Digital Commons Network^™

Maladaptive Positive Feedback Production Of Chrebpβ Underlies Glucotoxic Β-Cell Failure, Liora S Katz, Gabriel Brill, Pili Zhang, Anil Kumar, Sharon Baumel-Alterzon, Lee B Honig, Nicolás Gómez-Banoy, Esra Karakose, Marius Tanase, Ludivine Doridot, Alexandra Alvarsson, Bennett Davenport, Peng Wang, Luca Lambertini, Sarah A Stanley, Dirk Homann, Andrew F Stewart, James C Lo, Mark A Herman, Adolfo Garcia-Ocaña, Donald K Scott

Faculty, Staff and Students Publications

Preservation and expansion of β-cell mass is a therapeutic goal for diabetes. Here we show that the hyperactive isoform of carbohydrate response-element binding protein (ChREBPβ) is a nuclear effector of hyperglycemic stress occurring in β-cells in response to prolonged glucose exposure, high-fat diet, and diabetes. We show that transient positive feedback induction of ChREBPβ is necessary for adaptive β-cell expansion in response to metabolic challenges. Conversely, chronic excessive β-cell-specific overexpression of ChREBPβ results in loss of β-cell identity, apoptosis, loss of β-cell mass, and diabetes. Furthermore, β-cell "glucolipotoxicity" can be prevented by deletion of ChREBPβ. Moreover, ChREBPβ-mediated cell death is …

Stem Cell Transplantation For Systemic Sclerosis, Sebastian Bruera, Harish Sidanmat, Donald A Molony, Maureen D Mayes, Maria E Suarez-Almazor, Kate Krause, Maria Angeles Lopez-Olivo

Faculty, Staff and Students Publications

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment.

OBJECTIVES: To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide).

SEARCH METHODS: We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February …

Effect Of High- Vs Low-Dose Tranexamic Acid Infusion On Need For Red Blood Cell Transfusion And Adverse Events In Patients Undergoing Cardiac Surgery: The Optimal Randomized Clinical Trial, Jia Shi, Chenghui Zhou, Wei Pan, Hansong Sun, Sheng Liu, Wei Feng, Weijian Wang, Zhaoyun Cheng, Yang Wang, Zhe Zheng, Optimal Study Group

Faculty, Staff and Students Publications

IMPORTANCE: Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery.

OBJECTIVE: To compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to …

Persistent Ethnicity-Associated Disparity In Anti-Tumor Effectiveness Of Immune Checkpoint Inhibitors Despite Equal Access, Marcus A Florez, Jan O Kemnade, Nan Chen, Wendy Du, Anita L Sabichi, Daniel Y Wang, Quillan Huang, Courtney N Miller-Chism, Aparna Jotwani, Albert C Chen, David Hernandez, Vlad C Sandulache

Faculty, Staff and Students Publications

We reviewed response to immune checkpoint inhibitors (ICI) of 207 patients with diagnoses of lung or head and neck cancer treated with chemotherapy/ICI combination therapy and ICI monotherapy between 2015 and 2020 at one of three clinical pavilions associated with the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine. Two of these pavilions (Harris Health System and the Michael E. DeBakey Veterans Affairs Medical Center) serve large minority populations and provide equal access to care regardless of means. 174 patients had a diagnosis of lung cancer (non-small cell or small cell) and 33 had a diagnosis of …

An Integrated Proteomic And Glycoproteomic Investigation Reveals Alterations In The N-Glycoproteomic Network Induced By 2-Deoxy-D-Glucose In Colorectal Cancer Cells, Cheng Ma, Hong-Yuan Tsai, Qi Zhang, Lakmini Senavirathna, Lian Li, Lih-Shen Chin, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

As a well-known glycolysis inhibitor for anticancer treatment, 2-Deoxy-D-glucose (2DG) inhibits the growth and survival of cancer cells by interfering with the ATP produced by the metabolism of D-glucose. In addition, 2DG inhibits protein glycosylation in vivo by competing with D-mannose, leading to endoplasmic reticulum (ER) stress and unfolded protein responses in cancer cells. However, the molecular details underlying the impact of 2DG on protein glycosylation remain largely elusive. With an integrated approach to glycoproteomics and proteomics, we characterized the 2DG-induced alterations in N-glycosylation, as well as the cascading impacts on the whole proteome using the HT29 colorectal cancer …

Heart Failure In General And Cardiac Transplant Patients With Covid-19, Munish Sharma, Gowthami Sai Kogilathota Jagirdhar, Kalpalatha K Guntupalli, Rahul Kashyap, Salim Surani

Faculty, Staff and Students Publications

Coronavirus disease 2019 (COVID-19) is primarily an infection of the respiratory tract, but it can have multisystem manifestations. Cardiac complications of COVID-19 can range from acute myocardial injury, cardiac arrhythmias, or heart failure, amongst others. Heart failure (HF) in COVID-19 can be a de novo process or due to worsening of pre-existing cardiovascular ailment. HF in a patient with COVID-19 not only poses challenges in clinical presentation and management of COVID-19 but also affect prognosis of the patient. This article aims to succinctly revisit the implications of this pandemic regarding pre-existing HF or new-onset HF based on prevailing data. It …

Holarctic Species In The Pluteus Romellii Clade Five New Species Described And Old Names Reassessed, Hana Ševčíková, Ekaterina Malysheva, Giuliano Ferisin, Francesco Dovana, Egon Horak, Jacob Kalichman, Oğuzhan Kaygusuz, Renée Lebeuf, Guillermo Muñoz González, Andrew M Minnis, Stephen D Russell, Michal Sochor, Bálint Dima, Vladimír Antonín, Alfredo Justo

Faculty, Staff and Students Publications

We studied the taxonomy of Pluteus romellii, and morphologically similar Holarctic species in the/romellii clade of section Celluloderma, using morphological and molecular data (nrITS, TEF1-α). Pluteus romellii is lectotypified and epitypified and accepted as an exclusively Eurasian species. Pluteus lutescens and P. pallescens are considered synonyms of P. romellii. Pluteus fulvibadius is accepted as a related, but separate, North American species. Five species in the/romellii clade are described as new to science: two from North America (P. austrofulvus and P. parvisporus), one from Asia (P. parvicarpus), one from Europe (P. siccus …

