tbuckley/cabot-search huggingface dataset:
A Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms
Authors: Fresia Pareja, Higinio Dopeso, Yi Kan Wang, Andrea M. Gazzo, David N. Brown, Monami Banerjee, Pier Selenica, Jan H. Bernhard, Fatemeh Derakhshan, Edaise M. da Silva, Lorraine Colon-Cartagena, Thais Basili, Antonio Marra, Jillian Sue, Qiqi Ye, Arnaud Da Cruz Paula, Selma Yeni Yildirim, Xin Pei, Anton Safonov, Hunter Green, Kaitlyn Y. Gill, Yingjie Zhu, Matthew C.H. Lee, Ran A. Godrich, Adam Casson, Britta Weigelt, Nadeem Riaz, Hannah Y. Wen, Edi Brogi, Diana L. Mandelker, Matthew G. Hanna, Jeremy D. Kunz, Brandon Rothrock, Sarat Chandarlapaty, Christopher Kanan, Joe Oakley, David S. Klimstra, Thomas J. Fuchs, Jorge S. Reis-Filho
Journal: Cancer Research (2024)

Artificial intelligence (AI) systems can improve cancer diagnosis, yet their development often relies on subjective histologic features as ground truth for training. Herein, we developed an AI model applied to histologic whole-slide images using CDH1 biallelic mutations, pathognomonic for invasive lobular carcinoma (ILC) in breast neoplasms, as ground truth. The model accurately predicted CDH1 biallelic mutations (accuracy = 0.95) and diagnosed ILC (accuracy = 0.96). A total of 74% of samples classified by the AI model as having CDH1 biallelic mutations but lacking these alterations displayed alternative CDH1 inactivating mechanisms, including a deleterious CDH1 fusion gene and noncoding CDH1 genetic alterations. Analysis of internal and external validation cohorts demonstrated 0.95 and 0.89 accuracy for ILC diagnosis, respectively. The latent features of the AI model correlated with human-explainable histopathologic features. Taken together, this study reports the construction of an AI algorithm trained using a genetic rather than histologic ground truth that can robustly classify ILCs and uncover CDH1 inactivating mechanisms, providing the basis for orthogonal ground truth utilization for development of diagnostic AI models applied to whole-slide image. Significance: Genetic alterations linked to strong genotypic-phenotypic correlations can be utilized to develop AI systems applied to pathology that facilitate cancer diagnosis and biologic discoveries.
Structural Racism and Treatment Delay Among Black and White Patients With Breast Cancer
Authors: Katherine E. Reeder-Hayes, Bradford E. Jackson, Tzy-Mey Kuo, Chris D. Baggett, Juan Yanguela, Matthew R. LeBlanc, Mya L. Roberson, Stephanie B. Wheeler
Journal: Journal of Clinical Oncology (2024)

Structural racism (SR) is a potential driver of health disparities, but research quantifying its impacts on cancer outcomes has been limited. We aimed to develop a multidimensional county-level SR measure and to examine the association of SR with breast cancer (BC) treatment delays among Black and White patients.
The immunology of sickness metabolism
Authors: Felix M. Wensveen, Marko Šestan, Bojan Polić
Journal: Cellular and Molecular Immunology (2024)

