tbuckley/cabot-search huggingface dataset:
Two tiers, not one: Different sources of extrinsic mortality have opposing effects on life history traits
Authors: Bruce J. Ellis, Brie M. Reid, Karen L. Kramer
Journal: Behavioral and Brain Sciences (2024)

Abstract Guided by concepts from life history (LH) theory, a large human research literature has tested the hypothesis that exposures to extrinsic mortality (EM) promote the development of faster LH strategies (e.g., earlier/faster reproduction, higher offspring number). A competing model proposes that, because EM in the past was intimately linked to energetic constraints, such exposures specifically led to the development of slower LH strategies. We empirically address this debate by examining (1) LH variation among small-scale societies under different environmental conditions; (2) country-, regional- and community-level correlations between ecological conditions, mortality, maturational timing, and fertility; (3) individual-level correlations between this same set of factors; and (4) natural experiments leveraging the impact of externally-caused changes in mortality on LH traits. Partially supporting each model, we found that harsh conditions encompassing energetic stress and ambient cues to EM (external cues received through sensory systems) have countervailing effects on the development of LH strategies, both delaying pubertal maturation and promoting an accelerated pace of reproduction and higher offspring number. We conclude that, although energetics are fundamental to many developmental processes, providing a first tier of environmental influence, this first tier alone cannot explain these countervailing effects. An important second tier of environmental influence is afforded by ambient cues to EM. We advance a 2-tiered model that delineates this second tier and its central role in regulating development of LH strategies. Consideration of the first and second tier together is necessary to account for the observed countervailing shifts toward both slower and faster LH traits.
Ex vivo-generated human CD1c+ regulatory B cells by a chemically defined system suppress immune responses and alleviate graft-versus-host disease
Authors: Yingying Bao, Jialing Liu, Zhishan Li, Yueming Sun, Junhua Chen, Yuanchen Ma, Gang Li, Tao Wang, Huanyi Liu, Xiaoran Zhang, Rong Yan, Zhenxiao Yao, Xiaolu Guo, Rui Fang, Jianqi Feng, Wenjie Xia, Andy Peng Xiang, Xiaoyong Chen
Journal: Molecular Therapy (2024)
Implementation of a novel retrograde implantation technique for distal limb perfusion during extracorporeal cardiopulmonary resuscitation
Authors: Yalin Yildirim, Stefan Kluge, Hermann Reichenspurner, Alexander M. Bernhardt, Simon Pecha, Johannes Petersen, Yousuf Alassar, Shahabuddin Ohdah, Lukas Reuter, Nils Zabel
Journal: Intensive Care Medicine (2024)
Mechanism of lactic acidemia-promoted pulmonary endothelial cells death in sepsis: role for CIRP-ZBP1-PANoptosis pathway
Authors: Ting Gong, Qing-De Wang, Patricia A. Loughran, Yue-Hua Li, Melanie J. Scott, Timothy R. Billiar, You-Tan Liu, Jie Fan
Journal: Military Medical Research (2024)

Abstract Background Sepsis is often accompanied by lactic acidemia and acute lung injury (ALI). Clinical studies have established that high serum lactate levels are associated with increased mortality rates in septic patients. We further observed a significant correlation between the levels of cold-inducible RNA-binding protein (CIRP) in plasma and bronchoalveolar lavage fluid (BALF), as well as lactate levels, and the severity of post-sepsis ALI. The underlying mechanism, however, remains elusive. Methods C57BL/6 wild type (WT), Casp8 −/− , Ripk3 −/− , and Zbp1 −/− mice were subjected to the cecal ligation and puncture (CLP) sepsis model. In this model, we measured intra-macrophage CIRP lactylation and the subsequent release of CIRP. We also tracked the internalization of extracellular CIRP (eCIRP) in pulmonary vascular endothelial cells (PVECs) and its interaction with Z-DNA binding protein 1 (ZBP1). Furthermore, we monitored changes in ZBP1 levels in PVECs and the consequent activation of cell death pathways. Results In the current study, we demonstrate that lactate, accumulating during sepsis, promotes the lactylation of CIRP in macrophages, leading to the release of CIRP. Once eCIRP is internalized by PVEC through a Toll-like receptor 4 (TLR4)-mediated endocytosis pathway, it competitively binds to ZBP1 and effectively blocks the interaction between ZBP1 and tripartite motif containing 32 (TRIM32), an E3 ubiquitin ligase targeting ZBP1 for proteasomal degradation. This interference mechanism stabilizes ZBP1, thereby enhancing ZBP1-receptor-interacting protein kinase 3 (RIPK3)-dependent PVEC PANoptosis, a form of cell death involving the simultaneous activation of multiple cell death pathways, thereby exacerbating ALI. Conclusions These findings unveil a novel pathway by which lactic acidemia promotes macrophage-derived eCIRP release, which, in turn, mediates ZBP1-dependent PVEC PANoptosis in sepsis-induced ALI. This finding offers new insights into the molecular mechanisms driving sepsis-related pulmonary complications and provides potential new therapeutic strategies.