A Phospholipid Mimetic Targeting Lrh-1 Ameliorates Colitis, Suzanne G Mays, Emma H D'Agostino, Autumn R Flynn, Xiangsheng Huang, Guohui Wang, Xu Liu, Elizabeth J Millings, C Denise Okafor, Anamika Patel, Michael L Cato, Jeffery L Cornelison, Diana Melchers, René Houtman, David D Moore, John W Calvert, Nathan T Jui, Eric A Ortlund

Faculty, Staff and Students Publications

Phospholipids are ligands for nuclear hormone receptors (NRs) that regulate transcriptional programs relevant to normal physiology and disease. Here, we demonstrate that mimicking phospholipid-NR interactions is a robust strategy to improve agonists of liver receptor homolog-1 (LRH-1), a therapeutic target for colitis. Conventional LRH-1 modulators only partially occupy the binding pocket, leaving vacant a region important for phospholipid binding and allostery. Therefore, we constructed a set of molecules with elements of natural phospholipids appended to a synthetic LRH-1 agonist. We show that the phospholipid-mimicking groups interact with the targeted residues in crystal structures and improve binding affinity, LRH-1 transcriptional activity, …

Paclitaxel And Urolithin A Prevent Histamine-Induced Neurovascular Breakdown Alike, In An, Srijayaprakash Uppada, Dianxiong Zou, Erin M Scott, Gladys Ko, Stephen Pflugfelder, M N V Ravi Kumar, Raghu Ganugula

Faculty, Staff and Students Publications

Neurovascular eye problems are better prevented than managed or treated. Despite growing concern of occurrence in aging populations and development secondary to diseases such as diabetes and hypertension, we currently have very few options to tackle this global problem. Creating effective and high-throughput screening strategies is as important as the intervention itself. Here, we present for the first time a robust ex vivo rat eye model of histamine-induced vascular damage for investigating the therapeutic potential of paclitaxel (PTX) and urolithin A (UA) as alternatives to dexamethasone for preventing vascular damage in the retina. Extensive loss of vascularization and apoptosis were …

Hippo-Taz Signaling Is The Master Regulator Of The Onset Of Triple-Negative Basal-Like Breast Cancers, Hirotoshi Soyama, Miki Nishio, Junji Otani, Toshiko Sakuma, Shintaro Takao, Shigeo Hara, Takaaki Masuda, Koshi Mimori, Shinya Toyokuni, John P Lydon, Kazuwa Nakao, Hiroshi Nishina, Takumi Fukumoto, Tomohiko Maehama, Akira Suzuki

Faculty, Staff and Students Publications

A universal oncogenic driver of basal-like breast cancer (BLBC) has resisted identification. We show that continuous transcriptional coactivator with PDZ-binding motif (TAZ) activation in precancerous murine luminal cells generates luminal cancers that later become BLBCs. Subsequent TP53 alteration, a feature of invasive human BLBCs, accelerates tumor progression. Because BLBC development is inhibited by TAZ inactivation in vivo, our work provides a sound rationale for targeting Hippo-TAZ signaling as therapy for human BLBC. Our mouse model of BLBC represents a powerful tool for evaluating such drugs.

A Narrative Review On Yoga: A Potential Intervention For Augmenting Immunomodulation And Mental Health In Covid-19, Indranill Basu-Ray, Kashinath Metri, Dibbendhu Khanra, Rishab Revankar, Kavitha M Chinnaiyan, Nagaratna Raghuram, Mahesh Chandra Mishra, Bhushan Patwardhan, Manjunath Sharma, Ishwar V Basavaraddi, Akshay Anand, Shrinath Reddy, K K Deepak, Marian Levy, Sue Theus, Glenn N Levine, Holger Cramer, Gregory L Fricchione, Nagendra R Hongasandra

Faculty, Staff and Students Publications

BACKGROUND: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has a significant mortality rate of 3-5%. The principal causes of multiorgan failure and death are cytokine release syndrome and immune dysfunction. Stress, anxiety, and depression has been aggravated by the pandemic and its resultant restrictions in day-to-day life which may contribute to immune dysregulation. Thus, immunity strengthening and the prevention of cytokine release syndrome are important for preventing and minimizing mortality in COVID-19 patients. However, despite a few specific remedies that now exist for the SARS-CoV-2virus, the principal modes of prevention include vaccination, masking, and holistic healing methods, such as …

