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Articles 11491 - 11520 of 15181

Full-Text Articles in Medical Specialties

Identification Of Genetic Loci Simultaneously Associated With Multiple Cardiometabolic Traits, Alexis C Wood, Amit Arora, Michelle Newell, Victoria L Bland, Jin Zhou, Nicola Pirastu, Jose M Ordovas, Yann C Klimentidis Apr 2022

Identification Of Genetic Loci Simultaneously Associated With Multiple Cardiometabolic Traits, Alexis C Wood, Amit Arora, Michelle Newell, Victoria L Bland, Jin Zhou, Nicola Pirastu, Jose M Ordovas, Yann C Klimentidis

Children’s Nutrition Research Center Staff Publications

Background and aims: Cardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits.

Methods and results: We conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574-456,823). Multiple …


Metabolic Inflexibility In Youth With Obesity: Is It A Feature Of Obesity Or Distinctive Of Youth Who Are Metabolically Unhealthy?, Nour Y Gebara, Joon Young Kim, Fida Bacha, Sojung Lee, Silva Arslanian Apr 2022

Metabolic Inflexibility In Youth With Obesity: Is It A Feature Of Obesity Or Distinctive Of Youth Who Are Metabolically Unhealthy?, Nour Y Gebara, Joon Young Kim, Fida Bacha, Sojung Lee, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Background:

Individuals with obesity have metabolic inflexibility with diminished fasting fat oxidation and blunted increase in respiratory quotient (RQ) in insulin-stimulated states. However, it is unclear if metabolic inflexibility is a characteristic of obesity per se or is unique to youth who have metabolically unhealthy obesity (MUO) compared with metabolically healthy obesity (MHO).

Objective:

We investigated metabolic flexibility in youth with MUO, MHO and normal weight (NW) and compared their metabolic characteristics.

Patients/Design:

Youth (n=188) were divided, based on cut-off points for in vivo insulin sensitivity (IS) of adolescents with NW, into 137 with MUO and 51 with MHO. Fasting …


Enzymatic Characterization Of Mrna Cap Adenosine-N6 Methyltransferase Pcif1 Activity On Uncapped Rnas, Dan Yu, Nan Dai, Eric J Wolf, Ivan R Corrêa, Jujun Zhou, Tao Wu, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng Apr 2022

Enzymatic Characterization Of Mrna Cap Adenosine-N6 Methyltransferase Pcif1 Activity On Uncapped Rnas, Dan Yu, Nan Dai, Eric J Wolf, Ivan R Corrêa, Jujun Zhou, Tao Wu, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

The phosphorylated RNA polymerase II CTD interacting factor 1 (PCIF1) is a methyltransferase that adds a methyl group to the N6-position of 2′O-methyladenosine (Am), generating N6, 2′O-dimethyladenosine (m6Am) when Am is the cap-proximal nucleotide. In addition, PCIF1 has ancillary methylation activities on internal adenosines (both A and Am), although with much lower catalytic efficiency relative to that of its preferred cap substrate. The PCIF1 preference for 2′O-methylated Am over unmodified A nucleosides is due mainly to increased binding affinity for Am. Importantly, it was recently reported that PCIF1 can methylate viral RNA. Although some viral RNA can be translated in …


Loss Of Rnf43 Accelerates Kras-Mediated Neoplasia And Remodels The Tumor Immune Microenvironment In Pancreatic Adenocarcinoma, Abdel Nasser Hosein, Gita Dangol, Takashi Okumura, Jason Roszik, Kimal Rajapakshe, Megan Siemann, Mohamed Zaid, Bidyut Ghosh, Maria Monberg, Paola A Guerrero, Aatur Singhi, Cara L Haymaker, Hans Clevers, Lotfi Abou-Elkacem, Sonja M Woermann, Anirban Maitra Apr 2022

Loss Of Rnf43 Accelerates Kras-Mediated Neoplasia And Remodels The Tumor Immune Microenvironment In Pancreatic Adenocarcinoma, Abdel Nasser Hosein, Gita Dangol, Takashi Okumura, Jason Roszik, Kimal Rajapakshe, Megan Siemann, Mohamed Zaid, Bidyut Ghosh, Maria Monberg, Paola A Guerrero, Aatur Singhi, Cara L Haymaker, Hans Clevers, Lotfi Abou-Elkacem, Sonja M Woermann, Anirban Maitra

Faculty, Staff and Student Publications

Background & aims: RNF43 is an E3 ubiquitin ligase that is recurrently mutated in pancreatic ductal adenocarcinoma (PDAC) and precursor cystic neoplasms of the pancreas. The impact of RNF43 mutations on PDAC is poorly understood and autochthonous models have not been characterized sufficiently. In this study, we describe a genetically engineered mouse model (GEMM) of PDAC with conditional expression of oncogenic Kras and deletion of the catalytic domain of Rnf43 in exocrine cells.

Methods: We generated Ptf1a-Cre;LSL-KrasG12D;Rnf43flox/flox (KRC) and Ptf1a-Cre; LSL-KrasG12D (KC) mice and animal survival was assessed. KRC mice were sacrificed at 2 months, 4 months, and at moribund …


An Efficient Magnetic Resonance Image Data Quality Screening Dashboard, Evan D H Gates, Adrian Celaya, Dima Suki, Dawid Schellingerhout, David Fuentes Apr 2022

An Efficient Magnetic Resonance Image Data Quality Screening Dashboard, Evan D H Gates, Adrian Celaya, Dima Suki, Dawid Schellingerhout, David Fuentes

Faculty, Staff and Student Publications

Purpose: Complex data processing and curation for artificial intelligence applications rely on high-quality data sets for training and analysis. Manually reviewing images and their associated annotations is a very laborious task and existing quality control tools for data review are generally limited to raw images only. The purpose of this work was to develop an imaging informatics dashboard for the easy and fast review of processed magnetic resonance (MR) imaging data sets; we demonstrated its ability in a large-scale data review.

