tbuckley/cabot-search huggingface dataset:
Nerves at Play: The Peripheral Nervous System in Extracranial Malignancies
Authors: Paola D. Vermeer, Anthony C. Restaino, Jeffrey L. Barr, Dan Yaniv, Moran Amit
Journal: Cancer Discovery (2025)

The exponential growth of the cancer neuroscience field has shown that the host's immune, vascular, and nervous systems communicate with and influence each other in the tumor microenvironment, dictating the cancer malignant phenotype. Unraveling the nervous system's contributions toward this phenotype brings us closer to cancer cures. In this review, we summarize the peripheral nervous system's contributions to cancer. We highlight the effects of nerve recruitment and tumor innervation, the neuro-immune axis, glial cell activity, and neural regulation on cancer development and progression. We also discuss harnessing the neural control of peripheral cancers as a potential therapeutic approach in oncology. Significance: The continued and growing interest in cancer neuroscience by the scientific and medical communities reflects the rapidly accumulating interdisciplinary understanding of the nervous system's modulation of immune, vascular, and cancer cells' functions in malignancies. Understanding these regulatory functions can identify targets for intervention that may already be clinically available for other indications. This potential brings great excitement and hope for patients with cancer worldwide.
Conquering Overtreatment of DCIS: Lessons from PRECISION
Authors: Proteeti Bhattacharjee, Esther H. Lips, Elinor J. Sawyer, E. Shelley Hwang, Alastair M. Thompson, Jelle Wesseling, Fariba Behbod, Proteeti Bhattacharjee, Deborah Collyar, Helen Davies, Andrew Futreal, E. Shelley Hwang, Jos Jonkers, Esther H. Lips, Nicholas Navin, Serena Nik-Zainal, Donna Pinto, Daniel Rea, Elinor J. Sawyer, Marjanka Schmidt, Hilary Stobart, Alastair Thompson, Marja van Oirsouw, Jacco van Rheenen, Ellen Verschuur, Jelle Wesseling, Lodewyk F.A. Wessels
Journal: Cancer Discovery (2025)

Summary: As we cannot reliably distinguish indolent, low-risk ductal carcinoma in situ (DCIS) from potentially progressive, high-risk DCIS, all women with DCIS diagnosis undergo intensive treatment without any benefit. The PREvent ductal Carcinoma In Situ Invasive Overtreatment Now team was established to unravel DCIS biology and develop new multidisciplinary approaches for accurate risk stratification to tackle the global problem of DCIS overdiagnosis and overtreatment. See related article by Bressan et al., p. 16 See related article by Stratton et al., p. 22 See related article by Goodwin et al., p. 34
Atypical Small Cell Lung Cancer: A New Malignancy Characterized by Chromothripsis, Carcinoid Tumors, and Wild-type RB1 and TP53
Authors: Urooba Nadeem, Benjamin J. Drapkin
Journal: Cancer Discovery (2025)

Summary: Small cell lung cancer (SCLC) and pulmonary carcinoid tumors are traditionally seen as unrelated, with SCLC linked to smoking and characterized by biallelic loss of RB1 and TP53 and rapid progression. Rekhtman and colleagues upend these assumptions by discovering an “atypical” SCLC that arises in nonsmokers with intact RB1 and TP53 loci, chromothripsis-induced oncogene amplifications on extrachromosomal DNA, and frequent synchronous carcinoid tumors. See related article by Rekhtman et al., p. 83
Antigenic determinants underlying IgE-mediated anaphylaxis to peanut
Authors: Scott A Smith, Yasmin W Khan, Rebecca A Shrem, Jonathan A Hemler, Joshua E Doyle, Jacob Daniel, Jian Zhang, Glorismer Pena-Amelunxen, Lorenz Aglas, Robert G Hamilton, Robert Getts, Hugh A Sampson, Joyce J W Wong, Derek Croote, R Stokes Peebles, Benjamin W Spiller
Journal: Journal of Allergy and Clinical Immunology (2025)

