tbuckley/cabot-search huggingface dataset:
Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
Authors: Cátia Monteiro, Lauritz Miarka, María Perea-García, Neibla Priego, Pedro García-Gómez, Laura Álvaro-Espinosa, Ana de Pablos-Aragoneses, Natalia Yebra, Diana Retana, Patricia Baena, Coral Fustero-Torre, Osvaldo Graña-Castro, Kevin Troulé, Eduardo Caleiras, Patricia Tezanos, Pablo Muela, Elisa Cintado, José Luis Trejo, Juan Manuel Sepúlveda, Pedro González-León, Luis Jiménez-Roldán, Luis Miguel Moreno, Olga Esteban, Ángel Pérez-Núñez, Aurelio Hernández-Lain, José Mazarico Gallego, Irene Ferrer, Rocío Suárez, Eva M. Garrido-Martín, Luis Paz-Ares, Celine Dalmasso, Elizabeth Cohen-Jonathan Moyal, Aurore Siegfried, Aisling Hegarty, Stephen Keelan, Damir Varešlija, Leonie S. Young, Malte Mohme, Yvonne Goy, Harriet Wikman, Jose Fernández-Alén, Guillermo Blasco, Lucía Alcázar, Clara Cabañuz, Sergei I. Grivennikov, Andrada Ianus, Noam Shemesh, Claudia C. Faria, Rebecca Lee, Paul Lorigan, Emilie Le Rhun, Michael Weller, Riccardo Soffietti, Luca Bertero, Umberto Ricardi, Joaquim Bosch-Barrera, Elia Sais, Eduard Teixidor, Alejandro Hernández-Martínez, Alfonso Calvo, Javier Aristu, Santiago M. Martin, Alvaro Gonzalez, Omer Adler, Neta Erez, Cecilia Sobrino, Nuria Ajenjo, Maria-Jesus Artiga, Eva Ortega-Paino, Manuel Valiente
Journal: Nature Medicine (2022)

Abstract Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9–RAGE–NF-κB–JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.
Corrigendum to: ‘Hepatocyte-specific suppression of microRNA-221-3p mitigates liver fibrosis’ [J Hepatol (2019) 722-734]
Authors: Hsin-Chieh Tsay, Qinggong Yuan, Asha Balakrishnan, Marina Kaiser, Selina Möbus, Emilia Kozdrowska, Marwa Farid, Pia-Katharina Tegtmeyer, Katharina Borst, Florian W.R. Vondran, Ulrich Kalinke, Andreas Kispert, Michael P. Manns, Michael Ott, Amar Deep Sharma
Journal: Journal of Hepatology (2022)
Tyrosine Kinase Inhibitor discontinuation in Chronic Myeloid Leukemia: eligibility criteria and predictors of success
Authors: Elena Inzoli, Andrea Aroldi, Rocco Piazza, Carlo Gambacorti‐Passerini
Journal: American Journal of Hematology (2022)

Abstract TKI discontinuation proved to be safe and feasible in patients with CML with deep and durable molecular responses, introducing an additional treatment goal for these patients beyond overall survival. However, treatment interruption is a safe procedure only with appropriate patient selection and monitoring. Clinical and biological factors associated with better outcomes do not yet offer a precise stratification of patients according to their risk of relapse. This article aims at reviewing the leading studies present in the field in order to define eligibility criteria for discontinuation and predictors of success.
Point-of-care diagnostic tests for tuberculosis disease
Authors: Jia Mei Hong, Hyeyoung Lee, Nishanth V. Menon, Chwee Teck Lim, Luke P. Lee, Catherine W. M. Ong
Journal: Science Translational Medicine (2022)

