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JOURNAL ARTICLE
Douglas A Rubinson, Noritaka Tanaka, Ferran Fece de la Cruz, Kevin S Kapner, Michael H Rosenthal, Bryanna L Norden, Haley Barnes, Sara Ehnstrom, Alvin A Morales-Giron, Lauren K Brais, Christopher T Lemke, Andrew J Aguirre, Ryan B Corcoran
KRASG12C inhibitors, like sotorasib and adagrasib, potently and selectively inhibit KRASG12C through a covalent interaction with the mutant cysteine, driving clinical efficacy in KRASG12C tumors. Since amino acid sequences of the three main RAS isoforms-KRAS, NRAS and HRAS-are highly similar, we hypothesized that some KRASG12C inhibitors might also target NRASG12C and/or HRASG12C, which are less common but critical oncogenic driver mutations in some tumors. While some inhibitors, like adagrasib, were highly selective for KRASG12C, others also potently inhibited NRASG12C and/or HRASG12C...
January 18, 2024: Cancer Discovery
#22
JOURNAL ARTICLE
Aung M Tun, Yucai Wang, Seth Maliske, Ivana Micallef, David J Inwards, Thomas M Habermann, Luis Porrata, Jonas Paludo, Jose Villasboas Bisneto, Allison Rosenthal, Mohamed A Kharfan-Dabaja, Stephen M Ansell, Grzegorz S Nowakowski, Umar Farooq, Patrick B Johnston
Chimeric antigen receptor T-cell (CAR-T) therapy is the new standard of care in fit patients with refractory or early relapsed diffuse large B-cell lymphoma (DLBCL). However, there may still be a role for salvage chemotherapy (ST) and autologous stem cell transplant (ASCT) in certain circumstances (eg, lack of CAR-T resources, chemosensitive relapses, etc). We retrospectively studied 230 patients with refractory or early relapsed DLBCL who underwent ST and ASCT. Median line of ST was 1 (range 1-3). Best response before ASCT was complete response (CR) in 106 (46%) and partial response (PR) in 124 (54%) patients...
January 18, 2024: Haematologica
#23
MULTICENTER STUDY
Henry Chubb, Douglas Y Mah, Maully Shah, Kimberly Y Lin, David M Peng, Benjamin W Hale, Lindsay May, Susan Etheridge, William Goodyer, Scott R Ceresnak, Kara S Motonaga, David N Rosenthal, Christopher S Almond, Doff B McElhinney, Anne M Dubin
BACKGROUND: Evidence for the efficacy of cardiac resynchronization therapy (CRT) in pediatric and congenital heart disease (CHD) has been limited to surrogate outcomes. OBJECTIVES: This study aimed to assess the impact of CRT upon the risk of transplantation or death in a retrospective, high-risk, controlled cohort at 5 quaternary referral centers. METHODS: Both CRT patients and control patients were <21 years of age or had CHD; had systemic ventricular ejection fraction <45%; symptomatic heart failure; and significant electrical dyssynchrony (QRS duration z score >3 or single-site ventricular pacing >40%) at enrollment...
March 2024: JACC. Clinical Electrophysiology
#24
JOURNAL ARTICLE
Marcus R Bruce, Peter E Frasco, Kristen A Sell-Dottin, Carleen V Cuevas, Yu-Hui H Chang, Elisabeth S Lim, Julie L Rosenthal, Patrick A DeValeria, Bradford B Smith
OBJECTIVE: Evaluate days alive and out of the hospital (DAOH) as an outcome measure after orthotopic heart transplantation in patients with mechanical circulatory support (MCS) as a bridge to transplant compared to those patients without prior MCS. DESIGN: A retrospective observational study of adult patients who underwent cardiac transplantation between January 1, 2015, and January 1, 2020. The primary outcome was DAOH at 365 days (DAOH365 ) after an orthotopic heart transplant...
January 2024: Journal of Cardiothoracic and Vascular Anesthesia
#25
JOURNAL ARTICLE
Maayan Hadar, Michael Friger, Samuel Ariad, Michael Koretz, Bertha Delgado, Margarita Tokar, Michael Bayme, Ravit Agassi, Maia Rosenthal, Victor Dyomin, Olga Belochitski, Noa Amir, Shai Libson, Amichay Meirovitz, Irena Lazarev, Sara Abu-Ghanem, David B Geffen
INTRODUCTION: This study aimed to evaluate the long-term outcomes of stage I breast cancer (BC) patients diagnosed during the current era of screening mammography, immunohistochemistry receptor testing, and systemic adjuvant therapy. METHODS: A retrospective cohort study was conducted on 328 stage I BC patients treated consecutively in a single referral center with a follow-up period of at least 12 years. The primary endpoints were invasive disease-free survival (IDFS) and overall survival (OS)...