Scintillation Light Detection In The 6-M Drift-Length Protodune Dual Phase Liquid Argon Tpc, A Abed Abud, B Abi, R Acciarri, M A Acero, M R Adames, G Adamov, M Adamowski, D Adams, M Adinolfi, A Aduszkiewicz, J Aguilar, Z Ahmad, J Ahmed, B Aimard, B Ali-Mohammadzadeh, T Alion, K Allison, S Alonso Monsalve, M Alrashed, C Alt, A Alton, R Alvarez, P Amedo, J Anderson, C Andreopoulos, M Andreotti, M Andrews, F Andrianala, S Andringa, N Anfimov, A Ankowski, M Antoniassi, M Antonova, A Antoshkin, S Antusch, A Aranda-Fernandez, L Arellano, L O Arnold, M A Arroyave, J Asaadi, L Asquith, A Aurisano, V Aushev, D Autiero, V Ayala Lara, M Ayala-Torres, F Azfar, A Back, H Back, J J Back, C Backhouse, I Bagaturia, L Bagby, N Balashov, S Balasubramanian, P Baldi, B Baller, B Bambah, F Barao, G Barenboim, P Barham Alzas, G Barker, W Barkhouse, C Barnes, G Barr, J Barranco Monarca, A Barros, N Barros, J L Barrow, A Basharina-Freshville, A Bashyal, V Basque, C Batchelor, E Batista Das Chagas, J B R Battat, F Battisti, F Bay, M C Q Bazetto, J L L Bazo Alba, J F Beacom, E Bechetoille, B Behera, C Beigbeder, L Bellantoni, G Bellettini, V Bellini, O Beltramello, N Benekos, C Benitez Montiel, F Bento Neves, J Berger, S Berkman, P Bernardini, R M Berner, A Bersani, S Bertolucci, M Betancourt, A Betancur Rodríguez, A Bevan, Y Bezawada, T J C Bezerra, A Bhardwaj, V Bhatnagar, M Bhattacharjee, D Bhattarai, S Bhuller, B Bhuyan, S Biagi, J Bian, M Biassoni, K Biery, B Bilki, M Bishai, A Bitadze, A Blake, F Blaszczyk, G C Blazey, E Blucher, J Boissevain, S Bolognesi, T Bolton, L Bomben, M Bonesini, M Bongrand, C Bonilla-Diaz, F Bonini, A Booth, F Boran, S Bordoni, A Borkum, N Bostan, P Bour, C Bourgeois, D Boyden, J Bracinik, D Braga, D Brailsford, A Branca, A Brandt, J Bremer, D Breton, C Brew, S J Brice, C Brizzolari, C Bromberg, J Brooke, A Bross, G Brunetti, M Brunetti, N Buchanan, H Budd, I Butorov, I Cagnoli, T Cai, D Caiulo, R Calabrese, P Calafiura, J Calcutt, M Calin, S Calvez, E Calvo, A Caminata, M Campanelli, D Caratelli, D Carber, J C Carceller, G Carini, B Carlus, M F Carneiro, P Carniti, I Caro Terrazas, H Carranza, T Carroll, J F Castaño Forero, A Castillo, C Castromonte, E Catano-Mur, C Cattadori, F Cavalier, G Cavallaro, F Cavanna, S Centro, G Cerati, A Cervelli, A Cervera Villanueva, M Chalifour, A Chappell, E Chardonnet, N Charitonidis, A Chatterjee, S Chattopadhyay, M S S Chavarry Neyra, H Chen, M Chen, Y Chen, Z Chen, Z Chen-Wishart, Y Cheon, D Cherdack, C Chi, S Childress, R Chirco, A Chiriacescu, G Chisnall, K Cho, S Choate, D Chokheli, P S Chong, A Christensen, D Christian, G Christodoulou, A Chukanov, M Chung, E Church, V Cicero, P Clarke, G Cline, T E Coan, A G Cocco, J A B Coelho, N Colton, E Conley, R Conley, J Conrad, M Convery, S Copello, P Cova, L Cremaldi, L Cremonesi, J I Crespo-Anadón, M Crisler, E Cristaldo, J Crnkovic, R Cross, A Cudd, C Cuesta, Y Cui, D Cussans, O Dalager, H Da Motta, L Da Silva Peres, C David, Q David, G S Davies, S Davini, J Dawson, K De, S De, P Debbins, I De Bonis, M P Decowski, A De Gouvêa, P C De Holanda, I L De Icaza Astiz, A Deisting, P De Jong, A Delbart, D Delepine, M Delgado, A Dell'acqua, N Delmonte, P De Lurgio, J R T De Mello Neto, D M Demuth, S Dennis, C Densham, G W Deptuch, A De Roeck, V De Romeri, G De Souza, R Devi, R Dharmapalan, M Dias, F Diaz, J S Díaz, S Di Domizio, L Di Giulio, P Ding, L Di Noto, G Dirkx, C Distefano, R Diurba, M Diwan, Z Djurcic, D Doering, S Dolan, F Dolek, M Dolinski, L Domine, Y Donon, D Douglas, D Douillet, A Dragone, G Drake, F Drielsma, L Duarte, D Duchesneau, K Duffy, P Dunne, B Dutta, H Duyang, O Dvornikov, D Dwyer, A Dyshkant, M Eads, A Earle, D Edmunds, J Eisch, L Emberger, S Emery, P Englezos, A Ereditato, T Erjavec, C Escobar, G Eurin, J J Evans, E Ewart, A C Ezeribe, K Fahey, A Falcone, M Fani', C Farnese, Y Farzan, D Fedoseev, J Felix, Y Feng, E Fernandez-Martinez, P Fernandez Menendez, M Fernandez Morales, F Ferraro, L Fields, P Filip, F Filthaut, M Fiorini, V Fischer, R S Fitzpatrick, W Flanagan, B Fleming, R Flight, S Fogarty, W Foreman, J Fowler, W Fox, J Franc, K Francis, D Franco, J Freeman, J Freestone, J Fried, A Friedland, F Fuentes Robayo, S Fuess, I K Furic, K Furman, A P Furmanski, A Gabrielli, A Gago, H Gallagher, A Gallas, A Gallego-Ros, N Gallice, V Galymov, E Gamberini, T Gamble, F Ganacim, R Gandhi, R Gandrajula, F Gao, S Gao, D Garcia-Gamez, M Á García-Peris, S Gardiner, D Gastler, J Gauvreau, G Ge, N Geffroy, B Gelli, A Gendotti, S Gent, Z Ghorbani-Moghaddam, P Giammaria, T Giammaria, N Giangiacomi, D Gibin, I Gil-Botella, S Gilligan, C Girerd, A K Giri, D Gnani, O Gogota, M Gold, S Gollapinni, K