tbuckley/cabot-search huggingface dataset:
The 3D Revolution in Cancer Discovery
Authors: Linghua Wang, Mingyao Li, Tae Hyun Hwang
Journal: Cancer Discovery (2024)

Summary: The transition from 2D to 3D spatial profiling marks a revolutionary era in cancer research, offering unprecedented potential to enhance cancer diagnosis and treatment. This commentary outlines the experimental and computational advancements and challenges in 3D spatial molecular profiling, underscoring the innovation needed in imaging tools, software, artificial intelligence, and machine learning to overcome implementation hurdles and harness the full potential of 3D analysis in the field.
Somatic Mutations in Normal Tissues: Calm before the Storm
Authors: Zahraa Rahal, Paul Scheet, Humam Kadara
Journal: Cancer Discovery (2024)

Summary: We explore the phenomenon of somatic mutations, including those in cancer driver genes, that are present in healthy, normal-appearing tissues and their potential implications for cancer development. We also examine the landscape of these somatic mutations, discuss the role of clonal cell competition and external factors like inflammation in enhancing the fitness of mutant clones, and conclude by considering how understanding these mutations will aid in prevention and/or interception of cancer.
Radical Collaboration: Reimagining Cancer Team Science
Authors: Jesse S. Boehm, Tyler Jacks
Journal: Cancer Discovery (2024)

Summary: Here, we define a future of cancer team science adopting “radical collaboration”—in which six “Hallmarks of Cancer Collaboration” are utilized to propel cancer teams to reach new levels of productivity and impact in the modern era. This commentary establishes a playbook for cancer team science that can be readily adopted by others.
Correspondence: Intensity-Modulated Proton Therapy Versus Intensity-Modulated Radiotherapy for Inoperable Esophageal Squamous Cell Carcinoma: Methodologic Issues
Authors: Chia-Lun Chang, Kuan-Chou Lin, Wan-Ming Chen, Ben-Chang Shia, Szu-Yuan Wu
Journal: Journal of Thoracic Oncology (2024)
The Virtual Child
Authors: Richard J. Gilbertson, Sam Behjati, Anna-Lisa Böttcher, Marianne E. Bronner, Matthew Burridge, Henrick Clausing, Harry Clifford, Tracey Danaher, Laura K. Donovan, Jarno Drost, Alexander M.M. Eggermont, Chris Emerson, Mona G. Flores, Petra Hamerlik, Nada Jabado, Andrew Jones, Henrick Kaessmann, Claudia L. Kleinman, Marcel Kool, Lena M. Kutscher, Gavin Lindberg, Emily Linnane, John C. Marioni, John M. Maris, Michelle Monje, Alexandra Macaskill, Steven Niederer, Paul A. Northcott, Elizabeth Peeters, Willemijn Plieger-van Solkema, Liane Preußner, Anne C. Rios, Karsten Rippe, Peter Sandford, Nikolaos G. Sgourakis, Adam Shlien, Pete Smith, Karin Straathof, Patrick J. Sullivan, Mario L. Suvà, Michael D. Taylor, Emma Thompson, Roser Vento-Tormo, Brandon J. Wainwright, Robert J. Wechsler-Reya, Frank Westermann, Shannon Winslade, Bissan Al-Lazikani, Stefan M. Pfister
Journal: Cancer Discovery (2024)

Summary: We are building the world's first Virtual Child–a computer model of normal and cancerous human development at the level of each individual cell. The Virtual Child will “develop cancer” that we will subject to unlimited virtual clinical trials that pinpoint, predict, and prioritize potential new treatments, bringing forward the day when no child dies of cancer, giving each one the opportunity to lead a full and healthy life.
Tumor–Host Cometabolism Collaborates to Shape Cancer Immunity
Authors: Yingcheng Wu, Qiang Zou, Peng Jiang, Qiang Gao
Journal: Cancer Discovery (2024)

Summary: Nutrients are essential for supporting tumor growth and immune cell function in the tumor microenvironment, but emerging evidence reveals a paradoxical competition and collaboration between the metabolic demands of proliferating cancer cells and immune cell activation. Dietary interventions and metabolic immunoengineering offer promise to selectively modulate cancer and immune cell metabolism by targeting metabolic sensing processes rather than pathways directly, moving beyond conventional ideas and heralding an exciting new era of immunometabolism discovery and translation.
Accelerating Drug Development Using Spatial Multi-omics
Authors: Richard J.A. Goodwin, Stefan J. Platz, Jorge S. Reis-Filho, Simon T. Barry
Journal: Cancer Discovery (2024)