Everyone knows that an infection can make you feel sick. Although we perceive infection-induced changes in metabolism as a pathology, they are a part of a carefully regulated process that depends on tissue-specific interactions between the immune system and organs involved in the regulation of systemic homeostasis. Immune-mediated changes in homeostatic parameters lead to altered production and uptake of nutrients in circulation, which modifies the metabolic rate of key organs. This is what we experience as being sick. The purpose of sickness metabolism is to generate a metabolic environment in which the body is optimally able to fight infection while denying vital nutrients for the replication of pathogens. Sickness metabolism depends on tissue-specific immune cells, which mediate responses tailored to the nature and magnitude of the threat. As an infection increases in severity, so do the number and type of immune cells involved and the level to which organs are affected, which dictates the degree to which we feel sick. Interestingly, many alterations associated with metabolic disease appear to overlap with immune-mediated changes observed following infection. Targeting processes involving tissue-specific interactions between activated immune cells and metabolic organs therefore holds great potential for treating both people with severe infection and those with metabolic disease. In this review, we will discuss how the immune system communicates in situ with organs involved in the regulation of homeostasis and how this communication is impacted by infection.
Identifying genetic determinants of sarcopenia-related traits: a Mendelian randomization study of druggable genes
Authors: Jihao Wu, Xiong Chen, Ruijun Li, Qiying Lu, Yucheng Ba, Jiayun Fang, Yilin Liu, Ruijie Li, Yixuan Liu, Yiling Wang, Jinsi Chen, Yanbing Li, Yinong Huang
Journal: Metabolism (2024)
Cardiac Dysfunction in Children and Young Adults Treated With MEK Inhibitors
Authors: Jonathan D. Bender, Natasha Pillay-Smiley, Garick D. Hill, Peter de Blank, Trent R. Hummel, Brian D. Weiss, Ashish Kumar, Huaiyu Zang, Nicholas J. Ollberding, Thomas D. Ryan
Journal: JACC CardioOncology (2024)
Guidance of development, validation, and evaluation of algorithms for populating health status in observational studies of routinely collected data (DEVELOP-RCD)
Authors: Wen Wang, Ying-Hui Jin, Mei Liu, Qiao He, Jia-Yue Xu, Ming-Qi Wang, Guo-Wei Li, Bo Fu, Si-Yu Yan, Kang Zou, Xin Sun
Journal: Military Medical Research (2024)

Abstract Background In recent years, there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data (RCD). These studies rely on algorithms to identify specific health conditions (e.g. diabetes or sepsis) for statistical analyses. However, there has been substantial variation in the algorithm development and validation, leading to frequently suboptimal performance and posing a significant threat to the validity of study findings. Unfortunately, these issues are often overlooked. Methods We systematically developed guidance for the development, validation, and evaluation of algorithms designed to identify health status (DEVELOP-RCD). Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development, validation, and evaluation. Subsequently, we conducted an empirical study on an algorithm for identifying sepsis. Based on these findings, we formulated specific workflow and recommendations for algorithm development, validation, and evaluation within the guidance. Finally, the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it. Results A standardized workflow for algorithm development, validation, and evaluation was established. Guided by specific health status considerations, the workflow comprises four integrated steps: assessing an existing algorithm’s suitability for the target health status; developing a new algorithm using recommended methods; validating the algorithm using prescribed performance measures; and evaluating the impact of the algorithm on study results. Additionally, 13 good practice recommendations were formulated with detailed explanations. Furthermore, a practical study on sepsis identification was included to demonstrate the application of this guidance. Conclusions The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD. This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.
U.S. Selected Practice Recommendations for Contraceptive Use, 2024
Authors: Kathryn M. Curtis, Antoinette T. Nguyen, Naomi K. Tepper, Lauren B. Zapata, Emily M. Snyder, Kendra Hatfield-Timajchy, Katherine Kortsmit, Megan A. Cohen, Maura K. Whiteman, Courtney Baker, Divya Dethier, Sophia Garbarino, Heather Gold, Emma Halper, Nathalie Kapp, Gopika Krishna, Marielle Meurice, Stephanie Ramer, Jessica Rodenhizer, Nisha Verma, Steffanie Wright
Journal: MMWR Recommendations and Reports (2024)

