tbuckley/cabot-search huggingface dataset:
Effect of pulmonary artery pressure‐guided management on outcomes of patients with heart failure outside clinical trials: A systematic review and meta‐analysis of real‐world evidence with the <scp>CardioMEMS Heart Failure System</scp>
Authors: Chris J. Kapelios, Sotiria Liori, Michael Bonios, William T. Abraham, Gerasimos Filippatos
Journal: European Journal of Heart Failure (2025)

Aims Pulmonary artery pressure (PAP)‐guided heart failure (HF) management using the CardioMEMS HF System improves patient outcomes in randomized controlled trials (RCTs). Our aim was to systematically assess its impact on outcomes of HF patients receiving the device in a non‐RCT setting. Methods and results PubMed, ClinicalTrials.gov and Cochrane Clinical Trial Collection were searched on 8 January 2025. Studies were eligible if they included: (i) pre/post‐comparison of outcomes in patients receiving CardioMEMS; (ii) adult patients diagnosed with HF; (iii) follow‐up ≥6 months, and (iv) report of the primary outcome, i.e. HF hospitalization (HFH) rates. Other outcomes were changes in PAP, New York Heart Association (NYHA) class and quality of life. Quantitative analysis was performed by generating forest plots and calculating pooled means, mean differences and incidence rate ratio (IRR) by random‐effect models, as appropriate. Eight studies with a total of 3306 patients were included. Four studies were single‐arm, open‐label, industry‐funded studies and four real‐world practice studies. Four studies were performed in the US and four in Europe. Significant decreases in systolic PAP (−7.8 mmHg [−10.1 mmHg; −5.6 mmHg]), mean PAP (−5.2 mmHg [−6.7 mmHg; −3.8 mmHg]) and diastolic PAP (−4.4 mmHg [−5.5 mmHg; −3.3 mmHg]) were demonstrated. One year after CardioMEMS implantation, 56% [43%; 67%] of patients were NYHA class I/II with EQ‐5D‐5L visual analogue scale scores being significantly improved from baseline (7.2 [3.5; 10.9]). PAP‐guided HF management was associated with a significant, 61% decrease in HFHs at 1 year (IRR 0.39 [0.31; 0.47]). Conclusions Heart failure management with CardioMEMS leads to lower PAP, improved functional status and quality of life, and decrease of HFHs at 1 year in patients receiving the device in a real‐life, non‐RCT setting. Systematic review registration:PROSPERO database registration number CRD42025635206.
Genetics of Childhood‐onset Systemic Lupus Erythematosus (<scp>cSLE</scp>)
Authors: Raffaella Carlomagno, Nicholas Gold, Fangming Liao, Jingjing Cao, Paul D. Arnold, Christie L. Burton, Jennifer Crosbie, Daniela Dominguez, Dafna D. Gladman, Mariko Ishimori, Caroline Jefferies, Diane L. Kamen, Sylvia Kamphuis, Marisa S. Klein‐Gitelman, Andrea M. Knight, Chia‐Chi J. Lee, Deborah M. Levy, Karen B. Onel, Andrew D. Paterson, Christine A. Peschken, Janet E. Pope, Russell J. Schachar, Earl D. Silverman, Lisa Strug, Zahi Touma, Murray B. Urowitz, Daniel J. Wallace, Cheng Wang, Declan Webber, Joan E. Wither, Linda T. Hiraki
Journal: Arthritis & Rheumatology (2025)

Objectives Genome wide association studies (GWAS) have identified &gt;100 loci for systemic lupus erythematosus (SLE). These loci may also impact age of diagnosis. We aimed to identify genetic variants for age of SLE diagnosis, and to complete a GWAS of childhood‐onset SLE (cSLE) diagnosed &lt;18 years of age. Methods Patients met ACR and/or SLICC SLE classification criteria, had documented age at diagnosis and were genotyped on multiethnic arrays. Ungenotyped SNPs and HLA alleles were imputed to multi‐ethnic referents. Ancestry was genetically inferred. We tested known SLE loci (142 non‐HLA, 166 HLA) with log‐transformed age of SLE diagnosis, adjusted for sex and five PCs (significance threshold P &lt;1.6x10 ‐4 ). We also completed a GWAS of 346 cSLE patients and 4080 non‐SLE children/adolescents of European and East Asian ancestry (genome‐wide significance P &lt;5x10 ‐8 ). Results We included 1489 SLE patients, 51% cSLE, 88% female, 39% of European ancestry, 19% East Asian, 17% Admixed. The median age at diagnosis was 17.7 years (IQR:14.0, 30.9). One SLE risk SNP, intronic to CCDC113 (chr.16), was associated with younger age of SLE diagnosis (beta=‐0.12, SE=0.03, P=6.3x10 ‐6 ), and with cSLE versus adult‐onset SLE (aSLE). GWAS of cSLE compared to non‐SLE controls identified significant chr.6 SNP rs9268469, intronic to TSBP1‐AS1 (OR=2.04, [95%CI: 1.59, 2.63], P =1.79x10 ‐8 ), and HLA‐DQA1 . Conclusions We identified a significant locus for younger age of SLE diagnosis, intronic to CCDC113, among a large multi‐ancestral cohort of children and adults with SLE. In the first GWAS of cSLE we identified a TSBP1‐AS1 locus, and an HLA‐DQA1 previously identified for aSLE.