Summary: Spatial biology approaches enabled by innovations in imaging biomarker platforms and artificial intelligence–enabled data integration and analysis provide an assessment of patient and disease heterogeneity at ever-increasing resolution. The utility of spatial biology data in accelerating drug programs, however, requires balancing exploratory discovery investigations against scalable and clinically applicable spatial biomarker analysis.
Correlation of Professional Antigen‐Presenting Tbet<sup>+</sup>CD11c<sup>+</sup> B Cells With Bone Destruction in Untreated Rheumatoid Arthritis
Authors: Sarah McGrath, Kristoffer Grimstad, Katrin Thorarinsdottir, Kristina Forslind, Daniel Glinatsi, Monica Leu Agelii, Alaitz Aranburu, Timothy Sundell, Charlotte A. Jonsson, Alessandro Camponeschi, Anna‐Karin Hultgård Ekwall, Andreas Tilevik, Inger Gjertsson, Inga‐Lill Mårtensson
Journal: Arthritis & Rheumatology (2024)

Objective Subsets of CD21 −/low memory B cells (MBCs), including double‐negative (DN, CD27 − IgD − ) and Tbet + CD11c + cells, are expanded in chronic inflammatory diseases. In rheumatoid arthritis (RA), CD21 −/low MBCs correlate with joint destruction. However, whether this is due to the Tbet + CD11c + subset, its function and pathogenic contribution to RA are unknown. This study aims to investigate the association between CD21 −/low Tbet + CD11c + MBCs and joint destruction as well as other clinical parameters and to elucidate their functional properties in patients with untreated RA (uRA). Methods Clinical observations were combined with flow cytometry (n = 36) and single‐cell RNA sequencing (scRNA‐seq) and V(D)J sequencing (n = 4) of peripheral blood (PB) MBCs from patients with uRA. The transcriptome of circulating Tbet + CD11c + MBCs was compared with scRNA‐seq data of synovial B cells. In vitro coculture of Tbet + CD11c + B cells with T cells was used to assess costimulatory capacity. Results CD21 −/low Tbet + CD11c + MBCs in PB correlated with bone destruction but no other clinical parameters analyzed. The Tbet + CD11c + MBCs have undergone clonal expansion and express somatically mutated V genes. Gene expression analysis of these cells identified a unique signature of more than 150 up‐regulated genes associated with antigen presentation functions, including B cell receptor activation and clathrin‐mediated antigen internalization; regulation of actin filaments, endosomes, and lysosomes; antigen processing, loading, presentation, and costimulation; a transcriptome mirrored in their synovial tissue counterparts. In vitro, Tbet + CD11c + B cells induced retinoic acid receptor–related orphan nuclear receptor γT expression in CD4 + T cells, thereby polarizing to Th17 cells, a T cell subset critical for osteoclastogenesis and associated with bone destruction. Conclusion This study suggests that Tbet + CD11c + MBCs contribute to the pathogenesis of RA by promoting bone destruction through antigen presentation, T cell activation, and Th17 polarization. image
Oncostatin M signaling drives cancer-associated skeletal muscle wasting
Authors: Aylin Domaniku-Waraich, Samet Agca, Batu Toledo, Melis Sucuoglu, Sevgi Döndü Özen, Sevval Nur Bilgic, Dilsad Hilal Arabaci, Aynur Erkin Kashgari, Serkan Kir
Journal: Cell Reports Medicine (2024)

Progressive weakness and muscle loss are associated with multiple chronic conditions, including muscular dystrophy and cancer. Cancer-associated cachexia, characterized by dramatic weight loss and fatigue, leads to reduced quality of life and poor survival. Inflammatory cytokines have been implicated in muscle atrophy; however, available anticytokine therapies failed to prevent muscle wasting in cancer patients. Here, we show that oncostatin M (OSM) is a potent inducer of muscle atrophy. OSM triggers cellular atrophy in primary myotubes using the JAK/STAT3 pathway. Identification of OSM targets by RNA sequencing reveals the induction of various muscle atrophy-related genes, including Atrogin1. OSM overexpression in mice causes muscle wasting, whereas muscle-specific deletion of the OSM receptor (OSMR) and the neutralization of circulating OSM preserves muscle mass and function in tumor-bearing mice. Our results indicate that activated OSM/OSMR signaling drives muscle atrophy, and the therapeutic targeting of this pathway may be useful in preventing muscle wasting.
IgG4-related disease and B-cell malignancy due to an IKZF1 gain-of-function variant
Authors: Blanca García-Solís, María Tapia-Torres, Ana García-Soidán, Elisa Hernández-Brito, María Teresa Martínez-Saavedra, José M. Lorenzo-Salazar, Sonia García-Hernández, Ana Van Den Rym, Karan Mayani, José Vicente Govantes-Rodríguez, Adrian Gervais, Paul Bastard, Anne Puel, Jean-Laurent Casanova, Carlos Flores, Rebeca Pérez de Diego, Carlos Rodríguez-Gallego
Journal: Journal of Allergy and Clinical Immunology (2024)
Challenges and opportunities of deep learning for wearable-based objective sleep assessment
Authors: Bing Zhai, Greg J. Elder, Alan Godfrey
Journal: npj Digital Medicine (2024)