Efficacy and safety of ZX-7101A, an inhibitor of influenza cap-dependent endonuclease, in adults with uncomplicated influenza: a randomised, double-blind, placebo-controlled phase 2/3 Trial
Authors: Hongyu Wang, Gang Wang, Yan Gao, Lihong Qu, Hong Wang, Min Deng, Hainv Gao, Yilin Li, Nan Yang, Baogui Wang, Rongge Liu, Xuzhu Ma, Zhen Tao, Guoqiang Zhang, Qian Wang, Weifeng Zhao, Yunsong Yu, Lin Chen, Lianchun Liang, Shengyu Wang, Lei Shao, Tao Yang, Jinglei Cao, Yuan Cao, Xiaoli Qin, Jingwen Ai, Huadong Zhu, Wenhong Zhang
Journal: Clinical Microbiology and Infection (2024)
N6-Methyladenosine (m6A) modification activates serine synthesis pathway to mediate therapeutic resistance in liver cancer
Authors: For-Fan Chan, Kenneth Kin-Leung Kwan, Do-Hyun Seoung, Don Wai-Ching Chin, Irene Oi-Lin Ng, Carmen Chak-Lui Wong, Chun-Ming Wong
Journal: Molecular Therapy (2024)
Combined targeting of GPX4 and BCR-ABL tyrosine kinase selectively compromises BCR-ABL+ leukemia stem cells
Authors: Chengwu Zeng, Dingrui Nie, Xianfeng Wang, Shuxin Zhong, Xiangbo Zeng, Xin Liu, Kangjie Qiu, Xueting Peng, Wenyi Zhang, Shengting Chen, Xianfeng Zha, Cunte Chen, Zhenhua Chen, Weizhang Wang, Yangqiu Li
Journal: Molecular Cancer (2024)

In the ongoing battle against BCR-ABL+ leukemia, despite significant advances with tyrosine kinase inhibitors (TKIs), the persistent challenges of drug resistance and the enduring presence of leukemic stem cells (LSCs) remain formidable barriers to achieving a cure. In this study, we demonstrated that Disulfiram (DSF) induces ferroptosis to synergize with TKIs in inhibiting BCR-ABL+ cells, particularly targeting resistant cells and LSCs, using cell models, mouse models, and primary cells from patients. We elucidated the mechanism by which DSF promotes GPX4 degradation to induce ferroptosis through immunofluorescence, co-immunoprecipitation (CO-IP), RNA sequencing, lipid peroxidation assays, and rescue experiments. Here, we present compelling evidence elucidating the sensitivity of DSF, an USA FDA-approved drug for alcohol dependence, towards BCR-ABL+ cells. Our findings underscore DSF's ability to selectively induce a potent cytotoxic effect on BCR-ABL+ cell lines and effectively inhibit primary BCR-ABL+ leukemia cells. Crucially, the combined treatment of DSF with TKIs selectively eradicates TKI-insensitive stem cells and resistant cells. Of particular note is DSF's capacity to disrupt GPX4 stability, elevate the labile iron pool, and intensify lipid peroxidation, ultimately leading to ferroptotic cell death. Our investigation shows that BCR-ABL expression induces alterations in cellular iron metabolism and increases GPX4 expression. Additionally, we demonstrate the indispensability of GPX4 for LSC development and the initiation/maintenance of BCR-ABL+ leukemia. Mechanical analysis further elucidates DSF's capacity to overcome resistance by reducing GPX4 levels through the disruption of its binding with HSPA8, thereby promoting STUB1-mediated GPX4 ubiquitination and subsequent proteasomal degradation. Furthermore, the combined treatment of DSF with TKIs effectively targets both BCR-ABL+ blast cells and drug-insensitive LSCs, conferring a significant survival advantage in mouse models. In summary, the dual inhibition of GPX4 and BCR-ABL presents a promising therapeutic strategy to synergistically target blast cells and drug-insensitive LSCs in patients, offering potential avenues for advancing leukemia treatment.