Differences in dynamics of specific anti‐nuclear antibodies and their susceptibility to B cell targeting treatment in Systemic Lupus Erythematosus
Authors: Hugo J. van Dooren, Mieke van Schaik, Annemarie L. Dorjée, Eline J. Arends, Meggan Mackay, Cooney Laura, David A. Fox, David Wofsy, Dawn Smilek, Cynthia Aranow, Maria Dall'Era, Tom W.J. Huizinga, Cees van Kooten, René E.M. Toes, Betty Diamond, Y.K. Onno Teng, Jolien Suurmond
Journal: Arthritis & Rheumatology (2025)

Objective The presence of anti‐nuclear antibodies (ANAs) is characteristic for systemic lupus erythematosus (SLE). Antibody dynamics over time are thought to reflect the cellular source of ANAs and their therapeutic targetability. Anti‐dsDNA is the most prevalent and well‐studied of all ANAs, and fluctuations in anti‐dsDNA serum levels are associated with disease activity. Antibody dynamics of other ANAs, such as antibodies targeting RNA‐binding proteins (RBPs), are often considered more stable compared to anti‐dsDNA. However, anti‐RBPs may be heterogeneous in nature and their fluctuation has not been extensively analysed. Therefore, we aimed to study the dynamics of the different ANAs and their susceptibility to B cell targeting treatments in SLE patients. Methods Seroconversion of specific ANAs was analyzed using electronic health records from SLE patients. Titers of specific ANAs and anti‐varicella zoster virus (VZV) were determined in serum from a longitudinal SLE patient cohort, and serum from SLE patients treated with rituximab and belimumab. Results Anti‐Sm/RNP, like anti‐dsDNA titers, seroconverted more frequently compared to anti‐SS‐A/SS‐B. Furthermore, anti‐Sm/RNP as well as anti‐dsDNA titers, but not anti‐SS‐A/SS‐B titers, fluctuated significantly compared to stable anti‐VZV controls. Likewise, reductions in anti‐dsDNA and anti‐Sm/RNP titers after B cell depleting treatment were comparable in magnitude. However, only anti‐dsDNA titer reductions associated with clinical outcomes. Conclusions Together, these results show that anti‐Sm/RNP and anti‐dsDNA, in contrast to anti‐SS‐A/SS‐B, frequently fluctuate and their levels can decrease following B cell‐targeted treatments. Thus, distinct ANAs have variable kinetics, potentially reflecting their derivation from different B cell differentiation pathways.