January 5, 2024: Oncology
#26
JOURNAL ARTICLE
Miguel Hernandez-Gonzalez, Thomas Calcraft, Andrea Nans, Peter B Rosenthal, Michael Way
Poxviruses such as variola virus (smallpox) and monkeypox cause diseases in humans. Other poxviruses, including vaccinia and modified vaccinia Ankara, are used as vaccine vectors. Given their importance, a greater structural understanding of poxvirus virions is needed. We now performed cryo-electron tomography of purified intact vaccinia virions to study the structure of the palisade, a protein lattice that defines the viral core boundary. We identified the main viral proteins that form the palisade and their interaction surfaces and provided new insights into the organization of the viral core...
January 3, 2024: MBio
#27
JOURNAL ARTICLE
Louisa P Selvadurai, Susan L Perlman, Tetsuo Ashizawa, George R Wilmot, Chiadi U Onyike, Liana S Rosenthal, Vikram G Shakkottai, Henry L Paulson, Sub H Subramony, Khalaf O Bushara, Sheng-Han Kuo, Cameron Dietiker, Michael D Geschwind, Alexandra B Nelson, Christopher M Gomez, Puneet Opal, Theresa A Zesiewicz, Trevor Hawkins, Talene A Yacoubian, Peggy C Nopoulos, Sharon J Sha, Peter E Morrison, Karla P Figueroa, Stefan M Pulst, Jeremy D Schmahmann
The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function, and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS/Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls...
January 2, 2024: Cerebellum
#28
JOURNAL ARTICLE
Ami Patel, Kyle Rosenke, Elizabeth M Parzych, Friederike Feldmann, Suman Bharti, Amanda J Griffin, Blake Schouest, Matt Lewis, Jihae Choi, Neethu Chokkalingam, Viviane Machado, Brian J Smith, Drew Frase, Ali R Ali, Jamie Lovaglio, Brian Nguyen, Patrick W Hanley, Susanne N Walker, Ebony N Gary, Abhijeet Kulkarni, Allison Generotti, Joseph R Francica, Kim Rosenthal, Daniel W Kulp, Mark T Esser, Trevor R F Smith, Carl Shaia, David B Weiner, Heinz Feldmann
Abstract COVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addition to recombinant biologics, engineered synthetic DNA-encoded antibodies (DMAb) are an important strategy for direct in vivo delivery of protective mAb. A DMAb cocktail was synthetically engineered to encode the immunoglobulin heavy and light chains of two different two different Fc-engineered anti-SARS-CoV-2 antibodies...
January 2, 2024: Emerging Microbes & Infections
#29
JOURNAL ARTICLE
Philip K Tan, Traci Ostertag, Sara B Rosenthal, Daisy Chilin-Fuentes, Haylee Aidnik, Sara Linker, Keith Murphy, Jeffrey N Miner, David A Brenner
Nonalcoholic steatohepatitis (NASH) is an inflammatory and fibrotic liver disease that has reached epidemic proportions and has no approved pharmacological therapies. Research and drug development efforts are hampered by inadequate preclinical models. This research describes a three-dimensional bioprinted liver tissue model of NASH built using primary human hepatocytes and non-parenchymal liver cells (hepatic stellate cells, liver sinusoidal endothelial cells, and Kupffer cells) from either healthy or NASH donors...
December 27, 2023: American Journal of Pathology
#30
JOURNAL ARTICLE
Benjamin A Barsky, Devon Dunn, Elizabeth A Erdman, James R Jolin, Meredith B Rosenthal
No abstract text is available yet for this article.
December 1, 2023: JAMA health forum
#31
RANDOMIZED CONTROLLED TRIAL
Reza Zonozi, Frank B Cortazar, Anushya Jeyabalan, Gabriel Sauvage, Pravarut Nithagon, Noah R Huizenga, Jillian M Rosenthal, Alexander Sipilief, Katherine Cosgrove, Karen A Laliberte, Eugene P Rhee, William F Pendergraft, John L Niles
OBJECTIVE: To compare two long-term remission maintenance strategies for antineutrophil cytoplasmic antibody (ANCA) vasculitis. METHODS: We conducted a prospective, single-centre, open-label, randomised controlled trial of patients with ANCA vasculitis in remission after completing at least 2 years of fixed-schedule rituximab. In the B cell arm, rituximab was reinfused upon B cell repopulation; in the ANCA arm, rituximab was reinfused upon significant rise in ANCA level...
