tbuckley/cabot-search huggingface dataset:
Effects of Sacubitril/Valsartan on All-Cause Hospitalizations in Heart Failure
Authors: Henri Lu, Brian L. Claggett, Milton Packer, Carolyn S. P. Lam, Karl Swedberg, Jean Rouleau, Michael R. Zile, Martin Lefkowitz, Akshay S. Desai, Pardeep Jhund, John J. V. McMurray, Scott D. Solomon, Muthiah Vaduganathan
Journal: JAMA Cardiology (2024)

Sacubitril/valsartan is indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalizations in patients with chronic HF. However, many of these patients are older and have multiple comorbidities that increase the risk of hospitalization for causes other than HF.
Effect of Semaglutide on Cardiac Structure and Function in Patients With Obesity-Related Heart Failure
Authors: Scott D Solomon, John W Ostrominski, Xiaowen Wang, Sanjiv J Shah, Barry A Borlaug, Javed Butler, Melanie J Davies, Dalane W Kitzman, Subodh Verma, Steen Z Abildstrøm, Mette Nygaard Einfeldt, Søren Rasmussen, Walter P Abhayaratna, Fozia Z Ahmed, Tuvia Ben-Gal, Vijay Chopra, Hiroshi Ito, Bela Merkely, Julio Núñez, Michele Senni, Peter van der Meer, Dennis Wolf, Mark C Petrie, Mikhail N Kosiborod
Journal: Journal of the American College of Cardiology (2024)

Obesity is associated with adverse cardiac remodeling and is a key driver for the development and progression of heart failure (HF). Once-weekly semaglutide (2.4 mg) has been shown to improve HF-related symptoms and physical limitations, body weight, and exercise function in patients with obesity-related heart failure with preserved ejection fraction (HFpEF), but the effects of semaglutide on cardiac structure and function in this population remain unknown.
Atrial Fibrillation and Semaglutide Effects in Obesity-Related Heart Failure With Preserved Ejection Fraction
Authors: Subodh Verma, Javed Butler, Barry A. Borlaug, Melanie J. Davies, Dalane W. Kitzman, Mark C. Petrie, Sanjiv J. Shah, Thomas Jon Jensen, Søren Rasmussen, Cecilia Rönnbäck, Bela Merkely, Evan O’Keefe, Mikhail N. Kosiborod
Journal: Journal of the American College of Cardiology (2024)

Obesity is a key factor in the development and progression of both heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). In the STEP-HFpEF Program (comprising the STEP-HFpEF [Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity] and STEP-HFpEF DM [Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes] trials), once-weekly semaglutide 2.4 mg improved HF-related symptoms, physical limitations, and exercise function and reduced body weight in patients with obesity-related HFpEF. Whether the effects of semaglutide in this patient group differ in participants with and without AF (and across various AF types) has not been fully examined.
Fungal Enzyme‐Responsive Hydrogel Drug Delivery Platform for Triggered Antifungal Release
Authors: Noel Vera‐González, Carly Deusenbery, Veronica LaMastro, Anita Shukla
Journal: Advanced Healthcare Materials (2024)

