Digital Commons Network^™

Number Of Children In The Household Influences Respiratory Morbidities In Children With Bronchopulmonary Dysplasia In The Outpatient Setting, Joseph M Collaco, Katharine R Tsukahara, Michael C Tracy, Catherine A Sheils, Jessica L Rice, Lawrence M Rhein, Antonia P Popova, Leif Nelin, Audrey N Miller, Winston M Manimtim, Jonathan C Levin, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Manvi Bansal, Eric D Austin, Brianna Aoyama, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Sharon A Mcgrath-Morrow

Faculty, Staff and Students Publications

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD.

METHODS: The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations.

RESULTS: The mean gestational age of the study population was 26.5 …

Pulsatile Leucine Administration During Continuous Enteral Feeding Enhances Skeletal Muscle Mechanistic Target Of Rapamycin Complex 1 Signaling And Protein Synthesis In A Preterm Piglet Model, Marko Rudar, Agus Suryawan, Hanh V Nguyen, Shaji K Chacko, Caitlin Vonderohe, Barbara Stoll, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Continuous feeding does not elicit an optimal anabolic response in skeletal muscle but is required for some preterm infants. We reported previously that intermittent intravenous pulses of leucine (Leu; 800 μmol Leu·kg–1·h–1 every 4 h) to continuously fed pigs born at term promoted mechanistic target of rapamycin complex 1 (mTORC1) activation and protein synthesis in skeletal muscle.

OBJECTIVES: The aim was to determine the extent to which intravenous Leu pulses activate mTORC1 and enhance protein synthesis in the skeletal muscle of continuously fed pigs born preterm.

METHODS: Pigs delivered 10 d preterm was advanced to full oral feeding >4 …

Adverse Metabolic Phenotypes In Parenterally Fed Neonatal Pigs Do Not Persist Into Adolescence, Sarah K Elefson, Barbara Stoll, Teresa A Davis, Marta L Fiorotto, Samer W El-Kadi, Kenneth Genovese, Thomas Thymann, Per T Sangild, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity.

OBJECTIVES: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity.

METHODS: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d. After transitioning TPN pigs …

Circadian Dysfunction Induces Nafld-Related Human Liver Cancer In A Mouse Model, Jennifer Padilla, Noha M Osman, Beatrice Bissig-Choisat, Sandra L Grimm, Xuan Qin, Angela M Major, Li Yang, Dolores Lopez-Terrada, Cristian Coarfa, Feng Li, Karl-Dimiter Bissig, David D Moore, Loning Fu

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Chronic circadian dysfunction increases the risk of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), but the underlying mechanisms and direct relevance to human HCC have not been established. In this study, we aimed to determine whether chronic circadian dysregulation can drive NAFLD-related carcinogenesis from human hepatocytes and human HCC progression.

METHODS: Chronic jet lag of mice with humanized livers induces spontaneous NAFLD-related HCCs from human hepatocytes. The clinical relevance of this model was analysed by biomarker, pathological/histological, genetic, RNA sequencing, metabolomic, and integrated bioinformatic analyses.

RESULTS: Circadian dysfunction induces glucose intolerance, NAFLD-associated human HCCs, and human …

The Human Vaginal Microbiota: From Clinical Medicine To Models To Mechanisms, Samantha Ottinger, Clare M Robertson, Holly Branthoover, Kathryn A Patras

Faculty, Staff and Students Publications

The composition of the vaginal microbiota is linked to numerous reproductive health problems, including increased susceptibility to infection, pregnancy complications, and impaired vaginal tissue repair; however, the mechanisms contributing to these adverse outcomes are not yet fully defined. In this review, we highlight recent clinical advancements associating vaginal microbiome composition and function with health outcomes. Subsequently, we provide a summary of emerging models employed to identify microbe-microbe interactions contributing to vaginal health, including metagenomic sequencing, multi-omics approaches, and advances in vaginal microbiota cultivation. Last, we review new in vitro, ex vivo, and in vivo models, such as organoids and humanized …

