keyword
https://read.qxmd.com/read/38253266/deciphering-cell-states-and-genealogies-of-human-hematopoiesis
#21
JOURNAL ARTICLE
Chen Weng, Fulong Yu, Dian Yang, Michael Poeschla, L Alexander Liggett, Matthew G Jones, Xiaojie Qiu, Lara Wahlster, Alexis Caulier, Jeffrey A Hussmann, Alexandra Schnell, Kathryn E Yost, Luke Koblan, Jorge D Martin-Rufino, Joseph Min, Alessandro Hammond, Daniel Ssozi, Raphael Bueno, Hari Mallidi, Antonia Kreso, Javier Escabi, William M Rideout, Tyler Jacks, Sahand Hormoz, Peter van Galen, Jonathan S Weissman, Vijay G Sankaran
The human blood system is maintained through the differentiation and massive amplification of a limited number of long-lived hematopoietic stem cells (HSCs)1 . Perturbations to this process underlie diverse diseases, but the clonal contributions to human hematopoiesis and how this changes with age remain incompletely understood. While recent insights have emerged from barcoding studies in model systems4,5,16,17 , simultaneous detection of cell states and phylogenies from natural barcodes in humans has been challenging...
January 22, 2024: Nature
https://read.qxmd.com/read/38244540/uchl1-is-a-potential-molecular-indicator-and-therapeutic-target-for-neuroendocrine-carcinomas
#22
JOURNAL ARTICLE
Shiqin Liu, Timothy Chai, Fernando Garcia-Marques, Qingqing Yin, En-Chi Hsu, Michelle Shen, Angus Martin Shaw Toland, Abel Bermudez, Alifiani B Hartono, Christopher F Massey, Chung S Lee, Liwei Zheng, Maya Baron, Caden J Denning, Merve Aslan, Holly M Nguyen, Rosalie Nolley, Amina Zoubeidi, Millie Das, Christian A Kunder, Brooke E Howitt, H Tom Soh, Irving L Weissman, Michael A Liss, Arnold I Chin, James D Brooks, Eva Corey, Sharon J Pitteri, Jiaoti Huang, Tanya Stoyanova
Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis and limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme, is elevated in tissues and plasma from patients with neuroendocrine carcinomas. Loss of UCHL1 decreases tumor growth and inhibits metastasis of these malignancies. UCHL1 maintains neuroendocrine differentiation and promotes cancer progression by regulating nucleoporin, POM121, and p53...
January 9, 2024: Cell reports medicine
https://read.qxmd.com/read/38223537/systematic-development-of-ionizable-lipid-nanoparticles-for-placental-mrna-delivery-using-a-design-of-experiments-approach
#23
JOURNAL ARTICLE
Rachel E Young, Katherine M Nelson, Samuel I Hofbauer, Tara Vijayakumar, Mohamad-Gabriel Alameh, Drew Weissman, Charalampos Papachristou, Jason P Gleghorn, Rachel S Riley
Ionizable lipid nanoparticles (LNPs) have gained attention as mRNA delivery platforms for vaccination against COVID-19 and for protein replacement therapies. LNPs enhance mRNA stability, circulation time, cellular uptake, and preferential delivery to specific tissues compared to mRNA with no carrier platform. However, LNPs are only in the beginning stages of development for safe and effective mRNA delivery to the placenta to treat placental dysfunction. Here, we develop LNPs that enable high levels of mRNA delivery to trophoblasts in vitro and to the placenta in vivo with no toxicity...
April 2024: Bioactive Materials
https://read.qxmd.com/read/38191494/the-response-of-the-military-health-system-mhs-to-the-covid-19-pandemic-a-summary-of-findings-from-mhs-reviews
#24
REVIEW
Alysa Pomer, Satish Munigala, Christian L Coles, Jessica Pope Mitro, Andrew J Schoenfeld, Joel S Weissman, Tracey Perez Koehlmoos
INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused major disruptions to the US Military Health System (MHS). In this study, we evaluated the MHS response to the pandemic to understand the impact of the pandemic response in a large, national, integrated healthcare system providing care for ~ 9 million beneficiaries. METHODS: We performed a narrative literature review of 16 internal Department of Defense (DoD) reports, including reviews mandated by the US Congress in response to the pandemic...