Profiling triple-negative breast cancer-specific super-enhancers identifies high-risk mesenchymal development subtype and BETi-Targetable vulnerabilities
Authors: Qing-Shan Chen, Rui-Zhao Cai, Yan Wang, Ge-Hao Liang, Kai-Ming Zhang, Xiao-Yu Yang, Dong Yang, De-Chang Zhao, Xiao-Feng Zhu, Rong Deng, Jun Tang
Journal: Molecular Cancer (2025)

Abstract Background Super-enhancers (SEs) are critical regulators of tumorigenesis and represent promising targets for bromodomain and extra-terminal domain inhibitors (BETi). However, clinical studies across various solid tumors, including triple-negative breast cancer (TNBC), have demonstrated limited BETi efficacy. This study aims to investigate SE heterogeneity in TNBC and its influence on BETi effectiveness, with the goal of advancing BETi precision treatment strategies and enhancing therapeutic efficacy. Methods We conducted a comprehensive analysis of H3K27ac ChIP-Seq data from TNBC cell lines and clinical samples, integrating multiple bulk RNA-Seq, scRNA-Seq, and stRNA-Seq datasets to characterize the SE landscape and heterogeneity in TNBC. Utilizing various bioinformatics algorithms, CERES scoring, and clinical prognostic data on transcription factors (TFs), we identified core transcriptional regulatory circuits (CRCs) composed of TNBC-specific SEs and master regulators, characterizing different TNBC subtypes. The biological significance of CRCs in these different TNBC subtypes and their influence on BETi sensitivity were evaluated using in vitro and in vivo models. Results Our findings revealed a distinct SE landscape in TNBC compared to non-TNBC and normal breast epithelium, allowing TNBC to be classified into distinct subtypes based on TNBC-specific SEs. Importantly, we identified a high-risk mesenchymal development subtype, validated across cell lines and transcriptomic analyses, primarily driven by a CRC consisting of the master regulator VAX2 and a TNBC-specific SE. This SE-VAX2 CRC is essential for sustaining the malignant traits of this subtype and increasing its sensitivity to BETi. Conclusions Our research clarifies the heterogeneity of SEs in TNBC and identifies a high-risk mesenchymal development subtype driven by the SE-VAX2 CRC. The subtype shows more sensitivity to BETi, supporting its precision application in TNBC.
Innate Lymphoid Cell phenotypic and functional alterations in systemic Juvenile Idiopathic Arthritis
Authors: Linda Quatrini, Cecilia Ciancaglini, Ivan Caiello, Silvia Santopolo, Manuela Pardeo, Valentina Matteo, Elena Loricchio, Donato Amodio, Elena Morrocchi, Giulio Olivieri, Paolo Palma, Antonella Insalaco, Marco Francesco Natale, Arianna de Matteis, Nicola Tumino, Claudia Bracaglia, Paola Vacca, Lorenzo Moretta, Fabrizio De Benedetti, Giusi Prencipe
Journal: Arthritis & Rheumatology (2025)

Objectives Systemic juvenile idiopathic arthritis (sJIA) is a chronic childhood disease classically attributed to innate immune cell dysregulation. This study aimed to elucidate the role of innate lymphoid cells (ILCs), including natural killer (NK) cells and helper‐ILCs (hILCs), in sJIA during clinically inactive disease (CID) through phenotypic and functional analysis. Methods Peripheral ILCs from children with sJIA during CID receiving IL‐1 inhibitors (n=40) were analyzed by flow cytometry and compared to 23 healthy children (HC) and 22 patients with unrelated autoinflammatory diseases on IL‐1 inhibitors. Plasma proteomic profiling was also performed. Results sJIA patients showed a significant reduction in circulating NK cell frequencies compared to HC, with an increased proportion of CD56 bright NK cells. While overall hILC frequencies were comparable to HC, ILC1s were increased, whereas ILC precursors (ILCPs) were reduced. ILC1 frequency correlated positively with IL‐18 plasma levels, while ILC2 frequency correlated negatively. Functional assessments revealed that NK cells from sJIA patients had variable IFN‐γ production upon IL‐18/IL‐12 stimulation, inversely correlating with IL‐18 levels. Additionally, hILCs from these patients showed a specific impairment in IFN‐γ production despite normal IL‐13 production, potentially linked to decreased IL‐18 receptor α (IL‐18RA) expression in ILC1s. Proteomic analysis confirmed IL‐18 as the most upregulated cytokine in sJIA plasma. Conclusion sJIA patients in CID exhibit significant innate immune abnormalities, including altered ILC subset distribution and impaired IFN‐γ production, strongly associated with IL‐18 levels. These findings suggest ongoing immune dysregulation despite clinical remission, underscoring a potential role for ILCs and cytokine interaction in sJIA pathogenesis.
