tbuckley/cabot-search huggingface dataset:
Racial and Ethnic Disparities in Regulatory Air Quality Monitor Locations in the US
Authors: Brenna C. Kelly, Thomas J. Cova, Michelle P. Debbink, Tracy Onega, Simon C. Brewer
Journal: JAMA Network Open (2024)

Importance Understanding exposure to air pollution is important to public health, and disparities in the spatial distribution of regulatory air quality monitors could lead to exposure misclassification bias. Objective To determine whether racial and ethnic disparities exist in Environmental Protection Agency (EPA) regulatory air quality monitor locations in the US. Design, Setting, and Participants This national cross-sectional study included air quality monitors in the EPA Air Quality System regulatory monitoring repository, as well as 2022 American Community Survey Census block group estimates for racial and ethnic composition and population size. Bayesian mixed-effects models of the count of criteria pollutant monitors measuring an area were used, adjusting for population size and accounting for spatial autocorrelation. Data were analyzed from March to June 2024. Exposure Census block group–level racial and ethnic composition. Main Outcome and Measures Number of regulatory monitors measuring a census block group by criteria pollutant (particulate matter [PM], ozone [O 3 ], nitrogen dioxide [NO 2 ], sulfur dioxide [SO 2 ], lead [Pb], and carbon monoxide [CO]). Results This analysis included 329 725 481 individuals living in 237 631 block groups in the US (1 936 842 [0.6%] American Indian and Alaska Native, 18 554 697 [5.6%] Asian, 40 196 302 [12.2%] Black, 60 806 969 [18.4%] Hispanic, 555 712 [0.2%] Native Hawaiian and Other Pacific Islander, 196 010 370 [59.4%] White, 1 208 267 [0.3%] some other race, and 10 456 322 [0.4%] 2 or more races). Adjusting for population size, monitoring disparities were identified for each criteria pollutant. Relative to the White non-Latino population, all groups were associated with fewer NO 2 , O 3 , Pb, and PM monitors. Disparities were consistently largest for Native Hawaiian and Other Pacific Islander populations, followed by American Indian and Alaska Native populations and those of 2 or more races. An increase in percentage of Native Hawaiian and Other Pacific Islander race was associated with fewer monitors for SO 2 (adjusted odds ratio [aOR], 0.91; 95% BCI, 0.90-0.91), CO (aOR, 0.95; 95% BCI, 0.94-0.95), O 3 (aOR, 0.95; 95% BCI, 0.94-0.95), NO 2 (aOR, 0.97; 95% BCI, 0.91-0.94), and PM (aOR, 0.96; 95% BCI, 0.95-0.96). An increase in the percentage of those of Asian race was associated with slightly more SO 2 (aOR, 1.04; 95% BCI, 1.03-1.04) monitors. Conclusions and Relevance This cross-sectional study of racial and ethnic disparities in the location of EPA regulatory monitors determined that data may not be equitably representative of air quality, particularly for areas with predominantly Native Hawaiian and Other Pacific Islander or American Indian or Alaska Native populations. Integration of multiple data sources may aid in filling monitoring gaps across race and ethnicity. Where possible, researchers should quantify uncertainty in exposure estimates.
Modulation of TCR stimulation and pifithrin-α improves the genomic safety profile of CRISPR-engineered human T cells
Authors: Laurenz T Ursch, Jule S Müschen, Julia Ritter, Julia Klermund, Bettina E Bernard, Saskia Kolb, Linda Warmuth, Geoffroy Andrieux, Gregor Miller, Marina Jiménez-Muñoz, Fabian J Theis, Melanie Boerries, Dirk H Busch, Toni Cathomen, Kathrin Schumann
Journal: Cell Reports Medicine (2024)
Aspirin for Secondary Prevention of Atherosclerosis—Evidence or Dogma?
Authors: John G. F. Cleland
Journal: JAMA Cardiology (2024)