Abstract Fungal infections can lead to debilitating consequences if they are not treated effectively. Antifungal drugs used to treat these infections can be toxic and overuse contributes to growing antifungal resistance. Candida spp., particularly C. albicans , are implicated in a majority of these infections. Virulent C. albicans produce secreted aspartic proteases (Saps) that aid in pathogen tissue invasion and proliferation at an infected site. Here, fungi‐responsive hydrogels are developed that degrade in the presence of Saps to provide a triggered release of encapsulated liposomal antifungals. The hydrogel backbone incorporates a Sap‐cleavable peptide sequence enabling Sap‐responsive degradation. Hydrogels are found to effectively degrade in the presence of Saps extracted from C. albicans . Encapsulated liposomal antifungals show similar release kinetics as hydrogel degradation products in the presence of Saps, supporting a degradation‐dependent release mechanism. Antifungal liposome‐loaded responsive hydrogels exhibit successful eradication of C. albicans cultures and remain stable in sterile murine wound fluid. Finally, no significant cytotoxicity is observed for murine fibroblast cells and red blood cells exposed to hydrogel degradation products. These fungi‐responsive hydrogels have the potential to be used for local, on‐demand delivery of antifungal drugs, for effective treatment of fungal infections while helping to limit unnecessary exposure to these therapeutics.
Neuroprotection on ischemic brain injury by Mg2+/H2 released from endovascular Mg implant
Authors: Yang Zhang, Hongkang Zhang, Miaowen Jiang, Xiaofeng Cao, Xiaoxiao Ge, Baoying Song, Jing Lan, Wenhao Zhou, Zhengfei Qi, Xuenan Gu, Juzhe Liu, Yufeng Zheng, Ming Li, Xunming Ji
Journal: Bioactive Materials (2024)
Impact of somatic gene mutations on the risk of thrombosis in myelofibrosis
Authors: Irene Pastor-Galán, Arturo Pereira, Eduardo Arellano-Rodrigo, Iván Martín, Adrián Mosquera-Orgueira, María-Teresa Gómez-Casares, Alberto Hernández-Sánchez, Francisca Ferrer-Marín, Elvira Mora, Patricia Velez, Rosa Ayala, Anna Angona, Natalia de las Heras, Elena Magro, María-Isabel Mata-Vázquez, María-Laura Fox, Sonia González de Villambrosía, María-José Ramírez, Ana García, Valentín García-Gutiérrez, Amparo Cáceres, María-Antonia Durán, María-Alicia Senín, José-María Raya, José Antonio González, Beatriz Cuevas, Blanca Xicoy, Marta Garrote, Blanca Ferrer, Manuel Pérez-Encinas, Jesús María Hernández-Rivas, Beatriz Bellosillo, Alberto Álvarez-Larrán, Juan Carlos Hernández-Boluda
Journal: Leukemia (2024)
IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma
Authors: Jennifer Sun, Stefan Corradini, Feda Azab, Monica Shokeen, Barbara Muz, Katerina E. Miari, Mina Maksimos, Camila Diedrich, Obed Asare, Kinan Alhallak, Chaelee Park, Berit Lubben, Yixuan Chen, Ola Adebayo, Hannah Bash, Sarah Kelley, Mark Fiala, Diane E. Bender, Haibin Zhou, Shaomeng Wang, Ravi Vij, Mark T. S. Williams, Abdel Kareem Azab
Journal: Leukemia (2024)

Multiple myeloma (MM) is the cancer of plasma cells within the bone marrow and remains incurable. Tumor-associated macrophages (TAMs) within the tumor microenvironment often display a pro-tumor phenotype and correlate with tumor proliferation, survival, and therapy resistance. IL-10 is a key immunosuppressive cytokine that leads to recruitment and development of TAMs. In this study, we investigated the role of IL-10 in MM TAM development as well as the therapeutic application of IL-10/IL-10R/STAT3 signaling inhibition. We demonstrated that IL-10 is overexpressed in MM BM and mediates M2-like polarization of TAMs in patient BM, 3D co-cultures in vitro, and mouse models. In turn, TAMs promote MM proliferation and drug resistance, both in vitro and in vivo. Moreover, inhibition of IL-10/IL-10R/STAT3 axis using a blocking IL-10R monoclonal antibody and STAT3 protein degrader/PROTAC prevented M2 polarization of TAMs and the consequent TAM-induced proliferation of MM, and re-sensitized MM to therapy, in vitro and in vivo. Therefore, our findings suggest that inhibition of IL-10/IL-10R/STAT3 axis is a novel therapeutic strategy with monotherapy efficacy and can be further combined with current anti-MM therapy, such as immunomodulatory drugs, to overcome drug resistance. Future investigation is warranted to evaluate the potential of such therapy in MM patients.
Obstructive sleep apnea and obesity: A review of epidemiology, pathophysiology and the effect of weight-loss treatments
Authors: Ludovico Messineo, Jessie P Bakker, John Cronin, John Yee, David P White
Journal: Sleep Medicine Reviews (2024)