Rapid diagnosis is one key pillar to end tuberculosis (TB). Point-of-care tests (POCTs) facilitate early detection, immediate treatment, and reduced transmission of TB disease. This Review evaluates current diagnostic assays endorsed by the World Health Organization and identifies the gaps between existing conventional tests and the ideal POCT. We discuss the commercial development of new rapid tests and research studies on nonsputum-based diagnostic biomarkers from both pathogen and host. Last, we highlight advances in integrated microfluidics technology that may aid the development of new POCTs.
Pharmaceutical payments to Japanese certified hematologists: a retrospective analysis of personal payments from pharmaceutical companies between 2016 and 2019
Authors: Eiji Kusumi, Anju Murayama, Sae Kamamoto, Moe Kawashima, Makoto Yoshida, Hiroaki Saito, Toyoaki Sawano, Erika Yamashita, Tetsuya Tanimoto, Akihiko Ozaki
Journal: Blood Cancer Journal (2022)
Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer
Authors: Lillian Y Lai, Mary K Oerline, Megan E V Caram, Phoebe A Tsao, Samuel R Kaufman, Brent K Hollenbeck, Vahakn B Shahinian
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background Abiraterone and enzalutamide are the most common oral agents for the treatment of men with advanced prostate cancer. To understand their safety profiles in real-world settings, we examined the association between the use of abiraterone or enzalutamide and the risk of metabolic or cardiovascular adverse events while on treatment. Methods Men with advanced prostate cancer and their use of abiraterone or enzalutamide were identified in a 20% sample of the 2010-2017 national Medicare claims. The primary composite outcome was the occurrence of a major metabolic or cardiovascular adverse event, defined as an emergency room visit or hospitalization associated with a primary diagnosis of diabetes, hypertension, or cardiovascular disease. The secondary composite outcome was the occurrence of a minor metabolic or cardiovascular adverse event, defined as an outpatient visit associated with a primary diagnosis of the aforementioned conditions. Risks were assessed separately for abiraterone and enzalutamide using Cox regression. All statistical tests were 2-sided. Results Compared with men not receiving abiraterone, men receiving abiraterone were at increased risk of both a major composite adverse event (hazard ratio [HR] = 1.77, 95% confidence interval [CI] = 1.53 to 2.05; P &amp;lt; .001) and a minor composite adverse event (HR = 1.24, 95% CI = 1.05 to 1.47; P = .01). Compared with men not receiving enzalutamide, men receiving enzalutamide were at an increased risk of a major composite adverse event (HR = 1.22, 95% CI = 1.01 to 1.48; P = .04) but not a minor composite adverse event (HR = 1.04, 95% CI = 0.83 to 1.30; P = .75). Conclusion Careful monitoring and management of men on abiraterone or enzalutamide through team-based approaches are critical.
Global mental health research and practice: a decolonial approach
Authors: Eliut Rivera-Segarra, Franco Mascayano, Lubna Alnasser, Els van der Ven, Gonzalo Martínez-Alés, Sol Durand-Arias, Maria Francesca Moro, Elie Karam, Ruthmarie Hernández-Torres, Sebastián Alarcón, Alíxida Ramos-Pibernus, Rubén Alvarado, Ezra Susser
Journal: The Lancet Psychiatry (2022)
Toward an understanding of allogeneic conflict in pregnancy and transplantation
Authors: Samarth S. Durgam, Maria-Luisa Alegre, Anita S. Chong
Journal: The Journal of Experimental Medicine (2022)

Pregnancy is recognized as a spontaneously acquired state of immunological tolerance by the mother to her semi-allogeneic fetus, but it is a major cause of allosensitization in candidates for organ transplantation. This sensitization, assessed by the presence of anti-HLA IgG, contributes to sex disparity in access to transplantation and increases the risk for rejection and graft loss. Understanding this dual tolerance/sensitization conundrum may lead to new strategies for equalizing access to transplantation among sexes and improving transplant outcomes in parous women. Here, we review the clinical evidence that pregnancy results in humoral sensitization and query whether T cell responses are sensitized. Furthermore, we summarize preclinical evidence on the effects of pregnancy on fetus-specific CD4+ conventional, regulatory, and CD8+ T cells, and humoral responses. We end with a discussion on the impact of the divergent effects that pregnancy has upon alloantigen re-encounter in the context of solid organ transplantation, and how these insights point to a therapeutic roadmap for controlling pregnancy-dependent allosensitization.
NCI Leaders Optimistic about Meeting President’s Goal
Journal: Cancer Discovery (2022)

Current NCI Director Norman "Ned" Sharpless, MD, and Douglas Lowy, MD, who will become acting director following Sharpless's departure from the institute at the end of April, are confident that the cancer community can reach President Joe Biden's goal to cut deaths from cancer in half within 25 years. They identified several opportunities to improve cancer screening, prevention efforts, and treatment that could contribute to a declining death rate.
TCTAP C-155 Thrombosed Giant Coronary Artery Aneurysms Presenting With Ventricular Tachycardia
Authors: Muhammad Hanis Muhmad Hamidi, Roqiah Fatmawati Abdul Kadir, Huzairi Sani, Ahmad Bakhtiar Md Radzi, Hafisyatul Aiza Zainal Abidin
Journal: Journal of the American College of Cardiology (2022)
What is the appropriate interval between endoscopies for the early detection of gastric cancer?
Authors: Ken Haruma
Journal: Endoscopy (2022)

