tbuckley/cabot-search huggingface dataset:
PCI in Patients Undergoing Transcatheter Aortic-Valve Implantation
Authors: Jacob Lønborg, Reza Jabbari, Muhammad Sabbah, Karsten T Veien, Matti Niemelä, Phillip Freeman, Rickard Linder, Dan Ioanes, Christian J Terkelsen, Olli A Kajander, Sasha Koul, Mikko Savontaus, Pasi Karjalainen, Andrejs Erglis, Mikko Minkkinen, Rikke Sørensen, Hans-Henrik Tilsted, Lene Holmvang, Gintautas Bieliauskas, Julia Ellert, Jarkko Piuhola, Ashkan Eftekhari, Oskar Angerås, Andreas Rück, Evald H Christiansen, Troels Jørgensen, Burcu T Özbek, Charlotte Glinge, Lars Søndergaard, Ole De Backer, Thomas Engstrøm
Journal: New England Journal of Medicine (2024)

BackgroundThe benefit of percutaneous coronary intervention (PCI) in patients with stable coronary artery disease and severe aortic stenosis who are undergoing transcatheter aortic-valve implantation (TAVI) remains unclear.MethodsIn an international trial, we randomly assigned, in a 1:1 ratio, patients with severe symptomatic aortic stenosis and at least one coronary-artery stenosis with a fractional flow reserve of 0.80 or less or a diameter stenosis of at least 90% either to undergo PCI or to receive conservative treatment, with all patients also undergoing TAVI. The primary end point was a major adverse cardiac event, defined as a composite of death from any cause, myocardial infarction, or urgent revascularization. Safety, including bleeding events and procedural complications, was assessed.ResultsA total of 455 patients underwent randomization: 227 to the PCI group and 228 to the conservative-treatment group. The median age of the patients was 82 years (interquartile range, 78 to 85), and the median Society of Thoracic Surgeons–Procedural Risk of Mortality score (on a scale from 0 to 100%, with higher scores indicating a greater risk of death within 30 days after the procedure) was 3% (interquartile range, 2 to 4). At a median follow-up of 2 years (interquartile range, 1 to 4), a major adverse cardiac event (primary end point) had occurred in 60 patients (26%) in the PCI group and in 81 (36%) in the conservative-treatment group (hazard ratio, 0.71; 95% confidence interval [CI], 0.51 to 0.99; P=0.04). A bleeding event occurred in 64 patients (28%) in the PCI group and in 45 (20%) in the conservative-treatment group (hazard ratio, 1.51; 95% CI, 1.03 to 2.22). In the PCI group, 7 patients (3%) had PCI procedure–related complications.ConclusionsAmong patients with coronary artery disease who were undergoing TAVI, PCI was associated with a lower risk of a composite of death from any cause, myocardial infarction, or urgent revascularization at a median follow-up of 2 years than conservative treatment. (Funded by Boston Scientific and the Danish Heart Foundation; NOTION-3 ClinicalTrials.gov number, NCT03058627.)
Cellular senescence and SASP in tumor progression and therapeutic opportunities
Authors: Zening Dong, Yahan Luo, Zhangchen Yuan, Yu Tian, Tianqiang Jin, Feng Xu
Journal: Molecular Cancer (2024)

Cellular senescence (CS), a permanent and irreversible arrest of the cell cycle and proliferation leading to the degeneration of cellular structure and function, has been implicated in various key physiological and pathological processes, particularly in cancer. Initially, CS was recognized as a barrier to tumorigenesis, serving as an intrinsic defense mechanism to protect cells from malignant transformation. However, increasing evidence suggests that senescent cells can promote tumor progression to overt malignancy, primarily through a set of factors known as senescence-associated secretory phenotypes (SASPs), including chemokines, growth factors, cytokines, and stromal metalloproteinases. These factors significantly reshape the tumor microenvironment (TME), enabling tumors to evade immune destruction. Interestingly, some studies have also suggested that SASPs may impede tumor development by enhancing immunosurveillance. These opposing roles highlight the complexity and heterogeneity of CS and SASPs in diverse cancers. Consequently, there has been growing interest in pharmacological interventions targeting CS or SASPs in cancer therapy, such as senolytics and senomorphics, to either promote the clearance of senescent cells or mitigate the harmful effects of SASPs. In this review, we will interpret the concept of CS, delve into the role of SASPs in reshaping the TME, and summarize recent advances in anti-tumor strategies targeting CS or SASPs.