Despite the commonly-accepted paradigm that patients with obstructive sleep apnea (OSA) also invariably have obesity, OSA prevalence extends beyond obesity. This necessitates a reevaluation of screening strategies, biomarkers of increased OSA risk, and heightened awareness among healthcare providers about the array of OSA treatments for diverse adult populations. While obesity contributes importantly to OSA pathogenesis, there is substantial evidence that non-anatomical factors also play a crucial role, especially in patients who do not have obesity. In recent years, notwithstanding the recognition of diverse contributors to OSA pathogenesis, research has frequently focused on weight reduction to address OSA. Insights from past experiences with bariatric surgery in OSA serve as a lens to anticipate potential outcomes of emerging anti-obesity pharmacotherapies. Pharmacological alternatives, particularly incretin agonists, exhibit promise in weight reduction and OSA improvement, but encounter obstacles such as potential side effects and high costs. With this comprehensive narrative review, we delve into the complex epidemiological and pathophysiological connections between OSA and obesity. Additionally, we emphasize the importance of a multifaceted approach to OSA treatment, recognizing that while weight management is crucial, there is a need for comprehensive strategies that go beyond traditional weight-centric perspectives.
Interplay of multiple carbapenemases and tigecycline resistance in Acinetobacter species: a serious combined threat
Authors: Xinyang Li, Yilu Zhuang, Yawen Yu, Huiqiong Jia, Yingying Kong, Jun Zhang, Xinyou Xie, Eliana Guedes Stehling, João Pedro Rueda Furlan, Zhemin Zhou, Zhi Ruan
Journal: Clinical Microbiology and Infection (2024)
Bispecific antibodies: advancing precision oncology
Authors: Mercedes Herrera, Giulia Pretelli, Jayesh Desai, Elena Garralda, Lillian L Siu, Thiago M Steiner, Lewis Au
Journal: Trends in cancer (2024)

Bispecific antibodies (bsAbs) are engineered molecules designed to target two different epitopes or antigens. The mechanism of action is determined by the bsAb molecular targets and structure (or format), which can be manipulated to create variable and novel functionalities, including linking immune cells with tumor cells, or dual signaling pathway blockade. Several bsAbs have already changed the treatment landscape of hematological malignancies and select solid cancers. However, the mechanisms of resistance to these agents are understudied and the management of toxicities remains challenging. Herein, we review the principles in bsAb engineering, current understanding of mechanisms of action and resistance, data for clinical application, and provide a perspective on ongoing challenges and future developments in this field.
Late effects after allogeneic haematopoietic cell transplantation in children and adolescents with non-malignant disorders: a retrospective cohort study
Authors: Justine Kahn, Ruta Brazauskas, Stephanie Bo-Subait, David Buchbinder, Betty K Hamilton, Hélène Schoemans, Allistair A Abraham, Vaibhav Agrawal, Jeffery J Auletta, Sherif M Badawy, Amer Beitinjaneh, Neel S Bhatt, Larisa Broglie, Miguel Angel Diaz Perez, Nosha Farhadfar, Cesar O Freytes, Robert Peter Gale, Siddhartha Ganguly, Robert J Hayashi, Peiman Hematti, Gerhard C Hildebrandt, Yoshihiro Inamoto, Rammurti T Kamble, Jane Koo, Hillard M Lazarus, Samantha J Mayo, Parinda A Mehta, Kasiani C Myers, Taiga Nishihori, Tim Prestidge, Seth J Rotz, Bipin N Savani, Raquel M Schears, Akshay Sharma, Elizabeth Stenger, Celalettin Ustun, Kirsten M Williams, Lynda M Vrooman, Prakash Satwani, Rachel Phelan
Journal: The Lancet Child & Adolescent Health (2024)
Cyclic catalysis of intratumor Fe3+/2+ initiated by a hollow mesoporous iron sesquioxide nanoparticle for ferroptosis therapy of large tumors
Authors: Jing Yang, Bin Ren, Haobin Cai, Wei Xiong, Jie Feng, Qingdeng Fan, Zongheng Li, Lin Huang, Chenggong Yan, Yan Li, Chaomin Chen, Zheyu Shen
Journal: Biomaterials (2024)
Targeting m7G-enriched circKDM1A prevents colorectal cancer progression
Authors: Zhenqiang Sun, Yanxin Xu, Chaohua Si, Xiaoke Wu, Yaxin Guo, Chen Chen, Chengzeng Wang
Journal: Molecular Cancer (2024)

