tbuckley/cabot-search huggingface dataset:
Arg92Leu-cTnT Alters the cTnC-cTnI Interface Disrupting PKA-Mediated Relaxation
Authors: Melissa L. Lynn, Jesus Jimenez, Romi L. Castillo, Catherine Vasquez, Matthew M. Klass, Anthony Baldo, Andrew Kim, Cyonna Gibson, Anne M. Murphy, Jil C. Tardiff
Journal: Circulation Research (2024)

BACKGROUND: Impaired left ventricular relaxation, high filling pressures, and dysregulation of Ca 2+ homeostasis are common findings contributing to diastolic dysfunction in hypertrophic cardiomyopathy (HCM). Studies have shown that impaired relaxation is an early observation in the sarcomere-gene-positive preclinical HCM cohort, which suggests the potential involvement of myofilament regulators in relaxation. A molecular-level understanding of mechanism(s) at the level of the myofilament is lacking. We hypothesized that mutation-specific, allosterically mediated, changes to the cTnC (cardiac troponin C)-cTnI (cardiac troponin I) interface can account for the development of early-onset diastolic dysfunction via decreased PKA accessibility to cTnI. METHODS: HCM mutations R92L-cTnT (cardiac troponin T; Arg92Leu) and Δ160E-cTnT (Glu160 deletion) were studied in vivo, in vitro, and in silico via 2-dimensional echocardiography, Western blotting, ex vivo hemodynamics, stopped-flow kinetics, time-resolved fluorescence resonance energy transfer, and molecular dynamics simulations. RESULTS: The HCM-causative mutations R92L-cTnT and Δ160E-cTnT result in different time-of-onset diastolic dysfunction. R92L-cTnT demonstrated early-onset diastolic dysfunction accompanied by a localized decrease in phosphorylation of cTnI. Constitutive phosphorylation of cTnI (cTnI-D 23 D 24 ) was sufficient to recover diastolic function to non-Tg levels only for R92L-cTnT. Mutation-specific changes in Ca 2+ dissociation rates associated with R92L-cTnT reconstituted with cTnI-D 23 D 24 led us to investigate potential involvement of structural changes in the cTnC-cTnI interface as an explanation for these observations. We probed the interface via time-resolved fluorescence resonance energy transfer revealing a repositioning of the N-terminus of cTnI, closer to cTnC, and concomitant decreases in distance distributions at sites flanking the PKA consensus sequence. Implementing time-resolved fluorescence resonance energy transfer distances as constraints into our atomistic model identified additional electrostatic interactions at the consensus sequence. CONCLUSIONS: These data show that the early diastolic dysfunction observed in a subset of HCM is attributable to allosterically mediated structural changes at the cTnC-cTnI interface that impair accessibility of PKA, thereby blunting β-adrenergic responsiveness and identifying a potential molecular target for therapeutic intervention.
Visualizing Immune Checkpoint Inhibitors Derived Inflammation in Atherosclerosis
Authors: Lanlan Lou, Lisa Detering, Hannah Luehmann, Junedh M. Amrute, Deborah Sultan, Pan Ma, Alexandria Li, Divangana Lahad, Andreas Bredemeyer, Xiuli Zhang, Gyu Seong Heo, Kory Lavine, Yongjian Liu
Journal: Circulation Research (2024)

BACKGROUND: Immune checkpoint inhibitor (ICI) usage has resulted in immune-related adverse events in patients with cancer, such as accelerated atherosclerosis. Of immune cells involved in atherosclerosis, the role of CCR2+ (CC motif chemokine receptor 2-positive) proinflammatory macrophages is well documented. However, there is no noninvasive approach to determine the changes of these cells in vivo following ICI treatment and explore the underlying mechanisms of immune-related adverse events. Herein, we aim to use a CCR2 (CC motif chemokine receptor 2)–targeted radiotracer and positron emission tomography (PET) to assess the aggravated inflammatory response caused by ICI treatment in mouse atherosclerosis models and explore the mechanism of immune-related adverse events. METHODS: Apoe −/− mice and Ldlr −/− mice were treated with an ICI, anti-PD1 (programmed cell death protein 1) antibody, and compared with those injected with either isotype control IgG or saline. The radiotracer 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-ECL1i (extracellular loop 1 inverso) was used for PET imaging of CCR2+ macrophages. Atherosclerotic arteries were collected for molecular characterization. RESULTS: CCR2 PET revealed significantly higher radiotracer uptake in both Apoe −/− and Ldlr −/− mice treated with anti-PD1 compared with the control groups. The increased expression of CCR2+ cells in Apoe −/− and Ldlr −/− mice was confirmed by immunostaining and flow cytometry. Single-cell RNA sequencing revealed elevated expression of CCR2 in myeloid cells. Mechanistically, IFNγ (interferon gamma) was essential for aggravated inflammation and atherosclerotic plaque progression following anti-PD1 treatment. CONCLUSIONS: Accelerated atherosclerotic plaque inflammation triggered by anti-PD1 treatment can be noninvasively detected by 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-ECL1i PET. Aggravated plaque inflammation is time- and dose-dependent and predominately mediated by IFNγ signaling. This study warrants further investigation of CCR2 PET as a noninvasive approach to visualize atherosclerotic plaque inflammation and explore the underlying mechanism following ICI treatment.
Blunted Cardiac Mitophagy in Response to Metabolic Stress Contributes to HFpEF
Authors: Akira Yoshii, Timothy S. McMillen, Yajun Wang, Bo Zhou, Hongye Chen, Durba Banerjee, Melisa Herrero, Pei Wang, Naoto Muraoka, Wang Wang, Charles E. Murry, Rong Tian
Journal: Circulation Research (2024)

