tbuckley/cabot-search huggingface dataset:
Involvement of tachykinin NK1 and NK2 receptors in substance P-induced microvascular leakage hypersensitivity and airway hyperresponsiveness in guinea-pigs
Authors: E Boichot, K Biyah, N Germain, X Emonds-Alt, V Lagente, C Advenier
Journal: European Respiratory Journal (1996)

Tachykinins, such as substance P, might be involved in the development of airway hyperresponsiveness (AHR) and airway inflammation. However, it is unknown which tachykinin receptors mediate these biological activities. The effects of two antagonists of tachykinin neurokinin-1 (NK1) and tachykinin neurokinin-2 (NK2) receptors, SR 140333 and SR 48968, respectively, were investigated on substance P (SP)-induced airway hyperresponsiveness and potentiation of the histamine-induced increase in microvascular leakage, in phosphoramidon-pretreated guinea-pigs. Guinea-pigs were pretreated with phosphoramidon (0.1 mM aerosol for 15 min) and exposed 15 min later to saline solution alone or to saline solution containing SP (0.1 mg.mL-1 for 30 min). Twenty four hours later, the animals were anaesthetized and prepared for the recording of the pulmonary inflation pressure (PIP) to acetylcholine or for the investigation of microvascular leakage to histamine. Pretreatment of the guinea-pigs with a single dose of SR 48968 (1 mg.kg-1, i.p.) 30 min before SP exposure, significantly prevented the development of AHR, whereas SR 140333 (1 mg.kg-1, i.p.) did not. In a second set of experiments, phosphoramidon-pretreated guinea-pigs exposed to SP presented a significant potentiation of the histamine-induced increase in microvascular leakage in pulmonary airways. When the guinea-pigs were pretreated with SR 140333, an inhibition of the increased microvascular leakage to histamine was observed. In contrast, no significant inhibitory activity was noted when the guinea-pigs were pretreated with SR 48968. The present data demonstrate the importance of tachykinin NK2 receptor stimulation in the development of airway hyperresponsiveness and that of tachykinin NK1 receptor stimulation in microvascular leakage hypersensitivity in phosphoramidon-pretreated and substance P-exposed guinea-pigs. The results also suggest a dissociation between the presence of microvascular leakage and the occurrence of airway hyperresponsiveness.
Lungs in thalassaemia major patients receiving regular transfusion
Authors: DY Tai, YT Wang, J Lou, WY Wang, KH Mak, HK Cheng
Journal: European Respiratory Journal (1996)

Progressive tissue iron deposition from multiple blood transfusions is common in beta-thalassaemia and pulmonary iron deposition may result in parenchymal damage. The objectives of this study were to: 1) determine the predominant pulmonary dysfunction in patients with thalassaemia major; and 2) demonstrate that parenchymal disease, if present, is at the level of the alveolocapillary membrane. Fourteen thalassaemia major patients (13 nonsmokers) receiving regular blood transfusion and without any history of chronic respiratory disease were recruited. Pulmonary function tests and echocardiography were performed before the scheduled transfusions. Three patients with the most restricted lung function were selected for high resolution computerized tomography (CT) of the lungs. One patient had an obstructive pattern with a forced expiratory volume in one second as percentage of forced vital capacity (FEV1/FVC) of 71%. Four patients demonstrated a restrictive pattern, as defined by total lung capacity (TLC) less than 80% predicted with normal FEV1/FVC%. Twelve patients had pulmonary transfer factors for carbon monoxide (TL,CO) below 80% pred, even after correction for the anaemia, indicating parenchymal disease. Eight of these 12 patients had alveolocapillary membrane defect, as demonstrated by a gas transfer factor of the pulmonary membrane (Tm) less than 80% pred. Mean resting arterial oxygen saturation was 95 +/- 2 (range 92-98) %. Eleven patients had oxygen desaturation of 5% or more during exercise on a bicycle ergometer, consistent with interstitial lung disease. There was no clinical or echocardiographic evidence of heart failure. Percentage predicted TLC was inversely correlated with age (r = -0.547; p = 0.043). Both percentage predicted TLC and TL,CO were not correlated with iron burden or desferoxamine ratio. High resolution CT in the three selected patients showed no evidence of pulmonary fibrosis. We conclude that thalassaemia major patients have a predominant restrictive lung dysfunction with pulmonary parenchymal disease and alveolocapillary membrane block. The restrictive and interstitial lung disease could not be accounted for by iron loading or pulmonary fibrosis in our patients.