Plenty of circRNAs have been reported to play an important role in colorectal cancer (CRC), while the reason of abnormal circRNA expression in cancer still keep elusive. Here, we found that m7G RNA modifications were enriched in some circRNAs, these m7G modifications in circRNAs were catalyzed by METTL1, and the GG motif was the main site preference for m7G modifications in circRNAs. We further confirmed that METTL1 played a cancer-promoting role in CRC. We then screened a highly expressed circRNA, called circKDM1A, and found that METTL1 prevented the degradation of circKDM1A by m7G modification. CircKDM1A was further verified to promote proliferation, invasion and migration of CRC in vivo and in vitro. Its cancer-promoting ability was weakened after the m7G site mutation. CircKDM1A was verified to activate AKT pathway by upregulating PDK1, consequently promoting CRC progression. These results suggest that m7G-modified circRNA promotes CRC progression via activating AKT pathway. Our study uncovers an essential physiological function and mechanism of METTL1-mediated m7G modification in the regulation of circRNA stability and cancer progression.
Writers, readers, and erasers RNA modifications and drug resistance in cancer
Authors: Di Chen, Xinyu Gu, Yeltai Nurzat, Lixia Xu, Xueyuan Li, Lixin Wu, Henan Jiao, Peng Gao, Xuqiang Zhu, Dongming Yan, Shaohua Li, Chen Xue
Journal: Molecular Cancer (2024)

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing to this resistance is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing. These modifications are pivotal in regulating RNA splicing, translation, transport, degradation, and stability. Governed by "writers," "readers," and "erasers," RNA modifications impact numerous biological processes and cancer progression, including cell proliferation, stemness, autophagy, invasion, and apoptosis. Aberrant RNA modifications can lead to drug resistance and adverse outcomes in various cancers. Thus, targeting RNA modification regulators offers a promising strategy for overcoming drug resistance and enhancing treatment efficacy. This review consolidates recent research on the role of prevalent RNA modifications in cancer drug resistance, with a focus on m6A, m1A, m5C, m7G, Ψ, and A-to-I editing. Additionally, it examines the regulatory mechanisms of RNA modifications linked to drug resistance in cancer and underscores the existing limitations in this field.
Immune modulatory microRNAs in tumors, their clinical relevance in diagnosis and therapy
Authors: Christoforos Vaxevanis, Michael Bachmann, Barbara Seliger
Journal: Journal for ImmunoTherapy of Cancer (2024)

The importance of the immune system in regulating tumor growth by inducing immune cell-mediated cytotoxicity associated with patients' outcomes has been highlighted in the past years by an increasing life expectancy in patients with cancer on treatment with different immunotherapeutics. However, tumors often escape immune surveillance, which is accomplished by different mechanisms. Recent studies demonstrated an essential role of small non-coding RNAs, such as microRNAs (miRNAs), in the post-transcriptional control of immune modulatory molecules. Multiple methods have been used to identify miRNAs targeting genes involved in escaping immune recognition including miRNAs targeting CTLA-4, PD-L1, HLA-G, components of the major histocompatibility class I antigen processing machinery (APM) as well as other immune response-relevant genes in tumors. Due to their function, these immune modulatory miRNAs can be used as (1) diagnostic and prognostic biomarkers allowing to discriminate between tumor stages and to predict the patients' outcome as well as response and resistance to (immuno) therapies and as (2) therapeutic targets for the treatment of tumor patients. This review summarizes the role of miRNAs in tumor-mediated immune escape, discuss their potential as diagnostic, prognostic and predictive tools as well as their use as therapeutics including alternative application methods, such as chimeric antigen receptor T cells.
Myeloperoxidase-ANCA IgG induces different forms of small vessel vasculitis based on type of synergistic immune stimuli.
Authors: Peiqi Hu, Hong Xiao, Marco A Alba, Hannah M Atkins, Shenju Gou, Yanglin Hu, John C Gomez, Corey M Jania, Jessica R Martin, Thomas E Morrison, Stephen L Tilley, Mark T Heise, Claire M Doerschuk, Ronald J Falk, J Charles Jennette
Journal: Kidney International (2024)
Decreased serum levels of IL-4 correlate with the efficacy of the PAI-1 inhibitor TM5614 in patients with malignant melanoma refractory to anti-PD-1 antibodies: post hoc study of TM5614-MM trial
Authors: Emi Yamazaki, Taku Fujimura, Manami Takahashi- Watanabe, Satsuki Tada, Chisako Kitayama, Ryo Amagai, Yumi Kambayashi, Masahiro Watanabe, Masamitsu Maekawa, Nariyasu Mano, Yoshihide Asano
Journal: British Journal of Dermatology (2024)

