Medical Specialties Commons^™

Is It Time To Re-Think Fast? A Systematic Review And Meta-Analysis Of Contrast-Enhanced Ultrasound (Ceus) And Conventional Ultrasound For Initial Assessment Of Abdominal Trauma, Bayu Sutarjono, Matthew Kessel, Dorian Alexander, Ekjot Grewal

Faculty, Staff and Student Publications

BACKGROUND: The Focused Assessment with Sonography for Trauma (FAST) examination using conventional ultrasound has limited utility for detecting solid organ injury. Therefore, this systematic review and meta-analysis compares the performance of contrast-enhanced ultrasound (CEUS) to conventional ultrasound when used as the initial assessment for abdominal trauma prior to computed tomography (CT) imaging.

METHODS: A systematic literature search of major databases was conducted of human studies investigating the diagnostic accuracy of conventional ultrasound and CEUS occurring prior to CT imaging for abdominal trauma. The study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. The quality of studies …

Spleen Tyrosine Kinase/Fms-Like Tyrosine Kinase-3 Inhibition In Relapsed/Refractory B-Cell Lymphoma, Including Diffuse Large B-Cell Lymphoma: Updated Data With Mivavotinib (Tak-659/Cb-659), Leo I Gordon, Reem Karmali, Jason B Kaplan, Rakesh Popat, Howard A Burris, Silvia Ferrari, Sumit Madan, Manish R Patel, Giuseppe Gritti, Dima El-Sharkawi, F Ian Chau, John Radford, Jaime Pérez De Oteyza, Pier Luigi Zinzani, Swaminathan P Iyer, William Townsend, Harry Miao, Igor Proscurshim, Shining Wang, Shilpi Katyayan, Ying Yuan, Jiaxi Zhu, Kate Stumpo, Yaping Shou, Cecilia Carpio, Francesc Bosch

Faculty, Staff and Student Publications

We report an updated analysis from a phase I study of the spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 inhibitor mivavotinib, presenting data for the overall cohort of lymphoma patients, and the subgroup of patients with diffuse large B-cell lymphoma (DLBCL; including an expanded cohort not included in the initial report). Patients with relapsed/refractory lymphoma for which no standard treatment was available received mivavotinib 60-120 mg once daily in 28-day cycles until disease progression/unacceptable toxicity. A total of 124 patients with lymphoma, including 89 with DLBCL, were enrolled. Overall response rates (ORR) in response-evaluable patients were 45% (43/95) …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

Engineered Protac-Cid Systems For Mammalian Inducible Gene Regulation, Dacheng Ma, Qichen Yuan, Fei Peng, Victor Paredes, Hongzhi Zeng, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Anika Patel, Megan S Liu, Zheng Sun, Xue Gao

Faculty, Staff and Students Publications

Gene regulation via chemically induced dimerization (CID) is useful for biomedical research. However, the number, type, versatility, and in vivo applications of CID tools remain limited. Here, we demonstrate the development of proteolysis-targeting chimera-based scalable CID (PROTAC-CID) platforms by systematically engineering the available PROTAC systems for inducible gene regulation and gene editing. Further, we show orthogonal PROTAC-CIDs that can fine-tune gene expression at gradient levels or multiplex biological signals with different logic gating operations. Coupling the PROTAC-CID platform with genetic circuits, we achieve digitally inducible expression of DNA recombinases, base- and prime-editors for transient genome manipulation. Finally, we package a …