Complex regulatory interactions at <scp><i>GDF5</i></scp> shape joint morphology and osteoarthritis disease risk
Authors: Clarissa R. Coveney, David Maridas, Hao Chen, Pushpanathan Muthuirulan, Zun Liu, Evelyn Jagoda, Siddharth Yarlagadda, Mohammadreza Movahhedi, Benedikt Proffen, Babak Dashtdar, Mahdi Aghaalikhani, Daniel Richard, Vicki Rosen, Ata M. Kiapour, Terence D. Capellini
Journal: Arthritis & Rheumatology (2025)

Objectives To reveal causal level osteoarthritis (OA) disease biology by targeting regulatory interactions at GDF5. Methods By investigating different GDF5 regulatory regions ( R2, R3‐5, R7‐R9, R18‐20, GROW1) we explored their functional impacts on gene expression and joint morphology in vivo and in vitro . We additionally modeled OA variants in said enhancers in vitro and in vivo mouse models for expression and disease effects. Results For all regulatory regions we found evidence of activation/repression between or within said regions that impacted patterns of joint‐specific expression. Examples are: (1) the R4 enhancer, whilst considered to be activating, has dual roles repressing expression in adjacent tissues and sites; and (2) Growth plate‐specific expression patterns by the GROW1 regulatory region are confined by adjacent sequences to restrict its expression to the perichondrium. We next targeted different regions/variants in vivo. Testing the R2de region resulted in ~40% reduction in Gdf5 expression, joint morphology changes, but no increase in OA risk; likewise, modeling the most cited OA risk (rs143384) variant in mice had no impact on expression, joint morphology, or disease. However, we identified epistatic interactions between this rs143384 risk variant and downstream disease risk variants lying within regulatory regions subject to repression, that compound to impact expression. Conclusions These findings, at the best studied OA locus to date, serve as lessons on the nature of how gene regulatory interactions and local epistasis work in the etiology of OA disease risk, and that assessment of individual variants of high GWAS significance need not alone be considered causal.
Dietary polyunsaturated fatty acid and the risk of rheumatoid arthritis: Insights from genetic predisposition and proteomics
Authors: Li Chen, Tianqi Tan, Yashu Chen, Feipeng Cui, Huimin Chen, Ying Zhao, Yuhan Tang, Xia Xiang, Qianchun Deng
Journal: Arthritis & Rheumatology (2025)

Objective To investigate the associations of polyunsaturated fatty acids (PUFAs) intakes with rheumatoid arthritis (RA) risk, alongside the role of genetic predisposition and the potential mediating effects of circulating proteins. Methods Utilizing data from 188,597 RA‐free participants in the UK Biobank, Cox proportional hazard models assessed the association of PUFAs intakes with RA risk. The polygenic risk score for RA further allowed evaluation of genetic predisposition's modifying effects. Olink proteomics identified protein signatures associated with PUFAs intakes and RA risk, with mediation analyses highlighting specific proteins as potential mediators. Results Over a median follow‐up for 9.1 years, 1,640 RA cases were documented. Each one‐standard deviation increase in the intakes of stearidonic acid (SDA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) reduced RA risk by 9%‐10%. Among individuals with high genetic risk, n‐3 PUFAs intakes (including SDA, EPA, DPA, and DHA) significantly decreased RA risk, with antagonistic additive interactions against genetic predisposition. Olink‐based proteomic analysis displayed that RA risk and specific n‐3 PUFAs intakes (DHA, DPA, and SDA) were primarily associated with immune response and inflammation, cytokine interactions, signal transduction, cell adhesion and migration, and metabolic pathways. Mediation analyses identified 55 mediating proteins involved in immune regulation, inflammation, and cell homeostasis. Notably, CD80 and TNFRSF4 emerged as vital mediators in the relationship between specific n‐3 PUFAs intakes and RA risk. Conclusion These findings indicated the potential benefits of n‐3 PUFAs intakes in reducing RA risk and provided new insights into the mechanisms by which n‐3 PUFAs influence RA risk. image