In this issue of Endoscopy, Li et al. describe a population-based, 8-year, prospective study examining the effect of endoscopic gastric cancer screening on the detection of gastric cancer and the reduction of gastric cancer mortality [1]. The study included 375 800 residents of Linqu, a district in northeastern China that has among the highest mortality rates for gastric cancer in the world. The study also examined the optimal screening interval for repeated endoscopy. The results showed that endoscopic screening reduced the frequency of detection of gastric cancer and significantly reduced mortality from gastric cancer. It was concluded that the interval between endoscopic examinations should be no more than 2 years, and especially no more than 1 year, depending on the degree of precancerous lesions in the gastric mucosa and the presence of intestinal metaplasia or intraepithelial neoplasia.
Outcome of very high-risk patients treated by Sotrovimab for mild-to-moderate COVID-19 Omicron, a prospective cohort study (the ANRS 0003S COCOPREV study)
Authors: Guillaume Martin-Blondel, Anne-Genevieve Marcelin, Cathia Soulié, Sofia Kaisaridi, Clovis Lusivika-Nzinga, Céline Dorival, Laura Nailler, Anaïs Boston, Cléa Melenotte, Géraldine Gaube, Christophe Choquet, Roland Liblau, Fabrice Carrat, Youri Yordanov
Journal: Journal of Infection (2022)
TCTAP A-042 Comparison Between Drug-Coated Balloon and Drug-Eluting Stent in Very Small Coronary Artery Intervention
Authors: Cheng-Hsuan Tsai, Mao-Shin Lin, Ching-Chang Huang, Chih-Fan Yeh, Ying-Hsien Chen, Paul Hsien-Li Kao
Journal: Journal of the American College of Cardiology (2022)
The perspectives of augmentative and alternative communication experts on the clinical integration of non-invasive brain-computer interfaces
Authors: Kevin M. Pitt, Miechelle McKelvey, Kristy Weissling
Journal: Brain-Computer Interfaces (2022)