In recent years the intersection of wearable technologies and machine learning (ML) based deep learning (DL) approaches have highlighted their potential in sleep research. Yet, a recent study published in NPJ Digital Medicine highlights the generalization limitations of DL models in sleep-wake classification using actigraphy data. Here, this article discusses some of the challenges and opportunities presented by domain adaptation and self-supervised learning (SSL), innovative methodologies that use large-scale unlabeled data to bolster the generalizability of DL models in sleep assessment. These approaches not only improve sleep-wake classification but also hold promise for extending to more comprehensive sleep stage classification, potentially advancing the field of automated sleep assessment through efficient and user-friendly wearable monitoring systems.
A critical appraisal of blood-based biomarkers for Alzheimer’s disease
Authors: Simone Lista, Mark Mapstone, Filippo Caraci, Enzo Emanuele, Susana López-Ortiz, Juan Martín-Hernández, Viviana Triaca, Camillo Imbimbo, Audrey Gabelle, Michelle M. Mielke, Robert Nisticò, Alejandro Santos-Lozano, Bruno P. Imbimbo
Journal: Ageing Research Reviews (2024)
The Biden Cancer Moonshot: American Progress, Global Commitment
Authors: Catharine G. Young, Danielle M. Carnival
Journal: Cancer Discovery (2024)

Summary: The Biden Cancer Moonshot is mobilizing efforts toward achieving two clear goals that President Joe Biden and First Lady Jill Biden set: prevent more than 4 million cancer deaths by 2047 and improve the experience of people who are touched by cancer. To achieve these ambitious but achievable goals, the Biden Cancer Moonshot is driving progress across the cancer journey utilizing all facets of the oncology community – federal agencies, and departments, private companies, healthcare providers, patient groups, and philanthropies - to end cancer as we know it here in the United States and all around the world.
The Pharmacological Landscape for Fatty Change of the Pancreas
Authors: Maxim S. Petrov
Journal: Drugs (2024)

The quest for medications to reduce intra-pancreatic fat deposition is now quarter a century old. While no specific medication has been approved for the treatment of fatty change of the pancreas, drug repurposing shows promise in reducing the burden of the most common disorder of the pancreas. This leading article outlines the 12 classes of medications that have been investigated to date with a view to reducing intra-pancreatic fat deposition. Information is presented hierarchically—from preclinical studies to retrospective findings in humans to prospective interventional studies to randomised controlled trials. This lays the grounds for shepherding the most propitious drugs into medical practice through well-designed basic science studies and adequately powered randomised controlled trials.
Congestion patterns in severe tricuspid regurgitation and transcatheter treatment: Insights from a multicentre registry
Authors: Karl‐Philipp Rommel, Guillaume Bonnet, Vera Fortmeier, Lukas Stolz, Anne R. Schöber, Jennifer von Stein, Mohammad Kassar, Muhammed Gerçek, Sebastian Rosch, Thomas J. Stocker, Maria I. Körber, Karl‐Patrik Kresoja, Tanja K. Rudolph, Roman Pfister, Stephan Baldus, Stephan Windecker, Holger Thiele, Fabien Praz, Jörg Hausleiter, Volker Rudolph, Daniel Burkhoff, Philipp Lurz
Journal: European Journal of Heart Failure (2024)