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Type I IFN-mediated NET release promotes Mycobacterium tuberculosis replication and is associated with granuloma caseation
Authors: Chanchal Sur Chowdhury, Rachel L Kinsella, Michael E McNehlan, Sumanta K Naik, Daniel S Lane, Priyanka Talukdar, Asya Smirnov, Neha Dubey, Ananda N Rankin, Samuel R McKee, Reilly Woodson, Abigail Hii, Sthefany M Chavez, Darren Kreamalmeyer, Wandy Beatty, Joshua T Mattila, Christina L Stallings
Journal: Cell Host & Microbe (2024)

Neutrophils are the most abundant cell type in the airways of tuberculosis patients. Mycobacterium tuberculosis (Mtb) infection induces the release of neutrophil extracellular traps (NETs); however, the molecular regulation and impact of NET release on Mtb pathogenesis are unknown. We find that during Mtb infection in neutrophils, PAD4 citrullinates histones to decondense chromatin that gets released as NETs in a manner that can maintain neutrophil viability and promote Mtb replication. Type I interferon promotes the formation of chromatin-containing vesicles that allow NET release without compromising plasma membrane integrity. Analysis of nonhuman primate granulomas supports a model where neutrophils are exposed to type I interferon from macrophages as they migrate into the granuloma, thereby enabling the release of NETs associated with necrosis and caseation. Our data reveal NET release as a promising target to inhibit Mtb pathogenesis.
Interpretable multi-modal artificial intelligence model for predicting gastric cancer response to neoadjuvant chemotherapy
Authors: Peng Gao, Qiong Xiao, Hui Tan, Jiangdian Song, Yu Fu, Jingao Xu, Junhua Zhao, Yuan Miao, Xiaoyan Li, Yi Jing, Yingying Feng, Zitong Wang, Yingjie Zhang, Enbo Yao, Tongjia Xu, Jipeng Mei, Hanyu Chen, Xue Jiang, Yuchong Yang, Zhengyang Wang, Xianchun Gao, Minwen Zheng, Liying Zhang, Min Jiang, Yuying Long, Lijie He, Jinghua Sun, Yanhong Deng, Bin Wang, Yan Zhao, Yi Ba, Guan Wang, Yong Zhang, Ting Deng, Dinggang Shen, Zhenning Wang
Journal: Cell Reports Medicine (2024)
Characterizing the genetic architecture of drug response using gene-context interaction methods
Authors: Michal Sadowski, Mike Thompson, Joel Mefford, Tanushree Haldar, Akinyemi Oni-Orisan, Richard Border, Ali Pazokitoroudi, Na Cai, Julien F Ayroles, Sriram Sankararaman, Andy W Dahl, Noah Zaitlen
Journal: Cell Genomics (2024)
Hepatic real-world outcomes with obeticholic acid in primary biliary cholangitis (HEROES): A trial emulation study design
Authors: M. Alan Brookhart, Tracy J. Mayne, Charles Coombs, Alexander Breskin, Erik Ness, Leona Bessonova, Yucheng Julia Chu, Jing Li, Michael W. Fried, Bettina E. Hansen, Kris V. Kowdley, David Jones, George Mells, Palak J. Trivedi, Shaun Hiu, Dorcas N. Kareithi, James Wason, Rachel Smith, John D. Seeger, Gideon M. Hirschfield
Journal: Hepatology (2024)