Gollwitzer, R A Gomes, L V Gomez Bermeo, L S Gomez Fajardo, F Gonnella, D Gonzalez-Diaz, M Gonzalez-Lopez, M C Goodman, O Goodwin, S Goswami, C Gotti, E Goudzovski, C Grace, R Gran, E Granados, P Granger, A Grant, C Grant, D Gratieri, P Green, L Greenler, J Greer, J Grenard, W C Griffith, M Groh, J Grudzinski, K Grzelak, W Gu, E Guardincerri, V Guarino, M Guarise, R Guenette, E Guerard, M Guerzoni, D Guffanti, A Guglielmi, B Guo, A Gupta, V Gupta, K K Guthikonda, R Gutierrez, P Guzowski, M M Guzzo, S Gwon, C Ha, K Haaf, A Habig, H Hadavand, R Haenni, A Hahn, J Haiston, P Hamacher-Baumann, T Hamernik, P Hamilton, J Han, D A Harris, J Hartnell, T Hartnett, J Harton, T Hasegawa, C Hasnip, R Hatcher, K W Hatfield, A Hatzikoutelis, C Hayes, K Hayrapetyan, J Hays, E Hazen, M He, A Heavey, K M Heeger, J Heise, S Henry, M A Hernandez Morquecho, K Herner, J Hewes, C Hilgenberg, T Hill, S J Hillier, A Himmel, E Hinkle, L R Hirsch, J Ho, J Hoff, A Holin, E Hoppe, G A Horton-Smith, M Hostert, A Hourlier, B Howard, R Howell, J Hoyos, I Hristova, M S Hronek, J Huang, Z Hulcher, G Iles, N Ilic, A M Iliescu, R Illingworth, G Ingratta, A Ioannisian, B Irwin, L Isenhower, R Itay, C M Jackson, V Jain, E James, W Jang, B Jargowsky, F Jediny, D Jena, Y S Jeong, C Jesús-Valls, X Ji, L Jiang, S Jiménez, A Jipa, R Johnson, W Johnson, N Johnston, B Jones, S Jones, M Judah, C K Jung, T Junk, Y Jwa, M Kabirnezhad, A Kaboth, I Kadenko, I Kakorin, A Kalitkina, D Kalra, F Kamiya, N Kaneshige, D M Kaplan, G Karagiorgi, G Karaman, A Karcher, M Karolak, Y Karyotakis, S Kasai, S P Kasetti, L Kashur, N Kazaryan, E Kearns, P Keener, K J Kelly, E Kemp, O Kemularia, W Ketchum, S H Kettell, M Khabibullin, A Khotjantsev, A Khvedelidze, D Kim, B King, B Kirby, M Kirby, J Klein, A Klustova, T Kobilarcik, K Koehler, L W Koerner, D H Koh, S Kohn, P P Koller, L Kolupaeva, D Korablev, M Kordosky, T Kosc, U Kose, V A Kostelecký, K Kothekar, R Kralik, L Kreczko, F Krennrich, I Kreslo, W Kropp, T Kroupova, S Kubota, Y Kudenko, V A Kudryavtsev, S Kulagin, J Kumar, P Kumar, P Kunze, N Kurita, C Kuruppu, V Kus, T Kutter, J Kvasnicka, D Kwak, A Lambert, B Land, C E Lane, K Lang, T Langford, M Langstaff, J Larkin, P Lasorak, D Last, A Laundrie, G Laurenti, A Lawrence, I Lazanu, R Lazur, M Lazzaroni, T Le, S Leardini, J Learned, P Lebrun, T Lecompte, C Lee, S Y Lee, G Lehmann Miotto, R Lehnert, M A Leigui De Oliveira, M Leitner, L M Lepin, S W Li, Y Li, H Liao, C S Lin, Q Lin, S Lin, R A Lineros, J Ling, A Lister, B R Littlejohn, J Liu, Y Liu, S Lockwitz, T Loew, M Lokajicek, I Lomidze, K Long, T Lord, J M Losecco, W C Louis, X-G Lu, K B Luk, B Lunday, X Luo, E Luppi, T Lux, V P Luzio, J Maalmi, D Macfarlane, A A Machado, P Machado, C T Macias, J R Macier, A Maddalena, A Madera, P Madigan, S Magill, K Mahn, A Maio, A Major, J A Maloney, G Mandrioli, R C Mandujano, J Maneira, L Manenti, S Manly, A Mann, K Manolopoulos, M Manrique Plata, V N Manyam, L Manzanillas, M Marchan, A Marchionni, W Marciano, D Marfatia, C Mariani, J Maricic, R Marie, F Marinho, A D Marino, D Marsden, M Marshak, C Marshall, J Marshall, J Marteau, J Martín-Albo, N Martinez, D A Martinez Caicedo, P Martínez Miravé, S Martynenko, V Mascagna, K Mason, A Mastbaum, F Matichard, S Matsuno, J Matthews, C Mauger, N Mauri, K Mavrokoridis, I Mawby, R Mazza, A Mazzacane, E Mazzucato, T Mcaskill, E Mccluskey, N Mcconkey, K S Mcfarland, C Mcgrew, A Mcnab, A Mefodiev, P Mehta, P Melas, O Mena, H Mendez, P Mendez, D P Méndez, A Menegolli, G Meng, M D Messier, W Metcalf, T Mettler, M Mewes, H Meyer, T Miao, G Michna, T Miedema, V Mikola, R Milincic, G Miller, W Miller, J Mills, O Mineev, A Minotti, O G Miranda, S Miryala, C S Mishra, S R Mishra, A Mislivec, M Mitchell, D Mladenov, I Mocioiu, K Moffat, N Moggi, R Mohanta, T A Mohayai, N Mokhov, J Molina, L Molina Bueno, E Montagna, A Montanari, C Montanari, D Montanari, L M Montañno Zetina, S H Moon, M Mooney, A F Moor, D Moreno, D Moretti, C Morris, C Mossey, M Mote, E Motuk, C A Moura, J Mousseau, G Mouster, W Mu, L Mualem, J Mueller, M Muether, S Mufson, F Muheim, A Muir, M Mulhearn, D Munford, H Muramatsu, S Murphy, J Musser, J Nachtman, S Nagu, M Nalbandyan, R Nandakumar, D Naples, S Narita, A Nath, A Navrer-Agasson, N Nayak, M Nebot-Guinot, K Negishi, J K Nelson, J Nesbit, M Nessi, D Newbold, M Newcomer, H Newton, R Nichol, F Nicolas-Arnaldos, A Nikolica, E Niner, K Nishimura, A Norman, A Norrick, R Northrop, P Novella, J A Nowak, M Oberling, J Ochoa-Ricoux, A Olivier, A Olshevskiy, Y Onel, Y Onishchuk, J Ott, L Pagani, G Palacio, O Palamara, S Palestini, J M Paley, M Pallavicini, C Palomares, W Panduro Vazquez, E Pantic, V Paolone, V Papadimitriou, R