An immunotherapeutic hydrogel booster inhibits tumor recurrence and promotes wound healing for postoperative management of melanoma
Authors: Yuanyuan Yang, Bo Zhang, Yangtao Xu, Wenxiang Zhu, Zinian Zhu, Xibo Zhang, Wenze Wu, Jierong Chen, Zhiqiang Yu
Journal: Bioactive Materials (2024)

Low tumor immunogenicity, immunosuppressive tumor microenvironment, and bacterial infections have emerged as significant challenges in postsurgical immunotherapy and skin regeneration for preventing melanoma recurrence. Herein, an immunotherapeutic hydrogel booster (GelMA-CJCNPs) was developed to prevent postoperative tumor recurrence and promote wound healing by incorporating ternary carrier-free nanoparticles (CJCNPs) containing chlorine e6 (Ce6), a BRD4 inhibitor (JQ1), and a glutaminase inhibitor (C968) into methacrylic anhydride-modified gelatin (GelMA) dressings. GelMA-CJCNPs reduced glutathione production by inhibiting glutamine metabolism, thereby preventing the destruction of reactive oxygen species generated by photodynamic therapy, which could amplify oxidative stress to induce severe cell death and enhance immunogenic cell death. In addition, GelMA-CJCNPs reduced M2-type tumor-associated macrophage polarization by blocking glutamine metabolism to reverse the immunosuppressive tumor microenvironment, recruiting more tumor-infiltrating T lymphocytes. GelMA-CJCNPs also downregulated IFN-γ-induced expression of programmed cell death ligand 1 to mitigate acquired immune resistance. Benefiting from the amplified systemic antitumor immunity, GelMA-CJCNPs markedly inhibited the growth of both primary and distant tumors. Moreover, GelMA-CJCNPs demonstrated satisfactory photodynamic antibacterial effects against
Split Thickness Skin Graft Transplantation Inspired by Paper-cutting: A Feasible Approach to Mitigating Surgical Misorientation in Vitiligo
Authors: Zhanghui Yue, Maxwell A Kishengere, Xun Zhou, Junhao Li, Yan Wang, Hengguang Zhao, Jianyun Lu, Dan Wang
Journal: Journal of the American Academy of Dermatology (2024)
Mechanism of staphylococcal resistance to clinically relevant antibiotics
Authors: Daniela Brdová, Tomáš Ruml, Jitka Viktorová
Journal: Drug Resistance Updates (2024)

Staphylococcus aureus, a notorious pathogen with versatile virulence, poses a significant challenge to current antibiotic treatments due to its ability to develop resistance mechanisms against a variety of clinically relevant antibiotics. In this comprehensive review, we carefully dissect the resistance mechanisms employed by S. aureus against various antibiotics commonly used in clinical settings. The article navigates through intricate molecular pathways, elucidating the mechanisms by which S. aureus evades the therapeutic efficacy of antibiotics, such as β-lactams, vancomycin, daptomycin, linezolid, etc. Each antibiotic is scrutinised for its mechanism of action, impact on bacterial physiology, and the corresponding resistance strategies adopted by S. aureus. By synthesising the knowledge surrounding these resistance mechanisms, this review aims to serve as a comprehensive resource that provides a foundation for the development of innovative therapeutic strategies and alternative treatments for S. aureus infections. Understanding the evolving landscape of antibiotic resistance is imperative for devising effective countermeasures in the battle against this formidable pathogen.