Primary biliary cholangitis (PBC) is a rare, progressive liver disease. Obeticholic acid (OCA) received accelerated approval for treating patients with PBC in whom ursodeoxycholic acid (UDCA) failed, based on a surrogate endpoint of reduction in alkaline phosphatase. Analysis of the long-term safety extension with 2 external control groups demonstrated a significant increase in event-free survival in OCA-treated patients. This fully real-world evidence study assessed the effect of OCA treatment on the clinical outcomes.
The neonatal gut microbiota: A role in the encephalopathy of prematurity
Authors: Kadi Vaher, Manuel Blesa Cabez, Paula Lusarreta Parga, Justyna Binkowska, Gina J van Beveren, Mari-Lee Odendaal, Gemma Sullivan, David Q Stoye, Amy Corrigan, Alan J Quigley, Michael J Thrippleton, Mark E Bastin, Debby Bogaert, James P Boardman
Journal: Cell Reports Medicine (2024)
Publisher Correction: Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience
Authors: Sean J. Jurgens, Joel T. Rämö, Daria R. Kramarenko, Leonoor F. J. M. Wijdeveld, Jan Haas, Mark D. Chaffin, Sophie Garnier, Liam Gaziano, Lu-Chen Weng, Alex Lipov, Sean L. Zheng, Albert Henry, Jennifer E. Huffman, Saketh Challa, Frank Rühle, Carmen Diaz Verdugo, Christian Krijger Juárez, Shinwan Kany, Constance A. van Orsouw, Kiran Biddinger, Edwin Poel, Amanda L. Elliott, Xin Wang, Catherine Francis, Richard Ruan, Satoshi Koyama, Leander Beekman, Dominic S. Zimmerman, Jean-François Deleuze, Eric Villard, David-Alexandre Trégouët, Richard Isnard, Dorret I. Boomsma, Eco J. C. de Geus, Rafik Tadros, Yigal M. Pinto, Arthur A. M. Wilde, Jouke-Jan Hottenga, Juha Sinisalo, Teemu Niiranen, Roddy Walsh, Amand F. Schmidt, Seung Hoan Choi, Kyong-Mi Chang, Philip S. Tsao, Paul M. Matthews, James S. Ware, R. Thomas Lumbers, Saskia van der Crabben, Jari Laukkanen, Aarno Palotie, Ahmad S. Amin, Philippe Charron, Benjamin Meder, Patrick T. Ellinor, Mark Daly, Krishna G. Aragam, Connie R. Bezzina
Journal: Nature Genetics (2024)
Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin T vs I
Authors: Luca Koechlin, Jasper Boeddinghaus, Dimitrios Doudesis, Pedro Lopez-Ayala, Tobias Zimmermann, Klara Rumora, Jeanne du Fay de Lavallaz, Ziwen Li, Kuan Ken Lee, Andrew R Chapman, Karin Wildi, Danielle M Gualandro, Muntadher Al Karam, Maria Rubini Giménez, Gabrielle Huré, Òscar Miró, Zoe Klein, Paolo Bima, Desiree Wussler, Michael Christ, Ivo Strebel, F Javier Martin-Sanchez, Damian Kawecki, Dagmar I Keller, Oliver Reuthebuch, Katharina Rentsch, Anna Marsano, Andreas Buser, Thomas Nestelberger, Christian Puelacher, Felix Mahfoud, Nicholas L Mills, Christian Mueller
Journal: Journal of the American College of Cardiology (2024)
Targeted interferon therapy with modakafusp alfa for relapsed or refractory multiple myeloma
Authors: Dan T Vogl, Shebli Atrash, Sarah A Holstein, Omar Nadeem, Don M Benson, Maria Chaudhry, Noa Biran, Kaveri Suryanarayan, Cheryl Li, Yuyin Liu, Sabrina Christine Collins, Xavier Parot, Jonathan L Kaufman
Journal: Blood (2024)