Methods: We developed a custom R Shiny dashboard that displays key static snapshots of each imaging study and its …


Barriers, Access And Management Of Paediatric Epilepsy With Telehealth., Kari Gali, Sucheta Joshi, Sarah Hueneke, Alexis Katzenbach, Linda Radecki, Trisha Calabrese, Linda Fletcher, Cristina Trandafir, Carey Wilson, Monisha Goyal, Courtney J. Wusthoff, Jean-Baptist Lepichon, Rhonda Corvalan, April Golson, Jessica Hardy, Michael Smith, Elizabeth Cook, Joshua L. Bonkowsky Apr 2022

Barriers, Access And Management Of Paediatric Epilepsy With Telehealth., Kari Gali, Sucheta Joshi, Sarah Hueneke, Alexis Katzenbach, Linda Radecki, Trisha Calabrese, Linda Fletcher, Cristina Trandafir, Carey Wilson, Monisha Goyal, Courtney J. Wusthoff, Jean-Baptist Lepichon, Rhonda Corvalan, April Golson, Jessica Hardy, Michael Smith, Elizabeth Cook, Joshua L. Bonkowsky

Manuscripts, Articles, Book Chapters and Other Papers

Access to paediatric neurology care is complex, resulting in significant wait times and negative patient outcomes. The goal of the American Academy of Pediatrics National Coordinating Center for Epilepsy's project, Access Improvement and Management of Epilepsy with Telehealth (AIM-ET), was to identify access and management challenges in the deployment of telehealth technology. AIM-ET organised four paediatric neurology teams to partner with primary-care providers (PCP) and their multidisciplinary teams. Telehealth visits were conducted for paediatric epilepsy patients. A post-visit survey assessed access and satisfaction with the telehealth visit compared to an in-person visit. Pre/post surveys completed by PCPs and neurologists captured …


Association Of Abnormal Findings On Neonatal Cranial Ultrasound With Neurobehavior At Neonatal Intensive Care Unit Discharge In Infants Born Before 30 Weeks' Gestation., Jennifer Helderman, T Michael O'Shea, Lynne Dansereau, Jennifer Check, Julie A. Hofheimer, Lynne M. Smith, Elisabeth Mcgowan, Charles R. Neal, Brian S. Carter, Steven L. Pastyrnak, Bradford Betz, Joseph Junewick, Heather L. Borders, Sheri A. Dellagrotta, Barry M. Lester Apr 2022

Association Of Abnormal Findings On Neonatal Cranial Ultrasound With Neurobehavior At Neonatal Intensive Care Unit Discharge In Infants Born Before 30 Weeks' Gestation., Jennifer Helderman, T Michael O'Shea, Lynne Dansereau, Jennifer Check, Julie A. Hofheimer, Lynne M. Smith, Elisabeth Mcgowan, Charles R. Neal, Brian S. Carter, Steven L. Pastyrnak, Bradford Betz, Joseph Junewick, Heather L. Borders, Sheri A. Dellagrotta, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

Importance: Cranial ultrasound (CUS) findings are routinely used to identify preterm infants at risk for impaired neurodevelopment, and neurobehavioral examinations provide information about early brain function. The associations of abnormal findings on early and late CUS with neurobehavior at neonatal intensive care unit (NICU) discharge have not been reported.

Objective: To examine the associations between early and late CUS findings and infant neurobehavior at NICU discharge.

Design, Setting, and Participants: This prospective cohort study included infants enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants Study between April 2014 and June 2016. Infants born before 30 weeks' gestational …


Pediatric Growth Patterns In Youth-Onset Type 2 Diabetes Mellitus: Implications For Physiologically-Based Pharmacokinetic Models., Chelsea M. Hosey, Kelsee Halpin, Valentina Shakhnovich, Chengpeng Bi, Brooke Sweeney, Yun Yan, J Steven Leeder Apr 2022

Pediatric Growth Patterns In Youth-Onset Type 2 Diabetes Mellitus: Implications For Physiologically-Based Pharmacokinetic Models., Chelsea M. Hosey, Kelsee Halpin, Valentina Shakhnovich, Chengpeng Bi, Brooke Sweeney, Yun Yan, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

An accurate understanding of the changes in height and weight of children with age is critical to the development of models predicting drug concentrations in children (i.e., physiologically-based pharmacokinetic models). However, curves describing the growth of a typical population of children may not accurately characterize growth of children with various conditions, such as obesity. Therefore, to develop height and weight versus age growth curves for youth who were diagnosed with type 2 diabetes, we extracted data from electronic medical records. Robust nonlinear models were parameterized to the equations describing height and weight versus age as defined by the Centers for …


Characteristics And Predictors Of Intensive Care Unit Admission In Pediatric Blunt Abdominal Trauma, Steven C Mehl, Megan E Cunningham, Christian J Streck, Rowland Pettit, Eunice Y Huang, Matthew T Santore, Kuojen Tsao, Richard A Falcone, Melvin S Dassinger, Jeffrey H Haynes, Robert T Russell, Bindi J Naik-Mathuria, Shawn D St Peter, David Mooney, Jeffrey Upperman, Martin L Blakely, Adam M Vogel Apr 2022

Characteristics And Predictors Of Intensive Care Unit Admission In Pediatric Blunt Abdominal Trauma, Steven C Mehl, Megan E Cunningham, Christian J Streck, Rowland Pettit, Eunice Y Huang, Matthew T Santore, Kuojen Tsao, Richard A Falcone, Melvin S Dassinger, Jeffrey H Haynes, Robert T Russell, Bindi J Naik-Mathuria, Shawn D St Peter, David Mooney, Jeffrey Upperman, Martin L Blakely, Adam M Vogel

Faculty, Staff and Student Publications

BACKGROUND: Pediatric trauma patients sustaining blunt abdominal trauma (BAT) with intra-abdominal injury (IAI) are frequently admitted to the intensive care unit (ICU). This study was performed to identify predictors for ICU admission following BAT.