Responsive and Traceless Assembly of Iron Nanoparticles and 131I Labeled Radiopharmaceuticals for Ferroptosis Enhanced Radio-immunotherapy
Authors: Jingjing Shen, Kai Feng, Jing Yu, Yaxuan Zhao, Ruifang Chen, Hehua Xiong, Yiling Ruan, Zhengtao Xu, Tao Zhang, Xiaolian Sun
Journal: Biomaterials (2024)
Genetically engineered CD276-anchoring biomimetic nanovesicles target senescent escaped tumor cells to overcome chemoresistant and immunosuppressive breast cancer
Authors: Bin Liu, Minchao Lv, Yi Duan, Jiangtao Lin, Li Dai, Jian Yu, Jinghan Liao, Yuanyuan Li, Zhihua Wu, Jiping Li, Ying Sun, Hongze Liao, Jiali Zhang, Yourong Duan
Journal: Biomaterials (2024)
Investigating the Research Trajectory and Future Trends of Immune Disorders in Diabetes Cardiovascular Complications: A Bibliometric Analysis Over the Past Decade Based on Big Data
Authors: Xinglei Li, Zhou Xu, Tieqiu Huang, Yixin Jiang, Huan Wan, Deju Zhang, Jitao Ling, Yuting Wu, Xiao Liu, Pingping Yang, Linhua Fu, Jianping Liu, Jing Zhang, Peng Yu
Journal: Ageing Research Reviews (2024)
Mechanisms governing lineage plasticity and metabolic reprogramming in cancer
Authors: Lillian M. Perez, Smrruthi V. Venugopal, Anna St Martin, Stephen J. Freedland, Dolores Di Vizio, Michael R. Freeman
Journal: Trends in cancer (2024)

Dynamic alterations in cellular phenotypes during cancer progression are attributed to a phenomenon known as 'lineage plasticity'. This process is associated with therapeutic resistance and involves concurrent shifts in metabolic states that facilitate adaptation to various stressors inherent in malignant growth. Certain metabolites also serve as synthetic reservoirs for chromatin modification, thus linking metabolic states with epigenetic regulation. There remains a critical need to understand the mechanisms that converge on lineage plasticity and metabolic reprogramming to prevent the emergence of lethal disease. This review attempts to offer an overview of our current understanding of the interplay between metabolic reprogramming and lineage plasticity in the context of cancer, highlighting the intersecting drivers of cancer hallmarks, with an emphasis on solid tumors.
Continuation versus Interruption of Oral Anticoagulation during TAVI
Authors: Dirk Jan van Ginkel, Willem L Bor, Hugo M Aarts, Christophe Dubois, Ole De Backer, Maxim J P Rooijakkers, Liesbeth Rosseel, Leo Veenstra, Frank van der Kley, Kees H van Bergeijk, Nicolas M Van Mieghem, Pierfrancesco Agostoni, Michiel Voskuil, Carl E Schotborgh, Alexander J J IJsselmuiden, Jan A S Van Der Heyden, Renicus S Hermanides, Emanuele Barbato, Darren Mylotte, Enrico Fabris, Peter Frambach, Karl Dujardin, Bert Ferdinande, Joyce Peper, Benno J W M Rensing, Leo Timmers, Martin J Swaans, Jorn Brouwer, Vincent J Nijenhuis, Daniel C Overduin, Tom Adriaenssens, Yusuke Kobari, Pieter A Vriesendorp, Jose M Montero-Cabezas, Hicham El Jattari, Jonathan Halim, Ben J L Van den Branden, Remigio Leonora, Marc Vanderheyden, Michael Lauterbach, Joanna J Wykrzykowska, Arnoud W J van 't Hof, Niels van Royen, Jan G P Tijssen, Ronak Delewi, Jurriën M Ten Berg
Journal: New England Journal of Medicine (2024)

BackgroundOne third of patients undergoing transcatheter aortic-valve implantation (TAVI) have an indication for oral anticoagulation owing to concomitant diseases. Interruption of oral anticoagulation during TAVI may decrease the risk of bleeding, whereas continuation may decrease the risk of thromboembolism.MethodsWe conducted an international, open-label, randomized, noninferiority trial involving patients who were receiving oral anticoagulants and were planning to undergo TAVI. Patients were randomly assigned in a 1:1 ratio to periprocedural continuation or interruption of oral anticoagulation. The primary outcome was a composite of death from cardiovascular causes, stroke from any cause, myocardial infarction, major vascular complications, or major bleeding within 30 days after TAVI.ResultsA total of 858 patients were included in the modified intention-to-treat population: 431 were assigned to continuation and 427 to interruption of