We previously reported that the combination of the PAI-1 inhibitor TM5614 and nivolumab resulted in a 25.9% response rate in patients with anti-PD-1 antibody failure, . We therefore comprehensively evaluated serum levels of chemokines and cytokines from patients enrolled in the protocol per set cohort of the TM5614-MM clinical trial (jRCT2021210029). Our present study revealed significant reductions in IL-4, IL-16, and CXCL2 in the response group treated with TM5614.Our findings suggest that the induction of an anti-tumor response in our previous clinical trial is due to the activation of TAMs through the blockade of M2 polarization and the reduction of mo-MDSCs in the tumor-bearing host.
Natriuretic peptides, kidney function and clinical outcomes in heart failure with preserved ejection fraction
Authors: Brendon L Neuen, Muthiah Vaduganathan, Brian L Claggett, Iris Beldhuis, Peder Myhre, Akshay S Desai, Hicham Skali, Finnian R Mc Causland, Martina McGrath, Inder Anand, Michael R Zile, Marc A Pfeffer, John J V McMurray, Scott D Solomon
Journal: JACC Heart Failure (2024)

N-terminal pro-B-type natriuretic peptides (NT-proBNPs) are guideline-recommended biomarkers for risk stratification in patients with heart failure. However, NT-proBNP levels are often elevated in chronic kidney disease, introducing uncertainty about their prognostic relevance in persons across a broad range of estimated glomerular filtration rate (eGFR).
Bidirectional Relationship Between Kidney Disease Progression and Cardiovascular Events in Type 2 Diabetes
Authors: Brendon L. Neuen, John W. Ostrominski, Brian Claggett, Iris E. Beldhuis, Safia Chatur, Finnian R. McCausland, Sunil V. Badve, Clare Arnott, Hiddo J.L. Heerspink, Min Jun, Michael Falster, Juliana de Oliveira Costa, Carol Pollock, Meg J. Jardine, Kenneth W. Mahaffey, Vlado Perkovic, Scott D. Solomon, Muthiah Vaduganathan
Journal: Journal of the American College of Cardiology (2024)
Moral Injury and the Global Health Workforce Crisis — Insights from an International Partnership
Authors: Wendy Dean, Deborah Morris, Pierre-Michel Llorca, Simon G Talbot, Guillaume Fond, Antoine Duclos, Laurent Boyer
Journal: New England Journal of Medicine (2024)

With health care workforces in the United States and Europe shrinking at unsustainable rates, it's vital to understand the drivers of moral injury so that solutions can be developed.
Impact of Renal &amp; Liver Function on Clinical Outcomes Following Tricuspid Valve Transcatheter Edge-to-Edge Repair
Authors: Ulrich P Jorde, Raymond Benza, Patrick M McCarthy, Gorav Ailawadi, Brian Whisenant, Raj Makkar, Peter Tadros, Hursh Naik, Neil Fam, Andrew J Sauer, Sandhya Murthy, Saibal Kar, Ralph Stephan von Bardeleben, Rebecca T Hahn, Nadira Hamid, Jacob Zbinden, Paul Sorajja, David Adams
Journal: Journal of the American College of Cardiology (2024)
Optical coherence tomography angiography of the retina and choroid in systemic diseases
Authors: Jacqueline Chua, Bingyao Tan, Damon Wong, Gerhard Garhöfer, Xin Wei Liew, Alina Popa-Cherecheanu, Calvin Woon Loong Chin, Dan Milea, Christopher Li-Hsian Chen, Leopold Schmetterer
Journal: Progress in Retinal and Eye Research (2024)

Optical coherence tomography angiography (OCTA) has transformed ocular vascular imaging, revealing microvascular changes linked to various systemic diseases. This review explores its applications in diabetes, hypertension, cardiovascular diseases, and neurodegenerative diseases. While OCTA provides a valuable window into the body's microvasculature, interpreting the findings can be complex. Additionally, challenges exist due to the relative non-specificity of its findings where changes observed in OCTA might not be unique to a specific disease, variations between OCTA machines, the lack of a standardized normative database for comparison, and potential image artifacts. Despite these limitations, OCTA holds immense potential for the future. The review highlights promising advancements like quantitative analysis of OCTA images, integration of artificial intelligence for faster and more accurate interpretation, and multi-modal imaging combining OCTA with other techniques for a more comprehensive characterization of the ocular vasculature. Furthermore, OCTA's potential future role in personalized medicine, enabling tailored treatment plans based on individual OCTA findings, community screening programs for early disease detection, and longitudinal studies tracking disease progression over time is also discussed. In conclusion, OCTA presents a significant opportunity to improve our understanding and management of systemic diseases. Addressing current limitations and pursuing these exciting future directions can solidify OCTA as an indispensable tool for diagnosis, monitoring disease progression, and potentially guiding treatment decisions across various systemic health conditions.