January 8, 2024: Health Research Policy and Systems
https://read.qxmd.com/read/38191435/comparison-of-medical-students-considerations-in-choosing-a-specialty-2020-vs-2009-10
#25
JOURNAL ARTICLE
Hanna Schroeder, Alon Shacham, Shimon Amar, Charles Weissman, Josh E Schroeder
BACKGROUND: Workforce shortage in healthcare and particularly in physicians poses a threat to healthcare delivery and its quality. In comparison to other OECD countries, Israel currently has a small number of medical graduates relative to its number of physicians, naturally emphasizing the importance of ensuring that this population chooses to remain in medicine. Understanding what is most important to medical students can help improve working conditions in residency. Such information is particularly needed to facilitate policy planning that will encourage the next generation of physicians to specialize in medical fields that are experiencing shortages...
January 8, 2024: Human Resources for Health
https://read.qxmd.com/read/38187726/broadly-neutralizing-antibody-induction-by-non-stabilized-sars-cov-2-spike-mrna-vaccination-in-nonhuman-primates
#26
R Dilshan Malewana, Victoria Stalls, Aaron May, Xiaozhi Lu, David R Martinez, Alexandra Schäfer, Dapeng Li, Maggie Barr, Laura L Sutherland, Esther Lee, Robert Parks, Whitney Edwards Beck, Amanda Newman, Kevin W Bock, Mahnaz Minai, Bianca M Nagata, C Todd DeMarco, Thomas N Denny, Thomas H Oguin, Wes Rountree, Yunfei Wang, Katayoun Mansouri, Robert J Edwards, Gregory D Sempowski, Amanda Eaton, Hiromi Muramatsu, Rory Henderson, Ying Tam, Christopher Barbosa, Juanjie Tang, Derek W Cain, Sampa Santra, Ian N Moore, Hanne Andersen, Mark G Lewis, Hana Golding, Robert Seder, Surender Khurana, David C Montefiori, Norbert Pardi, Drew Weissman, Ralph S Baric, Priyamvada Acharya, Barton F Haynes, Kevin O Saunders
UNLABELLED: Immunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike elicits neutralizing antibodies (nAbs) against difficult-to-neutralize variants of concern (VOCs) remains an area of great interest. Here, we compare immunization of macaques with mRNA vaccines expressing ancestral spike either including or lacking diproline substitutions, and show the diproline substitutions were not required for protection against SARS-CoV-2 challenge or induction of broadly neutralizing B cell lineages...
December 19, 2023: bioRxiv
https://read.qxmd.com/read/38181743/vaccine-induction-of-cd4-mimicking-hiv-1-broadly-neutralizing-antibody-precursors-in-macaques
#27
JOURNAL ARTICLE
Kevin O Saunders, James Counts, Bhishem Thakur, Victoria Stalls, Robert Edwards, Kartik Manne, Xiaozhi Lu, Katayoun Mansouri, Yue Chen, Rob Parks, Maggie Barr, Laura Sutherland, Joena Bal, Nicholas Havill, Haiyan Chen, Emily Machiele, Nolan Jamieson, Bhavna Hora, Megan Kopp, Katarzyna Janowska, Kara Anasti, Chuancang Jiang, Elizabeth Van Itallie, Sravani Venkatayogi, Amanda Eaton, Rory Henderson, Christopher Barbosa, S Munir Alam, Sampa Santra, Drew Weissman, M Anthony Moody, Derek W Cain, Ying K Tam, Mark Lewis, Wilton B Williams, Kevin Wiehe, David C Montefiori, Priyamvada Acharya, Barton F Haynes
The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glycans, expansion of appropriate naive B cells with immunogens, and selection of functional antibody mutations. Here, we demonstrate that immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs...
January 4, 2024: Cell
https://read.qxmd.com/read/38145152/practice-profile-of-practicing-plastic-surgeons-a-20-year-review-of-plastic-surgery-statistics
#28
JOURNAL ARTICLE
Kristof S Gutowski, Emily S Chwa, Joshua P Weissman, Stuti P Garg, Christopher J Simmons, Keith E Brandt, Arun K Gosain
BACKGROUND: Evaluation of practice patterns by American Board of Plastic Surgery (ABPS) diplomates allows for a greater understanding as to how the field is progressing. Understanding evolving procedural trends can give insight into plastic surgeons' subspecialty focus and influence resident training to prepare them for future practice. METHODS: American Society of Plastic Surgeons member only projections for aesthetic and reconstructive procedures were reviewed from 1999 to 2018 in 5-year increments to identify shifts in frequency between the beginning (1999-2003) and end (2014-2018) of the timeframe...