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 …

Study Design And Methods: Us Study To Protect Brain Health Through Lifestyle Intervention To Reduce Risk (Us Pointer), Laura D Baker, Heather M Snyder, Mark A Espeland, Rachel A Whitmer, Miia Kivipelto, Nancy Woolard, Jeffrey Katula, Kathryn V Papp, Jennifer Ventrelle, Sarah Graef, Marcus A Hill, Scott Rushing, Julia Spell, Laura Lovato, Deborah Felton, Benjamin J Williams, Mina Ghadimi Nouran, Rema Raman, Tiia Ngandu, Alina Solomon, Sharon Wilmoth, Maryjo L Cleveland, Jeff D Williamson, Katherine L Lambert, Sarah Tomaszewski Farias, Claire E Day, Christy C Tangney, Darren R Gitelman, Olivia Matongo, Terrianne Reynolds, Valory N Pavlik, Melissa M Yu, Ashley S Alexander, Richard Elbein, Ann Marie Mcdonald, Stephen Salloway, Rena R Wing, Susan Antkowiak, Martha Clare Morris, Maria C Carrillo

Faculty, Staff and Students Publications

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans.

METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER.

RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and …

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 …

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 …

Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium

Faculty, Staff and Students Publications

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant ( …

Preparing Community Health Workers To Empower Latino(A)S With Diabetes: A Real-World Implementation Study, Laura Porterfield, Zuleica Santiago Delgado, Premal G Patel, Michael L Goodman, Kendall M Campbell, Elizabeth M Vaughan

Faculty, Staff and Students Publications

Purpose: The purpose of the study was to evaluate the delivery of diabetes self-management education (DSME) to Latino(a) adults by community health workers (CHWs).

Methods: Investigators developed an evidence-based, bilingual (Spanish/English) diabetes education curriculum and trained 10 CHWs on its content. CHWs then implemented the curriculum in 6-month diabetes group visit programs for low-income Latino(a)s with type 2 diabetes in nonacademic 501(c)3 community clinics. Investigators evaluated efficacy of the training through successful implementation, measured by participant group visit acceptance and attendance.

Results: Participants (n = 70) reported high levels of program satisfaction (3.8/4.0), improvement in quality of life (9.7/10), meeting …

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. …

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 …

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, …

Circulating Metabolic Profile In Idiopathic Pulmonary Fibrosis: Data From The Ipf-Pro Registry, Ross Summer, Jamie Todd, Megan Neely, L. Jason Lobo, Andrew Namen, L. Kristin Newby, Shirin Shafazand, Sally Suliman, Christian Hesslinger, Sascha Keller, Thomas Leonard, Scott M Palmer, Olga Ilkayeva, Michael Muehlbauer, Christopher Newgard, Jesse Roman

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: The circulating metabolome, reflecting underlying cellular processes and disease biology, has not been fully characterized in patients with idiopathic pulmonary fibrosis (IPF). We evaluated whether circulating levels of metabolites correlate with the presence of IPF, with the severity of IPF, or with the risk of clinically relevant outcomes among patients with IPF.

METHODS: We analyzed enrollment plasma samples from 300 patients with IPF in the IPF-PRO Registry and 100 individuals without known lung disease using a set of targeted metabolomics and clinical analyte modules. Linear regression was used to compare metabolite and clinical analyte levels between patients with IPF …

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.

The Effect Of Various Polyphenols On Associative Memory Loss And Dementia In A Drosophila Melanogaster Model Of Alzheimer’S Disease, Anagha Gowda

Journal of the South Carolina Academy of Science

Alzheimer’s Disease (AD), a prominent neurodegenerative disease (NDD), is the seventh leading cause of death in the United States; however, little is known about prevention. As a result, polyphenols (plant-based compounds) and other natural substances have been studied for their therapeutic potential in improving cognition and memory in AD cases. While the impacts of each polyphenol (phenolic acids, flavonoids, stilbenes, and lignans) contain fundamental similarities, each varies slightly in its impacts on the brain.The purpose of this study was to examine the impacts of polyphenol subgroups on associative memory in AD, tested by building an olfactory association, through the use …

