tbuckley/cabot-search huggingface dataset:
Piezo1-Mediated Neurogenic Inflammatory Cascade Exacerbates Ventricular Remodeling After Myocardial Infarction
Authors: Meiyan Sun, Sui Mao, Chao Wu, Xiaoyong Zhao, Chengxiao Guo, Jun Hu, Shijin Xu, Fen Zheng, Guoqing Zhu, Hui Tao, Shufang He, Ji Hu, Ye Zhang
Journal: Circulation (2024)

Heart failure is associated with a high rate of mortality and morbidity, and ventricular remodeling invariably precedes heart failure. Ventricular remodeling is fundamentally driven by mechanotransduction that is regulated by both the nervous system and the immune system. However, it remains unknown which key molecular factors govern the neuro/immune/cardio axis that underlies mechanotransduction during ventricular remodeling. Here, we investigated whether the mechanosensitive Piezo cation channel-mediated neurogenic inflammatory cascade underlies ventricular remodeling-related mechanotransduction.
Novel Role for Cardiolipin as a Target of Therapy to Mitigate Myocardial Injury Caused by Venoarterial Extracorporeal Membrane Oxygenation
Authors: Lija Swain, Shreyas Bhave, Xiaoying Qiao, Lara Reyelt, Kay D. Everett, Junya Awata, Rahul Raghav, Sarah N. Powers, Genya Sunagawa, Peter S. Natov, Elena Mahmoudi, Mary Warner, Greg Couper, Masashi Kawabori, Satoshi Miyashita, Tejasvi Aryaputra, Gordon S. Huggins, Michael T. Chin, Navin K. Kapur
Journal: Circulation (2024)

Cardiolipin is a mitochondrial-specific phospholipid that maintains integrity of the electron transport chain (ETC) and plays a central role in myocardial ischemia/reperfusion injury. Tafazzin is an enzyme that is required for cardiolipin maturation. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use to provide hemodynamic support for acute myocardial infarction has grown exponentially, is associated with poor outcomes, and is under active clinical investigation, yet the mechanistic effect of VA-ECMO on myocardial damage in acute myocardial infarction remains poorly understood. We hypothesized that VA-ECMO acutely depletes myocardial cardiolipin and exacerbates myocardial injury in acute myocardial infarction.
Perceived Interpersonal Racism in Relation to Incident Coronary Heart Disease Among Black Women
Authors: Shanshan Sheehy, Max Brock, Julie R. Palmer, Michelle A. Albert, Yvette C. Cozier, Lynn Rosenberg
Journal: Circulation (2024)

Racism is highly prevalent in the United States. Few data exist about whether perceived interpersonal racism is associated with risk of coronary heart disease (CHD).
Stiffness assisted cell-matrix remodeling trigger 3D mechanotransduction regulatory programs
Authors: Anna L. Kersey, Daniel Y. Cheng, Kaivalya A. Deo, Christina R. Dubell, Ting-Ching Wang, Manish K. Jaiswal, Min Hee Kim, Aparna Murali, Sarah E. Hargett, Sumana Mallick, Tanmay P. Lele, Irtisha Singh, Akhilesh K. Gaharwar
Journal: Biomaterials (2024)
Ophthalmologic Complications in Coronavirus Disease 2019 Immunization: A National Vaccine Adverse Event Reporting System Analysis
Authors: Owais M. Aftab, Anup Dupaguntla, Patrick Hughes, Paul D. Langer, Marco A. Zarbin, Neelakshi Bhagat
Journal: Ophthalmology (2024)

In this Vaccine Adverse Event Reporting System disproportionality analysis, COVID-19 immunization was rarely and generally not significantly associated with ophthalmologic complications. However, some symptoms were positive on Janssen vaccination, suggesting a need for continued investigation. In this Vaccine Adverse Event Reporting System disproportionality analysis, COVID-19 immunization was rarely and generally not significantly associated with ophthalmologic complications. However, some symptoms were positive on Janssen vaccination, suggesting a need for continued investigation.
Retraction Note: Glycogen synthase kinase-3β inhibition attenuates the development of ischaemia/reperfusion injury of the gut
Authors: Salvatore Cuzzocrea, Emanuela Mazzon, Emanuela Esposito, Carmelo Muià, Maha Abdelrahman, Rosanna Di Paola, Concetta Crisafulli, Placido Bramanti, Christoph Thiemermann
Journal: Intensive Care Medicine (2024)
Induced Self‐Assembly of Vitamin E‐Spermine/siRNA Nanocomplexes via Spermine/Helix Groove‐Specific Interaction for Efficient siRNA Delivery and Antitumor Therapy
Authors: Xiaoran Zhao, Qi Xu, Qian Wang, Xingxing Liang, Jing Wang, Hongwei Jin, Yizhi Man, Dongyang Guo, Feng Gao, Xinjing Tang
Journal: Advanced Healthcare Materials (2024)