METHODS: Prospective study of children (< 16 years) who presented to 14 Level-One Pediatric Trauma Centers following BAT over a 1-year period. Patients were categorized as ICU or non-ICU patients. Data collected included vitals, physical exam findings, laboratory results, imaging, and traumatic injuries. A multivariable hierarchical logistic regression model was used to identify predictors of ICU admission. Predictive ability of the model was assessed via tenfold cross-validated area under the receiver operating characteristic curves (cvAUC).

RESULTS: Included were 2,182 children with 21% (n = 463) admitted to the ICU. On univariate analysis, ICU patients were associated with abnormal age-adjusted shock index, increased injury severity scores (ISS), lower Glasgow coma scores (GCS), traumatic brain injury (TBI), and severe solid organ injury (SOI). With multivariable logistic regression, factors associated with ICU admission were severe trauma (ISS > 15), …


Mrna Coronavirus Disease 2019 Vaccine-Associated Myopericarditis In Adolescents: A Survey Study, Utkarsh Kohli, Lavina Desai, Devyani Chowdhury, Ashraf S Harahsheh, Alexandra B Yonts, Annette Ansong, Arash Sabati, Hoang H Nguyen, Tarique Hussain, Danyal Khan, David A Parra, Jennifer A Su, Jyoti K Patel, Christina Ronai, Monique Bohun, Bishara J Freij, Matthew J O'Connor, Joseph W Rosanno, Aamisha Gupta, Arash Salavitabar, Adam L Dorfman, Jesse Hansen, Olivia Frosch, Elizabeth L Profita, Shiraz Maskatia, Deepika Thacker, Shubhika Shrivastava, Tyler H Harris, Brian Feingold, Stuart Berger, Michael Campbell, Salim F Idriss, Srikant Das, Markus S Renno, Ken Knecht, S Yukiko Asaki, Sunil Patel, Ravi Ashwath, Renata Shih, John Phillips, Bibhuti Das, Preeti Ramachandran, Eyal Sagiv, Aarti H Bhat, Jonathan N Johnson, Nathaniel W Taggart, Jason Imundo, Natasha Nakra, Shashank Behere, Anjlee Patel, Avichal Aggarwal, Saif Aljemmali, Sean Lang, Sarosh P Batlivala, Daniel E Forsha, Gregory P Conners, Jana Shaw, Frank C Smith, Linda Pauliks, Joseph Vettukattil, Kenneth Shaffer, Stefanie Cheang, Sonia Voleti, Rajesh Shenoy, Rukmini Komarlu, Shea J Ryan, Christopher Snyder, Neha Bansal, Madhu Sharma, Jeffrey A Robinson, Sandra R Arnold, Christine M Salvatore, Madan Kumar, Michael A Fremed, Julie S Glickstein, Melissa Perrotta, William Orr, Tamika Rozema, Muthayipalayam Thirumoorthi, Charles J Mullett, Jocelyn Y Ang Apr 2022

Mrna Coronavirus Disease 2019 Vaccine-Associated Myopericarditis In Adolescents: A Survey Study, Utkarsh Kohli, Lavina Desai, Devyani Chowdhury, Ashraf S Harahsheh, Alexandra B Yonts, Annette Ansong, Arash Sabati, Hoang H Nguyen, Tarique Hussain, Danyal Khan, David A Parra, Jennifer A Su, Jyoti K Patel, Christina Ronai, Monique Bohun, Bishara J Freij, Matthew J O'Connor, Joseph W Rosanno, Aamisha Gupta, Arash Salavitabar, Adam L Dorfman, Jesse Hansen, Olivia Frosch, Elizabeth L Profita, Shiraz Maskatia, Deepika Thacker, Shubhika Shrivastava, Tyler H Harris, Brian Feingold, Stuart Berger, Michael Campbell, Salim F Idriss, Srikant Das, Markus S Renno, Ken Knecht, S Yukiko Asaki, Sunil Patel, Ravi Ashwath, Renata Shih, John Phillips, Bibhuti Das, Preeti Ramachandran, Eyal Sagiv, Aarti H Bhat, Jonathan N Johnson, Nathaniel W Taggart, Jason Imundo, Natasha Nakra, Shashank Behere, Anjlee Patel, Avichal Aggarwal, Saif Aljemmali, Sean Lang, Sarosh P Batlivala, Daniel E Forsha, Gregory P Conners, Jana Shaw, Frank C Smith, Linda Pauliks, Joseph Vettukattil, Kenneth Shaffer, Stefanie Cheang, Sonia Voleti, Rajesh Shenoy, Rukmini Komarlu, Shea J Ryan, Christopher Snyder, Neha Bansal, Madhu Sharma, Jeffrey A Robinson, Sandra R Arnold, Christine M Salvatore, Madan Kumar, Michael A Fremed, Julie S Glickstein, Melissa Perrotta, William Orr, Tamika Rozema, Muthayipalayam Thirumoorthi, Charles J Mullett, Jocelyn Y Ang

Faculty, Staff and Student Publications

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions.