BACKGROUND: Metabolic remodeling and mitochondrial dysfunction are hallmarks of heart failure with reduced ejection fraction. However, their role in the pathogenesis of HF with preserved ejection fraction (HFpEF) is poorly understood. METHODS: In a mouse model of HFpEF, induced by high-fat diet and Nω-nitrol-arginine methyl ester, cardiac energetics was measured by 31 P NMR spectroscopy and substrate oxidation profile was assessed by 13 C-isotopmer analysis. Mitochondrial functions were assessed in the heart tissue and human induced pluripotent stem cell–derived cardiomyocytes. RESULTS: HFpEF hearts presented a lower phosphocreatine content and a reduced phosphocreatine/ATP ratio, similar to that in heart failure with reduced ejection fraction. Decreased respiratory function and increased reactive oxygen species production were observed in mitochondria isolated from HFpEF hearts suggesting mitochondrial dysfunction. Cardiac substrate oxidation profile showed a high dependency on fatty acid oxidation in HFpEF hearts, which is the opposite of heart failure with reduced ejection fraction but similar to that in high-fat diet hearts. However, phosphocreatine/ATP ratio and mitochondrial function were sustained in the high-fat diet hearts. We found that mitophagy was activated in the high-fat diet heart but not in HFpEF hearts despite similar extent of obesity suggesting that mitochondrial quality control response was impaired in HFpEF hearts. Using a human induced pluripotent stem cell–derived cardiomyocyte mitophagy reporter, we found that fatty acid loading stimulated mitophagy, which was obliterated by inhibiting fatty acid oxidation. Enhancing fatty acid oxidation by deleting ACC2 (acetyl-CoA carboxylase 2) in the heart stimulated mitophagy and improved HFpEF phenotypes. CONCLUSIONS: Maladaptation to metabolic stress in HFpEF hearts impairs mitochondrial quality control and contributed to the pathogenesis, which can be improved by stimulating fatty acid oxidation.
Transparent MXene Microelectrode Arrays for Multimodal Mapping of Neural Dynamics
Authors: Sneha Shankar, Yuzhang Chen, Spencer Averbeck, Quincy Hendricks, Brendan Murphy, Benjamin Ferleger, Nicolette Driscoll, Mikhail Shekhirev, Hajime Takano, Andrew Richardson, Yury Gogotsi, Flavia Vitale
Journal: Advanced Healthcare Materials (2024)

Transparent microelectrode arrays have proven useful in neural sensing, offering a clear interface for monitoring brain activity without compromising high spatial and temporal resolution. The current landscape of transparent electrode technology faces challenges in developing durable, highly transparent electrodes while maintaining low interface impedance and prioritizing scalable processing and fabrication methods. To address these limitations, we introduce artifact-resistant transparent MXene microelectrode arrays optimized for high spatiotemporal resolution recording of neural activity. With 60% transmittance at 550 nm, these arrays enable simultaneous imaging and electrophysiology for multimodal neural mapping. Electrochemical characterization shows low impedance of 563 ± 99 kΩ at 1 kHz and a charge storage capacity of 58 mC cm⁻² without chemical doping. In vivo experiments in rodent models demonstrate the transparent arrays' functionality and performance. In a rodent model of chemically-induced epileptiform activity, we tracked ictal wavefronts via calcium imaging while simultaneously recording seizure onset. In the rat barrel cortex, we recorded multi-unit activity across cortical depths, showing the feasibility of recording high-frequency electrophysiological activity. The transparency and optical absorption properties of Ti₃C₂Tx MXene microelectrodes enable high-quality recordings and simultaneous light-based stimulation and imaging without contamination from light-induced artifacts.
Valence‐Transforming O<sub>2</sub>‐Depleting Nano‐Assembly Enable In Situ Tumor Depositional Embolization
Authors: Weiheng Kong, Qingyao Meng, Rong‐Mei Kong, Yan Zhao, Fengli Qu
Journal: Advanced Healthcare Materials (2024)