Gene therapy has been one of potential strategies for the treatment of different diseases, where efficient and safe gene delivery systems are also extremely in need. Current lipid nanoparticles (LNP) technology highly depends on the packing and condensation of nucleic acids with amine moieties. Here, an attempt to covalently link two natural compounds, spermine and vitamin E, is made to develop self-assembled nucleic acid delivery systems. Among them, the spermine moieties specifically interact with the major groove of siRNA helix through salt bridge interaction, while vitamin E moieties are located around siRNA duplex. Such amphiphilic vitamin E-spermine/siRNA complexes can further self-assemble into nanocomplexes like multiblade wheels. Further studies indicate that these siRNA nanocomplexes with the neutrally charged surface of vitamin E can enter cells via caveolin/lipid raft mediated endocytosis pathway and bypass lysosome trapping. With these self-assembled delivery systems, efficient siRNA delivery is successfully achieved for Eg5 and Survivin gene silencing as well as DNA plasmid delivery. Further in vivo study indicates that VE-Su-Sper/DSPE-PEG
Evaluation of an artificial intelligence-based decision support for the detection of cutaneous melanoma in primary care: a prospective real-life clinical trial
Authors: Panagiotis Papachristou, My Söderholm, Jon Pallon, Marina Taloyan, Sam Polesie, John Paoli, Chris D Anderson, Magnus Falk
Journal: British Journal of Dermatology (2024)

Abstract Background Use of artificial intelligence (AI), or machine learning, to assess dermoscopic images of skin lesions to detect melanoma has, in several retrospective studies, shown high levels of diagnostic accuracy on par with – or even outperforming – experienced dermatologists. However, the enthusiasm around these algorithms has not yet been matched by prospective clinical trials performed in authentic clinical settings. In several European countries, including Sweden, the initial clinical assessment of suspected skin cancer is principally conducted in the primary healthcare setting by primary care physicians, with or without access to teledermoscopic support from dermatology clinics. Objectives To determine the diagnostic performance of an AI-based clinical decision support tool for cutaneous melanoma detection, operated by a smartphone application (app), when used prospectively by primary care physicians to assess skin lesions of concern due to some degree of melanoma suspicion. Methods This prospective multicentre clinical trial was conducted at 36 primary care centres in Sweden. Physicians used the smartphone app on skin lesions of concern by photographing them dermoscopically, which resulted in a dichotomous decision support text regarding evidence for melanoma. Regardless of the app outcome, all lesions underwent standard diagnostic procedures (surgical excision or referral to a dermatologist). After investigations were complete, lesion diagnoses were collected from the patients’ medical records and compared with the app’s outcome and other lesion data. Results In total, 253 lesions of concern in 228 patients were included, of which 21 proved to be melanomas, with 11 thin invasive melanomas and 10 melanomas in situ. The app’s accuracy in identifying melanomas was reflected in an area under the receiver operating characteristic (AUROC) curve of 0.960 [95% confidence interval (CI) 0.928–0.980], corresponding to a maximum sensitivity and specificity of 95.2% and 84.5%, respectively. For invasive melanomas alone, the AUROC was 0.988 (95% CI 0.965–0.997), corresponding to a maximum sensitivity and specificity of 100% and 92.6%, respectively. Conclusions The clinical decision support tool evaluated in this investigation showed high diagnostic accuracy when used prospectively in primary care patients, which could add significant clinical value for primary care physicians assessing skin lesions for melanoma.
CD8+ T cell metabolic flexibility elicited by CD28-ARS2 axis-driven alternative splicing of PKM supports antitumor immunity
Authors: G. Aaron Holling, Colin A. Chavel, Anand P. Sharda, Mackenzie M. Lieberman, Caitlin M. James, Shivana M. Lightman, Jason H. Tong, Guanxi Qiao, Tiffany R. Emmons, Thejaswini Giridharan, Shengqi Hou, Andrew M. Intlekofer, Richard M. Higashi, Teresa W. M. Fan, Andrew N. Lane, Kevin H. Eng, Brahm H. Segal, Elizabeth A. Repasky, Kelvin P. Lee, Scott H. Olejniczak
Journal: Cellular and Molecular Immunology (2024)