Global Impact Of The Covid-19 Pandemic On Stroke Volumes And Cerebrovascular Events: A 1-Year Follow-Up., Thanh N Nguyen, Muhammad M Qureshi, Piers Klein, Hiroshi Yamagami, Robert Mikulik, Anna Czlonkowska, Mohamad Abdalkader, Petra Sedova, Anvitha Sathya, Hannah C Lo, Ossama Yassin Mansour, Husitha Reddy Vanguru, Emilie Lesaine, Georgios Tsivgoulis, Aaron I Loochtan, Jelle Demeestere, Ken Uchino, Violiza Inoa, Nitin Goyal, Andreas Charidimou, James E Siegler, Shadi Yaghi, Diana Aguiar De Sousa, Mahmoud H Mohammaden, Diogo C Haussen, Espen Saxhaug Kristoffersen, Virginia Pujol Lereis, Sergio Daniel Scollo, Bruce C V Campbell, Alice Ma, James Orton Thomas, Mark W Parsons, Shaloo Singhal, Lee-Anne Slater, Rodrigo Tomazini Martins, Chris Enzinger, Thomas Gattringer, Aminur Rahman, Thomas Bonnet, Noemie Ligot, Sylvie De Raedt, Robin Lemmens, Peter Vanacker, Fenne Vandervorst, Adriana Bastos Conforto, Raquel C T Hidalgo, Luciana De Oliveira Neves, Rodrigo Targa Martins, Daissy Liliana Mora Cuervo, Leticia C Rebello, Igor Bessa Santiago, Isabelle Lameirinhas Da Silva, Teodora Sakelarova, Rosen Kalpachki, Filip Alexiev, Luciana Catanese, Elena Adela Cora, Mayank Goyal, Michael D Hill, Michael E Kelly, Houman Khosravani, Pascale Lavoie, Lissa Peeling, Aleksandra Pikula, Rodrigo Rivera, Hui-Sheng Chen, Yimin Chen, Xiaochuan Huo, Zhongrong Miao, Shuiquan Yang, Marina Roje Bedekovic, Marina Bralic, Hrvoje Budincevic, Angel Basilio Corredor-Quintero, Osvaldo E Lara-Sarabia, Martin Cabal, Dusan Tenora, Petr Fibrich, Roman Herzig, Helena Hlaváčová, Emanuela Hrabanovska, David Hlinovsky, Lubomir Jurak, Jana Kadlcikova, Igor Karpowicz, Lukas Klecka, Martin Kovar, David Lauer, Jiri Neumann, Hana Palouskova, Martin Reiser, Petra Rekova, Vladimir Rohan, Ondrej Skoda, Miroslav Škorňa, Lenka Sobotková, Martin Sramek, Lenka Zakova, Hanne Christensen, Nicolas Drenck, Helle Klingenberg Iversen, Thomas Clement Truelsen, Troels Wienecke, Khalid Sobh, Pauli Ylikotila, Kemal Alpay, Daniel Strbian, Patricia Bernady, Philippe Casenave, Maria Dan, Jean-Marc Faucheux, Jean-Christophe Gentric, Elsa Magro, Candice Sabben, Peggy Reiner, Francois Rouanet, Ferdinand O Bohmann, Stefan Boskamp, Joshua Mbroh, Simon Nagel, Christian H Nolte, Peter A Ringleb, Michael Rosenkranz, Sven Poli, Götz Thomalla, Theodoros Karapanayiotides, Ioanna Koutroulou, Odysseas Kargiotis, Lina Palaiodimou, Jose Dominguo Barrientos Guerra, Vikram Huded, Bindu Menon, Shashank Nagendra, Chintan Prajapati, P N Sylaja, Nyoman Angga Krishna Pramana, Achmad Firdaus Sani, Abdoreza Ghoreishi, Mehdi Farhoudi, Elyar Sadeghi Hokmabadi, Tariq Abu Raya, Shani Avnery Kalmanovich, Levite Ronen, Sergiu Ionut Sabetay, Maurizio Acampa, Alessandro Adami, Lucio Castellan, Marco Longoni, Raffaele Ornello, Leonardo Renieri, Claudia Rolla Bigliani, Michele Romoli, Simona Sacco, Andrea Salmaggi, Davide Sangalli, Andrea Zini, Ryosuke Doijiri, Hiroki Fukuda, Toshiyuki Fujinaka, Kyohei Fujita, Hirotoshi Imamura, Nobuyuki Sakai, Takuya Kanamaru, Naoto Kimura, Ryuhei Kono, Kosuke Miyake, Manabu Sakaguchi, Kenichiro Sakai, Kazutaka Sonoda, Kenichi Todo, Fumio Miyashita, Naoki Tokuda, Yuji Matsumaru, Shoji Matsumoto, Nobuyuki Ohara, Seigo Shindo, Yohei Takenobu, Takeshi Yoshimoto, Kazunori Toyoda, Takeshi Uwatoko, Yoshiki Yagita, Takehiro Yamada, Nobuaki Yamamoto, Ryoo Yamamoto, Yukako Yazawa, Yuri Sugiura, Peter Kuria Waweru, Jang-Hyun Baek, Si Baek Lee, Kwon-Duk Seo, Sung-Il Sohn, Anita Ante Arsovska, Yong Chieh Chan, Wan Asyraf Wan Zaidi, Ainul Syahrilfazli Jaafar, Fernando Gongora-Rivera, Manuel Martinez-Marino, Adrian Infante-Valenzuela, Stanislav Groppa, Pavel Leahu, Jonathan M Coutinho, Leon A Rinkel, Diederik W J Dippel, Dianne H K Van Dam-Nolen, Annemarei Ranta, Teddy Y Wu, Tajudeen Temitayo Adebayo, Abiodun H Bello, Ernest Okwundu Nwazor, Taofiki Ajao Sunmonu, Kolawole Wasiu Wahab, Ole Morten Ronning, Else Charlotte Sandset, Amal M Al Hashmi, Saima Ahmad, Umair Rashid, Liliana Rodriguez-Kadota, Miguel Ángel Vences, Patrick Matic Yalung, Jon Stewart Hao Dy, Maria Carissa Pineda-Franks, Christian Oliver Co, Waldemar Brola, Aleksander Debiec, Malgorzata Dorobek, Michal Adam Karlinski, Beata M Labuz-Roszak, Anetta Lasek-Bal, Halina Sienkiewicz-Jarosz, Jacek Staszewski, Piotr Sobolewski, Marcin Wiacek, Justyna Zielinska-Turek, Andre Pinho Araujo, Mariana Rocha, Pedro Castro, Vitor Tedim Cruz, Paulo Venancio Ferreira, Patricia Ferreira, Ana Paiva Nunes, Luisa Fonseca, João Pedro Marto, Teresa Pinho E Melo, Miguel Rodrigues, M Luis Silva, Adela Dimitriade, Cristian Falup-Pecurariu, May Adel Hamid, Narayanaswamy Venketasubramanian, Georgi Krastev, Miroslav Mako, Oscar Ayo-Martin, Francisco Hernández-Fernández, Jordi Blasco, Alejandro Rodríguez-Vázquez, Antonio Cruz-Culebras, Francisco Moniche, Joan Montaner, Soledad Perez-Sanchez, María Jesús García Sánchez, Marta Guillán Rodríguez, Katarina Jood, Annika Nordanstig, Michael V Mazya, Tiago T P Moreira, Gianmarco Bernava, Morin Beyeler, Manuel Bolognese, Emmanuel Carrera, Tomas Dobrocky, Grzegorz Marek Karwacki, Emanuela Keller, Chang Yang Hsieh, Surawan Boonyakarnkul, Anchalee Churojana, Ozlem Aykac, Atilla Ã-Zcan Ozdemir, Arsida Bajrami, Songul Senadim, Syed Irteza Hussain, Seby John, Soma Banerjee, Joseph Kwan, Kailash Krishnan, Robert Lenthall, Ashok Matthews, Ken Wong, Liqun Zhang, Dorothea Altschul, Kaiz S Asif, Zeelalem Bahiru, Kristine Below, José Biller, Sean Ruland, Saqib A Chaudry, Michael Chen, Alex Chebl, Jackie Cibulka, Leon Cistrunk, Judith Clark, Marco Colasurdo, Alexandra Czap, Adam De Havenon, Salvatore D'Amato, Sushrut Dharmadhikari, Kasey B Grimmett, Adam A Dmytriw, Mark R Etherton, Chizoba Ezepue, Mudassir Farooqui, Steven K Feske, Lauren Fink, Ulviyya Gasimova, Amy K Guzik, Maryam Hakemi, Majesta Hovingh, Muhib Khan, Dinesh Jillela, Peter T Kan, Rakesh Khatri, Ayaz M Khawaja, Naim N Khoury, Nicole L Kiley, Benny S Kim, Murali K Kolikonda, Anna Luisa Kuhn, Stephanie Lara, Guillermo Linares, Italo Linfante, Timothy G Lukovits, Sarah Lycan, Shailesh S Male, Laith Maali, John Mancin, Hesham Masoud, Ghada A Mohamed, Andre Monteiro, Fadi Nahab, Krishna Nalleballe, Santiago Ortega-Gutierrez, Ajit S Puri, Yazan Radaideh, Rahul H Rahangdale, Ansaar Rai, Pankajavalli Ramakrishnan, Aravind B Reddy, Diana M Rojas-Soto, Jose Rafael Romero, Natalia S Rost, Aaron Rothstein, Setareh Salehi Omran, Sunil A Sheth, Adnan H Siddiqui, Amy K Starosciak, Nicholas E Tarlov, Robert A Taylor, Michael J Wang, Jared Wolfe, Ka-Ho Wong, Huynh Vu Le, Quy Viet Nguyen, Thong Nhu Pham, Trung Thanh Nguyen, Hoang Thi Phan, Mai Duy Ton, Urs Fischer, Patrik Michel, Davide Strambo, Sheila O Martins, Osama O Zaidat, Raul G Nogueira