Papaleo, A Papanestis, S Paramesvaran, S Parke, E Parozzi, Z Parsa, M Parvu, S Pascoli, L Pasqualini, J Pasternak, J Pater, C Patrick, L Patrizii, R B Patterson, S J Patton, T Patzak, A Paudel, B Paulos, L Paulucci, Z Pavlovic, G Pawloski, D Payne, V Pec, S J M Peeters, A Pena Perez, E Pennacchio, A Penzo, O L G Peres, J Perry, D Pershey, G Pessina, G Petrillo, C Petta, R Petti, V Pia, F Piastra, L Pickering, F Pietropaolo, V L Pimentel, G Pinaroli, K Plows, R Plunkett, R Poling, F Pompa, X Pons, N Poonthottathil, F Poppi, S Pordes, J Porter, M Potekhin, R Potenza, B V K S Potukuchi, J Pozimski, M Pozzato, S Prakash, T Prakash, M Prest, S Prince, F Psihas, D Pugnere, X Qian, J L Raaf, V Radeka, J Rademacker, B Radics, A Rafique, E Raguzin, M Rai, M Rajaoalisoa, I Rakhno, A Rakotonandrasana, L Rakotondravohitra, R Rameika, M A Ramirez Delgado, B Ramson, A Rappoldi, G Raselli, P Ratoff, S Raut, R F Razakamiandra, E M Rea, J S Real, B Rebel, R Rechenmacher, M Reggiani-Guzzo, J Reichenbacher, S D Reitzner, H Rejeb Sfar, A Renshaw, S Rescia, F Resnati, M Ribas, S Riboldi, C Riccio, G Riccobene, L C J Rice, J S Ricol, A Rigamonti, Y Rigaut, E V Rincón, H Ritchie-Yates, D Rivera, A Robert, L Rochester, M Roda, P Rodrigues, M J Rodriguez Alonso, E Rodriguez Bonilla, J Rodriguez Rondon, S Rosauro-Alcaraz, M Rosenberg, P Rosier, B Roskovec, M Rossella, M Rossi, J Rout, P Roy, A Rubbia, C Rubbia, B Russell, D Ruterbories, A Rybnikov, A Saa-Hernandez, R Saakyan, S Sacerdoti, T Safford, N Sahu, K Sakashita, P Sala, N Samios, O Samoylov, M C Sanchez, V Sandberg, D A Sanders, D Sankey, S Santana, M Santos-Maldonado, N Saoulidou, P Sapienza, C Sarasty, I Sarcevic, G Savage, V Savinov, A Scaramelli, A Scarff, A Scarpelli, T Schefke, H Schellman, S Schifano, P Schlabach, D Schmitz, A W Schneider, K Scholberg, A Schukraft, E Segreto, A Selyunin, C R Senise, J Sensenig, A Sergi, D Sgalaberna, M H Shaevitz, S Shafaq, F Shaker, M Shamma, R Sharankova, H R Sharma, R Sharma, R K Sharma, T Shaw, K Shchablo, C Shepherd-Themistocleous, A Sheshukov, S Shin, I Shoemaker, D Shooltz, R Shrock, H Siegel, L Simard, J Sinclair, G Sinev, J Singh, L Singh, P Singh, V Singh, R Sipos, F W Sippach, G Sirri, A Sitraka, K Siyeon, K Skarpaas, A Smith, E Smith, P Smith, J Smolik, M Smy, E Snider, P Snopok, D Snowden-Ifft, M Soares Nunes, H Sobel, M Soderberg, S Sokolov, C J Solano Salinas, S Söldner-Rembold, S R Soleti, N Solomey, V Solovov, W E Sondheim, M Sorel, A Sotnikov, J Soto-Oton, F A Soto Ugaldi, A Sousa, K Soustruznik, F Spagliardi, M Spanu, J Spitz, N J C Spooner, K Spurgeon, M Stancari, L Stanco, C Stanford, R Stein, H M Steiner, A F Steklain Lisbôa, J Stewart, B Stillwell, J Stock, F Stocker, T Stokes, M Strait, T Strauss, L Strigari, A Stuart, J G Suarez, J M Suárez Sunción, H Sullivan, D Summers, A Surdo, V Susic, L Suter, C M Sutera, R Svoboda, B Szczerbinska, A M Szelc, H Tanaka, S Tang, A Tapia, B Tapia Oregui, A Tapper, S Tariq, E Tarpara, N Tata, E Tatar, R Tayloe, A M Teklu, P Tennessen, M Tenti, K Terao, C A Ternes, F Terranova, G Testera, T Thakore, A Thea, J L Thompson, C Thorn, S C Timm, V Tishchenko, L Tomassetti, A Tonazzo, D Torbunov, M Torti, M Tortola, F Tortorici, N Tosi, D Totani, M Toups, C Touramanis, R Travaglini, J Trevor, S Trilov, W H Trzaska, Y Tsai, Y-T Tsai, Z Tsamalaidze, K V Tsang, N Tsverava, S Tufanli, C Tull, E Tyley, M Tzanov, L Uboldi, M A Uchida, J Urheim, T Usher, S Uzunyan, M R Vagins, P Vahle, S Valder, G D A Valdiviesso, E Valencia, R Valentim, Z Vallari, E Vallazza, J W F Valle, S Vallecorsa, R Van Berg, R G Van De Water, D Vanegas Forero, D Vannerom, F Varanini, D Vargas Oliva, G Varner, J Vasel, S Vasina, G Vasseur, N Vaughan, K Vaziri, S Ventura, A Verdugo, S Vergani, M A Vermeulen, M Verzocchi, M Vicenzi, H Vieira De Souza, C Vignoli, C Vilela, B Viren, T Vrba, T Wachala, A V Waldron, M Wallbank, C Wallis, H Wang, J Wang, L Wang, M H L S Wang, X Wang, Y Wang, K Warburton, D Warner, M O Wascko, D Waters, A Watson, K Wawrowska, P Weatherly, A Weber, M Weber, H Wei, A Weinstein, D Wenman, M Wetstein, A White, L H Whitehead, D Whittington, M J Wilking, A Wilkinson, C Wilkinson, Z Williams, F Wilson, R J Wilson, W Wisniewski, J Wolcott, T Wongjirad, A Wood, K Wood, E Worcester, M Worcester, K Wresilo, C Wret, W Wu, Y Xiao, F Xie, B Yaeggy, E Yandel, G Yang, K Yang, T Yang, A Yankelevich, N Yershov, K Yonehara, Y S Yoon, T Young, B Yu, H Yu, J Yu, Y Yu, W Yuan, R Zaki, J Zalesak, L Zambelli, B Zamorano, A Zani, L Zazueta, G P Zeller, J Zennamo, K Zeug, C Zhang, S Zhang, Y Zhang, M Zhao, E Zhivun, G Zhu, E D Zimmerman, S Zucchelli, J Zuklin, V Zutshi, R Zwaska, Dune Collaboration