A new protein isoform encoded by human circular RNA circSLC8a1 contributes to cardiac remodeling
Authors: Feiya Li, William W Du, Xiangmin Li, Shuoyang Wen, Jindong Xu, Qiwei Yang, Jinfeng Wei, Sheng Wang, Nan Wu, Javeria Qadir, Burton B Yang
Journal: Cardiovascular Research (2025)

Abstract Aims Circular RNA circSLC8a1 has been previously suggested to possess translation potential, but experimental evidence supporting this notion has been lacking. We aim to understand the functions of circSLC8a1 and its translated protein in cardiac remodeling. Methods and Results To elucidate the functional significance of circSLC8a1, we established a transgenic mouse line expressing circSLC8a1 and its translated protein SLC8a1-604. We present compelling evidence confirming the translation potential of circSLC8a1 (hsa_circ_0005232) both in vitro and in vivo. The back-splicing event within hsa_circ_0005232 leads to the generation of a novel circRNA-derived protein comprising 604 amino acids, named SLC8a1-604, which has not been previously reported. These SLC8a1-604 transgenic mice exhibited a heart failure phenotype. In further investigations, we induced pressure overload in the transgenic mice, revealing a significant decrease in heart function compared to litter-matched negative controls. Notably, our findings indicate that the reduced heart function observed in the transgenic mice can be attributed to the presence of the circRNA-translated protein, SLC8a1-604, rather than the circRNA itself. Mechanistically, we found that SLC8a1-604 translocated into mitochondria, where it exerted its effects by binding to POLRMT. This interaction results in a downregulation of mitochondrial gene transcription, leading to a decrease in ATP synthesis. Conclusion Our study provides evidence that circSLC8a1 has the capacity to encode a novel protein isoform, SLC8a1-604, which plays a pivotal role in the regulation of heart functions: circSLC8a1 modulates the remodeling process of cardiac pressure overload by translating into a functional protein. Translational Perspective This proof-of-concept study may lay the foundation for potential clinical applications in circular RNA therapy.
DNAJ-PKAc fusion heightens PLK1 inhibitor sensitivity in fibrolamellar carcinoma
Authors: Marina Chan, Songli Zhu, Manabu Nukaya, Luisa T Ferreira, Sean M Ronnekleiv-Kelly, Kimberly J Riehle, John D Scott, Raymond S Yeung, Taranjit S Gujral
Journal: Gut (2025)

Background Fibrolamellar carcinoma (FLC), a rare and fatal liver cancer lacking effective drug therapy, is driven by the DNAJ-PKAc fusion oncoprotein. However, the underlying mechanism of DNAJ-PKAc’s role in FLC tumour growth remains enigmatic. Objective We sought to determine the protein kinase-mediated signalling networks that drive growth and proliferation in FLC. Design We integrated a combination of newly established preclinical models of FLC and an unbiased polypharmacology-based approach to identify downstream kinases involved in DNAJ-PKAc-mediated FLC cell growth. We validated our findings in multiple patient-derived mouse models and patient tumours. Results Functional screening, coupled with computational analysis, highlighted Polo-like kinase 1 (PLK1) as vital for FLC cell viability. Genetic and pharmacological PLK1 inhibition significantly reduced FLC cell growth, inducing apoptosis. Further studies showed DNAJ-PKAc’s centrosomal presence and direct interaction with PLK1, revealing a novel mechanism that promotes PLK1 activation and mitotic progression. Clinical-grade PLK1 inhibitors effectively suppressed FLC tumour growth across multiple preclinical models, including patient-derived xenograft and an orthotopic model of FLC, suggesting promising therapeutic avenues. Conclusion Our findings underscore the role of DNAJ-PKAc in rewiring signalling networks and highlight valuable clinical implications for PLK1-targeted therapies for FLC.