Interferon-alpha has activity against multiple myeloma. Modakafusp alfa is an immunocytokine comprising two attenuated interferon-alpha2b molecules and an anti-CD38 IgG4 antibody, targeting delivery of interferon-alpha to CD38+ immune and myeloma cells. This phase I/II trial (NCT03215030) enrolled patients with relapsed/refractory multiple myeloma with ≥3 prior lines of treatment and refractory to or intolerant of ≥1 proteasome inhibitor and ≥1 immunomodulatory drug. During dose escalation, modakafusp alfa was administered at ten doses in four schedules across 13 cohorts. The primary endpoint was safety for dose escalation, and overall response rate for dose expansion. We enrolled 106 patients who had received a median of 6.5 lines of prior therapy; 84% of patients had myeloma previously refractory to an anti-CD38 antibody. The most feasible dosing schedule was every 4 weeks (Q4W), at which the maximum tolerated dose was 3 mg/kg. Among 30 patients treated at 1.5 mg/kg Q4W, the overall response rate was 43.3%, with a median duration of response of 15.1 months (95% CI, 7.1-26.1); median progression-free survival was 5.7 months (95% CI, 1.2-14.0). Grade ≥3 adverse events occurred in 28 (93.3%) patients, the most common were neutropenia (66.7%) and thrombocytopenia (46.7%); infections were reported in 8 (26.7%) patients (including grade 3 in 4 [16.7%]). Modakafusp alfa therapy induced upregulation of the type I interferon gene signature score, increased CD38 receptor density in CD38+ cells, and innate and adaptive immune cell activation. Modakafusp alfa resulted in anti-tumor activity and immune activation in patients with multiple myeloma. Adverse events were primarily hematologic.
BRAFV600E induces key features of LCH in iPSCs with cell type-specific phenotypes and drug responses
Authors: Giulio Abagnale, Raphaela Schwentner, Philipp Ben Soussia-Weiss, Wouter van Midden, Caterina Sturtzel, Ulrike Pötschger, Magdalena Rados, Sabine Taschner-Mandl, Ingrid Simonitsch-Klupp, Christoph Hafemeister, Florian Halbritter, Martin Distel, Sebastian Karl Eder, Caroline Hutter
Journal: Blood (2024)

Langerhans cell histiocytosis (LCH) is a clonal hematopoietic disorder defined by tumorous lesions containing CD1a+/CD207+ cells. Two severe complications of LCH are systemic hyperinflammation and progressive neurodegeneration. The scarcity of primary samples and lack of appropriate models limit our mechanistic understanding of LCH pathogenesis and affect patient care. We generated a human in vitro model for LCH using induced pluripotent stem cells (iPSCs) harboring the BRAFV600E mutation, the most common genetic driver of LCH. We show that BRAFV600E/WT iPSCs display myelomonocytic skewing during hematopoiesis and spontaneously differentiate into CD1a+/CD207+ cells that are similar to lesional LCH cells and are derived from a CD14+ progenitor. We show that BRAFV600E modulates the expression of key transcription factors regulating monocytic differentiation and leads to an upregulation of proinflammatory molecules and LCH marker genes early during myeloid differentiation. In vitro drug testing revealed that BRAFV600E-induced transcriptomic changes are reverted upon treatment with mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKis). Importantly, MAPKis do not affect myeloid progenitors but reduce only the mature CD14+ cell population. Furthermore, iPSC-derived neurons (iNeurons) cocultured with BRAFV600E/WT iPSC-derived microglia-like cells, differentiated from iPSC-derived CD34+ progenitors, exhibit signs of neurodegeneration with neuronal damage and release of neurofilament light chain. In summary, the iPSC-based model described here provides a platform to investigate the effects of BRAFV600E in different hematopoietic cell types and provides a tool to compare and identify novel approaches for the treatment of BRAFV600E-driven diseases.
HMX3 is a critical vulnerability in MECOM-negative KMT2A::MLLT3 acute myelomonocytic leukemia
Authors: Saioa Arza-Apalategi, Branco M. H. Heuts, Saskia M. Bergevoet, Roos Meering, Daan Gilissen, Pascal W. T. C. Jansen, Anja Krippner-Heidenreich, Peter J. M. Valk, Michiel Vermeulen, Olaf Heidenreich, Torsten Haferlach, Joop H. Jansen, Joost H. A. Martens, Bert A. van der Reijden
Journal: Leukemia (2024)
Establishing a cryopreserved biobank of living tumor tissues for drug sensitivity testing
Authors: Ping Chen, Jing-Bo Zhou, Xiang-Peng Chu, Yang-Yang Feng, Qi-Bing Zeng, Josh-Haipeng Lei, Ka-Pou Wong, Tai-Ip Chan, Chon-Wa Lam, Wen-Li Zhu, Wai-Kuok Chu, Feng Hu, Guang-Hui Luo, Kin-Iong Chan, Chu-Xia Deng
Journal: Bioactive Materials (2024)