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 …

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 …

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). …

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 …

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 …

Advancements In Revascularization Strategies For Acute Mesenteric Ischemia: A Comprehensive Review, Jacob J Gries, Hafeez Ul Hassan Virk, Bing Chen, Takashi Sakamoto, Mahboob Alam, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Even with modern advancements in the management of acute mesenteric ischemia over the past decade, morbidity and mortality remain high, and the best primary treatment modality is still debated amongst interventionalists. Traditionally, interventionalists have favored an open surgical approach but are now trending for endovascular interventions due to apparent reduced mortality and complications. Newer studies suggest hybrid approaches, and intestinal stroke centers may be superior to either strategy alone. This narrative review will explore the natural history of acute mesenteric ischemia with the aim of increasing interventionalist awareness of modern advancements in revascularization strategies for this devastating disease.

Organelle Proteomic Profiling Reveals Lysosomal Heterogeneity In Association With Longevity, Yong Yu, Shihong M Gao, Youchen Guan, Pei-Wen Hu, Qinghao Zhang, Jiaming Liu, Bentian Jing, Qian Zhao, David M Sabatini, Monther Abu-Remaileh, Sung Yun Jung, Meng C Wang

Faculty, Staff and Students Publications

Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked to longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using deep proteomic profiling, we systemically profiled lysosome-associated proteins linked with four different longevity mechanisms. We discovered the lysosomal recruitment of AMP-activated protein kinase and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with …

Dietary Folate And Cofactors Accelerate Age-Dependent P16 Epimutation To Promote Intestinal Tumorigenesis, Li Yang, Robert C Peery, Leah M Farmer, Xia Gao, Yiqun Zhang, Chad J Creighton, Lanjing Zhang, Lanlan Shen

Faculty, Staff and Students Publications

The extent to which non-genetic environmental factors, such as diet, contribute to carcinogenesis has been long debated. One potential mechanism for the effects of environmental factors is through epigenetic modifications that affect gene expression without changing the underlying DNA sequence. However, the functional cooperation between dietary factors and cancer-causing epigenetic regulation is largely unknown. Here, we use a mouse model of age-dependent p16 epimutation, in which the p16 gene activity is directly controlled by promoter DNA methylation. We show p16 epimutation is modulated by folate and cofactors in dietary supplementation, which leads to increased colon cancer risk. Importantly, our findings …

Complementary And Integrative Health Information In The Literature: Its Lexicon And Named Entity Recognition, Huixue Zhou, Robin Austin, Sheng-Chieh Lu, Greg Marc Silverman, Yuqi Zhou, Halil Kilicoglu, Hua Xu, Rui Zhang

Faculty, Staff and Student Publications

Objective: To construct an exhaustive Complementary and Integrative Health (CIH) Lexicon (CIHLex) to help better represent the often underrepresented physical and psychological CIH approaches in standard terminologies, and to also apply state-of-the-art natural language processing (NLP) techniques to help recognize them in the biomedical literature.

Materials and methods: We constructed the CIHLex by integrating various resources, compiling and integrating data from biomedical literature and relevant sources of knowledge. The Lexicon encompasses 724 unique concepts with 885 corresponding unique terms. We matched these concepts to the Unified Medical Language System (UMLS), and we developed and utilized BERT models comparing their efficiency …

Disruption Of The Arabidopsis Acyl-Activating Enzyme 3 Impairs Seed Coat Mucilage Accumulation And Seed Germination, Ninghui Cheng, Paul A Nakata

Faculty, Staff and Students Publications

The Acyl-activating enzyme (AAE) 3 gene encodes an oxalyl-CoA synthetase that catalyzes the conversion of oxalate to oxalyl-CoA as the first step in the CoA-dependent pathway of oxalate catabolism. Although the role of this enzyme in oxalate catabolism has been established, its biological roles in plant growth and development are less understood. As a step toward gaining a better understanding of these biological roles, we report here a characterization of the Arabidopsis thaliana aae3 (Ataae3) seed mucilage phenotype. Ruthidium red (RR) staining of Ataae3 and wild type (WT) seeds suggested that the observed reduction in Ataae3 …