February 15, 2024: Annals of the Rheumatic Diseases
#32
JOURNAL ARTICLE
Sina Asaadi, Kaushik Mukherjee, Ahmed M Abou-Zamzam, Liang Ji, Xian Luo-Owen, Maryam B Tabrizi, Richard D Catalano, Joseph J Dubose, Martin G Rosenthal
BACKGROUND: Tranexamic acid (TXA) is associated with lower mortality and transfusion requirements in trauma patients, but its role in thrombotic complications associated with vascular repairs remains unclear. We investigated whether TXA increases the risk of thrombosis-related technical failure (TRTF) in major vascular injuries (MVI). METHODS: The PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from 2013 to 2022 for MVI repaired with an open or endovascular intervention...
December 8, 2023: Journal of Trauma and Acute Care Surgery
#33
Gerard J Kleywegt, Paul D Adams, Sarah J Butcher, Cathy Lawson, Alexis Rohou, Peter B Rosenthal, Sriram Subramaniam, Maya Topf, Sanja Abbott, Philip R Baldwin, John M Berrisford, Gérard Bricogne, Preeti Choudhary, Tristan I Croll, Radostin Danev, Sai J Ganesan, Timothy Grant, Aleksandras Gutmanas, Richard Henderson, J Bernard Heymann, Juha T Huiskonen, Andrei Istrate, Takayuki Kato, Gabriel C Lander, Shee-Mei Lok, Steven J Ludtke, Ryan Pye, Grigore D Pintilie, Jane S Richardson, Carsten Sachse, Osman Salih, Sjors H W Scheres, Carlos Oscar S Sorzano, Scott M Stagg, Zhe Wang, Rangana Warshamanage, John D Westbrook, Martyn D Winn, Jasmine Y Young, Stephen K Burley, Jeffrey C Hoch, Genji Kurisu, Kyle Morris, Ardan Patwardhan, Sameer Velankar
In January 2020, a workshop was held at EMBL-EBI (Hinxton, UK) to discuss data requirements for deposition and validation of cryoEM structures, with a focus on single-particle analysis. The meeting was attended by 45 experts in data processing, model building and refinement, validation, and archiving of such structures. This report describes the workshop's motivation and history, the topics discussed, and consensus recommendations resulting from the workshop. Some challenges for future methods-development efforts in this area are also highlighted, as is the implementation to date of some of the recommendations...
November 29, 2023: ArXiv
#34
JOURNAL ARTICLE
Ajay Kumar Jain, Paula Buchannan, Katherine P Yates, Patricia Belt, Jeffrey B Schwimmer, Philip Rosenthal, Karen F Murray, Jean P Molleston, Ann Scheimann, Stavra A Xanthakos, Cynthia A Behling, Paula Hertel, Jamie Nilson, Brent A Neuschwander-Tetri, James Tonascia, Miriam B Vos
BACKGROUND: Pediatric metabolic-associated fatty liver disease (MAFLD) is a global health problem, with lifestyle modification as its major therapeutic strategy. Rigorous characterization of dietary content on MAFLD in children is lacking. We hypothesized an objectively measured healthier diet would positively modulate MAFLD. METHODS: Diet was assessed using the Nutrition Data System for Research in children enrolled from 10 tertiary clinical centers to determine the Healthy Eating Index (HEI, 0-100) and individual food components...
December 1, 2023: Hepatology Communications
#35
JOURNAL ARTICLE
Kavita Agarwal, Biswa Choudhury, Lloyd S Robinson, Sydney R Morrill, Yasmine Bouchibiti, Daisy Chilin-Fuentes, Sara B Rosenthal, Kathleen M Fisch, Jeffrey F Peipert, Carlito B Lebrilla, Jenifer E Allsworth, Amanda L Lewis, Warren G Lewis
Epithelial cells are covered in carbohydrates (glycans). This glycan coat or "glycocalyx" interfaces directly with microbes, providing a protective barrier against potential pathogens. Bacterial vaginosis (BV) is a condition associated with adverse health outcomes in which bacteria reside in direct proximity to the vaginal epithelium. Some of these bacteria, including Gardnerella , produce glycosyl hydrolase enzymes. However, glycans of the human vaginal epithelial surface have not been studied in detail. Here, we elucidate key characteristics of the "normal" vaginal epithelial glycan landscape and analyze the impact of resident microbes on the surface glycocalyx...