Short-term exposure to ultrafine particles and asthma hospital admissions in children in Copenhagen, Denmark
Authors: Marie Bergmann, Zorana J Andersen, Andreas Massling, Steffen Loft, Thomas Cole-Hunter, Claus Nordstrøm, Stéphane Tuffier, Jiawei Zhang, Youn-Hee Lim
Journal: Thorax (2025)

Background Ultrafine particles (UFP; &lt;0.1 µm in diameter) are not regulated or commonly monitored but may be harmful to human health, particularly for children. In this study, we aimed to examine the association between short-term exposure to UFP and asthma hospital admissions in children. Methods Daily UFP concentrations (2002–2018) were monitored at an urban background station in Copenhagen, Denmark. Asthma hospital admissions, demographic and socioeconomic information of children (0–18 years) were obtained from registries. A case-crossover design was applied to estimate the association between hospital admissions and up to 6-day UFP exposure windows for all children, and stratified by age, sex, family income, mother’s education, prior asthma or prior respiratory infection. Results We observed 15 903 asthma hospital admissions in total. An IQR increase in UFP was significantly associated with asthma hospital admissions, strongest at 2-day exposure windows (risk ratio (RR): 1.17 (95% CI: 1.09, 1.25)). These associations remained unchanged when adjusting for particulate matter &lt;2.5 µm in diameter (PM 2.5 ) or nitrogen dioxide (NO 2 ), for which we also detected significant positive associations. Associations with UFP were stronger for school-aged children (5–14 years: RR: 1.26 (95% CI: 1.15, 1.38)) than for children younger than 5 years (1.01 (95% CI: 0.93, 1.10)). Conclusions In this large study in a low-exposure setting, we find that short-term exposure to UFP can trigger asthma hospital admissions in children, independently of associations with PM 2.5 or NO 2 . This study adds evidence calling for the regulation and improvement of UFP exposure assessment to protect children’s health in urban areas.
Hormonal Intrauterine Devices Are Associated With Lower Long-Term Melasma Risk Compared to Combined and Progestin-Only Oral Contraceptives: a Population-Based Cohort Study
Authors: Debby Cheng, Ahana Gaurav, David Xiang, Helen Ji, David A Hirsh, Steven Chen, Arash Mostaghimi, Kevin Sheng-Kai Ma, Nicholas Theodosakis
Journal: Journal of the American Academy of Dermatology (2025)
Vascular Magnifier for Ultrahigh-Resolution Visualization of Cerebral Vessels in Vivo
Authors: Bingjie Li, Jinbin Pan, Ruijie Zhang, Bing Han, Yujie Zhao, Guijun Liu, Yujie Tong, Yujing He, Guangchao Xie, Ruxia Liu, Ting Zhou, Quan Zhang, Shao-Kai Sun
Journal: Biomaterials (2025)
ProtoASNet: Comprehensive evaluation and enhanced performance with uncertainty estimation for Aortic stenosis classification in echocardiography
Authors: Ang Nan Gu, Hooman Vaseli, Michael Y Tsang, Victoria Wu, S Neda Ahmadi Amiri, Nima Kondori, Andrea Fung, Teresa S M Tsang, Purang Abolmaesumi
Journal: Medical Image Analysis (2025)
Validation of POD24 as a robust early clinical indicator of poor survival in mantle cell lymphoma from 1280 patients on clinical trials, a LYSA study
Authors: Clémentine Sarkozy, Loïc Chartier, Vincent Ribrag, Remy Gressin, Christian H Geisler, Hanneke C Kluin-Nelemans, Catherine Thieblemont, Franck Morschhauser, François Lemonnier, Violaine Safar, Benoît Tessoulin, Lucie Oberic, Ghandi Damaj, Hervé Ghesquières, Krimo Bouabdallah, René Olivier Casasnovas, Roch Houot, Wolfram Klapper, Barbara Burroni, Christiane Pott, Marie-Hélène Delfau-Larue, Elizabeth Macintyre, Mary Callanan, Mats Jerkeman, Michael Unterhalt, Eva Hoster, Martin Dreyling, Steven Le Gouill, Olivier Hermine, Morgane Cheminant