Abstract Aims While invasively determined congestion holds mechanistic and prognostic significance in acute heart failure (HF), its role in patients with tricuspid regurgitation (TR)‐related right‐ heart failure (HF) undergoing transcatheter tricuspid valve intervention (TTVI) is less well established. A comprehensive understanding of congestion patterns might aid in procedural planning, risk stratification, and the identification of patients who may benefit from adjunctive therapies before undergoing TTVI. The aim of this study was to investigate the role of congestion patterns in patients with severe TR and its implications for TTVI. Methods and results Within a multicentre, international TTVI registry, 813 patients underwent right heart catheterization (RHC) prior to TTVI and were followed up to 24 months. The median age was 80 (interquartile range 76–83) years and 54% were women. Both mean right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were associated with 2‐year mortality on Cox regression analyses with Youden index‐derived cut‐offs of 17 mmHg and 19 mmHg, respectively ( p &lt; 0.01 for all). However, RAP emerged as an independent predictor of outcomes following multivariable adjustments. Pre‐interventionally, 42% of patients were classified as euvolaemic (RAP &lt;17 mmHg, PCWP &lt;19 mmHg), 23% as having left‐sided congestion (RAP &lt;17 mmHg, PCWP ≥19 mmHg), 8% as right‐sided congestion (RAP ≥17 mmHg, PCWP &lt;19 mmHg), and 27% as bilateral congestion (RAP ≥17 mmHg, PCWP ≥19 mmHg). Patients with right‐sided or bilateral congestion had the lowest procedural success rates and shortest survival times. Congestion patterns allowed for discerning specific patient's physiology and specifying prognostic implications of right ventricular to pulmonary artery coupling surrogates. Conclusion In this large cohort of invasively characterized patients undergoing TTVI, congestion patterns involving right‐sided congestion were associated with low procedural success and higher mortality rates after TTVI. Whether pre‐interventional reduction of right‐sided congestion can improve outcomes after TTVI should be established in dedicated studies.
Availability of paediatric dispersible fixed-dose combinations of tuberculosis drugs in Spain
Authors: Antoni Noguera-Julian, Cristina Latre, Ángeles Flores
Journal: European Respiratory Journal (2024)

<h3>Shareable abstract</h3> <b>After successfully overcoming prolonged regulatory and importing challenges, the paediatric dispersible fixed-dose combinations of first-line anti-tuberculosis drugs are now available for Spanish children. This experience may be useful for other countries.</b> https://bit.ly/3uQz0eO
As-needed ICS/formoterol or as-needed SABA in mild asthma?
Authors: Jerry A. Krishnan, Roland Buhl
Journal: European Respiratory Journal (2024)

<h3>Shareable abstract</h3> <b>We recommend re-scoring the importance of "mortality" as an outcome in the 2023 ERS short guidelines for as-needed therapy in mild asthma.</b> https://bit.ly/3NX0INc
Transcriptomic crosstalk between viral and host factors drives aberrant homeostasis of T-cell proliferation and cell death in HIV-infected immunological non-responders
Authors: Shengquan Tang, Yanqiu Lu, Feng Sun, Yuanyuan Qin, Vijay Harypursat, Renni Deng, Gong Zhang, Yaokai Chen, Tong Wang
Journal: Journal of Infection (2024)

Immunological non-responders (INRs) among people living with HIV have inherently higher mortality and morbidity rates. The underlying immunological mechanisms whereby failure of immune reconstitution occurs in INRs require elucidation.
“Rounding Third Base and Heading Home”: Arthritis &amp; Rheumatology in 2024
Authors: Daniel H. Solomon, Mariana J. Kaplan, Peter A. Nigrovic, Richard Bucala
Journal: Arthritis & Rheumatology (2024)

Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Dysfunctional breathing after COVID-19: recognition and ramifications
Authors: Adam Gaffney
Journal: European Respiratory Journal (2024)

<h3>Shareable abstract</h3> <b>Dysfunctional breathing is an important, and likely under-recognised driver of dyspnoea in the wake of a COVID-19 infection. Improved recognition and treatment of this clinical entity could provide meaningful benefit to some long COVID patients.</b>https://bit.ly/4a4i8jG
A new era in the science and care of kidney diseases
Authors: Carmine Zoccali, Francesca Mallamaci, Liz Lightstone, Vivek Jha, Carol Pollock, Katherine Tuttle, Peter Kotanko, Andrzej Wiecek, Hans Joachim Anders, Giuseppe Remuzzi, Kamyar Kalantar-Zadeh, Adeera Levin, Raymond Vanholder
Journal: Nature Reviews Nephrology (2024)
Genetic risk accentuates dietary effects on hepatic steatosis, inflammation and fibrosis in a population-based cohort
Authors: Vincent L. Chen, Xiaomeng Du, Antonino Oliveri, Yanhua Chen, Annapurna Kuppa, Brian D. Halligan, Michael A. Province, Elizabeth K. Speliotes
Journal: Journal of Hepatology (2024)