The 2024 U.S. Selected Practice Recommendations for Contraceptive Use (U.S. SPR) addresses a selected group of common, yet sometimes complex, issues regarding initiation and use of specific contraceptive methods. These recommendations for health care providers were updated by CDC after review of the scientific evidence and a meeting with national experts in Atlanta, Georgia, during January 25-27, 2023. The information in this report replaces the 2016 U.S. SPR (CDC. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. MMWR 2016;65[No. RR-4]:1-66). Notable updates include 1) updated recommendations for provision of medications for intrauterine device placement, 2) updated recommendations for bleeding irregularities during implant use, 3) new recommendations for testosterone use and risk for pregnancy, and 4) new recommendations for self-administration of injectable contraception. The recommendations in this report are intended to serve as a source of evidence-based clinical practice guidance for health care providers. The goals of these recommendations are to remove unnecessary medical barriers to accessing and using contraception and to support the provision of person-centered contraceptive counseling and services in a noncoercive manner. Health care providers should always consider the individual clinical circumstances of each person seeking contraceptive services. This report is not intended to be a substitute for professional medical advice for individual patients; when needed, patients should seek advice from their health care providers about contraceptive use.
U.S. Medical Eligibility Criteria for Contraceptive Use, 2024
Authors: Antoinette T. Nguyen, Kathryn M. Curtis, Naomi K. Tepper, Katherine Kortsmit, Anna W. Brittain, Emily M. Snyder, Megan A. Cohen, Lauren B. Zapata, Maura K. Whiteman, Courtney Baker, Divya Dethier, Sophia Garbarino, Heather Gold, Emma Halper, Nathalie Kapp, Gopika Krishna, Marielle Meurice, Stephanie Ramer, Jessica Rodenhizer, Nisha Verma, Steffanie Wright
Journal: MMWR Recommendations and Reports (2024)

The 2024 U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) comprises recommendations for the use of specific contraceptive methods by persons who have certain characteristics or medical conditions. These recommendations for health care providers were updated by CDC after review of the scientific evidence and a meeting with national experts in Atlanta, Georgia, during January 25-27, 2023. The information in this report replaces the 2016 U.S. MEC (CDC. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR 2016:65[No. RR-3]:1-103). Notable updates include 1) the addition of recommendations for persons with chronic kidney disease; 2) revisions to the recommendations for persons with certain characteristics or medical conditions (i.e., breastfeeding, postpartum, postabortion, obesity, surgery, deep venous thrombosis or pulmonary embolism with or without anticoagulant therapy, thrombophilia, superficial venous thrombosis, valvular heart disease, peripartum cardiomyopathy, systemic lupus erythematosus, high risk for HIV infection, cirrhosis, liver tumor, sickle cell disease, solid organ transplantation, and drug interactions with antiretrovirals used for prevention or treatment of HIV infection); and 3) inclusion of new contraceptive methods, including new doses or formulations of combined oral contraceptives, contraceptive patches, vaginal rings, progestin-only pills, levonorgestrel intrauterine devices, and vaginal pH modulator. The recommendations in this report are intended to serve as a source of evidence-based clinical practice guidance for health care providers. The goals of these recommendations are to remove unnecessary medical barriers to accessing and using contraception and to support the provision of person-centered contraceptive counseling and services in a noncoercive manner. Health care providers should always consider the individual clinical circumstances of each person seeking contraceptive services. This report is not intended to be a substitute for professional medical advice for individual patients; when needed, patients should seek advice from their health care providers about contraceptive use.
Spatially-resolved immune drivers of HBV-associated HCC relapse
Authors: Irun Bhan, Joseph W. Franses
Journal: Hepatology (2024)

1Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114 2Department of Medicine, Section of Hematology-Oncology, University of Chicago, Chicago, IL 60637 Correspondence Joseph W. Franses, University of Chicago, Medicine. Email:[email protected]
Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma
Authors: Pierre Sesques, Amy A. Kirkwood, Mi Kwon, Kai Rejeski, Michael D. Jain, Roberta Di Blasi, Gabriel Brisou, François-Xavier Gros, Fabien le Bras, Pierre Bories, Sylvain Choquet, Marie-Thérèse Rubio, Gloria Iacoboni, Maeve O’Reilly, René-Olivier Casasnovas, Jacques-Olivier Bay, Mohamad Mohty, Magalie Joris, Julie Abraham, Cristina Castilla Llorente, Mickael Loschi, Sylvain Carras, Adrien Chauchet, Laurianne Drieu La Rochelle, Olivier Hermine, Stéphanie Guidez, Pascale Cony-Makhoul, Patrick Fogarty, Steven Le Gouill, Franck Morschhauser, Thomas Gastinne, Guillaume Cartron, Marion Subklewe, Frederick L. Locke, Robin Sanderson, Pere Barba, Roch Houot, Emmanuel Bachy
Journal: Journal of Hematology & Oncology (2024)

Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count < 150 G/L, a C-reactive protein (CRP) level > 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets (< 150 G/L), use of axi-cel and no bridging therapy or SD/PD after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.
The ARDS microenvironment enhances MSC-induced repair via VEGF in experimental acute lung inflammation
Authors: Courteney Tunstead, Evelina Volkova, Hazel Dunbar, Ian J. Hawthorne, Alison Bell, Louise Crowe, Joanne C. Masterson, Claudia C. Dos Santos, Bairbre McNicholas, John G. Laffey, Karen English
Journal: Molecular Therapy (2024)

Clinical trials investigating the potential of mesenchymal stromal cells (MSCs) for the treatment of inflammatory diseases, such as acute respiratory distress syndrome (ARDS), have been disappointing, with less than 50% of patients responding to treatment.Licensed MSCs show enhanced therapeutic efficacy in response to cytokine-mediated activation signals.There are two distinct sub-phenotypes of ARDS: hypo-and hyper-inflammatory.We hypothesized that pre-licensing MSCs in a hyper-inflammatory ARDS environment would enhance their therapeutic efficacy in acute lung inflammation (ALI).Serum samples from patients with ARDS were segregated into hypoand hyper-inflammatory categories based on interleukin (IL)-6 levels.MSCs were licensed with pooled serum from patients with hypo-or hyper-inflammatory ARDS or healthy serum controls.Our findings show that hyper-inflammatory ARDS pre-licensed MSC conditioned medium (MSC-CM Hyper ) led to a significant enrichment in tight junction expression and enhanced barrier integrity in lung epithelial cells in vitro and in vivo in a vascular endothelial growth factor (VEGF)-dependent manner.Importantly, while both MSC-CM Hypo and MSC-CM Hyper significantly reduced IL-6 and tumor necrosis factor alpha (TNF-a) levels in the bronchoalveolar lavage fluid (BALF) of lipopolysaccharide (LPS)-induced ALI mice, only MSC-CM Hyper significantly reduced lung permeability and overall clinical outcomes including weight loss and clinical score.Thus, the hypo-and hyper-inflammatory ARDS environments may differentially influence MSC cytoprotective and immunomodulatory functions.
crVDAC3 alleviates ferroptosis by impeding HSPB1 ubiquitination and confers trastuzumab deruxtecan resistance in HER2-low breast cancer
Authors: Yutian Zou, Anli Yang, Bo Chen, Xinpei Deng, Jindong Xie, Danian Dai, Jinhui Zhang, Hailin Tang, Tao Wu, Zhigang Zhou, Xiaoming Xie, Jin Wang
Journal: Drug Resistance Updates (2024)
E<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si7.svg" display="inline" id="d1e2477"><mml:msup><mml:mrow/><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:math>-MIL: An explainable and evidential multiple instance learning framework for whole slide image classification
Authors: Jiangbo Shi, Chen Li, Tieliang Gong, Huazhu Fu
Journal: Medical Image Analysis (2024)
The Association between Exposure to Fine Particulate Air Pollution and the Trajectory of Internalizing and Externalizing Behaviors during Late Childhood and Early Adolescence: Evidence from the Adolescent Brain Cognitive Development (ABCD) Study
Authors: Harry R. Smolker, Colleen E. Reid, Naomi P. Friedman, Marie T. Banich
Journal: Environmental Health Perspectives (2024)