Journal: Blood Cancer Journal (2025)
KMT2C deficiency drives transdifferentiation of double-negative prostate cancer and confer resistance to AR-targeted therapy
Authors: Jiacheng Guo, Ni Li, Qiuli Liu, Zongyao Hao, Guanghui Zhu, Xuege Wang, Hanling Wang, Qiang Pan, Beitao Xu, Ying Han, Guoying Zhang, Yannan Lian, Wei Zhang, Yongqiang Gu, Naiheng Lin, Xin Zeng, Zige Jin, Weihua Lan, Jun Jiang, Dong Gao, Liang Dong, Huairui Yuan, Chaozhao Liang, Jun Qin
Journal: Cancer Cell (2025)
Stromal lipid species dictate melanoma metastasis and tropism
Authors: Shilpa Gurung, Timothy Budden, Karthik Mallela, Benjamin Jenkins, Alex von Kriegsheim, Esperanza Manrique, David Millán-Esteban, Isabel Romero-Camarero, Fabio Amaral, Sarah Craig, Pedro Durao, Joanna Pozniak, Laura Stennett, Duncan Smith, Garry Ashton, Alex Baker, Kang Zeng, Gilbert Fruhwirth, Victoria Sanz-Moreno, Jair Marques, Albert Koulman, Jean-Christophe Marine, Tim C P Somervaille, Luisa Motta, Caroline Gaudy-Marqueste, Eduardo Nagore, Amaya Virós
Journal: Cancer Cell (2025)
Immunothrombolytic monocyte-neutrophil axes dominate the single-cell landscape of human thrombosis and correlate with thrombus resolution
Authors: Kami Pekayvaz, Badr Kilani, Markus Joppich, Luke Eivers, Sophia Brambs, Viktoria Knottenberg, Sezer Akgöl, Keyang Yue, Lukas Li, Alejandro Martinez-Navarro, Rainer Kaiser, Nina Meißner, Heiko Schulz, Larissa Belz, Anastassia Akhalkatsi, Sven Stockhausen, Tonina T Mueller, Simon Millonig, Lea Hartelt, Christoph Gold, Aleksandar Janjic, Vivien Polewka, Franziska Wendler, Augustin Droste Zu Senden, Anna Titova, Alexander Leunig, Michael Voelkl, Bernd Engelmann, Moritz R Hernandez Petzsche, Tobias Boeckh-Behrens, Thomas Liebig, Sandra Winning, Joachim Fandrey, Martin Dichgans, Wolfgang Enard, Ralf Zimmer, Steffen Tiedt, Steffen Massberg, Leo Nicolai, Konstantin Stark
Journal: Immunity (2025)
Countries should strengthen their health information systems
Authors: Kathleen Strong, Amanuel Abajobir, Frances Aboud, Ambrose Agweyu, Sk Masum Billah, Maureen Black, Sally Brinkman, Ilan Cerna-Turoff, Rakhi Dandona, Carolin Ekman, Sayaka Horiuchi, Luis Huicho, Zeina Jamaluddine, Marzia Lazzerini, Abdoulaye Maiga, Melinda Munos, Ralf Weigel
Journal: BMJ (2025)
Sex and sex hormonal regulation of the atrial inward rectifier potassium current (IK1): insights into potential pro-arrhythmic mechanisms
Authors: Lucilla Giammarino, Lluis Matas, Nicolò Alerni, András Horváth, Varjany Vashanthakumar, Saranda Nimani, Miriam Barbieri, Sahej Bains, Ruben Lopez, Julien Louradour, Balazs Ördög, Thomas Hof, Ange Maguy, Giulio Conte, Angelo Auricchio, Ulrich Schotten, Katja E Odening
Journal: Cardiovascular Research (2025)