Studies of human IgE and its targeted epitopes on allergens have been very limited. We have an established method to immortalize IgE encoding B cells from allergic individuals. To develop an unbiased and comprehensive panel of peanut-specific human IgE mAbs to characterize key immunodominant antigenic regions and epitopes on peanut allergens to map the molecular interactions responsible for inducing anaphylaxis. Using human hybridoma technology to immortalize IgE encoding B cells from peripheral blood of subjects with severe peanut allergy, we generated a panel of naturally occurring human IgE mAbs in an unbiased manner. Isolated IgE mAbs were characterized extensively in allergen binding assays, peptide array analysis, antigenic mapping, binding kinetic analysis, serum blocking, skin testing inhibition, and functional assessment using human FcεRI transgenic mice. We created a large panel of 54 peanut-specific IgE mAbs, of which 63% were specific for Ara h 2 and/or 6. Pairs of IgE mAbs with the same antigen-specificity but different binding sites were able to mediate passive systemic anaphylaxis in FcεRI transgenic mice. A single mAb targeting the repetitive motif on Ara h 2 was able to induce degranulation and anaphylaxis on its own. IgG1 switched-variant immunoglobulins of the IgE mAb inhibited patients´ IgE binding to peanut extract between 30-60% (ImmunoCAP) and reduced peanut extract-induced skin wheal sizes by 1.6-7.4 millimeters in peanut allergic patients. We created a molecular map of the IgE antibody response to the most important peanut allergen proteins to enable the design of new allergy immunotherapies and vaccines.
Effect of Coupled Wing Motion on the Aerodynamic Performance During Different Flight Stage of Pigeon
Authors: Yishi Shen, Yi Xu, Weimin Huang, Chengrui Shang, Qing Shi
Journal: Cyborg and Bionic Systems (2025)

Birds achieve remarkable flight performance by flexibly morphing their wings during different flight stages. However, due to the lack of experimental data on the free morphing of wings and the complexity of coupled motion in aerodynamics studies, the intricate kinematic changes and aerodynamic mechanisms of wings during various flight stages still need to be explored. To address this issue, we collected comprehensive data on free-flight pigeons (Columba livia). We categorized the wing kinematic parameters during the takeoff, leveling flight, and landing stages into 5 kinematics parameters: flap, twist, sweep, fold, and bend. Based on this, we established a 3-dimensional pigeon wing model, defined its coupled motion using rotation matrices, and then used the computational fluid dynamics method to simulate the coupled motion in the 3 flight stages. We analyzed and compared the kinematic parameter changes, aerodynamic forces, and flow structures. It is found that, within a wingbeat cycle, pigeons during the takeoff stage cause the leading-edge vortex to attach earlier, enhancing instantaneous lift to overcome gravity and achieve ascending. During the leveling flight stage, the pigeon's average lift becomes stable, ensuring a steady flight posture. In the landing stage, the pigeon increases the wing area facing the airflow to maintain a stable landing posture, achieving a more minor, consistent average lift while increasing drag. This study enhances our understanding of birds' flight mechanisms and provides theoretical guidance for developing efficient bio-inspired flapping-wing aerial vehicles.
A randomised phase III study of bevacizumab and carboplatin-pemetrexed chemotherapy with or without atezolizumab, as first-line treatment for advanced pleural mesothelioma: results of the ETOP 13 18 BEAT-meso trial
Authors: E Felip, S Popat, U Dafni, K Ribi, A Pope, S Cedres, R Shah, F de Marinis, L Cove Smith, R Bernabé, M Früh, K Nackaerts, L Greillier, A Scherz, B Massuti, E Nadal, L Vila Martinez, T Talbot, H Roschitzki-Voser, G Dimopoulou, S Schär, B Ruepp, S Savic, S Peters, R Stahel
Journal: Annals of Oncology (2025)
The relationship between the early life gastrointestinal microbiome and childhood nocturnal cough
Authors: Amy A Eapen, Tengfei Ma, Alexandra R Sitarik, Ze Meng, Dennis R Ownby, Andrea E Cassidy-Bushrow, Ganesa Wegeinka, Edward M Zoratti, Susan V Lynch, Christine C Johnson, Albert M Levin
Journal: Journal of Allergy and Clinical Immunology (2025)
The effect of the foreign body response on drug elution from subdermal delivery systems
Authors: Simone Capuani, Nathanael Hernandez, Jocelyn Nikita Campa-Carranza, Nicola Di Trani, Takuma Yoshikawa, Marco Farina, Ashley L Joubert, Camden A Caffey, Alessio Simeone, Seo Won Cho, Patrick S Stayton, Corrine Ying Xuan Chua, Alessandro Grattoni
Journal: Biomaterials (2025)
Reply, <scp>SARD</scp>‐<scp>ILD</scp> Screening and Monitoring Recommendations with low certainty evidence
Authors: Sindhu R Johnson, Marcy Bolster, Sonye K Danoff, Michael George, Gordon Guyatt, Dinesh Khanna, Reza Mirza, Aberdeen Allen, Amy Turner, Elana J. Bernstein
Journal: Arthritis & Rheumatology (2025)