In-situ engineering of native extracellular matrix to improve vascularization and tissue regeneration at the ischemic injury site
Authors: Dake Hao, Lu Lu, Hengyue Song, Juan-Maria Lopez, Ruiwu Liu, Ping Zhou, Jan Nolta, Diana L. Farmer, Eric Kurzrock, Alyssa Panitch, Kit S. Lam, Aijun Wang
Journal: Med-X (2024)

Abstract Ischemic injury causes dynamic damage to the native extracellular matrix (ECM), which plays a key role in tissue homeostasis and regeneration by providing structural support, facilitating force transmission, and transducing key signals to cells. The main approach aimed at repairing injury to ischemic tissues is restoration of vascular function. Due to their potential to form capillary niches, endothelial cells (ECs) are of greatest interest for vascular regeneration. Integrin binding to ECM is crucial for cell anchorage to the surrounding matrix, spreading, migration, and further activation of intracellular signaling pathways. In this study, we proposed to establish an in-situ engineering strategy to remodel the ECM at the ischemic site to guide EC endogenous binding and establish effective EC/ECM interactions to promote revascularization. We designed and constructed a dual-function molecule (LXW7) 2 -SILY, which is comprised of two functional domains: the first one (LXW7) binds to integrin αvβ3 expressed on ECs, and the second one (SILY) binds to collagen. In vitro, we confirmed (LXW7) 2 -SILY improved EC adhesion and survival. After in situ injection, (LXW7) 2 -SILY showed stable retention at the injured area and promoted revascularization, blood perfusion, and tissue regeneration in a mouse hindlimb ischemia model. Graphical Abstract
CAR-Macrophage Therapy Alleviates Myocardial Ischemia-Reperfusion Injury
Authors: Jiawan Wang, Heng Du, Wanrun Xie, Jinmiao Bi, Hao Zhang, Xu Liu, Yuhan Wang, Shaolong Zhang, Anhua Lei, Chuting He, Hailong Yuan, Jiahe Zhang, Yujing Li, Pengfei Xu, Siqi Liu, Yanan Zhou, Jianghua Shen, Jingdong Wu, Yihong Cai, Chaofan Yang, Zeya Li, Yingxin Liang, Yang Zhao, Jin Zhang, Moshi Song
Journal: Circulation Research (2024)

BACKGROUND: Given the growing acknowledgment of the detrimental effects of excessive myocardial fibrosis on pathological remodeling after myocardial ischemia-reperfusion injury (I/R), targeting the modulation of myocardial fibrosis may offer protective and therapeutic advantages. However, effective clinical interventions and therapies that target myocardial fibrosis remain limited. As a promising chimeric antigen receptor (CAR) cell therapy, whether CAR macrophages (CAR-Ms) can be used to treat I/R remains unclear. METHODS: The expression of FAP (fibroblast activation protein) was studied in mouse hearts after I/R. FAP CAR-Ms were generated to target FAP-expressing cardiac fibroblasts in mouse hearts after I/R. The phagocytosis activity of FAP CAR-Ms was tested in vitro. The efficacy and safety of FAP CAR-Ms in treating I/R were evaluated in vivo. RESULTS: FAP was significantly upregulated in activated cardiac fibroblasts as early as 3 days after I/R. Upon demonstrating their ability to engulf FAP-overexpressing fibroblasts, we intravenously administered FAP CAR-Ms to mice at 3 days after I/R and found that FAP CAR-Ms significantly improved cardiac function and reduced myocardial fibrosis in mice after I/R. No toxicities associated with FAP CAR-Ms were detected in the heart or other organs at 2 weeks after I/R. Finally, we found that FAP CAR-Ms conferred long-term cardioprotection against I/R. CONCLUSIONS: Our proof-of-concept study demonstrates the therapeutic potential of FAP CAR-Ms in alleviating myocardial I/R and potentially opens new avenues for the treatment of a range of heart diseases that include a fibrotic phenotype.