Characterization of arrhythmia‐induced cardiomyopathy using magnetic resonance imaging in patients with persistent atrial fibrillation and left ventricular systolic dysfunction – insights from <scp>DECAAF II</scp>
Authors: Ala Assaf, Han Feng, Mayana Bsoul, Ghassan Bidaoui, Hadi Younes, Christian Massad, Mario Mekhael, Charbel Noujaim, Omar Kreidieh, Swati Rao, Amitabh Pandey, Philipp Sommer, Christian Mahnkopf, Nassir Marrouche, Christian Sohns
Journal: European Journal of Heart Failure (2025)
CSDE1 enhances genotoxic drug resistance in cancer by modulating RPA2 through CSDE1-eIF3a regulatory complex
Authors: Jia-Jia Cui, Cheng-Xian Guo, Jun Li, Ao-Xiang Guo, Zhao Zhang, Si-Yu Li, Lei-Yun Wang, Xiang-Bin Jia, Hui Guo, Kun Xia, Zheng-Mao Hu, Qian-Ying Ouyang, Yang Wang, Yu-Ting Xie, Zhao-Qian Liu, Jian-Ting Zhang, Wei Wu, Yong-Heng Chen, Ji-Ye Yin
Journal: Drug Resistance Updates (2025)

Genotoxic drug resistance is one of the major obstacles for cancer treatment. Our previous study demonstrates that cold shock domain containing E1 (CSDE1) is associated with drug resistance. In this study, we aim to demonstrate that CSDE1 regulates cellular response to genotoxic drugs and to investigate its mechanism of action in drug resistance. Tissues and blood samples from cancer patients were used to evaluate the relationship between CSDE1 and genotoxic drug response. Comet and immunofluorescence assays were conducted to investigate the role of CSDE1 in DNA damage repair. Systematic knockout mouse models were used to study the underlying mechanism involved. Biotin pull-down, EMSA and co-IP assays were used to probe the triplex structure of CSDE1-protein (eIF3a)-RNA (RPA2). CSDE1 elevation correlates with poor response in patient and increased resistance in cell lines to genotoxic drugs. CSDE1 upregulated the nucleotide excision repair (NER) and homologous recombination (HR) pathways. In X-ray irradiation or bleomycin-induced DNA damage mouse model, systemic CSDE1 knockout resulted in increased DNA damage. In both a CSDE1 knockout mouse model and cancer cell lines, CSDE1 inhibited the cGAS-STING pathway through RPA2. Mechanistic studies indicated that CSDE1 serves as a hub for the binding of the CSDE1-protein (eIF3a)-RNA (RPA2) ternary complex. This study reveals the new role of CSDE1 in enhancing resistance to genotoxic drugs, and the detailed zipper-like cross ternary structural of CSDE1. It provides a new strategy for enhancing genotoxic drugs sensitivity.
CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury
Authors: Yong Chen, Xue Yuan, Wei Yan, Yurong Zou, Haoche Wei, Yuhan Wei, Minghai Tang, Yulian Chen, Ziyan Ma, Tao Yang, Kongjun Liu, Baojian Xiong, Xiuying Hu, Jianhong Yang, Lijuan Chen
Journal: Acta Pharmaceutica Sinica B (2025)
The potential application of stroma modulation in targeting tumor cells: focus on pancreatic cancer and breast cancer models
Authors: Giuseppina Roscigno, Sacha Jacobs, Belen Toledo, Roberto Borea, Gianluca Russo, Francesco Pepe, Maria Jose Serrano, Viola Calabrò, Giancarlo Troncone, Roberto Giovannoni, Elisa Giovannetti, Umberto Malapelle
Journal: Seminars in Cancer Biology (2025)
CD44 and αV-Integrins Dual-targeting Bimetallic Nanozymes for Lung Adenocarcinoma Therapy via NIR-Enhanced Ferroptosis/Apoptosis