Abstract Abnormal metabolism and blood supply/O 2 imbalance in tumor cells affect drug transport delivery and increase the difficulty of tumor treatment. Controlling tumor growth by inhibiting tumor cell metabolism and regulating progressive embolization in the tumor region provides an innovative basis for constructing tumor therapeutic models. A highly biocompatible and efficient O 2 ‐depleting agent has been investigated to enable in situ precipitation and embolization within the tumor microenvironment. In situ deformation embolizer, Fe‐GA@CaCO 3 nano‐assembly (GA: gallic acid), can convert into the large granular size embolization components of Fe(III) precipitates and affluent Ca 2+ within the tumor microenvironment. In situ progressive O 2 depletion produces Fe(III) precipitates that embolize tumor regions, isolating O 2 and nutrients by blocking supply. Meanwhile, affluent Ca 2+ acts on the intracellular, causing mitochondrial dysfunction through calcium overload and contributing to irreversible tumor cell damage. Both internal and external routes work synergistically to produce precise functional inhibition of tumors from the inside out, simultaneously responding to both intracellular and the corresponding tumor regions, providing an innovative solution for anti‐tumor therapy.
Essential role of Dhx16-mediated ribosome assembly in maintenance of hematopoietic stem cells
Authors: Zhigang Li, Jiankun Fan, Yalan Xiao, Wei Wang, Changlin Zhen, Junbing Pan, Weiru Wu, Yuanyuan Liu, Zhe Chen, Qinrong Yan, Hanqing Zeng, Shuyu Luo, Lun Liu, Zhanhan Tu, Xueya Zhao, Yu Hou
Journal: Leukemia (2024)
CERS1 is a Biomarker of Staphylococcus aureus Abundance and Atopic Dermatitis Severity
Authors: H Mark Kenney, Takeshi Yoshida, Evgeny Berdyshev, Agustin Calatroni, Steven R Gill, Eric L Simpson, Stephanie Lussier, Mark Boguniewicz, Tissa Hata, Zelma C Chiesa Fuxench, Anna De Benedetto, Peck Y Ong, Justin Ko, Wendy Davidson, Gloria David, Patrick M Schlievert, Donald Y M Leung, Lisa A Beck
Journal: Journal of Allergy and Clinical Immunology (2024)
Persistent Desmoglein-1 downregulation and Periostin accumulation in histologic remission of Eosinophilic Esophagitis
Authors: Hannes Hoelz, Tim Faro, Marie-Luise Frank, Ignasi Forné, Daniela Kugelmann, Anja Jurk, Simon Buehler, Kolja Siebert, Monica Matchado, Tobias Straub, Annett Hering, Guido Piontek, Susanna Mueller, Sibylle Koletzko, Markus List, Katja Steiger, Martina Rudelius, Jens Waschke, Tobias Schwerd
Journal: Journal of Allergy and Clinical Immunology (2024)
Cardiovascular adaptations and pathological changes induced by spaceflight: from cellular mechanisms to organ-level impacts
Authors: Han Han, Hao Jia, Yi-Fan Wang, Jiang-Ping Song
Journal: Military Medical Research (2024)