Trends in heart failure mortality in Sweden between 1997 and 2022
Authors: Felix Lindberg, Lina Benson, Ulf Dahlström, Lars H. Lund, Gianluigi Savarese
Journal: European Journal of Heart Failure (2024)

Abstract Aims Data from US have shown a reversal in the improvement of heart failure (HF)‐related mortality over the last ~10 years. It is unknown whether these trends generalize to European universal healthcare systems. We assessed temporal trends in (i) HF‐related mortality in the overall national population; and (ii) all‐cause mortality following an incident HF diagnosis, overall and stratified by ejection fraction (EF), in Sweden between 1997 and 2022. Methods and results Annual mortality rates with a HF diagnosis as underlying cause were extracted from the Cause of Death Register. All‐cause mortality following incident HF was assessed in two HF cohorts derived from the National Patient Register (NPR) and the Swedish HF Registry (SwedeHF). Temporal trends were presented as average annual percentage change (AAPC). Between 1997 and 2022, age‐adjusted HF‐related mortality in the general population declined from 33.4 to 23.8 per 100 000 individuals (AAPC −2.15%, p &lt; 0.001). In the HF cohort from NPR ( n = 423 092), all‐cause mortality at 1, 3, and 5 years following a first diagnosis of HF was 25%, 46%, and 58%, respectively, in 2022; 1‐year mortality declined (AAPC −1.10%, p &lt; 0.001) over time regardless of age or sex. In SwedeHF ( n = 63 753), the decline in 1‐year mortality was less steep with increasing EF (AAPC −2.64%, p &lt; 0.001; −2.30%, p = 0.062; and −2.16%, p = 0.032 in EF &lt;40%, 40–49%, and ≥50%, respectively). Conclusions Heart failure‐related mortality has declined over the last ~25 years in Sweden. All‐cause mortality in patients with HF has also declined, more in HF with reduced than preserved EF, mirroring the different availability of life‐saving treatments across the EF spectrum.
Engineering Nanoclusters of Cell Adhesive Ligands on Biomaterial Surfaces: Superior Cell Proliferation and Myotube Formation for Skeletal Muscle Tissue Regeneration
Authors: Shirin Nour, Sadegh Shabani, Kristy Swiderski, Gordon S. Lynch, Andrea J. O'Connor, Greg Qiao, Daniel E. Heath
Journal: Advanced Healthcare Materials (2024)

Engineering biointerfaces with nanoscale clustering of integrin-binding cell adhesive peptides is critical for promoting receptor redistribution into signaling complexes. Skeletal muscle cells are exquisitely sensitive to integrin-mediated signaling, yet biomaterials supporting myogenesis through control of the density and nanodistribution of ligands have not been developed. Here, materials are developed with tailorable cell adhesive ligands distribution at the interface by independently controlling their global and local density to enhance myogenesis, by promoting myoblast growth and myotube formation. To this end, RGD-functionalized low-fouling polymer surfaces with global ligand densities (G) from 0-7 µg peptide/mg polymer and average local ligand densities (L) from 1-6.3 ligands/cluster, are generated and characterized. Cell studies demonstrate improvements in cell adhesion, spreading, growth, and myotube formation up to a density of 7 µg peptide/mg polymer with 4 ligands/cluster. Optimizing ligand density and distribution also promotes early myofiber maturation, identified by increased MF20 marker protein expression and sarcomere-forming myotubes. At higher ligand densities, these cell properties are decreased, indicating that ligand multivalency is a critical parameter for tailoring cell-material interactions, to a certain threshold. The findings provide new insights for designing next-generation biomaterials and hold promise for improved engineering of skeletal muscle.