Neuroscience Articles

BACKGROUND AND OBJECTIVES: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year …

Recent Advances In Understanding Of Pathogenesis Of Alcohol-Associated Liver Disease, Xiaoqin Wu, Xiude Fan, Tatsunori Miyata, Adam Kim, Christina K Cajigas-Du Ross, Semanti Ray, Emily Huang, Moyinoluwa Taiwo, Rakesh Arya, Jianguo Wu, Laura E Nagy

Faculty, Staff and Student Publications

Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related morbidity and mortality. ALD includes asymptomatic liver steatosis, fibrosis, cirrhosis, and alcohol-associated hepatitis and its complications. The progression of ALD involves complex cell-cell and organ-organ interactions. We focus on the impact of alcohol on dysregulation of homeostatic mechanisms and regulation of injury and repair in the liver. In particular, we discuss recent advances in understanding the disruption of balance between programmed cell death and prosurvival pathways, such as autophagy and membrane trafficking, in the pathogenesis …

Tumor-Infiltrating Lymphocytes And Macrophages As A Significant Prognostic Factor In Biliary Tract Cancer, Ryota Tanaka, Shimpei Eguchi, Kenjiro Kimura, Go Ohira, Shogo Tanaka, Ryosuke Amano, Hiroaki Tanaka, Masakazu Yashiro, Masaichi Ohira, Shoji Kubo

Department of Medical Oncology Faculty Papers

Background: The impact of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) on the prognosis of biliary tract cancer (BTC) is not completely understood. Therefore, in our study, we investigated the effects of the various immune cells infiltration in tumor microenvironment (TME).

Methods: A total of 130 patients with BTC who underwent surgical treatment at our institution were enrolled in this study. We retrospectively evaluated TILs and TAMs with immunohistochemical staining.

Results: With CD8-high, CD4-high, FOXP3-high, and CD68-low in TME as one factor, we calculated Immunoscore according to the number of factors. The high Immunoscore group showed significantly superior overall survival …

Multisite Detection Of Tn1549-Mediated Vanb Vancomycin Resistance In Multidrug-Resistant Enterococcus Faecalis St6 In Texas And Florida, Shelby R Simar, Truc T Tran, Kirsten B Rydell, Diana Panesso, German A Contreras, Jose M Munita, Renzo O Cifuentes, Lilian M Abbo, Pranoti Sahasrabhojane, An Q Dinh, Dierdre B Axell-House, Tor Savidge, Samuel A Shelburne, Blake M Hanson, Cesar A Arias

Faculty, Staff and Student Publications

In the United States, vanB-mediated resistance in enterococci is rare. We characterized three sequence type (ST) 6, vancomycin-resistant Enterococcus faecalis isolates causing bacteremia in unique patients in spatiotemporally distinct settings. Isolates were recovered between 2018 and 2020 in two cities in the United States (Houston, TX; Miami, FL). The isolates harbored the vanB operon on a chromosomally located Tn1549 transposon, and epidemiological data suggested multiple introductions of the vanB gene cluster into ST6 E. faecalis.

Cbx5 Loss Drives Egfr Inhibitor Resistance And Results In Therapeutically Actionable Vulnerabilities In Lung Cancer, Suresh Bugide, Yvonne J K Edwards, Romi Gupta, Michael R Green, Narendra Wajapeyee

Faculty, Staff and Student Publications

Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFRi) are approved for treating EGFR-mutant lung adenocarcinoma (LUAD), emergence of acquired resistance limits their clinical benefits. Several mechanisms for acquired resistance to EGFRi in LUAD have been identified; however, the molecular basis for this resistance remains unknown in ~30% of LUAD. Chromatin and DNA modifiers and their regulators play important roles in determining response to anticancer therapies. Therefore, to identify nongenetic mechanisms of EGFRi resistance in LUAD, we performed an epigenome-wide shRNA screen targeting 363 human epigenetic regulator genes. This screen identified loss of the transcriptional repressor chromobox homolog 5 …