Abstract Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving the metabolic flexibility of T cells have not been determined. In this study, we investigated the influence of the nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature T cells. In doing so, we discovered a novel signaling axis that endows activated CD8+ T cells with flexibility of glucose catabolism. ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events. Among these effects, the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2, a key determinant of CD8+ T-cell glucose utilization, interferon gamma production, and antitumor effector function. Importantly, PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation, revealing a novel means by which costimulation reprograms glucose metabolism in CD8+ T cells.
All cause and cause specific mortality in obsessive-compulsive disorder: nationwide matched cohort and sibling cohort study
Authors: Lorena Fernández de la Cruz, Kayoko Isomura, Paul Lichtenstein, Henrik Larsson, Ralf Kuja-Halkola, Zheng Chang, Brian M D’Onofrio, Isabell Brikell, Christian Rück, Anna Sidorchuk, David Mataix-Cols
Journal: BMJ (2024)

Abstract Objective To estimate the risk of all cause and cause specific mortality in people with obsessive-compulsive disorder (OCD) compared with matched unaffected people from the general population and with their unaffected siblings. Design Population based matched cohort and sibling cohort study. Setting Register linkage in Sweden. Participants Population based cohort including 61 378 people with OCD and 613 780 unaffected people matched (1:10) on sex, birth year, and county of residence; sibling cohort consisting of 34 085 people with OCD and 47 874 unaffected full siblings. Cohorts were followed up for a median time of 8.1 years during the period from 1 January 1973 to 31 December 2020. Main outcome measures All cause and cause specific mortality. Results 4787 people with OCD and 30 619 unaffected people died during the study period (crude mortality rate 8.1 and 5.1 per 1000 person years, respectively). In stratified Cox proportional hazards models adjusted for birth year, sex, county, migrant status (born in Sweden versus abroad), and sociodemographic variables (latest recorded education, civil status, and family income), people with OCD had an increased risk of all cause mortality (hazard ratio 1.82, 95% confidence interval 1.76 to 1.89) and mortality due to natural causes (1.31, 1.27 to 1.37) and unnatural causes (3.30, 3.05 to 3.57). Among the natural causes of death, those due to endocrine, nutritional, and metabolic diseases, mental and behavioural disorders, and diseases of the nervous, circulatory, respiratory, digestive, and genitourinary systems were higher in the OCD cohort. Conversely, the risk of death due to neoplasms was lower in the OCD cohort compared with the unaffected cohort. Among the unnatural causes, suicide showed the highest hazard ratio, followed by accidents. The results were robust to adjustment for psychiatric comorbidities and familial confounding. Conclusions Non-communicable diseases and external causes of death, including suicides and accidents, were major contributors to the risk of mortality in people with OCD. Better surveillance, prevention, and early intervention strategies should be implemented to reduce the risk of fatal outcomes in people with OCD.
Acute rehabilitation after traumatic shoulder dislocation
Authors: Margie Olds, Gisela Sole
Journal: BMJ (2024)

Most anterior shoulder dislocations occur for the first time related to sports (59% 1 to 74% 2 ), or from falls. 1 Following closed reduction, primary care for these injuries involves a supportive sling and individually tailored advice for optimising recovery such as rehabilitative exercises to improve range of motion, sensorimotor control, strength, and function.To inform decision making, a linked BMJ paper by Kearney and colleagues (doi:10.1136/bmj
Directed acyclic graph for epidemiological studies in childhood food allergy: Construction, user's guide, and application
Authors: Zhuoxin Peng, Christian Apfelbacher, Susanne Brandstetter, Roland Eils, Michael Kabesch, Irina Lehmann, Saskia Trump, Sven Wellmann, Jon Genuneit
Journal: Allergy (2024)