Biopharmaceutical and pharmacokinetic attributes to drive nanoformulations of small molecule tyrosine kinase inhibitors
Authors: Soumyadip Mukherjee, Vedant Joshi, Kolimi Prashanth Reddy, Nidhi Singh, Priyanka Das, Pallab Datta
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Buoyed by the discovery of small-molecule tyrosine kinase inhibitors (smTKIs), significant impact has been made in cancer chemotherapeutics. However, some of these agents still encounter off-target toxicities and suboptimal efficacies due to their inferior biopharmaceutical and/or pharmacokinetic properties. Almost all of these molecules exhibit significant inter- and intra-patient variations in plasma concentration-time profiles. Thus, therapeutic drug monitoring, dose adjustments and precision medicine are being contemplated by clinicians. Complex formulations or nanoformulation-based drug delivery systems offer promising approaches to provide drug encapsulation or spatiotemporal control over the release, overcoming the biopharmaceutical and pharmacokinetic limitations and improving the therapeutic outcomes. In this context, the present review comprehensively tabulates and critically analyzes all the relevant properties (T
Diagnostic Performance and Clinical Impact of Photon-Counting Detector Computed Tomography in Coronary Artery Disease
Authors: Koshiro Sakai, Doosup Shin, Mandeep Singh, Sarah Malik, Ali Dakroub, Zainab Sami, Jonathan Weber, J Jane Cao, Roosha Parikh, Lu Chen, Fernando Sosa, David J Cohen, Jeffrey W Moses, Richard A Shlofmitz, Carlos Collet, Evan Shlofmitz, Allen Jeremias, Omar K Khalique, Ziad A Ali
Journal: Journal of the American College of Cardiology (2024)
Tricuspid transcatheter edge-to-edge repair for severe tricuspid regurgitation: 1-year outcomes from the TRILUMINATE randomized cohort
Authors: Gilbert H L Tang, Rebecca T Hahn, Brian K Whisenant, Nadira Hamid, Hursh Naik, Raj R Makkar, Peter Tadros, Matthew J Price, Gagan D Singh, Neil P Fam, Saibal Kar, Shamir R Mehta, Richard Bae, Nishant K Sekaran, Travis Warner, Moody Makar, George Zorn, Raymond Benza, Ulrich P Jorde, Patrick M McCarthy, Vinod H Thourani, Qian Ren, Phillip M Trusty, Paul Sorajja, David H Adams
Journal: Journal of the American College of Cardiology (2024)
Transcatheter Valve Repair for Tricuspid Regurgitation
Authors: Mirjam G Wild, Lukas Stolz, Sebastian Rosch, Felix Rudolph, Björn Goebel, Benedikt Köll, Philipp von Stein, Wolfgang Rottbauer, Tienush Rassaf, Harald Beucher, Martin Kraus, Mohammad Kassar, Tobias Geisler, Andreas Rück, Joao Ferreira-Martins, Stefan Toggweiler, Paula Sagmeister, Dirk Westermann, Thomas J Stocker, Ludwig T Weckbach, Michael Näbauer, Magnus Settergren, Sam Dawkins, Tobias Kister, Fabien Praz, Marc Vorpahl, Mathias H Konstandin, Peter Lüdike, Mirjam Keßler, Christos Iliadis, Daniel Kalbacher, Philip Lauten, Muhammed Gerçek, Christian Besler, Philipp Lurz, Jörg Hausleiter
Journal: Journal of the American College of Cardiology (2024)
Sleep disorders associated with cranial radiation – a systematic review
Authors: Maeve Pascoe, Emma Byrne, Amanda King, Diane Cooper, Nancy Foldvary-Schaefer, Reena Mehra, Justin Lathia, Mark R Gilbert, Terri S Armstrong
Journal: Neuro-Oncology (2024)