Zanubrutinib For Treatment-Naïve And Relapsed/Refractory Chronic Lymphocytic Leukaemia: Long-Term Follow-Up Of The Phase I/Ii Au-003 Study, Akash Mukherjee, Denái R Milton, Elias J Jabbour, Alison M Gulbis, Tapan Kadia, Nitin Jain, Celina Ledesma, Jan Burger, Alessandra Ferrajoli, William Wierda, L Jeffrey Medeiros, Hagop Kantarjian, Richard Champlin, Issa F Khouri Apr 2022

Zanubrutinib For Treatment-Naïve And Relapsed/Refractory Chronic Lymphocytic Leukaemia: Long-Term Follow-Up Of The Phase I/Ii Au-003 Study, Akash Mukherjee, Denái R Milton, Elias J Jabbour, Alison M Gulbis, Tapan Kadia, Nitin Jain, Celina Ledesma, Jan Burger, Alessandra Ferrajoli, William Wierda, L Jeffrey Medeiros, Hagop Kantarjian, Richard Champlin, Issa F Khouri

Faculty, Staff and Student Publications

We aimed to study the risks of graft-versus-host disease (GVHD), non-relapse mortality (NRM) and survival outcomes of allogeneic stem cell transplantation (alloSCT) in patients with chronic lymphocytic leukemia (n = 17), Richter's syndrome (n = 14), or lymphoma (n = 18) after small molecule inhibitors (SMIs). Patients had a median of 4 prior therapies, including ibrutinib (n = 46; 94%), venetoclax (n = 19; 39%), and idelalisib (n = 6; 12%). Twenty-one (43%) had >1 SMI. P53 mutation was detected in 58% of patients. The 3-year overall and progression-free survival rates were 68% and …


Standardisation Of Protocols Can Be Crucial In Long Non-Coding Rna Research, Kinga Németh, George A Calin Apr 2022

Standardisation Of Protocols Can Be Crucial In Long Non-Coding Rna Research, Kinga Németh, George A Calin

Faculty, Staff and Student Publications

In this issue, Traversa et al. [1] reviewed our current knowledge about the role of circular and linear forms of PVT1 non-coding RNA in cancer and human diseases. They highlighted the technical challenges of these studies and raised a potential bias in the publications, which require more attention from researchers.


Myelodysplastic/Myeloproliferative Neoplasms-Unclassifiable With Isolated Isochromosome 17q Represents A Distinct Clinico-Biologic Subset: A Multi-Institutional Collaborative Study From The Bone Marrow Pathology Group, Rashmi Kanagal-Shamanna, Attilio Orazi, Robert P Hasserjian, Daniel A Arber, Kaaren Reichard, Eric D Hsi, Adam Bagg, Heesun Joyce Rogers, Julia Geyer, Faezeh Darbaniyan, Kim-Anh Do, Kyle M Devins, Olga Pozdnyakova, Tracy I George, Paola Dal Cin, Patricia T Greipp, Mark J Routbort, Keyur Patel, Guillermo Garcia-Manero, Srdan Verstovsek, L Jeffrey Medeiros, Sa A Wang, Carlos Bueso-Ramos Apr 2022

Myelodysplastic/Myeloproliferative Neoplasms-Unclassifiable With Isolated Isochromosome 17q Represents A Distinct Clinico-Biologic Subset: A Multi-Institutional Collaborative Study From The Bone Marrow Pathology Group, Rashmi Kanagal-Shamanna, Attilio Orazi, Robert P Hasserjian, Daniel A Arber, Kaaren Reichard, Eric D Hsi, Adam Bagg, Heesun Joyce Rogers, Julia Geyer, Faezeh Darbaniyan, Kim-Anh Do, Kyle M Devins, Olga Pozdnyakova, Tracy I George, Paola Dal Cin, Patricia T Greipp, Mark J Routbort, Keyur Patel, Guillermo Garcia-Manero, Srdan Verstovsek, L Jeffrey Medeiros, Sa A Wang, Carlos Bueso-Ramos

Faculty, Staff and Student Publications

Classification of myeloid neoplasms with isolated isochromosome i(17q) [17p deletion with inherent monoallelic TP53 loss plus 17q duplication] is controversial. Most cases fall within the WHO unclassifiable myelodysplastic/myeloproliferative neoplasms (MDS/MPN-U) category. The uniformly dismal outcomes warrant better understanding of this entity. We undertook a multi-institutional retrospective study of 92 adult MDS/MPN-U cases from eight institutions. Twenty-nine (32%) patients had isolated i(17q) [MDS/MPN-i(17q)]. Compared to MDS/MPN without i(17q), MDS/MPN-i(17q) patients were significantly younger, had lower platelet and absolute neutrophil counts, and higher frequency of splenomegaly and circulating blasts. MDS/MPN-i(17q) cases showed frequent bilobed neutrophils (75% vs. 23%; P = 0.03), hypolobated …


Pgc1Α/Β Expression Predicts Therapeutic Response To Oxidative Phosphorylation Inhibition In Ovarian Cancer, Carmen Ghilardi, Catarina Moreira-Barbosa, Laura Brunelli, Paola Ostano, Nicolò Panini, Monica Lupi, Alessia Anastasia, Fabio Fiordaliso, Monica Salio, Laura Formenti, Massimo Russo, Edoardo Arrigoni, Ferdinando Chiaradonna, Giovanna Chiorino, Giulio Draetta, Joseph R Marszalek, Christopher P Vellano, Roberta Pastorelli, Mariarosa Bani, Alessandra Decio, Raffaella Giavazzi Apr 2022

Pgc1Α/Β Expression Predicts Therapeutic Response To Oxidative Phosphorylation Inhibition In Ovarian Cancer, Carmen Ghilardi, Catarina Moreira-Barbosa, Laura Brunelli, Paola Ostano, Nicolò Panini, Monica Lupi, Alessia Anastasia, Fabio Fiordaliso, Monica Salio, Laura Formenti, Massimo Russo, Edoardo Arrigoni, Ferdinando Chiaradonna, Giovanna Chiorino, Giulio Draetta, Joseph R Marszalek, Christopher P Vellano, Roberta Pastorelli, Mariarosa Bani, Alessandra Decio, Raffaella Giavazzi