December 2023: Plastic and Reconstructive Surgery. Global Open
https://read.qxmd.com/read/38126844/filling-the-gaps-in-the-pandemic-response-impact-of-covid-19-on-telehealth-in-the-military-health-system
#29
JOURNAL ARTICLE
Vivitha Mani, Alysa Pomer, Cathaleen Madsen, Christian L Coles, Andrew J Schoenfeld, Joel S Weissman, Tracey Pèrez Koehlmoos
Introduction: As a result of the COVID-19 pandemic, telehealth use became widespread, allowing for continued health care while minimizing COVID-19 transmission risk for patients and providers. This rapid scale-up highlighted shortcomings of the current telehealth infrastructure in many health systems. We aimed to identify and address gaps in the United States Military Health System (MHS) response to the COVID-19 pandemic related to the implementation and utilization of telehealth. Methods: We conducted semistructured key informant interviews of MHS stakeholders, including policymakers, program managers, and health care providers...
December 21, 2023: Telemedicine Journal and E-health
https://read.qxmd.com/read/38110566/author-correction-optical-coherence-tomography-in-coronary-atherosclerosis-assessment-and-intervention
#30
Makoto Araki, Seung-Jung Park, Harold L Dauerman, Shiro Uemura, Jung-Sun Kim, Carlo Di Mario, Thomas W Johnson, Giulio Guagliumi, Adnan Kastrati, Michael Joner, Niels Ramsing Holm, Fernando Alfonso, William Wijns, Tom Adriaenssens, Holger Nef, Gilles Rioufol, Nicolas Amabile, Geraud Souteyrand, Nicolas Meneveau, Edouard Gerbaud, Maksymilian P Opolski, Nieves Gonzalo, Guillermo J Tearney, Brett Bouma, Aaron D Aguirre, Gary S Mintz, Gregg W Stone, Christos V Bourantas, Lorenz Räber, Sebastiano Gili, Kyoichi Mizuno, Shigeki Kimura, Toshiro Shinke, Myeong-Ki Hong, Yangsoo Jang, Jin Man Cho, Bryan P Yan, Italo Porto, Giampaolo Niccoli, Rocco A Montone, Vikas Thondapu, Michail I Papafaklis, Lampros K Michalis, Harmony Reynolds, Jacqueline Saw, Peter Libby, Giora Weisz, Mario Iannaccone, Tommaso Gori, Konstantinos Toutouzas, Taishi Yonetsu, Yoshiyasu Minami, Masamichi Takano, O Christopher Raffel, Osamu Kurihara, Tsunenari Soeda, Tomoyo Sugiyama, Hyung Oh Kim, Tetsumin Lee, Takumi Higuma, Akihiro Nakajima, Erika Yamamoto, Krzysztof L Bryniarski, Luca Di Vito, Rocco Vergallo, Francesco Fracassi, Michele Russo, Lena M Seegers, Iris McNulty, Sangjoon Park, Marc Feldman, Javier Escaned, Francesco Prati, Eloisa Arbustini, Fausto J Pinto, Ron Waksman, Hector M Garcia-Garcia, Akiko Maehara, Ziad Ali, Aloke V Finn, Renu Virmani, Annapoorna S Kini, Joost Daemen, Teruyoshi Kume, Kiyoshi Hibi, Atsushi Tanaka, Takashi Akasaka, Takashi Kubo, Satoshi Yasuda, Kevin Croce, Juan F Granada, Amir Lerman, Abhiram Prasad, Evelyn Regar, Yoshihiko Saito, Mullasari Ajit Sankardas, Vijayakumar Subban, Neil J Weissman, Yundai Chen, Bo Yu, Stephen J Nicholls, Peter Barlis, Nick E J West, Armin Arbab-Zadeh, Jong Chul Ye, Jouke Dijkstra, Hang Lee, Jagat Narula, Filippo Crea, Sunao Nakamura, Tsunekazu Kakuta, James Fujimoto, Valentin Fuster, Ik-Kyung Jang
No abstract text is available yet for this article.
December 18, 2023: Nature Reviews. Cardiology
https://read.qxmd.com/read/38106070/sirp%C3%AE-controls-cd47-dependent-platelet-clearance-in-mice-and-humans
#31
Maia Shoham, Ying Ying Yiu, Paige S Hansen, Aanya Subramaniam, Martin Broberg, Eric Gars, Tal Raveh, Irving L Weissman, Nasa Sinnott-Armstrong, Anandi Krishnan, Hanna M Ollila, Michal Caspi Tal
UNLABELLED: Over the last decade, more data has revealed that increased surface expression of the "don't eat me" CD47 protein on cancer cells plays a role in immune evasion and tumor progression, with CD47 blockade emerging as a new therapy in immuno-oncology. CD47 is critical in regulating cell homeostasis and clearance, as binding of CD47 to the inhibitory receptor SIRPα can prevent phagocytosis and macrophage-mediated cell clearance. The purpose of this study was to examine the role of the CD47-SIRPα signal in platelet homeostasis and clearance...