Abstract Aims Pronounced sex-differences are known in the incidence of atrial fibrillation (AF). In this study, we aimed to investigate the atrial electrophysiological properties that may underlie sex-differences in AF incidence in the younger population, focusing on IK1, a cardiac ion current important for action potential (AP) stability and triggered activity. Methods and Results We assessed sex-differences in P-wave morphology in 12-lead ECG in healthy young New Zealand White rabbits. Males presented longer P-wave duration and larger P-wave area compared to females. Patch-clamp experiments were performed in isolated rabbit atrial cardiomyocytes (CMs). Male atrial CMs presented higher DAD incidence, amplitude, and area under the curve (AUC) than females, potentially facilitating the presence of atrial triggered activity in males. Male atrial CMs showed a less hyperpolarized resting membrane potential (RMP), a 50% smaller IK1, and a 26% reduction in Kir2.1 protein expression, a pore forming subunit of IK1, than females. Dihydrotestosterone (DHT) effects were investigated acutely and semi-chronically ex vivo. Experiments showed that the sex-difference in IK1 could be mimicked by DHT. In female atrial CMs, acute and semi-chronic (24h) DHT administration reduced IK1. In the presence of a PKC-inhibitor, DHT-mediated IK1 reduction was not observed in atrial female CMs, suggesting it to be PKC-mediated. Chronic DHT-effects were investigated in vivo in female rabbits after hormone-releasing pellet implantation. After two weeks, animals showed a significantly prolonged and larger P-wave, a smaller atrial IK1 and a trend towards an increased DAD amplitude and AUC. Conclusions Sex impacts on atrial electrophysiology, leading to sex-differences in P-wave morphology, triggered activity, RMP, and IK1. These sex-differences can be mimicked by sex hormone-treatment, suggesting that sex hormones ‒ particularly DHT ‒ play a pivotal role in mediating sex-differences in atrial electrophysiology. Such sex-differences might impact on the propensity to develop AF, particularly in the younger population.
CHIP’ing Signal from Noise in Liquid Biopsy
Authors: Elsa Bernard, Jean-Baptiste Micol
Journal: Clinical Cancer Research (2025)

Abstract The presence of clonal hematopoiesis (CH) in cell-free DNA (cfDNA) analysis can distort the interpretation of results and impact cancer treatment decisions. This CCR Translations discusses the importance of distinguishing the origin of cfDNA variants as tumoral or hematopoietic and its potential clinical implications.
Sympathetic axonogenesis promotes adenoid cystic carcinoma progression
Authors: Chun-Hao Chen, Boris Reva, Nora Katabi, Avishai Wizel, Hongbo Xu, Alan L. Ho, Luc G.T. Morris, Richard L. Bakst, Anuraag S. Parikh, Yotam Drier, Sylvie Deborde, Richard J. Wong
Journal: The Journal of Experimental Medicine (2025)

Nerves are integral to the adenoid cystic carcinoma (ACC) microenvironment. The strong association of ACC with perineural invasion (PNI) is considered a hallmark of this disease. In human salivary ACC, we identify intratumoral, small-caliber, disorganized sympathetic nerves not observed in other salivary neoplasms. Norepinephrine or sympathetic ganglia explants enhance ACC proliferation in vitro. Two novel orthotopic ACC patient-derived xenograft (PDX) models recapitulate ACC morphology and demonstrate sympathetic innervation. Pharmacologic or surgical blockade of sympathetic nerves decreases ACC PDX growth. Bulk RNA sequencing of salivary ACC reveals correlations between noradrenergic nerve development signatures and worse patient survival. Metastatic ACC foci exhibit lower nerve signature gene expression levels than primary ACC. Sympathetic innervation in ACC is distinct from PNI and reflects tumor axonogenesis driven by noradrenergic neural development programs. These programs support ACC progression, are associated with poor prognosis, and may be inhibited as a therapeutic strategy.
