads. Over 28% of BMV or CCMV RNA reads did not perfectly map to the viral genomes. ViReMa identified 1.40% and 1.83% of these unmapped reads as the RNA recombinants, respectively, in BMV and …

Microglia-Derived Exosomes Modulate Myelin Regeneration Via Mir-615-5p/Myrf Axis, Xiao-Yu Ji, Yu-Xin Guo, Li-Bin Wang, Wen-Cheng Wu, Jia-Qi Wang, Jin He, Rui Gao, Javad Rasouli, Meng-Yuan Gao, Zhen-Hai Wang, Dan Xiao, Wei-Feng Zhang, Bogoljub Ciric, Yuan Zhang, Xing Li

Department of Neurology Faculty Papers

Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to …

Bispecific Bcma/Cd24 Car-T Cells Control Multiple Myeloma Growth, Fumou Sun, Yan Cheng, Visanu Wanchai, Wancheng Guo, David Mery, Hongwei Xu, Dongzheng Gai, Eric Siegel, Clyde Bailey, Cody Ashby, Samer Al Hadidi, Carolina Schinke, Sharmilan Thanendrarajan, Yupo Ma, Qing Yi, Robert Z Orlowski, Maurizio Zangari, Frits Van Rhee, Siegfried Janz, Gail Bishop, Guido Tricot, John D Shaughnessy, Fenghuang Zhan

Faculty, Staff and Student Publications

Anti-multiple myeloma B cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies represent a promising treatment strategy with high response rates in myeloma. However, durable cures following anti-BCMA CAR-T cell treatment of myeloma are rare. One potential reason is that a small subset of minimal residual myeloma cells seeds relapse. Residual myeloma cells following BCMA-CAR-T-mediated treatment show less-differentiated features and express stem-like genes, including CD24. CD24-positive myeloma cells represent a large fraction of residual myeloma cells after BCMA-CAR-T therapy. In this work, we develop CD24-CAR-T cells and test their ability to eliminate myeloma cells. We find that CD24-CAR-T cells …