Authors: Jingchuan He, Tingting Li, Xiaoqin Pan, Zhihua Deng, Jifu Huang, Xiaocheng Mo, Xiaoju Shen, Xiumei Qin, Xingye Yang, Ming Gao, Jie Yang
Journal: Biomaterials (2025)
Single-cell and spatial transcriptomics reveals an anti-tumor neutrophil subgroup in microwave thermochemotherapy-treated lip cancer
Authors: Bingjun Chen, Huayang Fan, Xin Pang, Zeliang Shen, Rui Gao, Haofan Wang, Zhenwei Yu, Tianjiao Li, Mao Li, Yaling Tang, Xinhua Liang
Journal: International Journal of Oral Science (2025)
Ending nuclear weapons, before they end us
Authors: Kamran Abbasi, Parveen Ali, Virginia Barbour, Marion Birch, Inga Blum, Peter Doherty, Andy Haines, Ira Helfand, Richard Horton, Kati Juva, Jose F Lapena, Robert Mash, Olga Mironova, Arun Mitra, Carlos Monteiro, Elena N Naumova, David Onazi, Tilman Ruff, Peush Sahni, James Tumwine, Carlos Umaña, Paul Yonga, Chris Zielinski
Journal: BMJ (2025)
Transforming women's health, empowerment, and gender equality with digital health: evidence-based policy and practice
Authors: Israel Júnior Borges do Nascimento, Hebatullah Mohamed Abdulazeem, Ishanka Weerasekara, Jodie Marquez, Lenny T Vasanthan, Genevieve Deeken, Rosemary Morgan, Heang-Lee Tan, Isabel Yordi Aguirre, Lasse Østeengaard, Indunil Kularathne, Natasha Azzopardi-Muscat, Robin van Kessel, Edson Zangiacomi Martinez, Govin Permanand, David Novillo-Ortiz
Journal: The Lancet Digital Health (2025)
Africa's renaissance amid declining overseas health aid
Authors: Nelson K Sewankambo, Hossein Akbarialiabad, Serigne Magueye Gueye, Sabrina Bakeera-Kitaka, Judy N Khanyola, Kiguli-Malwadde Elsie, Chiratidzo E Ndhlovu, Bruce Kirenga, Abigail Kazembe, Prisca Olabisi Adejumo, Majid Sadigh, Mosa Moshabela
Journal: The Lancet (2025)
Consensus position statement on advancing the classification of patients and tests of cure in studies of antibiotic treatment of complicated urinary tract infections
Authors: Truls E Bjerklund Johansen, Christina Bahrs, Franck Bruyere, Tommaso Cai, Amelia Joseph, Béla Köves, David M Livermore, Alessandra Oliva, Alex Soriano, Florian Wagenlehner, Per H Zahl, Manuel Etienne
Journal: The Lancet Infectious Diseases (2025)
Core GRADE 4: rating certainty of evidence—risk of bias, publication bias, and reasons for rating up certainty
Authors: Gordon Guyatt, Ying Wang, Prashanti Eachempati, Alfonso Iorio, M Hassan Murad, Monica Hultcrantz, Derek K Chu, Ivan D Florez, Lars G Hemkens, Thomas Agoritsas, Liang Yao, Per Olav Vandvik, Victor M Montori, Romina Brignardello-Petersen
Journal: BMJ (2025)
Effects of Janus kinase inhibitors in adults admitted to hospital due to COVID-19: a systematic review and individual participant data meta-analysis of randomised clinical trials
Authors: Alain Amstutz, Stefan Schandelmaier, Hannah Ewald, Benjamin Speich, Johannes M Schwenke, Christof M Schönenberger, Stephan Schobinger, Thomas Agoritsas, Kay M Tomashek, Seema Nayak, Mat Makowski, Alejandro Morales-Ortega, David Bernal-Bello, Giovanni Pomponio, Alessia Ferrarini, Monireh Ghazaeian, Frances Hall, Simon Bond, María Teresa García-Morales, María Jiménez-González, José R Arribas, Patricia O Guimaraães, Caio A M Tavares, Otavio Berwanger, Yazdan Yazdanpanah, Victoria C Simensen, Karine Lacombe, Maya Hites, Florence Ader, Evelina Tacconelli, France Mentré, Drifa Belhadi, Clément R Massonnaud, Cédric Laouénan, Alpha Diallo, Aliou Baldé, Lambert Assoumou, Dominique Costagliola, Erica Ponzi, Corina S Rueegg, Inge C Olsen, Marius Trøseid, Matthias Briel
Journal: The Lancet Respiratory Medicine (2025)
Erratum to ‘Diabetic Ketoacidosis During Lorlatinib Treatment: Case Report’ [Journal of Thoracic Oncology Volume 20, Issue 5 (2025) 676-679]
Authors: Atsushi Yanagisawa, Takayuki Shiroyama, Kotaro Miyake, Yoshito Takeda, Atsushi Kumanogoh
Journal: Journal of Thoracic Oncology (2025)