Exposure to high levels of fine particulate matter (PM) with aerodynamic diameter ≤2.5μm (PM2.5) via air pollution may be a risk factor for psychiatric disorders during adulthood. Yet few studies have examined associations between exposure and the trajectory of symptoms across late childhood and early adolescence.
Unlocking the Potential of Clustering and Classification Approaches: Navigating Supervised and Unsupervised Chemical Similarity
Authors: Kamel Mansouri, Kyla Taylor, Scott Auerbach, Stephen Ferguson, Rachel Frawley, Jui-Hua Hsieh, Gloria Jahnke, Nicole Kleinstreuer, Suril Mehta, José T. Moreira-Filho, Fred Parham, Cynthia Rider, Andrew A. Rooney, Amy Wang, Vicki Sutherland
Journal: Environmental Health Perspectives (2024)

The field of toxicology has witnessed substantial advancements in recent years, particularly with the adoption of new approach methodologies (NAMs) to understand and predict chemical toxicity. Class-based methods such as clustering and classification are key to NAMs development and application, aiding the understanding of hazard and risk concerns associated with groups of chemicals without additional laboratory work. Advances in computational chemistry, data generation and availability, and machine learning algorithms represent important opportunities for continued improvement of these techniques to optimize their utility for specific regulatory and research purposes. However, due to their intricacy, deep understanding and careful selection are imperative to align the adequate methods with their intended applications.
Pseudocin 196, a novel lantibiotic produced by <i>Bifidobacterium pseudocatenulatum</i> elicits antimicrobial activity against clinically relevant pathogens
Authors: Rocio Sanchez-Gallardo, Paula M. O’Connor, Ian J. O’Neill, Brian McDonnell, Ciaran Lee, Rebecca L. Moore, Fionnuala M. McAuliffe, Paul D. Cotter, Douwe van Sinderen
Journal: Gut Microbes (2024)

Bacteriocins are broad or narrow-spectrum antimicrobial compounds that have received significant scientific attention due to their potential to treat infections caused by antibiotic-resistant pathogenic bacteria. The genome of
Hif-2α programmes oxygen chemosensitivity in chromaffin cells
Authors: Maria Prange-Barczynska, Holly A. Jones, Yoichiro Sugimoto, Xiaotong Cheng, Joanna D.C.C. Lima, Indrika Ratnayaka, Gillian Douglas, Keith J. Buckler, Peter J. Ratcliffe, Thomas P. Keeley, Tammie Bishop
Journal: Journal of Clinical Investigation (2024)

The study of transcription factors that determine specialized neuronal functions has provided invaluable insights into the physiology of the nervous system. Peripheral chemoreceptors are neurone-like electrophysiologically excitable cells that link the oxygen concentration of arterial blood to the neuronal control of breathing. In the adult, this oxygen chemosensitivity is exemplified by type I cells of the carotid body, and recent work has revealed one isoform of the hypoxia-inducible transcription factor (HIF), HIF-2α, as having a nonredundant role in the development and function of that organ. Here, we show that activation of HIF-2α, including isolated overexpression of HIF-2α but not HIF-1α, is sufficient to induce oxygen chemosensitivity in adult adrenal medulla. This phenotypic change in the adrenal medulla was associated with retention of extra-adrenal paraganglioma-like tissues resembling the fetal organ of Zuckerkandl, which also manifests oxygen chemosensitivity. Acquisition of chemosensitivity was associated with changes in the adrenal medullary expression of gene classes that are ordinarily characteristic of the carotid body, including G protein regulators and atypical subunits of mitochondrial cytochrome oxidase. Overall, the findings suggest that, at least in certain tissues, HIF-2α acts as a phenotypic driver for cells that display oxygen chemosensitivity, thus linking 2 major oxygen-sensing systems.
Drosophila Nephrocyte as a Model for Studying Glomerular Basement Membrane Physiology
Authors: Joyce van de Leemput, Zhe Han
Journal: Journal of the American Society of Nephrology (2024)

Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, and Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland Correspondence: Dr. Zhe Han, email: [email protected] See related article, "Linking Basement Membrane and Slit Diaphragm in Drosophila Nephrocytes," on pages 1208–1226.