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.
RNA-Targeting CRISPR/CasRx system relieves disease symptoms in Huntington’s disease models
Authors: Yingqi Lin, Caijuan Li, Yizhi Chen, Jiale Gao, Jiawei Li, Chunhui Huang, Zhaoming Liu, Wei Wang, Xiao Zheng, Xichen Song, Jianhao Wu, Jiaxi Wu, Oscar Junhong Luo, Zhuchi Tu, Shihua Li, Xiao-Jiang Li, Liangxue Lai, Sen Yan
Journal: Molecular Neurodegeneration (2025)
Immune Aging in Rheumatoid Arthritis
Authors: Cornelia M. Weyand, Jörg J. Goronzy
Journal: Arthritis & Rheumatology (2025)

Rheumatoid arthritis (RA) is a life‐long autoimmune disease caused by the confluence of genetic and environmental variables that lead to loss of self‐tolerance and persistent joint inflammation. RA occurs at the highest incidence in individuals &gt;65 years old, implicating the aging process in disease susceptibility. Transformative approaches in molecular immunology and in functional genomics have paved the way for pathway paradigms underlying the replacement of immune homeostasis with auto‐destructive immunity in affected patients, including the process of immune aging. Patients with RA have a signature of premature immune aging, best understood for CD4 + T cells which function as pathogenic effectors in this HLA class II‐associated disease. Premature immune aging is present in healthy HLA‐DRB1*04 + individuals, placing accelerated immune aging prior to joint inflammation. Aging‐related molecular abnormalities directly implicated in turning RA CD4 + T cells into pro‐inflammatory effector cells are linked to malfunction of subcellular organelles, such as mitochondria, lysosomes, lipid droplets and the endoplasmic reticulum. Resulting changes in T cell behavior include cellular hypermobility; tissue invasiveness; unopposed mTORC activation; excessive release of tumor necrosis factor α (TNF); lysosomal failure; clonal expansion and immunogenic cell death. Aged and metabolically reprogrammed T cells in RA patients are accompanied by age‐associated B cells (ABC), which specialize in autoantibody production. Clonal hematopoiesis drives myeloid cell aging by producing aged monocytes and hypermetabolic macrophages (Mϕ) that sustain the process of inflammaging. Here, we synthesize insights into the relationship of RA risk and immune aging and discuss mechanisms through which immune aging can cause autoimmunity. image
Associations of fire smoke and other pollutants with incident rheumatoid arthritis and rheumatoid arthritis‐associated interstitial lung disease
Authors: Vanessa L. Kronzer, Yangyuna Yang, Punyasha Roul, James L. Crooks, Cynthia S. Crowson, John M. Davis, Jeffrey A. Sparks, Jeffrey R. Pierce, Katelyn O'Dell, Brian C. Sauer, Grant W. Cannon, Joshua F. Baker, Ted R. Mikuls, Bryant R. England
Journal: Arthritis & Rheumatology (2025)