Interfering With Lipid Metabolism Through Targeting Ces1 Sensitizes Hepatocellular Carcinoma For Chemotherapy, Gang Li, Xin Li, Iqbal Mahmud, Jazmin Ysaguirre, Baharan Fekry, Shuyue Wang, Bo Wei, Kristin L Eckel-Mahan, Philip L Lorenzi, Richard Lehner, Kai Sun

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the most common lethal form of liver cancer. Apart from surgical removal and transplantation, other treatments have not yet been well established for patients with HCC. In this study, we found that carboxylesterase 1 (CES1) is expressed at various levels in HCC. We further revealed that blockage of CES1 by pharmacological and genetical approaches leads to altered lipid profiles that are directly linked to impaired mitochondrial function. Mechanistically, lipidomic analyses indicated that lipid signaling molecules, including polyunsaturated fatty acids (PUFAs), which activate PPARα/γ, were dramatically reduced upon CES1 inhibition. As a result, the expression of SCD, …

Global Impact Of The Covid-19 Pandemic On Stroke Volumes And Cerebrovascular Events: A 1-Year Follow-Up, Thanh N Nguyen, Muhammad M Qureshi, Piers Klein, Hiroshi Yamagami, Robert Mikulik, Anna Czlonkowska, Mohamad Abdalkader, Petra Sedova, Anvitha Sathya, Hannah C Lo, Ossama Yassin Mansour, Husitha Reddy Vanguru, Emilie Lesaine, Georgios Tsivgoulis, Aaron I Loochtan, Jelle Demeestere, Ken Uchino, Violiza Inoa, Nitin Goyal, Andreas Charidimou, James E Siegler, Shadi Yaghi, Diana Aguiar De Sousa, Mahmoud H Mohammaden, Diogo C Haussen, Espen Saxhaug Kristoffersen, Virginia Pujol Lereis, Sergio Daniel Scollo, Bruce C V Campbell, Alice Ma, James Orton Thomas, Mark W Parsons, Shaloo Singhal, Lee-Anne Slater, Rodrigo Tomazini Martins, Chris Enzinger, Thomas Gattringer, Aminur Rahman, Thomas Bonnet, Noemie Ligot, Sylvie De Raedt, Robin Lemmens, Peter Vanacker, Fenne Vandervorst, Adriana Bastos Conforto, Raquel C T Hidalgo, Luciana De Oliveira Neves, Rodrigo Targa Martins, Daissy Liliana Mora Cuervo, Leticia C Rebello, Igor Bessa Santiago, Isabelle Lameirinhas Da Silva, Teodora Sakelarova, Rosen Kalpachki, Filip Alexiev, Luciana Catanese, Elena Adela Cora, Mayank Goyal, Michael D Hill, Michael E Kelly, Houman Khosravani, Pascale Lavoie, Lissa Peeling, Aleksandra Pikula, Rodrigo Rivera, Hui-Sheng Chen, Yimin Chen, Xiaochuan Huo, Zhongrong Miao, Shuiquan Yang, Marina Roje Bedekovic, Marina Bralic, Hrvoje Budincevic, Angel Basilio Corredor-Quintero, Osvaldo E Lara-Sarabia, Martin Cabal, Dusan Tenora, Petr Fibrich, Roman Herzig, Helena Hlaváčová, Emanuela Hrabanovska, David Hlinovsky, Lubomir Jurak, Jana Kadlcikova, Igor Karpowicz, Lukas Klecka, Martin Kovar, David Lauer, Jiri Neumann, Hana Palouskova, Martin Reiser, Petra Rekova, Vladimir Rohan, Ondrej Skoda, Miroslav Škorňa, Lenka Sobotková, Martin Sramek, Lenka Zakova, Hanne Christensen, Nicolas Drenck, Helle Klingenberg Iversen, Thomas Clement Truelsen, Troels Wienecke, Khalid Sobh, Pauli Ylikotila, Kemal Alpay, Daniel Strbian, Patricia Bernady, Philippe Casenave, Maria Dan, Jean-Marc Faucheux, Jean-Christophe Gentric, Elsa Magro, Candice Sabben, Peggy Reiner, Francois Rouanet, Ferdinand O Bohmann, Stefan Boskamp, Joshua Mbroh, Simon Nagel, Christian H Nolte, Peter A Ringleb, Michael Rosenkranz, Sven Poli, Götz Thomalla, Theodoros Karapanayiotides, Ioanna Koutroulou, Odysseas Kargiotis, Lina Palaiodimou, Jose Dominguo Barrientos Guerra, Vikram Huded, Bindu Menon, Shashank Nagendra, Chintan Prajapati, P N Sylaja, Nyoman Angga Krishna Pramana, Achmad Firdaus Sani, Abdoreza Ghoreishi, Mehdi Farhoudi, Elyar Sadeghi Hokmabadi, Tariq Abu Raya, Shani Avnery Kalmanovich, Levite Ronen, Sergiu Ionut Sabetay, Maurizio Acampa, Alessandro Adami, Lucio Castellan, Marco Longoni, Raffaele Ornello, Leonardo Renieri, Claudia Rolla Bigliani, Michele Romoli, Simona Sacco, Andrea Salmaggi, Davide Sangalli, Andrea Zini, Ryosuke Doijiri, Hiroki Fukuda, Toshiyuki Fujinaka, Kyohei Fujita, Hirotoshi Imamura, Nobuyuki Sakai, Takuya Kanamaru, Naoto Kimura, Ryuhei Kono, Kosuke Miyake, Manabu Sakaguchi, Kenichiro Sakai, Kazutaka Sonoda, Kenichi Todo, Fumio Miyashita, Naoki Tokuda, Yuji Matsumaru, Shoji Matsumoto, Nobuyuki