November 29, 2023: Science Translational Medicine
#36
JOURNAL ARTICLE
Madiha Iqbal, Deepa Jagadeesh, Julio Chavez, Arushi Khurana, Allison Rosenthal, Emily Craver, Narendranath Epperla, Zhuo Li, Iris Isufi, Farrukh T Awan, Bhagirathbhai R Dholaria, Joseph E Maakaron, Jose D Sandoval-Sus, Rahul Mishra, Aditi Saha, Kaitlin Annunzio, Shakthi T Bhaskar, Nuttavut Sumransub, Andrew Fijalka, Stanislav A Ivanov, Yi Lin, Mohamed A Kharfan-Dabaja
Outcomes are poor for patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) post chimeric antigen receptor T-cell (CAR-T) therapy. Two CD19-directed therapies, tafasitamab- cxix plus lenalidomide (tafa-len) and loncastuximab tesirine (loncaT) are approved in R/R LBCL. The efficacy of these CD19 directed therapies in patients who relapse after CD19 directed CAR-T (CD19-CART) therapy is not well understood. We conducted a multi-center study of patients with R/R LBCL that received either tafa-len or loncaT at any timepoint for R/R disease after CD19-CART therapy...
November 16, 2023: Bone Marrow Transplantation
#37
Elisabeth A Rosenthal, Li Hsu, Minta Thomas, Ulrike Peters, Christopher Kachulis, Karynne Patterson, Gail P Jarvik
BACKGROUND: Colorectal cancer (CRC) is a complex disease with monogenic, polygenic and environmental risk factors. Polygenic risk scores (PRS) are being developed to identify high polygenic risk individuals. Due to differences in genetic background, PRS distributions vary by ancestry, necessitating calibration. METHODS: We compared four calibration methods using the All of Us Research Program Whole Genome Sequence data for a CRC PRS previously developed in participants of European and East Asian ancestry...
January 8, 2024: medRxiv
#38
JOURNAL ARTICLE
Gkreti-Maria Manesi, Ioannis Moutsios, Dimitrios Moschovas, Georgios Papadopoulos, Christos Ntaras, Martin Rosenthal, Loic Vidal, Georgiy G Ageev, Dimitri A Ivanov, Apostolos Avgeropoulos
In this study, the use of anionic polymerization for the synthesis of living poly(dimethylsiloxane) or PDMS-Li+ , as well as poly(2-vinylpyridine) or P2VP-Li+ homopolymers, and the subsequent use of chlorosilane chemistry in order for the two blocks to be covalently joined leading to PDMS- b -P2VP copolymers is proposed. High vacuum manipulations enabled the synthesis of well-defined materials with different molecular weights (Μ¯n, from 9.8 to 36.0 kg/mol) and volume fraction ratios (φ, from 0...
October 25, 2023: Polymers
#39
REVIEW
Omran Saifi, Scott C Lester, William G Breen, William G Rule, Yi Lin, N Nora Bennani, Allison Rosenthal, Javier Munoz, Hemant S Murthy, Mohamed A Kharfan-Dabaja, Jennifer L Peterson, Bradford S Hoppe
Anti-CD19 chimeric antigen receptor T-cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B-cell non-Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life-threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre-existing sites of disease present pre-CART...
January 2024: American Journal of Hematology
#40
JOURNAL ARTICLE
Tomoko Marumo, Chima V Maduka, Evran Ural, Ehsanul Hoque Apu, Seock-Jin Chung, Koji Tanabe, Nynke S van den Berg, Quan Zhou, Brock A Martin, Tadashi Miura, Eben L Rosenthal, Takahiko Shibahara, Christopher H Contag
The molecular basis of reduced autofluorescence in oral squamous cell carcinoma (OSCC) cells relative to normal cells has been speculated to be due to lower levels of free flavin adenine dinucleotide (FAD). This speculation, along with differences in the intrinsic optical properties of extracellular collagen, lies at the foundation of the design of currently-used clinical optical detection devices. Here, we report that free FAD levels may not account for differences in autofluorescence of OSCC cells, but that the differences relate to FAD as a co-factor for flavination...
November 9, 2023: Communications Biology
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