Background & AimsSteatotic liver disease (SLD), characterized by elevated liver fat content (LFC), is influenced by genetics and diet. However, whether diet has differential effect based on genetic risk is not well-characterized. We aimed to determine how genetic factors interact with diet to affect SLD in a large national biobank.MethodsWe included UK Biobank participants with dietary intake measured by 24-hour recall and genotyping. The primary predictors were dietary pattern, PNPLA3-rs738409-G, TM6SF2-rs58542926-T, a 16-variant hepatic steatosis polygenic risk score (PRS), and gene-environment interactions. The primary outcome was LFC, and secondary outcomes were iron-controlled T1 time (cT1, a measure of liver inflammation and fibrosis) and liver-related events/mortality.Results21,619 participants met inclusion criteria. In non-interaction models, Mediterranean diet and intake of fruit/vegetables/legumes and fish associated with lower LFC, while higher red/processed meat intake and all genetic predictors associated with higher LFC. In interaction models, all genetic predictors interacted with Mediterranean diet and fruit/vegetable/legume intake; the steatosis PRS interacted with fish intake; and TM6SF2 genotype interacted with red/processed meat intake, to affect LFC. Dietary effects on LFC were up to 3.8 times as high in PNPLA3-rs738409-GG vs. -CC individuals, and 1.4-3.0 times as high in the top vs. bottom quartile of the steatosis PRS. Gene-diet interactions were stronger in participants with vs. without overweight. The steatosis PRS interacted with Mediterranean diet and fruit/vegetable/legume intake to affect cT1 and most dietary and genetic predictors associated with risk of liver-related events or mortality by age 70.ConclusionsEffects of diet on LFC and cT1 were markedly accentuated in patients at increased genetic risk for SLD, implying dietary interventions may be more impactful in these populations.
Combined pulmonary fibrosis and emphysema syndrome: the age of majority
Authors: Vincent Cottin
Journal: European Respiratory Journal (2024)

<h3>Shareable abstract</h3> <b>Patients with combined pulmonary fibrosis and emphysema clinical syndrome have an increased risk of complications (pulmonary hypertension, lung cancer and mortality) compared to those with IPF and no emphysema or emphysema less than 10–15%</b>https://bit.ly/4a4viNJ
When liars are considered honest
Authors: Stephan Lewandowsky, David Garcia, Almog Simchon, Fabio Carrella
Journal: Trends in Cognitive Sciences (2024)

This article introduces a theoretical model of truth and honesty from a psychological perspective. We examine its application in political discourse and discuss empirical findings distinguishing between conceptions of honesty and their influence on public perception, misinformation dissemination, and the integrity of democracy.
Crosstalk between metabolism and cell death in tumorigenesis
Authors: Shichao Yang, Caden Hu, Xiaomei Chen, Yi Tang, Juanjuan Li, Hanqing Yang, Yi Yang, Binwu Ying, Xue Xiao, Shang‑Ze Li, Li Gu, Yahui Zhu
Journal: Molecular Cancer (2024)

Abstract It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.
A randomised controlled trial of a nurse facilitator to promote communication for family members of critically ill patients
Authors: Nancy Kentish-Barnes, Elie Azoulay, Jean Reignier, Alain Cariou, Antoine Lafarge, Olivier Huet, Thomas Gargadennec, Anne Renault, Virginie Souppart, Pamela Clavier, Fanny Dilosquer, Ludivine Leroux, Sébastien Légé, Anne Renet, Lyndia C. Brumback, Ruth A. Engelberg, Frédéric Pochard, Matthieu Resche-Rigon, J. Randall Curtis
Journal: Intensive Care Medicine (2024)
IκBε deficiency accelerates disease development in chronic lymphocytic leukemia
Authors: Jessica Bordini, Chiara Lenzi, Michela Frenquelli, Alessia Morabito, Athanasios Pseftogas, Daniela Belloni, Larry Mansouri, George Tsiolas, Eleonora Perotta, Pamela Ranghetti, Francesca Gandini, Francesca Genova, Daniel Hägerstrand, Georgios Gavriilidis, Sofoklis Keisaris, Nikolaos Pechlivanis, Frederic Davi, Neil E. Kay, Anton W. Langerak, Sarka Pospisilova, Lydia Scarfò, Antonios Makris, Fotis E. Psomopoulos, Kostas Stamatopoulos, Richard Rosenquist, Alessandro Campanella, Paolo Ghia
Journal: Leukemia (2024)