Ohara, Seigo Shindo, Yohei Takenobu, Takeshi Yoshimoto, Kazunori Toyoda, Takeshi Uwatoko, Yoshiki Yagita, Takehiro Yamada, Nobuaki Yamamoto, Ryoo Yamamoto, Yukako Yazawa, Yuri Sugiura, Peter Kuria Waweru, Jang-Hyun Baek, Si Baek Lee, Kwon-Duk Seo, Sung-Il Sohn, Anita Ante Arsovska, Yong Chieh Chan, Wan Asyraf Wan Zaidi, Ainul Syahrilfazli Jaafar, Fernando Gongora-Rivera, Manuel Martinez-Marino, Adrian Infante-Valenzuela, Stanislav Groppa, Pavel Leahu, Jonathan M Coutinho, Leon A Rinkel, Diederik W J Dippel, Dianne H K Van Dam-Nolen, Annemarei Ranta, Teddy Y Wu, Tajudeen Temitayo Adebayo, Abiodun H Bello, Ernest Okwundu Nwazor, Taofiki Ajao Sunmonu, Kolawole Wasiu Wahab, Ole Morten Ronning, Else Charlotte Sandset, Amal M Al Hashmi, Saima Ahmad, Umair Rashid, Liliana Rodriguez-Kadota, Miguel Ángel Vences, Patrick Matic Yalung, Jon Stewart Hao Dy, Maria Carissa Pineda-Franks, Christian Oliver Co, Waldemar Brola, Aleksander Debiec, Malgorzata Dorobek, Michal Adam Karlinski, Beata M Labuz-Roszak, Anetta Lasek-Bal, Halina Sienkiewicz-Jarosz, Jacek Staszewski, Piotr Sobolewski, Marcin Wiacek, Justyna Zielinska-Turek, Andre Pinho Araujo, Mariana Rocha, Pedro Castro, Vitor Tedim Cruz, Paulo Venancio Ferreira, Patricia Ferreira, Ana Paiva Nunes, Luisa Fonseca, João Pedro Marto, Teresa Pinho E Melo, Miguel Rodrigues, M Luis Silva, Adela Dimitriade, Cristian Falup-Pecurariu, May Adel Hamid, Narayanaswamy Venketasubramanian, Georgi Krastev, Miroslav Mako, Oscar Ayo-Martin, Francisco Hernández-Fernández, Jordi Blasco, Alejandro Rodríguez-Vázquez, Antonio Cruz-Culebras, Francisco Moniche, Joan Montaner, Soledad Perez-Sanchez, María Jesús García Sánchez, Marta Guillán Rodríguez, Katarina Jood, Annika Nordanstig, Michael V Mazya, Tiago T P Moreira, Gianmarco Bernava, Morin Beyeler, Manuel Bolognese, Emmanuel Carrera, Tomas Dobrocky, Grzegorz Marek Karwacki, Emanuela Keller, Chang Yang Hsieh, Surawan Boonyakarnkul, Anchalee Churojana, Ozlem Aykac, Atilla Ã-Zcan Ozdemir, Arsida Bajrami, Songul Senadim, Syed Irteza Hussain, Seby John, Soma Banerjee, Joseph Kwan, Kailash Krishnan, Robert Lenthall, Ashok Matthews, Ken Wong, Liqun Zhang, Dorothea Altschul, Kaiz S Asif, Zeelalem Bahiru, Kristine Below, José Biller, Sean Ruland, Saqib A Chaudry, Michael Chen, Alex Chebl, Jackie Cibulka, Leon Cistrunk, Judith Clark, Marco Colasurdo, Alexandra Czap, Adam De Havenon, Salvatore D'Amato, Sushrut Dharmadhikari, Kasey B Grimmett, Adam A Dmytriw, Mark R Etherton, Chizoba Ezepue, Mudassir Farooqui, Steven K Feske, Lauren Fink, Ulviyya Gasimova, Amy K Guzik, Maryam Hakemi, Majesta Hovingh, Muhib Khan, Dinesh Jillela, Peter T Kan, Rakesh Khatri, Ayaz M Khawaja, Naim N Khoury, Nicole L Kiley, Benny S Kim, Murali K Kolikonda, Anna Luisa Kuhn, Stephanie Lara, Guillermo Linares, Italo Linfante, Timothy G Lukovits, Sarah Lycan, Shailesh S Male, Laith Maali, John Mancin, Hesham Masoud, Ghada A Mohamed, Andre Monteiro, Fadi Nahab, Krishna Nalleballe, Santiago Ortega-Gutierrez, Ajit S Puri, Yazan Radaideh, Rahul H Rahangdale, Ansaar Rai, Pankajavalli Ramakrishnan, Aravind B Reddy, Diana M Rojas-Soto, Jose Rafael Romero, Natalia S Rost, Aaron Rothstein, Setareh Salehi Omran, Sunil A Sheth, Adnan H Siddiqui, Amy K Starosciak, Nicholas E Tarlov, Robert A Taylor, Michael J Wang, Jared Wolfe, Ka-Ho Wong, Huynh Vu Le, Quy Viet Nguyen, Thong Nhu Pham, Trung Thanh Nguyen, Hoang Thi Phan, Mai Duy Ton, Urs Fischer, Patrik Michel, Davide Strambo, Sheila O Martins, Osama O Zaidat, Raul G Nogueira

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year …

The Improve Trial: Study Protocol For A Pragmatic Cluster Randomised Controlled Trial To Assess The Effectiveness Of Using Lay Health Workers To Improve Uptake And Completion Of Pulmonary Rehabilitation In Patients With Chronic Obstructive Pulmonary Disease, Rui Li, Hosamadin Assadi, Gareth Matthews, Zia Mehmood, Ciaran Grafton-Clarke, Bahman Kasmai, David Hewson, Richard Greenwood, Hilmar Spohr, Liang Zhong, Xiaodan Zhao, Chris Sawh, Rudolf Duehmke, Vassilios S Vassiliou, Faye Nelthorpe, David Ashman, John Curtin, Gurung-Koney Yashoda, Rob J Van Der Geest, Samer Alabed, Andrew J Swift, Marina Hughes, Pankaj Garg