Faculty, Staff and Student Publications

Ovarian cancer is the deadliest gynecologic cancer, and novel therapeutic options are crucial to improve overall survival. Here we provide evidence that impairment of oxidative phosphorylation (OXPHOS) can help control ovarian cancer progression, and this benefit correlates with expression of the two mitochondrial master regulators PGC1α and PGC1β. In orthotopic patient-derived ovarian cancer xenografts (OC-PDX), concomitant high expression of PGC1α and PGC1β (PGC1α/β) fostered a unique transcriptional signature, leading to increased mitochondrial abundance, enhanced tricarboxylic acid cycling, and elevated cellular respiration that ultimately conferred vulnerability to OXPHOS inhibition. Treatment with the respiratory chain complex I inhibitor IACS-010759 caused mitochondrial swelling …


Camk2/Camkii Activates Mlkl In Short-Term Starvation To Facilitate Autophagic Flux, Qionghui Zhan, Jaepyo Jeon, Ying Li, Yu Huang, Jian Xiong, Qiaochu Wang, Tian-Le Xu, Yong Li, Fu-Hai Ji, Guangwei Du, Michael X Zhu Apr 2022

Camk2/Camkii Activates Mlkl In Short-Term Starvation To Facilitate Autophagic Flux, Qionghui Zhan, Jaepyo Jeon, Ying Li, Yu Huang, Jian Xiong, Qiaochu Wang, Tian-Le Xu, Yong Li, Fu-Hai Ji, Guangwei Du, Michael X Zhu

Faculty, Staff and Student Publications

MLKL (mixed lineage kinase domain like pseudokinase) is a well-known core component of necrosome that executes necroptotic cell death upon phosphorylation by RIPK3 (receptor interacting serine/threonine kinase 3). Recent studies also implicate a role of MLKL in endosomal trafficking, which is not always dependent on RIPK3. Using mouse Neuro-2a and L929 as well as human HEK293 and HT29 cells, we show here that MLKL is phosphorylated in response to serum and amino acid deprivation from the culture medium, in a manner that depends on CAMK2/CaMKII (calcium/calmodulin dependent protein kinase II) but not RIPK3. The starvation-induced increase in MLKL phosphorylation was …


The Paradox Of Immunosuppressants And Covid-19, Guang-Shing Cheng, Scott E Evans Apr 2022

The Paradox Of Immunosuppressants And Covid-19, Guang-Shing Cheng, Scott E Evans

Faculty, Staff and Student Publications

Lessons learned from a large registry analysis show worse COVID-19 outcomes for patients previously exposed to glucocorticoids https://bit.ly/306rNrk


The Nephrocheck Bedside System For Detecting Stage 3 Acute Kidney Injury After Open Thoracoabdominal Aortic Repair, Mark Hwang, Michael H Weisman Apr 2022

The Nephrocheck Bedside System For Detecting Stage 3 Acute Kidney Injury After Open Thoracoabdominal Aortic Repair, Mark Hwang, Michael H Weisman

Faculty, Staff and Student Publications

No abstract provided.


Inhibiting Type I Arginine Methyltransferase Activity Promotes T Cell-Mediated Antitumor Immune Responses, Andrew Fedoriw, Leilei Shi, Shane O'Brien, Kimberly N Smitheman, Yunfei Wang, Jiakai Hou, Christian Sherk, Satyajit Rajapurkar, Jenny Laraio, Leila J Williams, Chunyu Xu, Guangchun Han, Qin Feng, Mark T Bedford, Linghua Wang, Olena Barbash, Ryan G Kruger, Patrick Hwu, Helai P Mohammad, Weiyi Peng Apr 2022

Inhibiting Type I Arginine Methyltransferase Activity Promotes T Cell-Mediated Antitumor Immune Responses, Andrew Fedoriw, Leilei Shi, Shane O'Brien, Kimberly N Smitheman, Yunfei Wang, Jiakai Hou, Christian Sherk, Satyajit Rajapurkar, Jenny Laraio, Leila J Williams, Chunyu Xu, Guangchun Han, Qin Feng, Mark T Bedford, Linghua Wang, Olena Barbash, Ryan G Kruger, Patrick Hwu, Helai P Mohammad, Weiyi Peng

Faculty, Staff and Student Publications

Protein arginine methyltransferases (PRMT) are a widely expressed class of enzymes responsible for catalyzing arginine methylation on numerous protein substrates. Among them, type I PRMTs are responsible for generating asymmetric dimethylarginine. By controlling multiple basic cellular processes, such as DNA damage responses, transcriptional regulation, and mRNA splicing, type I PRMTs contribute to cancer initiation and progression. A type I PRMT inhibitor, GSK3368715, has been developed and has entered clinical trials for solid and hematologic malignancies. Although type I PRMTs have been reported to play roles in modulating immune cell function, the immunologic role of tumor-intrinsic pathways controlled by type I …


Comparative Molecular Genomic Analyses Of A Spontaneous Rhesus Macaque Model Of Mismatch Repair-Deficient Colorectal Cancer, Nejla Ozirmak Lermi, Stanton B Gray, Charles M Bowen, Laura Reyes-Uribe, Beth K Dray, Nan Deng, R Alan Harris, Muthuswamy Raveendran, Fernando Benavides, Carolyn L Hodo, Melissa W Taggart, Karen Colbert Maresso, Krishna M Sinha, Jeffrey Rogers, Eduardo Vilar Apr 2022

Comparative Molecular Genomic Analyses Of A Spontaneous Rhesus Macaque Model Of Mismatch Repair-Deficient Colorectal Cancer, Nejla Ozirmak Lermi, Stanton B Gray, Charles M Bowen, Laura Reyes-Uribe, Beth K Dray, Nan Deng, R Alan Harris, Muthuswamy Raveendran, Fernando Benavides, Carolyn L Hodo, Melissa W Taggart, Karen Colbert Maresso, Krishna M Sinha, Jeffrey Rogers, Eduardo Vilar