Faculty, Staff and Students Publications

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6 × 6 × 6 m3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019–2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the …

Triplet Therapy, Transplantation, And Maintenance Until Progression In Myeloma, Paul G Richardson, Susanna J Jacobus, Edie A Weller, Hani Hassoun, Sagar Lonial, Noopur S Raje, Eva Medvedova, Philip L Mccarthy, Edward N Libby, Peter M Voorhees, Robert Z Orlowski, Larry D Anderson, Jeffrey A Zonder, Carter P Milner, Cristina Gasparetto, Mounzer E Agha, Abdullah M Khan, David D Hurd, Krisstina Gowin, Rammurti T Kamble, Sundar Jagannath, Nitya Nathwani, Melissa Alsina, R Frank Cornell, Hamza Hashmi, Erica L Campagnaro, Astrid C Andreescu, Teresa Gentile, Michaela Liedtke, Kelly N Godby, Adam D Cohen, Thomas H Openshaw, Marcelo C Pasquini, Sergio A Giralt, Jonathan L Kaufman, Andrew J Yee, Emma Scott, Pallawi Torka, Amy Foley, Mariateresa Fulciniti, Kyle Hebert, Mehmet K Samur, Kelly Masone, Michelle E Maglio, Andrea A Zeytoonjian, Omar Nadeem, Robert L Schlossman, Jacob P Laubach, Claudia Paba-Prada, Irene M Ghobrial, Aurore Perrot, Philippe Moreau, Hervé Avet-Loiseau, Michel Attal, Kenneth C Anderson, Nikhil C Munshi, Determination Investigators

Faculty, Staff and Students Publications

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown.

METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received …

The Testis-Specific E3 Ubiquitin Ligase Rnf133 Is Required For Fecundity In Mice, Kaori Nozawa, Yoshitaka Fujihara, Darius J Devlin, Ricardo E Deras, Katarzyna Kent, Irina V Larina, Kohei Umezu, Zhifeng Yu, Courtney M Sutton, Qiuji Ye, Laura K Dean, Chihiro Emori, Masahito Ikawa, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

BACKGROUND: Ubiquitination is a post-translational modification required for a number of physiological functions regulating protein homeostasis, such as protein degradation. The endoplasmic reticulum (ER) quality control system recognizes and degrades proteins no longer needed in the ER through the ubiquitin-proteasome pathway. E2 and E3 enzymes containing a transmembrane domain have been shown to function in ER quality control. The ER transmembrane protein UBE2J1 is a E2 ubiquitin-conjugating enzyme reported to be essential for spermiogenesis at the elongating spermatid stage. Spermatids from Ube2j1 KO male mice are believed to have defects in the dislocation step of ER quality control. However, associated …

Internal Standard Triggered-Parallel Reaction Monitoring Mass Spectrometry Enables Multiplexed Quantification Of Candidate Biomarkers In Plasma, Jacob J Kennedy, Jeffrey R Whiteaker, Richard G Ivey, Aura Burian, Shrabanti Chowdhury, Chia-Feng Tsai, Tao Liu, Chenwei Lin, Oscar D Murillo, Rachel A Lundeen, Lisa A Jones, Philip R Gafken, Gary Longton, Karin D Rodland, Steven J Skates, John Landua, Pei Wang, Michael T Lewis, Amanda G Paulovich

Faculty, Staff and Students Publications

Despite advances in proteomic technologies, clinical translation of plasma biomarkers remains low, partly due to a major bottleneck between the discovery of candidate biomarkers and costly clinical validation studies. Due to a dearth of multiplexable assays, generally only a few candidate biomarkers are tested, and the validation success rate is accordingly low. Previously, mass spectrometry-based approaches have been used to fill this gap but feature poor quantitative performance and were generally limited to hundreds of proteins. Here, we demonstrate the capability of an internal standard triggered-parallel reaction monitoring (IS-PRM) assay to greatly expand the numbers of candidates that can be …

Selected Transesophageal Echocardiographic Parameters Of Left Ventricular Diastolic Function Predict Length Of Stay Following Coronary Artery Bypass Graft-A Prospective Observational Study, Samhati Mondal, Nauder Faraday, Wei Dong Gao, Sarabdeep Singh, Sachidanand Hebbar, Kimberly N Hollander, Thomas S Metkus, Lee A Goeddel, Maria Bauer, Brian Bush, Brian Cho, Stephanie Cha, Stephanie O Ibekwe, Domagoj Mladinov, Noah S Rolleri, Laeben Lester, Jochen Steppan, Rosanne Sheinberg, Nadia B Hensley, Anubhav Kapoor, Jeffrey M Dodd-O

Faculty, Staff and Students Publications

(1) Importance: Abnormal left ventricular (LV) diastolic function, with or without a diagnosis of heart failure, is a common finding that can be easily diagnosed by intra-operative transesophageal echocardiography (TEE). The association of diastolic function with duration of hospital stay after coronary artery bypass (CAB) is unknown. (2) Objective: To determine if selected TEE parameters of diastolic dysfunction are associated with length of hospital stay after coronary artery bypass surgery (CAB). (3) Design: Prospective observational study. (4) Setting: A single tertiary academic medical center. (5) Participants: Patients with normal systolic function undergoing isolated CAB from September 2017 through June 2018. …

Long-Term Follow-Up For The Development Of Subsequent Malignancies In Patients Treated With Genetically Modified Iecs, David H M Steffin, Ibrahim N Muhsen, Laquisa C Hill, Carlos A Ramos, Nabil Ahmed, Meenakshi Hegde, Tao Wang, Mengfen Wu, Stephen Gottschalk, Sarah B Whittle, Premal D Lulla, Maksim Mamonkin, Bilal Omer, Rayne H Rouce, Andras Heczey, Leonid S Metelitsa, Bambi J Grilley, Catherine Robertson, Virginia Torrano, Natalia Lapteva, Adrian P Gee, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop

Faculty, Staff and Students Publications

Subsequent malignancies are well-documented complications in long-term follow-up of cancer patients. Recently, genetically modified immune effector (IE) cells have shown benefit in hematologic malignancies and are being evaluated in clinical trials for solid tumors. Although the short-term complications of IE cells are well described, there is limited literature summarizing long-term follow-up, including subsequent malignancies. We retrospectively reviewed data from 340 patients treated across 27 investigator-initiated pediatric and adult clinical trials at our center. All patients received IE cells genetically modified with γ-retroviral vectors to treat relapsed and/or refractory hematologic or solid malignancies. In a cumulative 1027 years of long-term follow-up, …