Faculty, Staff and Student Publications

There remains a debate whether the ventricular volume within prolapsing mitral valve (MV) leaflets should be included in the left ventricular (LV) end-systolic volume, and therefore factored in LV stroke volume (SV), in cardiac magnetic resonance (CMR) assessments. This study aims to compare LV volumes during end-systolic phases, with and without the inclusion of the volume of blood on the left atrial aspect of the atrioventricular groove but still within the MV prolapsing leaflets, against the reference LV SV by four-dimensional flow (4DF). A total of 15 patients with MV prolapse (MVP) were retrospectively enrolled in this study. We compared …

Tmem161b Regulates Cerebral Cortical Gyration, Sonic Hedgehog Signaling, And Ciliary Structure In The Developing Central Nervous System, Shyam K Akula, Jack H Marciano, Youngshin Lim, David Exposito-Alonso, Norma K Hylton, Grace H Hwang, Jennifer E Neil, Nicole Dominado, Rosie K Bunton-Stasyshyn, Janet H T Song, Maya Talukdar, Aloisia Schmid, Lydia Teboul, Alisa Mo, Taehwan Shin, Benjamin Finander, Samantha G Beck, Rebecca C Yeh, Aoi Otani, Xuyu Qian, Ellen M Degennaro, Fowzan S Alkuraya, Sateesh Maddirevula, Gregory D Cascino, Caterina Giannini, Undiagnosed Diseases Network, Lindsay C Burrage, Jill A Rosenfield, Shamika Ketkar, Gary D Clark, Carlos Bacino, Richard A Lewis, Rosalind A Segal, J Fernando Bazan, Kelly A Smith, Jeffrey A Golden, Ginam Cho, Christopher A Walsh

Faculty, Staff and Students Publications

Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh signaling remain poorly understood. Exome sequencing of families with polymicrogyria (disordered cortical folding) revealed multiple individuals with biallelic deleterious variants in TMEM161B, which encodes a multi-pass transmembrane protein of unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes consistent with impaired Shh signaling, but were without limb defects, suggesting a CNS-specific role of Tmem161b. Tmem161b depletion impaired the response to Smoothened activation in vitro and disrupted cortical histogenesis in vivo in both mouse and ferret …

Genetics And Pathogenesis Of Parkinson's Syndrome, Hui Ye, Laurie A Robak, Meigen Yu, Matthew Cykowski, Joshua M Shulman

Faculty, Staff and Students Publications

Parkinson's disease (PD) is clinically, pathologically, and genetically heterogeneous, resisting distillation to a single, cohesive disorder. Instead, each affected individual develops a virtually unique form of Parkinson's syndrome. Clinical manifestations consist of variable motor and nonmotor features, and myriad overlaps are recognized with other neurodegenerative conditions. Although most commonly characterized by alpha-synuclein protein pathology throughout the central and peripheral nervous systems, the distribution varies and other pathologies commonly modify PD or trigger similar manifestations. Nearly all PD is genetically influenced. More than 100 genes or genetic loci have been identified, and most cases likely arise from interactions among many common …

Effect Of Intensive Blood Pressure Control On Troponin And Natriuretic Peptide Levels: Findings From Sprint, Jarett D Berry, Haiying Chen, Vijay Nambi, Walter T Ambrosius, Simon B Ascher, Michael G Shlipak, Joachim H Ix, Rajesh Gupta, Anthony Killeen, Robert D Toto, Dalane W Kitzman, Christie M Ballantyne, James A De Lemos

Faculty, Staff and Students Publications

Background: Given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong associations observed between hypertension and its sequelae on hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, we hypothesized that intensive systolic blood pressure (SBP) lowering would decrease levels of hs-cTnT and NT-proBNP.

Methods: hs-cTnT and NT-proBNP were measured at baseline and 1 year from stored specimens in SPRINT (Systolic Blood Pressure Intervention Trial). Changes in biomarkers were evaluated continuously on the log scale and according to categories (≥50% increase, ≥50% decrease, or < 50% change). The effect of intensive SBP lowering on continuous and categorical changes in biomarker levels were assessed using linear and multinomial logistic regression models, respectively. The association between changes in biomarkers on heart failure and death was assessed using multivariable-adjusted Cox proportional hazards models.

Results: Randomization …

Going Back In Time: Increasing Penicillin Susceptibility Among Methicillin-Susceptible Staphylococcus Aureus Osteoarticular Infections In Children, J Chase Mcneil, Lauren M Sommer, Jesus G Vallejo, Mary Boyle, Kristina G Hulten, Sheldon L Kaplan, Stephanie A Fritz

Faculty, Staff and Students Publications

In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children’s and St. Louis Children’s Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ …

Enhancer-Promoter Entanglement Explains Their Transcriptional Interdependence, Anil K Panigrahi, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Enhancers not only activate target promoters to stimulate messenger RNA (mRNA) synthesis, but they themselves also undergo transcription to produce enhancer RNAs (eRNAs), the significance of which is not well understood. Transcription at the participating enhancer-promoter pair appears coordinated, but it is unclear why and how. Here, we employ cell-free transcription assays using constructs derived from the human GREB1 locus to demonstrate that transcription at an enhancer and its target promoter is interdependent. This interdependence is observable under conditions where direct enhancer-promoter contact (EPC) takes place. We demonstrate that transcription activation at a participating enhancer-promoter pair is dependent on i) …

Mixcan: A Framework For Cell-Type-Aware Transcriptome-Wide Association Studies With An Application To Breast Cancer, Xiaoyu Song, Jiayi Ji, Joseph H Rothstein, Stacey E Alexeeff, Lori C Sakoda, Adriana Sistig, Ninah Achacoso, Eric Jorgenson, Alice S Whittemore, Robert J Klein, Laurel A Habel, Pei Wang, Weiva Sieh