Faculty, Staff and Student Publications

Colorectal cancer (CRC) remains the third most common cancer in the US with 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. A cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1 (c.1029C


Effect Of Perfluorocarbon Composition On Activation Of Phase-Changing Ultrasound Contrast Agents, Trevor M Mitcham, Dmitry Nevozhay, Yunyun Chen, Linh D Nguyen, Gianmarco F Pinton, Stephen Y Lai, Konstantin V Sokolov, Richard R Bouchard Apr 2022

Effect Of Perfluorocarbon Composition On Activation Of Phase-Changing Ultrasound Contrast Agents, Trevor M Mitcham, Dmitry Nevozhay, Yunyun Chen, Linh D Nguyen, Gianmarco F Pinton, Stephen Y Lai, Konstantin V Sokolov, Richard R Bouchard

Faculty, Staff and Student Publications

BACKGROUND: While microbubble contrast agents (MCAs) are commonly used in ultrasound (US), they are inherently limited to vascular targets due to their size. Alternatively, phase-changing nanodroplet contrast agents (PNCAs) can be delivered as nanoscale agents (i.e., small enough to extravasate), but when exposed to a US field of sufficient mechanical index (MI), they convert to MCAs, which can be visualized with high contrast using nonlinear US.

PURPOSE: To investigate the effect of perfluorocarbon (PFC) core composition and presence of cholesterol in particle coatings on stability and image contrast generated from acoustic activation of PNCAs using high-frequency US suitable for clinical …


Notch-Induced Mdsc Recruitment After Ohsv Virotherapy In Cns Cancer Models Modulates Antitumor Immunotherapy, Yoshihiro Otani, Ji Young Yoo, Cole T Lewis, Samantha Chao, Jessica Swanner, Toshihiko Shimizu, Jin Muk Kang, Sara A Murphy, Kimberly Rivera-Caraballo, Bangxing Hong, Joseph C Glorioso, Hiroshi Nakashima, Sean E Lawler, Yeshavanth Banasavadi-Siddegowda, John D Heiss, Yuanqing Yan, Guangsheng Pei, Michael A Caligiuri, Zhongming Zhao, E Antonio Chiocca, Jianhua Yu, Balveen Kaur Apr 2022

Notch-Induced Mdsc Recruitment After Ohsv Virotherapy In Cns Cancer Models Modulates Antitumor Immunotherapy, Yoshihiro Otani, Ji Young Yoo, Cole T Lewis, Samantha Chao, Jessica Swanner, Toshihiko Shimizu, Jin Muk Kang, Sara A Murphy, Kimberly Rivera-Caraballo, Bangxing Hong, Joseph C Glorioso, Hiroshi Nakashima, Sean E Lawler, Yeshavanth Banasavadi-Siddegowda, John D Heiss, Yuanqing Yan, Guangsheng Pei, Michael A Caligiuri, Zhongming Zhao, E Antonio Chiocca, Jianhua Yu, Balveen Kaur

Faculty, Staff and Student Publications

PURPOSE: Oncolytic herpes simplex virus-1 (oHSV) infection of brain tumors activates NOTCH, however the consequences of NOTCH on oHSV-induced immunotherapy is largely unknown. Here we evaluated the impact of NOTCH blockade on virus-induced immunotherapy.

EXPERIMENTAL DESIGN: RNA sequencing (RNA-seq), TCGA data analysis, flow cytometry, Luminex- and ELISA-based assays, brain tumor animal models, and serum analysis of patients with recurrent glioblastoma (GBM) treated with oHSV was used to evaluate the effect of NOTCH signaling on virus-induced immunotherapy.

RESULTS: TCGA data analysis of patients with grade IV glioma and oHSV treatment of experimental brain tumors in mice showed that NOTCH signaling significantly …


Prevalence Of Metabolic Syndrome Among The Adult Population In Western China And The Association With Socioeconomic And Individual Factors: Four Cross-Sectional Studies, Xinyin Xu, Jing Zeng, Wei Yang, Ting Dong, Xin Zhang, Shuwen Cheng, Xiaobo Zhou, Maigeng Zhou, Ling Niu, Guanghui Yi, You Li, Lishi Zhang, Yin Deng, Xianping Wu Apr 2022

Prevalence Of Metabolic Syndrome Among The Adult Population In Western China And The Association With Socioeconomic And Individual Factors: Four Cross-Sectional Studies, Xinyin Xu, Jing Zeng, Wei Yang, Ting Dong, Xin Zhang, Shuwen Cheng, Xiaobo Zhou, Maigeng Zhou, Ling Niu, Guanghui Yi, You Li, Lishi Zhang, Yin Deng, Xianping Wu

Faculty, Staff and Student Publications

Objectives: This study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation.

Design: Four cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015.

Setting: From 2010 to 2018, 8-15 counties/districts of West China were included.

Participants: A total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors.

Results: …


Development And Characterization Of Anti-Galectin-9 Antibodies That Protect T Cells From Galectin-9-Induced Cell Death, Riyao Yang, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Weiya Xia, Boning Liu, Yu-Yi Chu, Laura Bover, Long Vien, Mien-Chie Hung Apr 2022

Development And Characterization Of Anti-Galectin-9 Antibodies That Protect T Cells From Galectin-9-Induced Cell Death, Riyao Yang, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Weiya Xia, Boning Liu, Yu-Yi Chu, Laura Bover, Long Vien, Mien-Chie Hung

Faculty, Staff and Student Publications

Antibodies that target immune checkpoint proteins such as programmed cell death protein 1, programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 in human cancers have achieved impressive clinical success; however, a significant proportion of patients fail to respond to these treatments. Galectin-9 (Gal-9), a β-galactoside-binding protein, has been shown to induce T-cell death and facilitate immunosuppression in the tumor microenvironment by binding to immunomodulatory receptors such as T-cell immunoglobulin and mucin domain-containing molecule 3 and the innate immune receptor dectin-1, suggesting that it may have potential as a target for cancer immunotherapy. Here, we report the development of two …