Understanding modifiable prenatal and early life causal determinants of food allergy is important for the prevention of the disease. Randomized clinical trials studying environmental and dietary determinants of food allergy may not always be feasible. Identifying risk/protective factors for early-life food allergy often relies on observational studies, which may be affected by confounding bias. The directed acyclic graph (DAG) is a causal diagram useful to guide causal inference from observational epidemiological research. To date, research on food allergy has made little use of this promising method. We performed a literature review of existing evidence with a systematic search, synthesized 32 known risk/protective factors, and constructed a comprehensive DAG for early-life food allergy development. We present an easy-to-use online tool for researchers to re-construct, amend, and modify the DAG along with a user's guide to minimize confounding bias. We estimated that adjustment strategies in 57% of previous observational studies on modifiable factors of childhood food allergy could be improved if the researchers determined their adjustment sets by DAG. Future researchers who are interested in the causal inference of food allergy development in early life can apply the DAG to identify covariates that should and should not be controlled in observational studies.
More Considerations for Risk Stratification of Fetal Atrioventricular Block Beyond <scp>Anti‐Ro</scp> Titer: comment on the article by Buyon et al
Authors: Jui‐Hung Kao, Chin‐Fang Su
Journal: Arthritis & Rheumatology (2024)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Scabies therapy update: Should 25% benzyl benzoate emulsion be reconsidered as a first-line agent in classical scabies?
Authors: Lucinda Claire Fuller, Cord Sunderkötter
Journal: British Journal of Dermatology (2024)

Journal Article Scabies therapy update: Should 25% benzyl benzoate emulsion be reconsidered as a first-line agent in classical scabies? Get access Lucinda Claire Fuller, Lucinda Claire Fuller Conceptualization, Writing - original draft International Alliance for the Control of Scabies (IACS), London Bridge Hospital, London, UK Correspondence: Lucinda Claire Fuller. Email: claire.fuller@nhs.net https://orcid.org/0000-0001-6561-8731 Search for other works by this author on: Oxford Academic Google Scholar Cord Sunderkötter Cord Sunderkötter Writing - review & editing Department of Dermatology and Venereology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Germany https://orcid.org/0000-0002-2929-145X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 190, Issue 4, April 2024, Pages 459–460, https://doi.org/10.1093/bjd/ljae016 Published: 17 January 2024 Article history Accepted: 30 November 2023 Received: 09 January 2024 Published: 17 January 2024 Corrected and typeset: 01 March 2024
A critique of motivation constructs to explain higher-order behavior: We should unpack the black box
Authors: Kou Murayama, Hayley K. Jach
Journal: Behavioral and Brain Sciences (2024)

The constructs of motivation (or needs, motives, etc.) to explain higher-order behavior have burgeoned in psychology. In this article, we critically evaluate such high-level motivation constructs that many researchers define as causal determinants of behavior. We identify a fundamental issue with this predominant view of motivation, which we call the black-box problem. Specifically, high-level motivation constructs have been considered as causally instigating a wide range of higher-order behavior, but this does not explain what they actually are or how behavioral tendencies are generated. The black-box problem inevitably makes the construct ill-defined and jeopardizes its theoretical status. To address the problem, we discuss the importance of mental computational processes underlying motivated behavior. Critically, from this perspective, motivation is not a unitary construct that causes a wide range of higher-order behavior - it is an emergent property that people construe through the regularities of subjective experiences and behavior. The proposed perspective opens new avenues for future theoretical development, that is, the examination of how motivated behavior is realized through mental computational processes.
Stigma in vitiligo: associated factors and severity strata of the Patient Unique Stigmatization Holistic tool in Dermatology (PUSH-D) score
Authors: Ali Fakih, Rim Tannous, Mohamed Lajnef, Julien Seneschal, Nicolas Andreu, Viet-Thi Tran, Khaled Ezzedine
Journal: British Journal of Dermatology (2024)

Vitiligo is the most common cause of skin depigmentation worldwide. Patients with vitiligo may experience stigma and this needs to be addressed.
Electrospun Composite PLLA‐PPSB Nanofiber Nerve Conduits for Peripheral Nerve Defects Repair and Regeneration
Authors: Yuan Dai, Tingwei Lu, Linli Li, Fan Zhang, Haocheng Xu, Hailong Li, Weizhong Wang, Minghao Shao, Feizhou Lyu
Journal: Advanced Healthcare Materials (2024)