The cryopreservation of cancer tissues to generate frozen libraries is a common practice used worldwide for storing patient samples for later applications. However, frozen samples stored by existing methods cannot be used for initiating living cell cultures, such as patient-derived tumor organoids (PDOs), which offer great potential for personalized treatment. To overcome this challenge, we developed a novel procedure for culturing PDOs using frozen live tumor tissues. We show that tumor specimens stored using this technique maintain their viability and can be successfully used to generate organoids even after long-term freezing, with an impressive success rate of 95.2 %. Importantly, we found that the structural features, tumor marker expression, and drug responses of organoids derived from frozen tissues are similar to those derived from fresh tissues. Moreover, organoids derived from frozen tissues can be routinely passaged and frozen, making them ideal for high-throughput drug screening at any time. Notably, cryopreserved tumor tissues can also be utilized in air-liquid interface (ALI) culture. This method allows for preserving the original tumor microenvironment, making it an invaluable resource for conducting tests on antitumor drug responses, including immune checkpoint inhibitors (ICIs). This innovation has the potential to enable the identification of potentially effective drugs for patients and facilitate the development of novel therapeutic drugs. Thus, we have established protocols for the long-term cryopreservation of cancer tissues to maintain their viability and microenvironment, which are useful for personalized therapy.
Transformation of Natural Resin Resina Draconis to 3D Functionalized Fibrous Scaffolds for Efficient Chronic Wound Healing (Adv. Healthcare Mater. 30/2024)
Authors: Shijie Guo, Pengyu Wang, Yu Sun, Can Cao, Junwei Gao, Shihao Hong, Ning Li, Ruodan Xu
Journal: Advanced Healthcare Materials (2024)
DNA Tetrahedron Delivering miR‐21‐5p Promotes Senescent Bone Defects Repair through Synergistic Regulation of Osteogenesis and Angiogenesis (Adv. Healthcare Mater. 30/2024)
Authors: Lei Qi, Shebin Hong, Tong Zhao, Jinge Yan, Weiwen Ge, Jing Wang, Xin Fang, Weidong Jiang, Steve GF Shen, Lei Zhang
Journal: Advanced Healthcare Materials (2024)
Unleashing Novel Therapeutic Strategies for Dry Eye: Targeting ROS and the cGAS‐STING Signaling Pathway with Tetrahedral Framework Nucleic Acids (Adv. Healthcare Mater. 30/2024)
Authors: Dan Yan, Caihong Huang, Weijie Ouyang, Jiaoyue Hu, Zuguo Liu
Journal: Advanced Healthcare Materials (2024)
Leveraging natural language processing to aggregate field safety notices of medical devices across the EU
Authors: Yijun Ren, Enrico Gianluca Caiani
Journal: npj Digital Medicine (2024)

The European Union (EU) Medical Device Regulation and In Vitro Medical Device Regulation have introduced more rigorous regulatory requirements for medical devices, including new rules for post-market surveillance. However, EU market vigilance is limited by the absence of harmonized reporting systems, languages and nomenclatures among Member States. Our aim was to develop a framework based on Natural Language Processing capable of automatically collecting publicly available Field Safety Notices (FSNs) reporting medical device problems by applying web scraping to EU authority websites, to attribute the most suitable device category based on the European Medical Device Nomenclature (EMDN), and to display processed FSNs in an aggregated way to allow multiple queries. 65,036 FSNs published up to 31/12/2023 were retrieved from 16 EU countries, of which 40,212 (61.83%) were successfully assigned the proper EMDN. The framework's performance was successfully tested, with accuracies ranging from 87.34% to 98.71% for EMDN level 1 and from 64.15% to 85.71% even for level 4.
Is there really an accelerated phase of chronic myeloid leukaemia at presentation?
Authors: Sen Yang, Xiaoshuai Zhang, Robert Peter Gale, Xiaojun Huang, Qian Jiang
Journal: Leukemia (2024)