Citation Analysis Of The Most Influential Ependymoma Research Articles Illustrates Improved Knowledge Of The Molecular Biology Of Ependymoma, Nolan J Brown, Bayard Wilson, Brian V Lien, Alexander Himstead, Ali R Tafreshi, Shane Shahrestani, Jack Birkenbeuel, Katelynn Tran, David Horton, Anushka Paladugu, Lydia R Kirillova, Chen Yi Yang, Seth C Ransom, Ronald Sahyouni, Isaac Yang Apr 2022

Citation Analysis Of The Most Influential Ependymoma Research Articles Illustrates Improved Knowledge Of The Molecular Biology Of Ependymoma, Nolan J Brown, Bayard Wilson, Brian V Lien, Alexander Himstead, Ali R Tafreshi, Shane Shahrestani, Jack Birkenbeuel, Katelynn Tran, David Horton, Anushka Paladugu, Lydia R Kirillova, Chen Yi Yang, Seth C Ransom, Ronald Sahyouni, Isaac Yang

Faculty, Staff and Student Publications

The history of academic research on ependymoma is expansive. This review summarizes its history with a bibliometric analysis of the 100 most cited articles on ependymoma. In March 2020, we queried the Web of Science database to identify the most cited articles on ependymoma using the terms "ependymoma" or "ependymal tumors," yielding 3145 publications. Results were arranged by the number of times each article was cited in descending order. The top 100 articles spanned across nearly a century; the oldest article was published in 1924, while the most recent was in 2017. These articles were published in 35 unique journals, …


Predictive Radiation Oncology - A New Nci-Doe Scientific Space And Community, Jeffrey C Buchsbaum, David A Jaffray, Demba Ba, Lynn L Borkon, Christine Chalk, Caroline Chung, Matthew A Coleman, C Norman Coleman, Maximilian Diehn, Kelvin K Droegemeier, Heiko Enderling, Michael G Espey, Emily J Greenspan, Christopher M Hartshorn, Thuc Hoang, H Timothy Hsiao, Cynthia Keppel, Nathan W Moore, Fred Prior, Eric A Stahlberg, Georgia Tourassi, Karen E Willcox Apr 2022

Predictive Radiation Oncology - A New Nci-Doe Scientific Space And Community, Jeffrey C Buchsbaum, David A Jaffray, Demba Ba, Lynn L Borkon, Christine Chalk, Caroline Chung, Matthew A Coleman, C Norman Coleman, Maximilian Diehn, Kelvin K Droegemeier, Heiko Enderling, Michael G Espey, Emily J Greenspan, Christopher M Hartshorn, Thuc Hoang, H Timothy Hsiao, Cynthia Keppel, Nathan W Moore, Fred Prior, Eric A Stahlberg, Georgia Tourassi, Karen E Willcox

Faculty, Staff and Student Publications

With a widely attended virtual kickoff event on January 29, 2021, the National Cancer Institute (NCI) and the Department of Energy (DOE) launched a series of 4 interactive, interdisciplinary workshops-and a final concluding "World Café" on March 29, 2021-focused on advancing computational approaches for predictive oncology in the clinical and research domains of radiation oncology. These events reflect 3,870 human hours of virtual engagement with representation from 8 DOE national laboratories and the Frederick National Laboratory for Cancer Research (FNL), 4 research institutes, 5 cancer centers, 17 medical schools and teaching hospitals, 5 companies, 5 federal agencies, 3 research centers, …


Trends In Acromioplasty Utilization During Arthroscopic Rotator Cuff Repair: An Epidemiological Study Of 139,586 Patients, Taylor J Willenbring, Marijke J Devos, Ryan J Warth, James M Gregory Apr 2022

Trends In Acromioplasty Utilization During Arthroscopic Rotator Cuff Repair: An Epidemiological Study Of 139,586 Patients, Taylor J Willenbring, Marijke J Devos, Ryan J Warth, James M Gregory

Faculty, Staff and Student Publications

INTRODUCTION: Acromioplasty remains very common during rotator cuff repair (RCR) despite limited evidence of clinical efficacy. This study observed the incidence of acromioplasty from 2010 to 2018 in Texas using a publicly available database.

METHODS: A total of 139,586 records were analyzed from the Texas Healthcare Information Collection database ranging from 2010 to 2018. These cases were divided into those with and without acromioplasty (N = 107,427 and N = 32,159, respectively). Acromioplasty use was standardized as the number of acromioplasties per RCR (acromioplasty rate). Two subgroup analyses were conducted: surgical institution type and payor status.

RESULTS: In 2010, acromioplasty …


The Effect Of Scan And Patient Parameters On The Diagnostic Performance Of Ai For Detecting Coronary Stenosis On Coronary Ct Angiography, Rebecca Jonas, Emil Barkovich, Andrew D Choi, William F Griffin, Joanna Riess, Hugo Marques, Hyuk-Jae Chang, Jung Hyun Choi, Joon-Hyung Doh, Ae-Young Her, Bon-Kwon Koo, Chang-Wook Nam, Hyung-Bok Park, Sang-Hoon Shin, Jason Cole, Alessia Gimelli, Muhammad Akram Khan, Bin Lu, Yang Gao, Faisal Nabi, Ryo Nakazato, U Joseph Schoepf, Roel S Driessen, Michiel J Bom, Randall C Thompson, James J Jang, Michael Ridner, Chris Rowan, Erick Avelar, Philippe Généreux, Paul Knaapen, Guus A De Waard, Gianluca Pontone, Daniele Andreini, Marco Guglielmo, Mouaz H Al-Mallah, Robert S Jennings, Tami R Crabtree, James P Earls Apr 2022