December 10, 2023: bioRxiv
https://read.qxmd.com/read/38091441/hyperpigmented-flexural-plaques-hypohidrosis-and-hypotrichosis
#32
JOURNAL ARTICLE
India A Loyd, Amanda S Weissman, Jarad Levin
No abstract text is available yet for this article.
November 2023: Cutis; Cutaneous Medicine for the Practitioner
https://read.qxmd.com/read/38079078/correction-to-the-hera-hyper%C3%A2-response-risk-assessment-delphi-consensus-for-the-management-of-hyper%C3%A2-responders-in-in-vitro-fertilization
#33
I Feferkorn, S Santos-Ribeiro, F M Ubaldi, J G Velasco, B Ata, C Blockeel, A Conforti, S C Esteves, H M Fatemi, L Gianaroli, M Grynberg, P Humaidan, G T Lainas, A La Marca, L B Craig, R Lathi, R J Norman, R Orvieto, R Paulson, A Pellicer, N P Polyzos, M Roque, S K Sunkara, S L Tan, B Urman, C Venetis, A Weissman, H Yarali, M H Dahan
No abstract text is available yet for this article.
December 11, 2023: Journal of Assisted Reproduction and Genetics
https://read.qxmd.com/read/38078748/the-genetic-contribution-to-the-comorbidity-of-depression-and-anxiety-a-multi-site-electronic-health-records-study-of-almost-178-000-people
#34
JOURNAL ARTICLE
Brandon J Coombes, Isotta Landi, Karmel W Choi, Kritika Singh, Brian Fennessy, Greg D Jenkins, Anthony Batzler, Richard Pendegraft, Nicolas A Nunez, Y Nina Gao, Euijung Ryu, Priya Wickramaratne, Myrna M Weissman, Jyotishman Pathak, J John Mann, Jordan W Smoller, Lea K Davis, Mark Olfson, Alexander W Charney, Joanna M Biernacka
BACKGROUND: Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation. METHODS: Diagnostic codes were extracted from electronic health records for four biobanks [ N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]...
November 2023: Psychological Medicine
https://read.qxmd.com/read/38076212/critical-appraisal-for-racial-and-ethnic-equity-in-clinical-prediction-models-extension-development-of-a-critical-appraisal-tool-extension-to-assess-racial-and-ethnic-equity-related-risk-of-bias-for-clinical-prediction-models
#35
JOURNAL ARTICLE
Shazia M Siddique, Corinne V Evans, Michael Harhay, Eric S Johnson, Jaya Aysola, Gary E Weissman, Nikhil K Mull, Emilia Flores, Harald Schmidt, Kelley Tipton, Brian Leas, Jennifer S Lin
INTRODUCTION: Despite mounting evidence that the inclusion of race and ethnicity in clinical prediction models may contribute to health disparities, existing critical appraisal tools do not directly address such equity considerations. OBJECTIVE: This study developed a critical appraisal tool extension to assess algorithmic bias in clinical prediction models. METHODS: A modified e-Delphi approach was utilized to develop and obtain expert consensus on a set of racial and ethnic equity-based signaling questions for appraisal of risk of bias in clinical prediction models...
2023: Health Equity
https://read.qxmd.com/read/38073056/do-race-and-socioeconomic-status-affect-date-of-initial-presentation-and-repair-of-patients-with-cleft-lip%C3%A2-%C3%A2-%C3%A2-palate-and-head-shape-conditions
#36
JOURNAL ARTICLE
Joshua P Weissman, Iulianna Taritsa, Narainsai K Reddy, Emily S Chwa, Anitesh Bajaj, Stuti Garg, Ian Erkkila, Arun K Gosain
OBJECTIVE: To evaluate regarding the effect of race and socioeconomic status (SES) on the timing of cleft lip and/or palate (CL ± P), craniosynostosis, and plagiocephaly presentation to clinic and possible repair. DESIGN/METHODS: A retrospective review of patients with CL ± P and head shape conditions from Jan 2001 to Feb 2022 were included. Age at first plastic surgery clinic appointment, age at repair if applicable, gender, race, and zip code were collected...