The aim of this study was to determine whether pollutants such as fire smoke-related particulate matter <2.5 μm (PM2.5) are associated with incident rheumatoid arthritis (RA) and RA-associated interstitial lung disease (RA-ILD). This patient-control study used Veterans Affairs (VA) data from October 1, 2009, to December 31, 2018. We identified patients with incident RA and RA-ILD using validated algorithms, matching each patient to ≤10 controls on age, sex, and VA enrollment year. We obtained pollutants including fire smoke PM2.5, carbon monoxide, nitrogen oxides (NOx), ozone, overall PM2.5, PM10, and sulfur dioxide (SO2) at least one year before the index date. We fit conditional logistic regression models to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for incident RA and RA-ILD, adjusted for confounders. We identified 9,701 patients with incident RA (mean age 65 years, 86% male), including 531 patients with RA-ILD (mean age 69 years, 91% male), and 68,852 matched controls. Fire smoke PM2.5 was not associated with RA (aOR 1.07, 95% CI 0.92-1.23) but was associated with RA-ILD (aOR 1.98, 95% CI 1.08-3.62, per 1 μg/m3). Increased levels of NOx were associated with RA (aOR 1.16, 95% CI 1.06-1.27, highest vs lowest quartile). The highest quartiles of ozone (aOR 1.19, 95% CI 1.06-1.34) and PM10 (aOR 1.25, 95% CI 1.10-1.43) were associated with seronegative RA. Carbon monoxide, overall PM2.5, and SO2 were not, or negatively, associated with RA and RA-ILD. Increased fire smoke PM2.5 was associated with RA-ILD, whereas NOx, ozone, and PM10 were associated with RA risk. Thus, air pollution may increase the risk of RA and RA-ILD.
Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine
Authors: Izabella Sall, Randi Foxall, Lindsey Felth, Soren Maret, Zachary Rosa, Anirudh Gaur, Jennifer Calawa, Nadia Pavlik, Jennifer L. Whistler, Cheryl A. Whistler
Journal: Gut Microbes (2025)

The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.
Air Pollution's Hidden Toll: Risks for Rheumatoid Arthritis and <scp>RA</scp>‐Associated Lung Disease
Authors: S. Ajeganova, J. Sokolove
Journal: Arthritis & Rheumatology (2025)

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.
Tissue‐Engineered Therapeutics for Lymphatic Regeneration: Solutions for Myocardial Infarction and Secondary Lymphedema
Authors: Alvis Chiu, Joseph M. Rutkowski, Qixu Zhang, Feng Zhao
Journal: Advanced Healthcare Materials (2025)

Abstract The lymphatic system, which regulates inflammation and fluid homeostasis, is damaged in various diseases including myocardial infarction (MI) and breast‐cancer‐related lymphedema (BCRL). Mounting evidence suggests that restoring tissue fluid drainage and clearing excess immune cells by regenerating damaged lymphatic vessels can aid in cardiac repair and lymphedema amelioration. Current treatments primarily address symptoms rather than underlying causes due to a lack of regenerative therapies, highlighting the importance of the lymphatic system as a promising novel therapeutic target. Here cutting‐edge research on engineered lymphatic tissues, growth factor therapies, and cell‐based approaches designed to enhance lymphangiogenesis and restore lymphatic function is explored. Special focus is placed on how therapies with potential for immediate lymphatic reconstruction, originally designed for treating BCRL, can be applied to MI to augment cardiac repair and reduce heart failure risk. The integration of these novel treatments can significantly improve patient outcomes by promoting lymphatic repair, preventing pathological remodeling, and offering new avenues for managing lymphatic‐associated diseases.
Senescent cell-derived extracellular vesicles inhibit cancer recurrence by coordinating immune surveillance
Authors: Tahereh Ziglari, Nicholas L. Calistri, Jennifer M. Finan, Daniel S. Derrick, Ernesto S. Nakayasu, Meagan C. Burnet, Jennifer E. Kyle, Matthew Hoare, Laura M. Heiser, Ferdinando Pucci
Journal: Cancer Research (2025)

Abstract Senescence is a non-proliferative, survival state that cancer cells can enter to escape therapy. In addition to soluble factors, senescence cells secrete extracellular vesicles (EVs), which are important mediators of intercellular communication. To explore the role of senescent cell-derived EVs (senEVs) in inflammatory responses to senescence, we developed an engraftment-based senescence model in wild-type mice and genetically blocked senEV release in vivo, without significantly affecting soluble mediators. SenEVs were both necessary and sufficient to trigger immune-mediated clearance of senescent cells, thereby suppressing tumor growth. In the absence of senEVs, the recruitment of MHC-II+ antigen-presenting cells to the senescence microenvironment was markedly impaired. Blocking senEV release redirected the primary target of senescent cell signaling from antigen-presenting cells to neutrophils. Comprehensive transcriptional and proteomic analyses identified six ligands specific to senEVs, highlighting their role in promoting antigen-presenting cell–T cell adhesion and synapse formation. Antigen-presenting cells activated CCR2+CD4+ TH17 cells, which appeared to inhibit B cell activation, and CD4+ T cells were essential for preventing tumor recurrence. These findings suggest that senEVs complement the activity of secreted inflammatory mediators by recruiting and activating distinct immune cell subsets, thereby enhancing the efficient clearance of senescent cells. These conclusions may have implications not only for tumor recurrence but also for understanding senescence during de novo carcinogenesis. Consequently, this work could inform the development of early detection strategies for cancer based on the biology of cellular senescence.
Quantitative proteomic analysis unveils a critical role of VARS1 in hepatocellular carcinoma aggressiveness through the modulation of MAGI1 expression
Authors: Natalia Hermán-Sánchez, Mercedes del Rio-Moreno, Rubén Ciria, Marina E. Sánchez-Frias, Maite G. Fernández-Barrena, Iker Uriarte, Eduardo Chicano-Galvez, Ignacio Ortea, Ángela Peralbo-Molina, Javier Briceño, Matías A. Avila, Manuel Rodríguez-Perálvarez, Raúl M. Luque, Juan L. López-Cánovas, Manuel D. Gahete
Journal: Molecular Cancer (2025)