Abstract The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions. Human development occurs under the influence of gravity, shielded from space radiation by Earth’s magnetic field, and within an environment characterized by 24-hour day-night cycles resulting from Earth’s rotation, thus deviating from these conditions necessitates adaptive responses for survival. With upcoming manned lunar and Martian missions approaching rapidly, it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health. This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth, to analyze how microgravity, space radiation, and disrupted circadian affect cardiovascular well-being. Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction, which may be exacerbated by space radiation. Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations, cytoskeletal damage, and myofibril changes. Disruptions in circadian rhythms caused by factors such as microgravity, light exposure, and irregular work schedules, could further exacerbate cardiovascular issues. However, current research tends to predominantly focus on disruptions in the core clock gene, overlooking the multifactorial nature of circadian rhythm disturbances in space. Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks, to preserve astronaut health and ensure mission success.
Author Correction: NERD-seq: a novel approach of Nanopore direct RNA sequencing that expands representation of non-coding RNAs
Authors: Luke Saville, Li Wu, Jemaneh Habtewold, Yubo Cheng, Babita Gollen, Liam Mitchell, Matthew Stuart-Edwards, Travis Haight, Majid Mohajerani, Athanasios Zovoilis
Journal: Genome biology (2024)
Charting the metabolic biogeography of the colorectum in cancer: challenging the right sided versus left sided classification
Authors: Abhishek Jain, Montana T Morris, Domenica Berardi, Trisha Arora, Xavier Domingo-Almenara, Philip B Paty, Nicholas J W Rattray, Daniel Kerekes, Lingeng Lu, Sajid A Khan, Caroline H Johnson
Journal: Molecular Cancer (2024)
CD16+ as predictive marker for early relapse in aggressive B-NHL/DLBCL patients
Authors: Sylvia Zöphel, Nadja Küchler, Johanna Jansky, Cora Hoxha, Gertrud Schäfer, Julius J Weise, Joanne Vialle, Lea Kaschek, Gebhard Stopper, Hermann Eichler, Daniela Yildiz, Alina Moter, Philipp Wendel, Evelyn Ullrich, Claudia Schormann, Torben Rixecker, Onur Cetin, Frank Neumann, Patrick Orth, Moritz Bewarder, Markus Hoth, Lorenz Thurner, Eva C Schwarz
Journal: Molecular Cancer (2024)
RNA m6A modification in ferroptosis: implications for advancing tumor immunotherapy
Authors: Jun-Xiao Shi, Zhi-Chao Zhang, Hao-Zan Yin, Xian-Jie Piao, Cheng-Hu Liu, Qian-Jia Liu, Jia-Cheng Zhang, Wen-Xuan Zhou, Fu-Chen Liu, Fu Yang, Yue-Fan Wang, Hui Liu
Journal: Molecular Cancer (2024)
Inpatient burden of respiratory syncytial virus (RSV) in Switzerland, 2003 to 2021: an analysis of administrative data
Authors: Michael Stucki, Golda Lenzin, Philipp KA Agyeman, Klara M Posfay-Barbe, Nicole Ritz, Johannes Trück, Angela Fallegger, Susanne G Oberle, Oliver Martyn, Simon Wieser
Journal: Eurosurveillance (2024)

BackgroundRespiratory syncytial virus (RSV) is a leading cause of acute respiratory infections and hospitalisations in infants (age < 1 year) and young children. Little is known on RSV epidemiology and related inpatient healthcare resource use (HCRU) in Switzerland.AimTo explore RSV-related hospitalisations, inpatient HCRU and medical costs in all age groups, and risk factors for infant hospitalisations in Switzerland.MethodsWe used national hospital registry data from 2003 to 2021 identifying RSV cases with ICD-10-GM codes, and described demographic characteristics, HCRU and associated medical costs of RSV inpatients. The effect of risk factors on infant hospitalisation was estimated with logistic regression.ResultsWe observed a general increase and biannual pattern in RSV hospitalisations between 2003/04 and 2018/19, with 3,575 hospitalisations in 2018/19 and 2,487 in 2019/20 before numbers declined in 2020/21 (n = 902). Around two thirds of all hospitalisations occurred in infants. Mean (median) age was 118 (85) days in hospitalised infants and 74 (77) years in hospitalised adult patients (> 18 years); 7.2% of cases required intensive care unit stay. Mean inpatient medical costs were estimated at EUR 8,046. Most (90.8%) hospitalised infants with RSV were born after 35 weeks of gestation without bronchopulmonary dysplasia or congenital heart disease. Low birth weight, gestational age and congenital disorders were associated with a higher risk for hospitalisation.ConclusionsRSV leads to a substantial number of hospitalisations and peaks in hospital capacity utilisation. Measures to protect all infants from an RSV hospitalisation are essential in addressing this public health challenge.
Reconceptualizing and Defining Exposomics within Environmental Health: Expanding the Scope of Health Research
Authors: Caspar W. Safarlou, Karin R. Jongsma, Roel Vermeulen
Journal: Environmental Health Perspectives (2024)