Faculty, Staff and Student Publications

Human bulk tissue samples comprise multiple cell types with diverse roles in disease etiology. Conventional transcriptome-wide association study approaches predict genetically regulated gene expression at the tissue level, without considering cell-type heterogeneity, and test associations of predicted tissue-level expression with disease. Here we develop MiXcan, a cell-type-aware transcriptome-wide association study approach that predicts cell-type-level expression, identifies disease-associated genes via combination of cell-type-level association signals for multiple cell types, and provides insight into the disease-critical cell type. As a proof of concept, we conducted cell-type-aware analyses of breast cancer in 58,648 women and identified 12 transcriptome-wide significant genes using MiXcan compared …

Epigenomic Charting And Functional Annotation Of Risk Loci In Renal Cell Carcinomaepigenomic Charting And Functional Annotation Of Risk Loci In Renal Cell Carcinoma, Amin H Nassar, Sarah Abou Alaiwi, Sylvan C Baca, Elio Adib, Rosario I Corona, Ji-Heui Seo, Marcos A S Fonseca, Sandor Spisak, Talal El Zarif, Viktoria Tisza, David A Braun, Heng Du, Monica He, Abdallah Flaifel, Michel Alchoueiry, Thomas Denize, Sayed G Matar, Andres Acosta, Sachet Shukla, Yue Hou, John Steinharter, Gabrielle Bouchard, Jacob E Berchuck, Edward O'Connor, Connor Bell, Pier Vitale Nuzzo, Gwo-Shu Mary Lee, Sabina Signoretti, Michelle S Hirsch, Mark Pomerantz, Elizabeth Henske, Alexander Gusev, Kate Lawrenson, Toni K Choueiri, David J Kwiatkowski, Matthew L Freedman

Faculty, Staff and Student Publications

While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays. We integrate 153 individual data sets from 42 patients and nominate 50 histology-specific master transcription factors (MTF) to define RCC histologic subtypes, including EPAS1 and ETS-1 in ccRCC, HNF1B in pRCC, and FOXI1 in chRCC. We confirm histology-specific MTFs via immunohistochemistry including a ccRCC-specific TF, BHLHE41. FOXI1 overexpression with knock-down of EPAS1 in the 786-O ccRCC cell line induces transcriptional …

Cost-Effectiveness Analysis Of Overground Robotic Training Versus Conventional Locomotor Training In People With Spinal Cord Injury, Daniel Pinto, Allen W Heinemann, Shuo-Hsiu Chang, Susan Charlifue, Edelle C Field-Fote, Catherine L Furbish, Arun Jayaraman, Candace Tefertiller, Heather B Taylor, Dustin D French

Faculty, Staff and Student Publications

BACKGROUND: Few, if any estimates of cost-effectiveness for locomotor training strategies following spinal cord injury (SCI) are available. The purpose of this study was to estimate the cost-effectiveness of locomotor training strategies following spinal cord injury (overground robotic locomotor training versus conventional locomotor training) by injury status (complete versus incomplete) using a practice-based cohort.

METHODS: A probabilistic cost-effectiveness analysis was conducted using a prospective, practice-based cohort from four participating Spinal Cord Injury Model System sites. Conventional locomotor training strategies (conventional training) were compared to overground robotic locomotor training (overground robotic training). Conventional locomotor training included treadmill-based training with body weight …

Baloxavir Safety And Clinical And Virologic Outcomes In Influenza Virus-Infected Pediatric Patients By Age Group: Age-Based Pooled Analysis Of Two Pediatric Studies Conducted In Japan, Nobuo Hirotsu, Hiroki Sakaguchi, Keita Fukao, Satoshi Kojima, Pedro A Piedra, Kenji Tsuchiya, Takeki Uehara

Faculty, Staff and Students Publications

BACKGROUND: Anti-influenza treatment is important for children and is recommended in many countries. This study assessed safety, clinical, and virologic outcomes of baloxavir marboxil (baloxavir) treatment in children based on age and influenza virus type/subtype.

METHODS: This was a post hoc pooled analysis of two open-label non-controlled studies of a single weight-based oral dose of baloxavir (day 1) in influenza virus-infected Japanese patients aged < 6 years (n = 56) and ≥ 6 to < 12 years (n = 81). Safety, time to illness alleviation (TTIA), time to resolution of fever (TTRF), recurrence of influenza illness symptoms and fever (after day 4), virus titer, and outcomes by polymerase acidic protein variants at position I38 (PA/I38X) were evaluated.

RESULTS: Adverse events were reported in 39.0 and 39.5% of patients < 6 years and ≥ 6 to < 12 years, respectively. Median (95% confidence interval) TTIA was 43.2 (36.3-68.4) and 45.4 (38.9-61.0) hours, and TTRF was 32.2 (26.8-37.8) and 20.7 (19.2-23.8) hours, for patients < 6 years and ≥ 6 to < 12 years, respectively. Symptom and fever recurrence was more common in patients < 6 years with influenza B (54.5 and 50.0%, respectively) compared with older patients (0 and 25.0%, respectively). Virus titers declined (day 2) for both age groups. Transient virus titer increase and PA/I38X-variants were more common for patients < 6 years.