oral anticoagulation. A primary-outcome event occurred in 71 patients (16.5%) in the continuation group and in 63 (14.8%) in the interruption group (risk difference, 1.7 percentage points; 95% confidence interval [CI], −3.1 to 6.6; P=0.18 for noninferiority). Thromboembolic events occurred in 38 patients (8.8%) in the continuation group and in 35 (8.2%) in the interruption group (risk difference, 0.6 percentage points; 95% CI, −3.1 to 4.4). Bleeding occurred in 134 patients (31.1%) in the continuation group and in 91 (21.3%) in the interruption group (risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6).ConclusionsIn patients undergoing TAVI with a concomitant indication for oral anticoagulation, periprocedural continuation was not noninferior to interruption of oral anticoagulation during TAVI with respect to the incidence of a composite of death from cardiovascular causes, stroke, myocardial infarction, major vascular complications, or major bleeding at 30 days. (Funded by the Netherlands Organization for Health Research and Development and the St. Antonius Research Fund; POPular PAUSE TAVI ClinicalTrials.gov number, NCT04437303.)
Heart failure treatment in the last years of life: A nationwide study of 364 000 individuals
Authors: Johan Sundström, Stefan Gustafsson, Thomas Cars, Daniel Lindholm
Journal: European Journal of Heart Failure (2024)

Aims In patients with heart failure, treatment patterns in the last years of life have not been assessed at large scale. We aimed to assess whether heart failure treatment patterns up to 5 years prior to death changed over time. Methods and results In a cohort study covering the whole Swedish population, we assessed all heart failure patients who died between 1 July 2007 and 31 December 2020 for evidence‐based treatments. The proportion on the respective treatment at the time of death was examined by year of death using binomial regression. Looking back in time, treatment discontinuation rates were estimated using Poisson regression on time‐split data. Combining these models, the proportion on each medication was estimated up to 5 years prior to death. A total of 364 480 patients died with heart failure during the study period. Half were women, and the median (interquartile range) age at death was 86 (79–90). The use of all heart failure treatments decreased gradually closer to death, but the discontinuation rate of beta blockers decreased over time, resulting in an increasing proportion of patients on treatment at the time of death. Conclusion In patients with heart failure, a changing pattern of medical treatment during the last years of life was observed, most notably with an increasing use of beta blockers. This may in part be due to a changing pattern of comorbidities over time, with an increase in e.g. hypertension and atrial fibrillation, but a decline in ischaemic heart disease.
Excess Mortality and Hospitalizations Associated With Seasonal Influenza in Patients With Heart Failure
Authors: Daniel Modin, Brian Claggett, Niklas Dyrby Johansen, Scott D Solomon, Ramona Trebbien, Thyra Grove Krause, Jens-Ulrik Stæhr Jensen, Mikkel Porsborg Andersen, Gunnar Gislason, Tor Biering-Sørensen
Journal: Journal of the American College of Cardiology (2024)
Aspirin Monotherapy vs No Antiplatelet Therapy in Stable Patients With Coronary Stents Undergoing Low-to-Intermediate Risk Noncardiac Surgery
Authors: Do-Yoon Kang, Sang-Hyup Lee, Se-Whan Lee, Cheol Hyun Lee, Choongki Kim, Ji-Yong Jang, Nihar Mehta, Jun-Hyok Oh, Young Rak Cho, Kyung Ho Yoon, Sung Gyun Ahn, Jung-Hee Lee, Deok-Kyu Cho, Yongcheol Kim, Jeongsu Kim, Gyeong Hun Cho, Kyu-Sup Lee, Hanbit Park, Mutlu Vural, Young-Hyo Lim, Kyoung-Ha Park, Bong-Ki Lee, Jong-Young Lee, Hyun-Woo Park, Yong-Hoon Yoon, Jae-Hwan Lee, Seung-Yul Lee, Kyung Woo Park, Jeehoon Kang, Hyun Kuk Kim, Si-Hyuck Kang, Jae-Hyoung Park, In-Cheol Choi, Chang Sik Yu, Sung-Cheol Yun, Duk-Woo Park, Myeong-Ki Hong, Seung-Jung Park, Jung-Sun Kim, Jung-Min Ahn
Journal: Journal of the American College of Cardiology (2024)

Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited.
Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction With or Without ST-Segment Elevation
Authors: Marta Cocco, Gianluca Campo, Vincenzo Guiducci, Gianni Casella, Caterina Cavazza, Enrico Cerrato, Giorgio Sacchetta, Raul Moreno, Alberto Menozzi, Ignacio Amat Santos, José Luis Díez Gil, Roberto Scarsini, Andrea Picchi, Giuseppe Vadalà, Gerlando Pilato, Iginio Colaiori, Marco Barbierato, Manfredi Arioti, Rita Pavasini, Valerio Lanzilotti, Mila Menozzi, Ferdinando Varbella, Andrea Erriquez, Simone Biscaglia
Journal: Journal of the American College of Cardiology (2024)
Activation and inhibition of sirtuins: From bench to bedside
Authors: Francesco Fiorentino, Emanuele Fabbrizi, Antonello Mai, Dante Rotili
Journal: Medicinal Research Reviews (2024)

Abstract The sirtuin family comprises seven NAD + ‐dependent enzymes which catalyze protein lysine deacylation and mono ADP‐ribosylation. Sirtuins act as central regulators of genomic stability and gene expression and control key processes, including energetic metabolism, cell cycle, differentiation, apoptosis, and aging. As a result, all sirtuins play critical roles in cellular homeostasis and organism wellness, and their dysregulation has been linked to metabolic, cardiovascular, and neurological diseases. Furthermore, sirtuins have shown dichotomous roles in cancer, acting as context‐dependent tumor suppressors or promoters. Given their central role in different cellular processes, sirtuins have attracted increasing research interest aimed at developing both activators and inhibitors. Indeed, sirtuin modulation may have therapeutic effects in many age‐related diseases, including diabetes, cardiovascular and neurodegenerative disorders, and cancer. Moreover, isoform selective modulators may increase our knowledge of sirtuin biology and aid to develop better therapies. Through this review, we provide critical insights into sirtuin pharmacology and illustrate their enzymatic activities and biological functions. Furthermore, we outline the most relevant sirtuin modulators in terms of their modes of action, structure–activity relationships, pharmacological effects, and clinical applications.
MED12 loss activates endogenous retroelements to sensitise immunotherapy in pancreatic cancer
Authors: Yingying Tang, Shijie Tang, Wenjuan Yang, Zhengyan Zhang, Teng Wang, Yuyun Wu, Junyi Xu, Christian Pilarsky, Massimiliano Mazzone, Lei-Wei Wang, Yongwei Sun, Ruijun Tian, Yujie Tang, Yu Wang, Chaochen Wang, Jing Xue
Journal: Gut (2024)

Objective Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal cancers, marked by its lethality and limited treatment options, including the utilisation of checkpoint blockade (ICB) immunotherapy. Epigenetic dysregulation is a defining feature of tumourigenesis that is implicated in immune surveillance, but remains elusive in PDAC. Design To identify the factors that modulate immune surveillance, we employed in vivo epigenetic-focused CRISPR-Cas9 screen in mouse PDAC tumour models engrafted in either immunocompetent or immunodeficient mice. Results Here, we identified MED12 as a top hit, emerging as a potent negative modulator of immune tumour microenviroment (TME) in PDAC. Loss of Med12 significantly promoted infiltration and cytotoxicity of immune cells including CD8 + T cells, natural killer (NK) and NK1.1 + T cells in tumours, thereby heightening the sensitivity of ICB treatment in a mouse model of PDAC. Mechanistically, MED12 stabilised heterochromatin protein HP1A to repress H3K9me3-marked endogenous retroelements. The derepression of retrotransposons induced by MED12 loss triggered cytosolic nucleic acid sensing and subsequent activation of type I interferon pathways, ultimately leading to robust inflamed TME . Moreover, we uncovered a negative correlation between MED12 expression and immune resposne pathways, retrotransposon levels as well as the prognosis of patients with PDAC undergoing ICB therapy. Conclusion In summary, our findings underscore the pivotal role of MED12 in remodelling immnue TME through the epigenetic silencing of retrotransposons, offering a potential therapeutic target for enhancing tumour immunogenicity and overcoming immunotherapy resistance in PDAC.