Radiation is the standard-of-care treatment for primary brain tumors (PBTs) but may have profound effects on sleep that have not yet been fully characterized. This systematic review aims to further our understanding of radiation therapy on the risk of development of sleep disorders in patients with PBTs, as well as potential opportunities for prevention and treatment. A systematic search of PubMed, Embase, and Web of Science was performed (last Jan 2024) with predefined inclusion (PBT patients, radiation therapy, somnolence/circadian disruption) and exclusion (reviews/abstracts/cases/chapters, non-PBT cancer, lack of radiation) criteria, yielding 267 papers initially and 38 studies included. Data extraction and analysis (descriptive statistics, individual study summary) focused on the incidence of sleep disturbances, radiation types/doses, and pharmacologic interventions. Risk of bias assessment was conducted with the Effective Public Health Practice Project's Quality Assessment Tool for Quantitative Studies. The included 38 studies (n = 2948 patients) demonstrated a high incidence of sleep disturbances in patients with PBTs throughout radiation therapy, but primarily from the end of radiation to 6 months after. Sleep symptoms were associated with radiation (dose-dependent), and pharmacotherapies were helpful in patients with formal sleep disorder diagnoses. Terminology and incidence reporting of sleep symptoms are inconsistent, and many studies had a high risk of bias. This systematic review highlights the ongoing challenges with sleep symptoms/disorders related to cranial irradiation treatment in the primary brain tumor population. Further investigations on the interconnectedness of sleep disturbance constructs and possible pharmacotherapies to alleviate symptoms are warranted.
Feasibility validation of automatic diagnosis of mitral valve prolapse from multi-view echocardiographic sequences based on deep neural network
Authors: Zijian Wu, Zhenyi Ge, Zhengdan Ge, Yumeng Xing, Weipeng Zhao, Lili Dong, Yongshi Wang, Dehong Kong, Chunqiang Hu, Yixiu Liang, Haiyan Chen, Wufeng Xue, Cuizhen Pan, Dong Ni, Xianhong Shu
Journal:  (2024)

Abstract Aims To address the limitations of traditional diagnostic methods for mitral valve prolapse (MVP), specifically fibroelastic deficiency (FED) and Barlow’s disease (BD), by introducing an automated diagnostic approach utilizing multi-view echocardiographic sequences and deep learning. Methods and results An echocardiographic data set, collected from Zhongshan Hospital, Fudan University, containing apical 2 chambers (A2C), apical 3 chambers (A3C), and apical 4 chambers (A4C) views, was employed to train the deep learning models. We separately trained view-specific and view-agnostic deep neural network models, which were denoted as MVP-VS and MVP view-agonistic (VA), for MVP diagnosis. Diagnostic accuracy, precision, sensitivity, F1-score, and specificity were evaluated for both BD and FED phenotypes. MVP-VS demonstrated an overall diagnostic accuracy of 0.94 for MVP. In the context of BD diagnosis, precision, sensitivity, F1-score, and specificity were 0.83, 1.00, 0.90, and 0.92, respectively. For FED diagnosis, the metrics were 1.00, 0.83, 0.91, and 1.00. MVP-VA exhibited an overall accuracy of 0.95, with BD-specific metrics of 0.85, 1.00, 0.92, and 0.94 and FED-specific metrics of 1.00, 0.83, 0.91, and 1.00. In particular, the MVP-VA model using mixed views for training demonstrated efficient diagnostic performance, eliminating the need for repeated development of MVP-VS models and improving the efficiency of the clinical pipeline by using arbitrary views in the deep learning model. Conclusion This study pioneers the integration of artificial intelligence into MVP diagnosis and demonstrates the effectiveness of deep neural networks in overcoming the challenges of traditional diagnostic methods. The efficiency and accuracy of the proposed automated approach suggest its potential for clinical applications in the diagnosis of valvular heart disease.