As brain-computer interface for augmentative and alternative communication access (BCI-AAC) development continues to consider avenues for translation into the clinical setting, the perspectives of clinican experts in AAC should be considered. Therefore, 11 USA-based speech-language pathologists who are experts in AAC completed a semistructured interview along with Likert scale measures to assess their perspectives on BCI-AAC. The interviews and scales explored the potential impact of BCI-AAC, along with barriers and solutions to BCI-AAC implementation. Speech-language pathologists estimated that 1.5% to 50% of their caseload may benefit from BCI-AAC across various settings. Further, identified barriers and solutions included (a) BCI-AAC implementation and support, (b) funding and access, (c) applicability and literacy skills, (d) assessment and training in supporting outcomes, and (e) motivation and customization. Results reinforce and extend existing directions for BCI-AAC translation such as user-centered assessment, stakeholder support, and populations who may benefit from intervention, such as children.
Sex-Related Outcomes of Medical, Percutaneous, and Surgical Interventions for Coronary Artery Disease
Authors: Mario Gaudino, Antonino Di Franco, Davide Cao, Gennaro Giustino, C. Noel Bairey Merz, Stephen E. Fremes, Ajay J. Kirtane, Vijay Kunadian, Jennifer S. Lawton, Ruth Marie Masterson Creber, Sigrid Sandner, Birgit Vogel, Brittany A. Zwischenberger, George D. Dangas, Roxana Mehran
Journal: Journal of the American College of Cardiology (2022)
Reply to Benjamin Davies, Keith Kowalczyk RE: Zachary Klaassen, Emily Vertosick, Andrew J. Vickers, et al. Optimal Dissemination of Scientific Manuscripts via Social Media: A Prospective Trial Comparing Visual Abstracts Versus Key Figures in Consecutive Original Manuscripts. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2022.01.041
Authors: Zachary Klaassen, James W.F. Catto, Andrew J. Vickers, Matthew R. Cooperberg, Alexander Kutikov
Journal: European Urology (2022)
<i>Notes from the Field: </i>SARS-CoV-2 Omicron Variant Infection in 10 Persons Within 90 Days of Previous SARS-CoV-2 Delta Variant Infection — Four States, October 2021–January 2022
Authors: Mellisa Roskosky, Brian F. Borah, Peter M. DeJonge, Catherine V. Donovan, Lynn Zanardi Blevins, Allison G. Lafferty, Julia C. Pringle, Patsy Kelso, Jonathan L. Temte, Emily Temte, Shari Barlow, Maureen Goss, Amra Uzicanin, Allen Bateman, Kelsey Florek, Vance Kawakami, James Lewis, Julie Loughran, Sargis Pogosjans, Meagan Kay, Jeff Duchin, Stephanie Lunn, Hannah Schnitzler, Shivani Arora, Jacqueline Tate, Jessica Ricaldi, Hannah Kirking
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Vaccination protects against infection with SARS-CoV-2 (the virus that causes COVID-19) and related hospitalizations (1,2), and surviving a previous infection protects against B.1.1.7 (Alpha) and B.1.617.2 (Delta) variant reinfections † (2).Since the SARS-CoV-2 B.1.1.529(Omicron) variant became predominant in the United States in late December 2021, reported reinfections have increased § (3).Early reinfections (those occurring within 90 days of previous infection) are not well understood (4).Because some persons have prolonged detection of viral RNA after infection, ¶ repeat positive nucleic acid amplification test (NAAT) results within 90 days could reflect prolonged shedding from earlier infection, presenting technical challenges to documenting and characterizing early reinfections.This report describes 10 patients from four states, with whole genome sequencing (WGS)-confirmed Omicron variant infections within 90 days of a previous Delta infection.This activity was reviewed by CDC, approved by respective institutional review boards, and was conducted consistent with applicable federal law and CDC policy.
Relationship Between Coronary Artery Calcium and Atherosclerosis Progression Among Patients With Suspected Coronary Artery Disease
Authors: Emma J. Hollenberg, Fay Lin, Michael J. Blaha, Matthew J. Budoff, Inge J. van den Hoogen, Umberto Gianni, Yao Lu, A. Maxim Bax, Alexander R. van Rosendael, Sara W. Tantawy, Daniele Andreini, Filippo Cademartiri, Kavitha Chinnaiyan, Jung Hyun Choi, Edoardo Conte, Pedro de Araújo Gonçalves, Martin Hadamitzky, Erica Maffei, Gianluca Pontone, Sanghoon Shin, Yong-Jin Kim, Byoung Kwon Lee, Eun Ju Chun, Ji Min Sung, Alessia Gimelli, Sang-Eun Lee, Jeroen J. Bax, Daniel S. Berman, Stephanie L. Sellers, Jonathon A. Leipsic, Ron Blankstein, Jagat Narula, Hyuk-Jae Chang, Leslee J. Shaw
Journal: JACC. Cardiovascular imaging (2022)
Type 2 immune polarization is associated with cardiopulmonary disease in preterm infants
Authors: Jason C. Lao, Christine B. Bui, Merrin A. Pang, Steven X. Cho, Ina Rudloff, Kirstin Elgass, Jan Schröder, Anton Maksimenko, Niamh E. Mangan, Malcolm R. Starkey, Elisabeth M. Skuza, Yu B. Y. Sun, Friederike Beker, Clare L. Collins, Omar F. Kamlin, Kai König, Atul Malhotra, Kenneth Tan, Christiane Theda, Morag J. Young, Catriona A. McLean, Nicholas J. Wilson, Arvind Sehgal, Philip M. Hansbro, James T. Pearson, Jose M. Polo, Alex Veldman, Philip J. Berger, Claudia A. Nold-Petry, Marcel F. Nold
Journal: Science Translational Medicine (2022)

Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension. These are both cardiopulmonary inflammatory diseases that cause substantial mortality and morbidity with high treatment costs. Here, we characterized blood samples collected from 51 preterm infants longitudinally at five time points, 20 healthy term infants at birth and age 3 to 16 weeks, and 5 healthy adults. We observed strong associations between type 2 immune polarization in circulating CD3 + CD4 + T cells and cardiopulmonary illness, with odds ratios up to 24. Maternal magnesium sulfate therapy, delayed hepatitis B vaccination, and increasing fetal, but not maternal, chorioamnionitis severity were associated with attenuated type 2 polarization. Blocking type 2 mediators such as interleukin-4 (IL-4), IL-5, IL-13, or signal transducer and activator of transcription 6 (STAT6) in murine neonatal cardiopulmonary disease in vivo prevented changes in cell type composition, increases in IL-1β and IL-13, and losses of pulmonary capillaries, but not gains in larger vessels. Thereby, type 2 blockade ameliorated lung inflammation, protected alveolar and vascular integrity, and confirmed the pathological impact of type 2 cytokines and STAT6. In-depth flow cytometry and single-cell transcriptomics of mouse lungs further revealed complex associations between immune polarization and cardiopulmonary disease. Thus, this work advances knowledge on developmental immunology and its impact on early life disease and identifies multiple therapeutic approaches that may relieve inflammation-driven suffering in the youngest patients.
P53 deficiency affects cholesterol esterification to exacerbate hepatocarcinogenesis
Authors: Yahui Zhu, Li Gu, Xi Lin, Xinyi Zhou, Bingjun Lu, Cheng Liu, Yajun Li, Edward V. Prochownik, Michael Karin, Fubing Wang, Youjun Li
Journal: Hepatology (2022)