Whether there is really a distinct accelerated phase (AP) at diagnosis in chronic myeloid leukaemia (CML) in the context of tyrosine kinase-inhibitor (TKI)-therapy is controversial. We studied 2122 consecutive subjects in chronic phase (CP, n = 1837) or AP (n = 285) at diagnosis classified according to the 2020 European LeukemiaNet (ELN) classification. AP subjects with increased basophils only had similar transformation-free survival (TFS) and survival compared with CP subjects classified as ELTS intermediate-risk. Those with increased blasts only had worse TFS but similar survival compared with CP subjects classified as ELTS high-risk. AP subjects with decreased platelets only had similar TFS but worse survival compared with subjects classified as ELTS high-risk. Proportions of CP and AP subjects meeting the 2020 ELN TKI-response milestones were similar. However, worse TFS at 3-month and survival at 6- or 12-month were only in AP subjects failing to meet ELN milestones. Findings were similar using the 2022 International Consensus Classification (ICC) criteria for AP replacing decreased platelets with additional cytogenetic abnormalities. Our data support the 2022 WHO classification of CML eliminating AP. We suggest adding a very high-risk cohort to the ELTS score including people with increased blasts or decreased platelets and dividing CML into 2 phases at diagnosis: CP and acute or blast phases.
Superscan in First Posttherapeutic 177Lu-PSMA Scan
Authors: Merve Nida Calderon Tobar, Farise Yilmaz, Lütfü Perktaş
Journal: Clinical Nuclear Medicine (2024)

Abstract This case highlights the effectiveness of 177 Lu-PSMA therapy in a 70-year-old man with castration-resistant prostate cancer who has extensive skeletal metastases in posttherapeutic whole-body imaging. A 70-year-old man with extensive skeletal metastases underwent 4 cycles of 177 Lu-PSMA-617 therapy. A whole-body 177 Lu-PSMA scan after the first cycle showed diffuse skeletal lesions, with minimal PSMA uptake in the kidneys and salivary glands. A whole-body scan after the fourth cycle of 177 Lu-PSMA showed a complete response of skeletal metastases with normal PSMA uptake in the kidneys and salivary glands. According to RECİP 1.0, the patient was considered a complete response.
Longitudinal Evaluation of FDG Uptake in a Synovial Herniation Pit in 8 Years
Authors: Chenxi Wu, Amol Madan Takalkar
Journal: Clinical Nuclear Medicine (2024)

Abstract Synovial herniation pit, also known as Pitt’s pit, is a benign osseous lesion incidentally seen on imaging studies. Most of them will not show FDG uptake, but some herniation pits could show intense FDG uptake on PET/CT scans mimicking osseous metastasis. Here we report a case of synovial herniation pit in a patient with T-cell lymphoma through 8-year trajectory of FDG PET/CT scans, revealing its changing FDG uptake in relation to chemotherapy and final outcome.
Solitary Scapula Metastasis From Intrahepatic Cholangiocarcinoma Detected by PET/CT
Authors: Churun Xu, Pengcheng Ren, Guoxing Zhao, Lingge Wei, Peng Xie
Journal: Clinical Nuclear Medicine (2024)

Abstract A 59-year-old man presented with a mass and pain in the left side of his back for 6 months. 18 F-FDG PET/CT demonstrated increased FDG uptake in the inferior aspect of his left scapula and the left hepatic lobe, highly suggesting the possibility of hepatic malignancy with solitary scapula metastasis. Finally, solitary scapula metastasis from intrahepatic cholangiocarcinoma was confirmed.