Maternal Adipocyte Connexin43 Gap Junctions Affect Breastmilk Lactose Levels And Neonate Growth In Mice, Mingyang Huang, Anying Song, Xi Chen, Sarah Ishtiaq, Chunmei Wang, Darryl L Hadsell, Qiong A Wang, Yi Zhu

Faculty, Staff and Students Publications

Simple Summary

Breastfeeding offers many health benefits for both mothers and infants. However, overnutrition and a steady increase in obesity in the U.S. has made it harder for many mothers to produce and express breastmilk. Moreover, the quality of breastmilk from obese mothers is frequently compromised in that it contains fewer nutrients and more inflammatory components. In this study, we used mice to model this phenomenon. We found that short-term high-fat feeding at the start of breeding reduces litter size and pups’ body weight. It also impairs adipocyte remodeling during lactation. Connexin43 is the primary building block for gap junctions …

Extracellular Domain Of Pept1 Interacts With Tm1 To Facilitate Substrate Transport, Jiemin Shen, Miaohui Hu, Xiao Fan, Zhenning Ren, Corinne Portioli, Xiuwen Yan, Mingqiang Rong, Ming Zhou

Faculty, Staff and Students Publications

Mammalian peptide transporters, PepT1 and PepT2, mediate uptake of small peptides and are essential for their absorption. PepT also mediates absorption of many drugs and prodrugs to enhance their bioavailability. PepT has twelve transmembrane (TM) helices that fold into an N-terminal domain (NTD, TM1–6) and a C-terminal domain (CTD, TM7–12), and has a large extracellular domain (ECD) between TM9–10. It is well-recognized that peptide transport requires movements of the NTD and CTD, but the role of the ECD in PepT1 remains unclear. Here we report the structure of horse PepT1 encircled in lipid nanodiscs and captured in the inward-open apo …

Multifaceted Intervention To Improve P2y12 Inhibitor Adherence After Percutaneous Coronary Intervention: A Stepped Wedge Trial, P Michael Ho, Colin I O'Donnell, Marina Mccreight, Anthony A Bavry, Hayden B Bosworth, Saket Girotra, P Michael Grossman, Christian Helfrich, Faisal Latif, David Lu, Michael Matheny, Kreton Mavromatis, Jose Ortiz, Amitabh Parashar, Devona M Ratliff, Gary K Grunwald, Michael Gillette, Hani Jneid

Faculty, Staff and Students Publications

Background P2Y12 inhibitor medications are critical following percutaneous coronary intervention (PCI); however, adherence remains suboptimal. Our objective was to assess the effectiveness of a multifaceted intervention to improve P2Y12 inhibitor adherence following PCI. Methods and Results This was a modified stepped wedge trial of 52 eligible hospitals, of which 15 were randomly selected and agreed to participate (29 hospitals declined, and 8 eligible hospitals were not contacted). At each intervention hospital, patient recruitment occurred for 6 months and enrolled patients were followed up for 1 year after PCI. Three control groups were used: patients at intervention hospitals undergoing PCI (1) …

Structure-Activity Relationship And Antitumor Activity Of 1,4-Pyrazine-Containing Inhibitors Of Histone Acetyltransferases P300/Cbp, Shenyou Nie, Fangrui Wu, Jingyu Wu, Xin Li, Chao Zhou, Yuan Yao, Yongcheng Song

Faculty, Staff and Students Publications

Acetylation of histone lysine residues by histone acetyltransferase (HAT) p300 and its paralog CBP play important roles in gene regulation in health and diseases. The HAT domain of p300/CBP has been found to be a potential drug target for cancer. Compound screening followed by structure-activity relationship studies yielded a novel series of 1,4-pyrazine-containing inhibitors of p300/CBP HAT with their IC50s as low as 1.4 μM. Enzyme kinetics and other studies support the most potent compound 29 is a competitive inhibitor of p300 HAT against the substrate histone. It exhibited a high selectivity for p300 and CBP, with negligible activity on …

Changing Global Epidemiology Of Liver Cancer From 2010 To 2019: Nash Is The Fastest Growing Cause Of Liver Cancer, Daniel Q Huang, Amit G Singal, Yuko Kono, Darren J H Tan, Hashem B El-Serag, Rohit Loomba

Faculty, Staff and Students Publications

Liver cancer epidemiology is changing due to increasing alcohol consumption, rising prevalence of obesity, and advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) treatment. However, the impact of these changes on global liver cancer burden remains unclear. We estimated global and regional temporal trends in the burden of liver cancer and the contributions of various liver disease etiologies using the methodology framework of the Global Burden of Disease study. Between 2010 and 2019, there was a 25% increase in liver cancer deaths. Age-standardized death rates (ASDRs) increased only in the Americas and remained stable or fell in …

A Practical Focus On Milk Oral Immunotherapy, Aikaterini Anagnostou

Faculty, Staff and Students Publications

Cow's milk allergy (CMA) is a common childhood food allergy associated with a significant burden for those children who are affected and their families, including unintentional exposures that result in allergic reactions, severe allergic reactions, and anaphylaxis. In young children, cow's milk is one of the most frequent food triggers in anaphylactic episodes, and fatalities have also been described as a result of unintentional exposures, which reinforces the notion that milk allergy can be severe in some individuals. The natural history of CMA is favorable, with the allergy resolving over time in the majority of individuals, although some will have …

A Role For Insulin-Like Growth Factor 1 In The Generation Of Epileptic Spasms In A Murine Model, Carlos J Ballester-Rosado, John T Le, Trang T Lam, Carrie A Mohila, Sandi Lam, Anne E Anderson, James D Frost, John W Swann

Faculty, Staff and Students Publications

Objective: Infantile spasms are associated with a wide variety of clinical conditions, including perinatal brain injuries. We have created a model in which prolonged infusion of tetrodotoxin (TTX) into the neocortex, beginning in infancy, produces a localized lesion and reproduces the behavioral spasms, electroencephalogram (EEG) abnormalities, and drug responsiveness seen clinically. Here, we undertook experiments to explore the possibility that the growth factor IGF-1 plays a role in generating epileptic spasms.