Background and Aims: Cholesterol ester (CE) biosynthesis and homeostasis play critical roles in many cancers, including HCC, but their exact mechanistic contributions to HCC disease development require further study. Approach and Results: Here, we report on a proposed role of tumor suppressor P53 in its repressing ubiquitin‐specific peptidase 19 (USP19) and sterol O‐acyltransferase (SOAT) 1, which maintains CE homeostasis. USP19 enhances cholesterol esterification and contributes to hepatocarcinogenesis (HCG) by deubiquitinating and stabilizing SOAT1. Loss of either SOAT1 or USP19 dramatically attenuates cholesterol esterification and HCG in P53‐deficient mice fed with either a normal chow diet or a high‐cholesterol, high‐fat diet (HCHFD). SOAT1 inhibitor avasimibe has more inhibitory effect on HCC progression in HCHFD‐maintained P53‐deficient mice when compared to the inhibitors of de novo cholesterol synthesis. Consistent with our findings in the mouse model, the P53‐USP19‐SOAT1 signaling axis is also dysregulated in human HCCs. Conclusions: Collectively, our findings demonstrate that SOAT1 participates in HCG by increasing cholesterol esterification, thus indicating that SOAT1 is a potential biomarker and therapeutic target in P53‐deficient HCC.
Risk of cardiovascular disease and loss in life expectancy in NAFLD
Authors: Ying Shang, Patrik Nasr, Linnea Widman, Hannes Hagström
Journal: Hepatology (2022)

Abstract Background and Aims Conflicting evidence exists on cardiovascular disease (CVD) risk in patients with NAFLD, and data are lacking on whether NAFLD increases mortality after a CVD event. Moreover, life expectancy in NAFLD has not been studied. We therefore examined CVD risk and life expectancy in patients with NAFLD compared with the general population. Approach and Results In this nationwide population‐based cohort, all patients with NAFLD diagnosis and without baseline CVD (ascertaining from the Swedish National Patient Register from 1987 to 2016, n = 10,023) were matched 10:1 on age, sex, and municipality to individuals from the general population (controls, n = 96,313). CVD diagnosis and mortality were derived from national registers. Multistate models and flexible parametric survival models were used to estimate adjusted hazard ratios (aHRs) for CVD risk and loss in life expectancy due to NAFLD. We identified 1037 (10.3%) CVD events in patients with NAFLD and 4041 (4.2%) in controls. CVD risk was 2.6‐fold higher in NAFLD compared with controls (aHR = 2.61, 95% CI = 2.36–2.88) and was strongest for nonfatal CVD (aHR = 3.71, 95% CI = 3.29–4.17). After a nonfatal CVD event, the risk for all‐cause mortality was similar between patients with NAFLD and controls (aHR = 0.89, 95% CI = 0.64–1.25). Life expectancy in patients with NAFLD was, on average, 2.8 years lower than controls, with the highest loss of life‐years when NAFLD was diagnosed in middle age (40–60 years). Conclusions NAFLD was associated with a higher risk of nonfatal CVD but did not affect post‐CVD mortality risk. Patients diagnosed with NAFLD have a lower life expectancy than the general population.
Supporting Diagnosis With Next-Generation Artificial Intelligence—Reply
Authors: Julia Adler-Milstein, Jonathan Chen, Gurpreet Dhaliwal
Journal: JAMA (2022)

In Reply We agree with Drs Bousquet and Coulet that worthwhile artificial intelligence wayfinding systems should avoid alert fatigue, support and not preempt clinician judgment, and operate variably in the foreground or background, depending on the clinical context.
Transfigured in the Underground
Authors: Sara Michas-Martin
Journal: JAMA (2022)

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