December 10, 2023: Cleft Palate-craniofacial Journal
https://read.qxmd.com/read/38072809/in-vivo-mrna-car-t-cell-engineering-via-targeted-ionizable-lipid-nanoparticles-with-extrahepatic-tropism
#37
JOURNAL ARTICLE
Margaret M Billingsley, Ningqiang Gong, Alvin J Mukalel, Ajay S Thatte, Rakan El-Mayta, Savan K Patel, Ann E Metzloff, Kelsey L Swingle, Xuexiang Han, Lulu Xue, Alex G Hamilton, Hannah C Safford, Mohamad-Gabriel Alameh, Tyler E Papp, Hamideh Parhiz, Drew Weissman, Michael J Mitchell
With six therapies approved by the Food and Drug Association, chimeric antigen receptor (CAR) T cells have reshaped cancer immunotherapy. However, these therapies rely on ex vivo viral transduction to induce permanent CAR expression in T cells, which contributes to high production costs and long-term side effects. Thus, this work aims to develop an in vivo CAR T cell engineering platform to streamline production while using mRNA to induce transient, tunable CAR expression. Specifically, an ionizable lipid nanoparticle (LNP) is utilized as these platforms have demonstrated clinical success in nucleic acid delivery...
December 10, 2023: Small
https://read.qxmd.com/read/38029740/vegfa-mrna-lnp-promotes-biliary-epithelial-cell-to-hepatocyte-conversion-in-acute-and-chronic-liver-diseases-and-reverses-steatosis-and-fibrosis
#38
JOURNAL ARTICLE
Fatima Rizvi, Yu-Ri Lee, Ricardo Diaz-Aragon, Pushpinder S Bawa, Juhoon So, Rodrigo M Florentino, Susan Wu, Arianna Sarjoo, Emily Truong, Anna R Smith, Feiya Wang, Elissa Everton, Alina Ostrowska, Kyounghwa Jung, Ying Tam, Hiromi Muramatsu, Norbert Pardi, Drew Weissman, Alejandro Soto-Gutierrez, Donghun Shin, Valerie Gouon-Evans
The liver is known for its remarkable regenerative ability through proliferation of hepatocytes. Yet, during chronic injury or severe hepatocyte death, proliferation of hepatocytes is exhausted. To overcome this hurdle, we propose vascular-endothelial-growth-factor A (VEGFA) as a therapeutic means to accelerate biliary epithelial-cell (BEC)-to-hepatocyte conversion. Investigation in zebrafish establishes that blocking VEGF receptors abrogates BEC-driven liver repair, while VEGFA overexpression promotes it. Delivery of VEGFA via nonintegrative and safe nucleoside-modified mRNA encapsulated into lipid nanoparticles (mRNA-LNPs) in acutely or chronically injured mouse livers induces robust BEC-to-hepatocyte conversion and elimination of steatosis and fibrosis...
November 20, 2023: Cell Stem Cell
https://read.qxmd.com/read/37991048/development-and-evaluation-of-a-list-of-high-risk-inpatient-procedures-in-patients-65%C3%A2-years-and-older
#39
JOURNAL ARTICLE
Samir K Shah, Lingwei Xiang, Adoma Manful, Mihir M Shah, Gaurav Sharma, Rachel R Adler, Joel S Weissman
BACKGROUND: Inpatient procedures are common and important health events for older Americans. To facilitate surgical outcomes research, we sought to create and evaluate lists of International Classification of Disease, Tenth Revision (ICD-10) codes for high-risk inpatient procedures, defined as having at least a 1% inpatient mortality. METHODS: This retrospective national cohort study analyzes Medicare claims from 2018 for patients 65 years and older undergoing inpatient procedures...
November 22, 2023: Journal of the American Geriatrics Society
https://read.qxmd.com/read/37972039/study-of-heavy-metal-resistance-genes-in-escherichia-coli-isolates-from-a-marine-ecosystem-with-a-history-of-environmental-pollution-arsenic-cadmium-copper-and-mercury
#40
JOURNAL ARTICLE
Ashley S Tseng, Marilyn C Roberts, Scott J Weissman, Peter M Rabinowitz
We analyzed whole genome sequences of 308 Escherichia coli isolates from a marine ecosystem to determine the prevalence and relationships of heavy metal resistance genes (HMRGs) and antibiotic resistance genes (ARGs), as well as the presence of plasmid sequences. We screened all genomes for presence of 18 functional HMRGs conferring resistance to arsenic, cadmium, copper, or cadmium/mercury. In subset analyses, we examined geographic variations of HMRG carriage patterns in 224 isolates from water sources, and sought genetic linkages between HMRGs and ARGs in 25 genomes of isolates resistant to antibiotics...
2023: PloS One
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