High‐risk features of early relapse in newly‐diagnosed multiple myeloma: The impact of cytogenetics and response to initial therapy
Authors: Andrea Manubens, Bruno Paiva, Norma C. Gutiérrez, Manuela Fernandez, Maria‐José Calasanz, Laura Rosiñol, Albert Oriol, Ma Jesús Blanchard, Estrella Carrillo, Celina Benavente, Joaquín Martínez‐López, Joan Bargay, Miguel Teodoro Hernández, Javier de la Rubia, Yolanda González, Miguel Paricio, Felipe de Arriba, Enrique M. Ocio, Ana Isabel Teruel, Ana López de la Guia, Maialen Sirvent, Mercedes Gironella, Antonia Sampol, José Ma Arguiñano, Carmen Cabrera, Adrián Alegre, Miquel Granell, Valentín Cabañas, Jorge M. Núñez‐Córdoba, María Victoria Mateos, Juan José Lahuerta, Jesús F. San Miguel, Joan Bladé, Paula Rodriguez‐Otero
Journal: HemaSphere (2025)

Abstract Patients with newly‐diagnosed multiple myeloma (MM) who experience early relapse (ER) have dismal overall survival (OS). Their prospective identification, either before or soon after treatment initiation, is paramount to use alternative approaches and prevent ER. In this study, we investigated the frequency and disease characteristics of ER during the first 18 months after treatment initiation (ER18), in a series of 1215 newly‐diagnosed MM patients enrolled in four PETHEMA/GEM clinical trials for the transplant‐eligible and transplant‐ineligible populations. ER18 was observed in 266 of the 1215 patients (22%) and resulted in a median OS of 19 versus 114 months in cases without ER18. When compared to the ISS and the presence of ≥2 high‐risk cytogenetic abnormalities, a modified version of the new high‐risk definition from the International Myeloma Society (mHR‐IMS) showed the most balanced negative and positive predictive values of ER18 (83.5% and 40%, respectively). In addition to the mHR‐IMS, an ECOG = 2, ISS 3, and calcium levels ≥ 11 mg/dL were independently associated with ER18. These variables were modeled into a predictive score in which the rates of ER18 were 2%, 24.5%, and 59% in patients with low‐, intermediate‐, and high‐risk score. The risk of ER18 and OS were modulated by the VGPR status at 6–9 months after treatment initiation. In conclusion, we present a risk model that predicts ER18 and can be readily applied in clinical trials and routine practice to identify treatment strategies empowered to prevent ER18 and improve survival outcomes of newly‐diagnosed patients with functional high‐risk MM.
Comparing functional and genomic‐based precision medicine in blood cancer patients
Authors: Lukas Kazianka, Alexander Pichler, Christiane Agreiter, Johannes Rohrbeck, Christoph Kornauth, Edit Porpaczy, Christian Sillaber, Wolfgang R. Sperr, Karoline V. Gleixner, Alexander Hauswirth, Ulrich Jäger, Peter Valent, Constanze Jonak, Stefanie Porkert, Ruth Exner, Wolfgang Willenbacher, Dominik Wolf, Peter Neumeister, Katharina Prochazka, Alexander Deutsch, Richard Greil, Clemens Schmitt, Robin Ristl, Marius Mayerhoefer, Ingrid Simonitsch‐Klupp, Tea Pemovska, Philipp B. Staber
Journal: HemaSphere (2025)

Abstract Tumor‐agnostic precision medicine (PM) strategies promise to support treatment decisions in relapsed/refractory blood cancer patients. Genomic‐based PM (gPM) and drug screening‐based functional PM (fPM) currently represent the most prominent PM methodologies. In this study, we report the feasibility analysis of the first 55 patients enrolled in the multicentric, randomized controlled EXALT‐2 trial (NCT04470947) comparing treatment recommendations of gPM, fPM, and physicians' choice (PC) head to head. In 54 patients (98%), the diagnostic workflow was successfully implemented, resulting in treatment recommendations for 42 patients (76%), of whom 29 (69%) received the suggested individualized treatments. Actionable targets were identified in 65% by gPM and 80% by fPM (64% microscopy‐based, 86% flow cytometry‐based fPM). The median time to report was shorter for fPM than for gPM testing. The two strategies revealed overlapping drug targets in 60% of cases. Both, gPM and fPM can efficiently be integrated into the clinical routine to guide therapy decisions for the majority of patients.
Immune profiling of smoldering multiple myeloma patients treated in a phase lb study of PVX-410 vaccine targeting XBP1/CD138/CS1 antigens, and citarinostat, a histone deacetylase inhibitor (HDACi) with and without lenalidomide
Authors: Diana Cirstea, Rajib Shome, Mehmet Samur, Srikanth Talluri, Joseph J Connolly, Alexandra Jean Wright, Emilie Duvallet, Amanda N R Joyce, Kathleen Lively, Gina Basinsky, Andrew J Yee, Cristiana Costa Chase, Ehsan Malek, Ruben Niesvizky, Paul G Richardson, Noopur S Raje
Journal: Blood Cancer Journal (2025)