Peripheral nerve injury (PNI) is a common clinical problem and regenerating peripheral nerve defects remain a significant challenge. Poly(polyol sebacate) (PPS) polymers are developed as promising materials for biomedical applications due to their biodegradability, biocompatibility, elastomeric properties, and ease of production. However, the application of PPS-based biomaterials in nerve tissue engineering, especially in PNI repair, is limited. In this study, PPS-based composite nanofibers poly(l-lactic acid)-poly(polycaprolactone triol-co-sebacic acid-co-N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid sodium salt) (PLLA-PPSB) are aimed to construct through electrospinning and assess their in vitro biocompatibility with Schwann cells (SCs) and in vivo repair capabilities for peripheral nerve defects. For the first time, the biocompatibility and bioactivity of PPS-based nanomaterial are examined at the molecular, cellular, and animal levels for PNI repair. Electrospun PLLA-PPSB nanofibers display favorable physicochemical properties and biocompatibility, providing an effective interface for the proliferation, glial expression, and adhesion of SCs in vitro. In vivo experiments using a 10-mm rat sciatic nerve defect model show that PLLA-PPSB nanofiber nerve conduits enhance myelin formation, axonal regeneration, angiogenesis, and functional recovery. Transcriptome analysis and biological validation indicate that PLLA-PPSB nanofibers may promote SC proliferation by activating the PI3K/Akt signaling pathway. This suggests the promising potential of PLLA-PPSB nanomaterial for PNI repair.
Efficacy and safety of cladribine, low-dose cytarabine and venetoclax in relapsed/refractory acute myeloid leukemia: results of a pilot study
Authors: Yan-Yan Li, Shuai-Shuai Ge, Yuan-Hong Huang, Ming-Zhu Xu, Chao-Ling Wan, Kai-Wen Tan, Tao Tao, Hai-Xia Zhou, Sheng-Li Xue, Hai-Ping Dai
Journal: Blood Cancer Journal (2024)

Efficacy and safety of cladribine, low-dose cytarabine
CRISPR Activation Reverses Haploinsufficiency and Functional Deficits Caused by <i>TTN</i> Truncation Variants
Authors: Shahnaz Ghahremani, Aditya Kanwal, Anthony Pettinato, Feria Ladha, Nicholas Legere, Ketan Thakar, Yanfen Zhu, Harianto Tjong, Andrea Wilderman, W. Tom Stump, Lina Greenberg, Michael J. Greenberg, Justin Cotney, Chia-Lin Wei, J. Travis Hinson
Journal: Circulation (2024)

truncation variants (TTNtvs) are the most common genetic lesion identified in individuals with dilated cardiomyopathy, a disease with high morbidity and mortality rates. TTNtvs reduce normal TTN (titin) protein levels, produce truncated proteins, and impair sarcomere content and function. Therapeutics targeting TTNtvs have been elusive because of the immense size of TTN, the rarity of specific TTNtvs, and incomplete knowledge of TTNtv pathogenicity.
Structure-primed embedding on the transcription factor manifold enables transparent model architectures for gene regulatory network and latent activity inference
Authors: Andreas Tjärnberg, Maggie Beheler-Amass, Christopher A. Jackson, Lionel A. Christiaen, David Gresham, Richard Bonneau
Journal: Genome biology (2024)

Abstract Background Modeling of gene regulatory networks (GRNs) is limited due to a lack of direct measurements of genome-wide transcription factor activity (TFA) making it difficult to separate covariance and regulatory interactions. Inference of regulatory interactions and TFA requires aggregation of complementary evidence. Estimating TFA explicitly is problematic as it disconnects GRN inference and TFA estimation and is unable to account for, for example, contextual transcription factor-transcription factor interactions, and other higher order features. Deep-learning offers a potential solution, as it can model complex interactions and higher-order latent features, although does not provide interpretable models and latent features. Results We propose a novel autoencoder-based framework, StrUcture Primed Inference of Regulation using latent Factor ACTivity (SupirFactor) for modeling, and a metric, explained relative variance (ERV), for interpretation of GRNs. We evaluate SupirFactor with ERV in a wide set of contexts. Compared to current state-of-the-art GRN inference methods, SupirFactor performs favorably. We evaluate latent feature activity as an estimate of TFA and biological function in S. cerevisiae as well as in peripheral blood mononuclear cells (PBMC). Conclusion Here we present a framework for structure-primed inference and interpretation of GRNs, SupirFactor, demonstrating interpretability using ERV in multiple biological and experimental settings. SupirFactor enables TFA estimation and pathway analysis using latent factor activity, demonstrated here on two large-scale single-cell datasets, modeling S. cerevisiae and PBMC. We find that the SupirFactor model facilitates biological analysis acquiring novel functional and regulatory insight.