Exposomics, the study of the exposome, is flourishing, but the field is not well defined. The term "exposome" refers to all environmental influences and associated biological responses throughout the lifespan. However, this definition is very similar to that of the term "environment"-the external elements and conditions that surround and affect the life and development of an organism. Consequently, the exposome seems to be nothing more than a synonym for the environment, and exposomics a synonym for environmental research. As a result, some have rebranded their "standard" environmental health research with the neologistic exposome term, whereas others ignore or seek to abandon the seemingly redundant concept of the exposome.
Development of oral pH-sensitive redox nanotherapeutics for gastric ulcer therapy
Authors: Minh-Dat Quoc Tang, Nhi Bao Tran, Thu-Ha Thi Nguyen, Khanh-Uyen Hoang Nguyen, Nhu-Thuy Trinh, Toi Van Vo, Makoto Kobayashi, Toru Yoshitomi, Yukio Nagasaki, Long Binh Vong
Journal: Journal of Controlled Release (2024)
“Vaccinating your child during an emergency is more important than ever”: a randomised controlled trial on message framing among Ukrainian refugees in Poland, 2023
Authors: Maike Winters, Agnieszka Sochoń-Latuszek, Anastasiia Nurzhynska, Kseniia Yoruk, Katarzyna Kukuła, Mutribjon Bahruddinov, Aleksandra Kusek, Dorota Kleszczewska, Anna Dzielska, Tomasz Maciejewski, Joanna Mazur, Hannah Melchinger, John Kinsman, Piotr Kramarz, Sarah Christie, Saad B Omer
Journal: Eurosurveillance (2024)

BackgroundSince February 2022, the start of the full-scale war in Ukraine, millions of women and children have fled the country. Vaccination of refugee children is important to protect this vulnerable population from disease.AimWe investigate the determinants of vaccination intention in refugee mothers from Ukraine residing in Poland and test the effect of three message frames.MethodsParticipants were randomised into either a control group or one of three intervention groups encouraging vaccination using a specific frame: (i) trust in the Polish health system, (ii) ease of access to vaccination or (iii) risk aversion. Primary outcomes were intention to vaccinate a child in Poland and clicking on a vaccination scheduling link.ResultsThe study was completed by 1,910 Ukrainian refugee mothers. Compared with the control group, the risk aversion message significantly increased vaccination intention (adjusted odds ratio (AOR): 2.35, 95% confidence interval (CI): 1.25-4.42) and clicking on the vaccine scheduling link (AOR: 1.53, 95% CI: 1.12-2.09). Messages around trust and ease of access did not have an effect. Important determinants of vaccination intention were perceived importance of vaccination (AOR: 1.12 95% CI: 1.01-1.25) and trusting vaccination information official health institutes (AOR: 1.40 95% CI: 1.06-1.83) and social media (AOR: 2.09 95% CI: 1.33-3.27).DiscussionUsing a risk aversion frame highlighting the vulnerability to infection that refugees face resulted in increased vaccination intention and clicks on a vaccination scheduler. Health workers who interact with Ukrainian refugees could use this frame in their vaccination communication.
Increased circulation of GII.17 noroviruses, six European countries and the United States, 2023 to 2024
Authors: Preeti Chhabra, Shan Wong, Sandra Niendorf, Ingeborg Lederer, Harry Vennema, Mirko Faber, Athinna Nisavanh, Sonja Jacobsen, Rachel Williams, Aoife Colgan, Zoe Yandle, Patricia Garvey, Haider Al-Hello, Katia Ambert-Balay, Leslie Barclay, Miranda de Graaf, Cristina Celma, Judith Breuer, Jan Vinjé, Amy Douglas
Journal: Eurosurveillance (2024)

We report an increase in GII.17 norovirus outbreaks and sporadic infections of acute gastroenteritis in Austria, Germany, France, Ireland, the Netherlands, England and the United States during the 2023/24 season. A decrease in GII.4 coincided with GII.17 prevalence increasing to between 17% and 64% of all GII detections. Overall, 84% of the GII.17 strains clustered closely with strains first reported in Romania in 2021 and two new sub-lineages were identified. Norovirus surveillance and molecular characterisation should be prioritised this winter.
Improved Disease-Specific Survival in Lentigo Maligna Treated with Mohs Surgery over Wide Local Excision: A Retrospective Cohort Analysis
Authors: Mitchell A Taylor, Sierra I Thomas, Divya Sharma, Vanessa B Voss, Ashley Wysong
Journal: British Journal of Dermatology (2024)

Lentigo maligna (LM), a subtype of melanoma in-situ, typically occurs on sun-damaged skin of the head and neck in older males. Using the SEER database, the aim of this study was to compare disease-specific survival (DSS) outcomes between patients treated with wide local excision (WLE) and Mohs micrographic surgery (MMS), finding that MMS demonstrated improved 5- and 10-year DSS rates and a lower disease-specific mortality risk than WLE on multivariable analysis. Our findings highlight a potential DSS benefit of MMS for treating LM, although further research is required to confirm these findings and explore factors influencing treatment choices.