Hepatocellular carcinoma (HCC) genetic/transcriptomic signatures have been widely described. However, its proteomic characterization is incomplete. We performed non-targeted quantitative proteomics of HCC samples and explored its clinical, functional, and molecular consequences. Non-targeted quantitative proteomics were performed on cytosolic and nuclear fractions of liver samples [HCC vs. non-tumour adjacent tissue (NTAT), n = 42 patients]. Changes were confirmed in 7 in silico HCC cohorts. Functional and molecular implications were evaluated on HCC-derived cell lines after silencing/overexpressing VARS1 and/or MAGI1. VARS1-overexpressing Hep3B cells were used for in vivo studies [Extreme Limiting Dilution Assay (ELDA) and orthotopic tumour formation]. Quantitative proteomics were performed on VARS1-overexpressing HCC cell lines. Quantitative proteomics revealed the dysregulation of the cytosolic and nuclear proteomes in HCC, and defined two proteomic HCC subgroups, the most aggressive associated to the dysregulation of the aminoacyl-tRNA synthetases (ARSs). ARSs dysregulation was corroborated in in silico HCC cohorts and associated to poor prognosis. Patients with ARSs upregulation had genomic/transcriptomic characteristics of the proliferative HCC. Valine tRNA-aminoacyl synthetase (VARS1) was the ARSs most consistently overexpressed and associated to aggressiveness. VARS1 modulation (silencing/overexpression) altered tumour establishment-associated parameters in vitro and/or in vivo. Quantitative proteomics on cells overexpressing VARS1 and rescue experiments identified the downregulation of MAGI1, a tumour suppressor in HCC, as a mediator of VARS1 function. Quantitative proteomics defines two prognosis-related proteomic HCC subgroups. ARSs machinery is dysregulated in the aggressive subgroup, bearing potential as prognostic biomarkers. VARS1 promotes aggressiveness through the modulation of MAGI1, representing a novel targetable vulnerability in HCC.
Ribosome profiling reveals hidden world of small proteins
Authors: Gregory Tong, Thomas F Martinez
Journal: Trends in Genetics (2025)

The development of ribosome profiling (Ribo-seq) by Ingolia et al. introduced a powerful new method for monitoring translation genome-wide. Application of Ribo-seq across multiple organisms has since revealed thousands of unannotated translated small open reading frames (ORFs) and enhanced efforts to study their encoded proteins, called microproteins.
Pathways to Racial/Ethnic Inequalities in Dementia
Authors: Jordan D. Palms, Ketlyne Sol, Laura B. Zahodne
Journal: Annual Review of Clinical Psychology (2025)

Individuals from minoritized racial/ethnic groups face a disproportionate burden of Alzheimer's disease and related dementias. This health inequality reflects structural racism, which creates and sustains racial differences in social determinants of health, including education access and quality, economic stability, social and community context, neighborhood and built environment, and health care access and quality. Thus, understanding pathways that lead to dementia inequalities requires addressing individual- and system-level factors. This article summarizes evidence linking each social determinant of health to racial/ethnic inequalities in dementia, emphasizing upstream factors and mechanisms as potential levels of intervention. The importance of resilience in marginalized groups as well as critical research considerations for dementia inequalities are also discussed. Future directions highlight the need to understand the common and unique mechanisms driving inequalities across minoritized groups, where research is lacking.