Predicting Long-Term Clinical Outcomes of Patients With Recurrent Pericarditis
Authors: Abdullah Yesilyaprak, Ashwin K Kumar, Ankit Agrawal, Muhammad M Furqan, Beni R Verma, Alveena B Syed, Muhammad Majid, Kevser Akyuz, Danny L Rayes, David Chen, Tom Kai Ming Wang, Paul C Cremer, Allan L Klein
Journal: Journal of the American College of Cardiology (2024)
Meningeal lymphatic function promotes oligodendrocyte survival and brain myelination
Authors: Sofia P das Neves, Nickoleta Delivanoglou, Yingxue Ren, Chiara Starvaggi Cucuzza, Mateusz Makuch, Francisco Almeida, Guadalupe Sanchez, Megan J Barber, Shanon Rego, Racquelle Schrader, Ayman H Faroqi, Jean-Leon Thomas, Pamela J McLean, Tiago Gil Oliveira, Sarosh R Irani, Fredrik Piehl, Sandro Da Mesquita
Journal: Immunity (2024)
Serial Shock Severity Assessment Within 72 Hours After Diagnosis
Authors: Van-Khue Ton, Song Li, Kevin John, Borui Li, Elric Zweck, Manreet K Kanwar, Shashank S Sinha, Jaime Hernandez-Montfort, A Reshad Garan, Rachel Goodman, Anthony Faugno, Maryjane Farr, Shelley Hall, Rachna Kataria, Maya Guglin, Esther Vorovich, Mohit Pahuja, Saraschandra Vallabhajosyula, Sandeep Nathan, Jacob Abraham, Neil M Harwani, Gavin W Hickey, Andrew D Schwartzman, Wissam Khalife, Claudius Mahr, Ju H Kim, Arvind Bhimaraj, Paavni Sangal, Qiuyue Kong, Karol D Walec, Peter Zazzali, Justin Fried, Daniel Burkhoff, Navin K Kapur
Journal: Journal of the American College of Cardiology (2024)
De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: a systematic review and individual patient-level meta-analysis of randomised trials
Authors: Marco Valgimigli, Sung-Jin Hong, Felice Gragnano, Konstantina Chalkou, Anna Franzone, Bruno R da Costa, Usman Baber, Byeong-Keuk Kim, Yangsoo Jang, Shao-Liang Chen, Gregg W Stone, Joo-Yong Hahn, Stephan Windecker, Michael C Gibson, Young Bin Song, Zhen Ge, Pascal Vranckx, Shamir Mehta, Hyeon-Cheol Gwon, Renato D Lopes, George D Dangas, Eùgene P McFadden, Dominick J Angiolillo, Sergio Leonardi, Dik Heg, Paolo Calabrò, Peter Jüni, Roxana Mehran, Myeong-Ki Hong
Journal: The Lancet (2024)
Race in Heart Failure
Authors: Henri Lu, Brian L. Claggett, Milton Packer, Maria A. Pabon, Marc A. Pfeffer, Eldrin F. Lewis, Carolyn S.P. Lam, Jean Rouleau, Michael R. Zile, Martin Lefkowitz, Akshay S. Desai, Pardeep S. Jhund, John J.V. McMurray, Scott D. Solomon, Muthiah Vaduganathan
Journal: JACC Heart Failure (2024)