CONCLUSIONS: The safety and effectiveness of single-dose baloxavir were observed in children across all age groups and influenza virus types. Higher rates of fever recurrence …

Acquired Genomic Alterations On First-Line Chemotherapy With Cetuximab In Advanced Colorectal Cancer: Circulating Tumor Dna Analysis Of The Calgb/Swog-80405 Trial (Alliance), Kanwal Raghav, Fang-Shu Ou, Alan P Venook, Federico Innocenti, Ryan Sun, Heinz-Josef Lenz, Scott Kopetz

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Acquired genomic alterations (Acq-GAs), specifically RAS, BRAF, and EGFR-ectodomain mutations and ERBB2 and MET amplifications, are recognized as major mechanisms of resistance to later-line anti-EGFR-antibody therapy in metastatic colorectal cancer (mCRC). However, data regarding …

Resistance Mechanisms To Anti–Epidermal Growth Factor Receptor Therapy In Ras/Raf Wild-Type Colorectal Cancer Vary By Regimen And Line Of Therapy, Christine M Parseghian, Ryan Sun, Melanie Woods, Stefania Napolitano, Hey Min Lee, Jumanah Alshenaifi, Jason Willis, Shakayla Nunez, Kanwal P Raghav, Van K Morris, John P Shen, Madhulika Eluri, Alexey Sorokin, Preeti Kanikarla, Eduardo Vilar, Marko Rehn, Agnes Ang, Teresa Troiani, Scott Kopetz

Faculty, Staff and Student Publications

Purpose: Acquired resistance to anti-epidermal growth factor receptor (EGFR) inhibitor (EGFRi) therapy in colorectal cancer (CRC) has previously been explained by the model of acquiring new mutations in KRAS/NRAS/EGFR, among other MAPK-pathway members. However, this was primarily on the basis of single-agent EGFRi trials and little is known about the resistance mechanisms of EGFRi combined with effective cytotoxic chemotherapy in previously untreated patients.

Methods: We analyzed paired plasma samples from patients with RAS/BRAF/EGFR wild-type metastatic CRC enrolled in three large randomized trials evaluating EGFRi in the first line in combination with chemotherapy and as a single agent in third …

Substrate Electronics Dominate The Rate Of Reductive Dehalogenation Promoted By The Flavin-Dependent Iodotyrosine Deiodinase, Jeffrey M Carlson, Ayzsa Tannis, Kate R Woodworth, Megan R Reynolds, Neha Shinde, Breanne Anderson, Keivon Hobeheidar, Aisha Praag, Kristen Campbell, Cynthia Carpentieri, Teri Willabus, Elizabeth Burkhardt, Elizabeth Torrone, Kevin P O'Callaghan, Kathryn Miele, Dana Meaney-Delman, Suzanne M Gilboa, Emily O'Malley Olsen, Van T Tong

Faculty, Staff and Student Publications

Despite universal prenatal syphilis screening recommendations and availability of effective antibiotic treatment, syphilis prevalence during pregnancy and the incidence of congenital syphilis have continued to increase in the United States (1,2). Concurrent increases in methamphetamine, injection drug, and heroin use have been described in women with syphilis (3). CDC used data on births that occurred during January 1, 2018-December 31, 2021, from two states (Arizona and Georgia) that participate in the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET) to describe the prevalence of substance use among pregnant persons with syphilis by congenital syphilis pregnancy outcome (defined …

Prediction Of Pathologic Complete Response To Neoadjuvant Systemic Therapy In Triple Negative Breast Cancer Using Deep Learning On Multiparametric Mri, Zijian Zhou, Beatriz E Adrada, Rosalind P Candelaria, Nabil A Elshafeey, Medine Boge, Rania M Mohamed, Sanaz Pashapoor, Jia Sun, Zhan Xu, Bikash Panthi, Jong Bum Son, Mary S Guirguis, Miral M Patel, Gary J Whitman, Tanya W Moseley, Marion E Scoggins, Jason B White, Jennifer K Litton, Vicente Valero, Kelly K Hunt, Debu Tripathy, Wei Yang, Peng Wei, Clinton Yam, Mark D Pagel, Gaiane M Rauch, Jingfei Ma

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Neoadjuvant systemic therapy (NAST) followed by surgery are currently standard of care for TNBC with 50-60% of patients achieving pathologic complete response (pCR). We investigated ability of deep learning (DL) on dynamic contrast enhanced (DCE) MRI and diffusion weighted imaging acquired early during NAST to predict TNBC patients' pCR status in the breast. During the development phase using the images of 130 TNBC patients, the DL model achieved areas under the receiver operating characteristic curves (AUCs) of 0.97 ± 0.04 and 0.82 ± 0.10 for the training and the …

Approach To The Patient: Pharmacological Therapies For Fracture Risk Reduction In Adults With Osteogenesis Imperfecta, Winnie Liu, Brendan Lee, Sandesh C S Nagamani, Lindsey Nicol, Frank Rauch, Eric T Rush, V Reid Sutton, Eric Orwoll

Faculty, Staff and Students Publications

Context

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational processing of type I collagen. The effectiveness of medications used for fracture reduction in adults with OI is understudied and practice recommendations are not well established. Drugs currently used to improve skeletal health in OI were initially developed to treat osteoporosis. Oral and intravenous bisphosphonates have been shown to improve bone mineral density (BMD) in adults with OI and are commonly used; however, conclusive data confirming fracture protection are lacking. Similarly, teriparatide appears to increase BMD, an effect …

Svhound: Detection Of Regions That Harbor Yet Undetected Structural Variation, Luis F Paulin, Muthuswamy Raveendran, R Alan Harris, Jeffrey Rogers, Arndt Von Haeseler, Fritz J Sedlazeck

Faculty, Staff and Students Publications

BACKGROUND: Recent population studies are ever growing in number of samples to investigate the diversity of a population or species. These studies reveal new polymorphism that lead to important insights into the mechanisms of evolution, but are also important for the interpretation of these variations. Nevertheless, while the full catalog of variations across entire species remains unknown, we can predict which regions harbor additional not yet detected variations and investigate their properties, thereby enhancing the analysis for potentially missed variants.

RESULTS: To achieve this we developed SVhound ( https://github.com/lfpaulin/SVhound ), which based on a population level SVs dataset can predict …