The Effect Of Scan And Patient Parameters On The Diagnostic Performance Of Ai For Detecting Coronary Stenosis On Coronary Ct Angiography, Rebecca Jonas, Emil Barkovich, Andrew D Choi, William F Griffin, Joanna Riess, Hugo Marques, Hyuk-Jae Chang, Jung Hyun Choi, Joon-Hyung Doh, Ae-Young Her, Bon-Kwon Koo, Chang-Wook Nam, Hyung-Bok Park, Sang-Hoon Shin, Jason Cole, Alessia Gimelli, Muhammad Akram Khan, Bin Lu, Yang Gao, Faisal Nabi, Ryo Nakazato, U Joseph Schoepf, Roel S Driessen, Michiel J Bom, Randall C Thompson, James J Jang, Michael Ridner, Chris Rowan, Erick Avelar, Philippe Généreux, Paul Knaapen, Guus A De Waard, Gianluca Pontone, Daniele Andreini, Marco Guglielmo, Mouaz H Al-Mallah, Robert S Jennings, Tami R Crabtree, James P Earls

Division of Internal Medicine Faculty Papers & Presentations

Objectives: To determine whether coronary computed tomography angiography (CCTA) scanning, scan preparation, contrast, and patient based parameters influence the diagnostic performance of an artificial intelligence (AI) based analysis software for identifying coronary lesions with ≥50% stenosis.

Background: CCTA is a noninvasive imaging modality that provides diagnostic and prognostic benefit to patients with coronary artery disease (CAD). The use of AI enabled quantitative CCTA (AI-QCT) analysis software enhances our diagnostic and prognostic ability, however, it is currently unclear whether software performance is influenced by CCTA scanning parameters.

Methods: CCTA and quantitative coronary CT (QCT) data from 303 stable patients (64 ± …


Prevalence And Predictors Of Missed Dysplasia On Index Barrett's Esophagus Diagnosing Endoscopy In A Veteran Population, Theresa H Nguyen, Aaron P Thrift, Rollin George, Daniel G Rosen, Hashem B El-Serag, Gyanprakash A Ketwaroo Apr 2022

Prevalence And Predictors Of Missed Dysplasia On Index Barrett's Esophagus Diagnosing Endoscopy In A Veteran Population, Theresa H Nguyen, Aaron P Thrift, Rollin George, Daniel G Rosen, Hashem B El-Serag, Gyanprakash A Ketwaroo

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Limitations of endoscopic sampling may result in missed dysplasia at the diagnosis of Barrett's esophagus (BE). However, the role of close follow-up endoscopy is unclear. The aim was to evaluate the proportion of patients diagnosed with "missed" dysplasia within 18 months of their index nondysplastic BE (NDBE) diagnosis.

METHODS: This was a retrospective analysis of a cohort of BE patients diagnosed during 1990-2019 at the Houston VA. Patients with BE on index esophagogastroduodenoscopy (EGD) were classified as NDBE, indefinite dysplasia, or dysplastic (low- or high-grade dysplasia) based on initial biopsies. We identified NDBE patients who had follow-up …


Differences In Covid-19-Related Testing And Healthcare Utilization By Race And Ethnicity In The Veterans Health Administration, Javad Razjouyan, Drew A Helmer, Ang Li, Aanand D Naik, Christopher I Amos, Venkata Bandi, Amir Sharafkhaneh Apr 2022

Differences In Covid-19-Related Testing And Healthcare Utilization By Race And Ethnicity In The Veterans Health Administration, Javad Razjouyan, Drew A Helmer, Ang Li, Aanand D Naik, Christopher I Amos, Venkata Bandi, Amir Sharafkhaneh

Faculty, Staff and Students Publications

IMPORTANCE: Recent reports indicate differences in COVID-19-related care and outcomes between Black and White Americans.

OBJECTIVE: We examine the COVID-19-related healthcare utilization and mortality by race and ethnicity of patients tested for SARS-CoV-2 in the Veterans Health Administration (VHA).

DESIGN: A retrospective cohort study.

SETTING: We used the VHA COVID-19 shared data resources between February 1 and June 30, 2020.

PARTICIPANTS: Veterans tested for SARS-CoV-2 virus by VHA.

EXPOSURE(S): Three racial-ethnicity groups of Black, Hispanic, and White (as reference) veterans.

MAIN OUTCOME(S) AND MEASURE(S): Main outcomes are testing rate, positivity rate, hospitalization rate, ICU admission rate, and in-hospital mortality. Controlling …


Does Age-Related Macular Degeneration (Amd) Treatment Influence Patient Falls And Mobility? A Systematic Review., Hannah Garrigan, Jacquelyn N. Hamati, Parth Lalakia, Rosemary Frasso, Brooke Salzman, Leslie Hyman Apr 2022

Does Age-Related Macular Degeneration (Amd) Treatment Influence Patient Falls And Mobility? A Systematic Review., Hannah Garrigan, Jacquelyn N. Hamati, Parth Lalakia, Rosemary Frasso, Brooke Salzman, Leslie Hyman

Student Papers, Posters & Projects

PURPOSE: Age-related macular degeneration (AMD), a leading cause of irreversible blindness, increases fall risk through impaired central vision. Falls place an enormous economic burden on healthcare systems. We hypothesized that AMD treatments may reduce patients' falls risk. This systematic review (ID #: 172623) synthesized the current understanding of wet and dry AMD treatments' impact on patient falls and mobility, connecting these two public health issues.

METHODS: On April 17, 2020, PubMed, Scopus, CINAHL, and the Cochrane Central Register of Controlled Trials were queried. Clinical trials and observational studies were included, while non-English and non-primary studies were excluded. Two authors screened, …