Methods: We combined long-term video EEG recordings with quantitative immunohistochemical and biochemical analyses to unravel IGF-1's role in spasm generation. Immunohistochemistry was undertaken in surgically resected tissue from infantile …

Analysis Of An Antibiotic Stewardship Program For Asymptomatic Bacteriuria In The Veterans Affairs Health Care System, Larissa Grigoryan, Aanand D Naik, Paola Lichtenberger, Christopher J Graber, Payal K Patel, Dimitri M Drekonja, Timothy P Gauthier, Bhavarth Shukla, Anne E Sales, Sarah L Krein, John N Van, Laura M Dillon, Sylvia J Hysong, Jennifer R Kramer, Annette Walder, David Ramsey, Barbara W Trautner

Faculty, Staff and Students Publications

IMPORTANCE: Antibiotic stewardship for asymptomatic bacteriuria (ASB) is an important quality improvement target. Understanding how to implement successful antibiotic stewardship interventions is limited.

OBJECTIVE: To evaluate the effectiveness of a quality improvement stewardship intervention on reducing unnecessary urine cultures and antibiotic use in patients with ASB.

DESIGN, SETTING, AND PARTICIPANTS: This interrupted time series quality improvement study was performed at the acute inpatient medical and long-term care units of 4 intervention sites and 4 comparison sites in the Veterans Affairs (VA) health care system from October 1, 2017, through April 30, 2020. Participants included the clinicians who order or collect …

United States Healthcare Burden Of Pediatric Functional Gastrointestinal Pain Disorder Hospitalizations From 2002 To 2018, John M Hollier, Jason L Salemi, Robert J Shulman

Faculty, Staff and Students Publications

BACKGROUND: The healthcare burden of pediatric functional gastrointestinal pain disorders (FGIDs) is unclear. Our study aimed to characterize the burden of these hospitalizations in the United States (US).

METHODS: We utilized the US National Inpatient Sample from 2002 to 2018 to capture pediatric hospitalizations (ages 4 to 18 years old) with a primary discharge diagnosis of abdominal pain, constipation, irritable bowel syndrome, dyspepsia, abdominal migraine, cyclic vomiting syndrome, or fecal incontinence. We calculated the FGID hospitalization prevalence rate, length of stay (LOS), and inflation-adjusted costs annually and assessed for statistically significant trend changes using joinpoint analyses.

KEY RESULTS: 22.3 million …

Chronic Lung Allograft Dysfunction, Anupam Kumar, Puneet Singh Garcha

Faculty, Staff and Students Publications

Lung transplantation remains the only cure for selected patients with advanced irreversible lung diseases. More than 4000 lung transplants are performed worldwide annually. In the last two decades, significant advances have been made in this arena, the most impactful being a modest but improved survival of the recipients. Unfortunately majority of recipients still succumb to chronic lung allograft dysfunction (CLAD), and it remains the most common cause of death after the first year of transplantation. Below is a concise review of the current definition of CLAD, including the various phenotypes, and a brief discussion of the tools available for its …

White Coat Hypertension Persistence In Children And Adolescents: The Pediatric Nephrology Research Consortium Study, Yosuke Miyashita, Coral Hanevold, Anna Faino, Julia Scher, Marc Lande, Ikuyo Yamaguchi, Joel Hernandez, Alisa Acosta, Donald J Weaver, Jason Thomas, Mahmoud Kallash, Michael Ferguson, Ketan N Patel, Andrew M South, Megan Kelton, Joseph T Flynn

Faculty, Staff and Students Publications

OBJECTIVES: To determine whether youth with white coat hypertension on initial ambulatory blood pressure monitoring (ABPM) continue to demonstrate the same pattern on repeat ABPM.

STUDY DESIGN: Retrospective longitudinal cohort study of patients referred for high blood pressure (BP) and diagnosed with white coat hypertension by ABPM who had follow-up ABPM 0.5-4.6 years later at 11 centers in the Pediatric Nephrology Research Consortium. We classified ABPM phenotype using the American Heart Association guidelines. At baseline, we classified those with hypertensive BP in the clinic as "stable white coat hypertension," and those with normal BP as "intermittent white coat hypertension." We …

Innovation And Missed Opportunities In Internal Medicine Undergraduate Education During Covid-19: Results From A National Survey, Irene Alexandraki, Katherine J Walsh, Temple Ratcliffe, Chavon Onumah, Karen Szauter, Camilla Curren, Nora Osman, Cindy J Lai, Deborah Dewaay, Nicholas S Duca, Amy Weinstein, Nadia Ismail, Jackcy Jacob, Michael Kisielewski, Amber T Pincavage

Faculty, Staff and Students Publications

BACKGROUND: COVID-19 disrupted undergraduate clinical education when medical schools removed students from clinical rotations following AAMC recommendations. Clerkship directors (CDs) had to adapt rapidly and modify clerkship curricula. However, the scope and effects of these modifications are unknown.

OBJECTIVE: To examine the effects of the initial phase of COVID-19 on the internal medicine (IM) undergraduate clinical education.

DESIGN: A nationally representative web survey.

PARTICIPANTS: IM CDs from 137 LCME-accredited US medical schools in 2020.

MAIN MEASURES: Items (80) assessed clerkship structure and curriculum, assessment in clerkships, post-clerkship IM clinical experiences, and CD roles and support. The framework of Understanding Crisis …

Spatial Analysis Of Drug Absorption, Distribution, Metabolism, And Toxicology Using Mass Spectrometry Imaging, Michelle L Spruill, Mirjana Maletic-Savatic, Howard Martin, Feng Li, Xinli Liu

Faculty, Staff and Students Publications

Mass spectrometry imaging (MSI) is emerging as a powerful analytical tool for detection, quantification, and simultaneous spatial molecular imaging of endogenous and exogenous molecules via in situ mass spectrometry analysis of thin tissue sections without the requirement of chemical labeling. The MSI generates chemically specific and spatially resolved ion distribution information for administered drugs and metabolites, which allows numerous applications for studies involving various stages of drug absorption, distribution, metabolism, excretion, and toxicity (ADMET). MSI-based pharmacokinetic imaging analysis provides a histological context and cellular environment regarding dynamic drug distribution and metabolism processes, and facilitates the understanding of the spatial pharmacokinetics …