tbuckley/cabot-search huggingface dataset:
Exposure of Ldlr−/− Mice to a PFAS Mixture and Outcomes Related to Circulating Lipids, Bile Acid Excretion, and the Intestinal Transporter ASBT
Authors: Katherine Roth, Zhao Yang, Manisha Agarwal, Johnna Birbeck, Judy Westrick, Todd Lydic, Katherine Gurdziel, Michael C. Petriello
Journal: Environmental Health Perspectives (2024)

Previous epidemiological studies have repeatedly found per- and polyfluoroalkyl substances (PFAS) exposure associated with higher circulating cholesterol, one of the greatest risk factors for development of coronary artery disease. The main route of cholesterol catabolism is through its conversion to bile acids, which circulate between the liver and ileum via enterohepatic circulation. Patients with coronary artery disease have decreased bile acid excretion, indicating that PFAS-induced impacts on enterohepatic circulation may play a critical role in cardiovascular risk.
Genetic Screen in a Pre-Clinical Model of Sarcoma Development Defines Drivers and Therapeutic Vulnerabilities
Authors: Jack Freeland, Maria Muñoz, Edmond O’Donnell, Justin Langerman, Morgan Darrow, Jessica Bergonio, Julissa Suarez-Navarro, Steven Thorpe, Robert Canter, Robert Lor Randall, Kathrin Plath, Kermit L. Carraway, Owen N. Witte, Thomas G. Graeber, Janai R. Carr-Ascher
Journal: Clinical Cancer Research (2024)

High-grade complex karyotype sarcomas are a heterogeneous group of tumors with a uniformly poor prognosis. Within complex karyotype sarcomas, there are innumerable genetic changes but identifying those that are clinically relevant has been challenging.
Translational Imaging in Cerebral Tumors
Authors: Alexey Surov, Jan Borggrefe
Journal: Clinical Cancer Research (2024)

Summary Despite emerging possibilities of molecular histopathologic characterization, multiparametric MRI plays a key role in the diagnosis and classification of cerebral tumors. Imaging may also provide additional information about relevant histopathologic features of these tumors. See related article by Gao et al., p. 4876
Clinical and genomic diversity of Treponema pallidum subspecies pallidum to inform vaccine research: an international, molecular epidemiology study
Authors: Arlene C Seña, Mitch M Matoga, Ligang Yang, Eduardo Lopez-Medina, Farhang Aghakhanian, Jane S Chen, Everton B Bettin, Melissa J Caimano, Wentao Chen, Jonny A Garcia-Luna, Christopher M Hennelly, Edward Jere, Yinbo Jiang, Jonathan J Juliano, Petra Pospíšilová, Lady Ramirez, David Šmajs, Joseph D Tucker, Fabio Vargas Cely, Heping Zheng, Irving F Hoffman, Bin Yang, M Anthony Moody, Kelly L Hawley, Juan C Salazar, Justin D Radolf, Jonathan B Parr
Journal: The Lancet Microbe (2024)

The increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We aimed to explore Treponema pallidum subspecies pallidum (TPA) molecular epidemiology essential for vaccine research by analysing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data.
Real-time identification of epistatic interactions in SARS-CoV-2 from large genome collections
Authors: Gabriel Innocenti, Maureen Obara, Bibiana Costa, Henning Jacobsen, Maeva Katzmarzyk, Luka Cicin-Sain, Ulrich Kalinke, Marco Galardini
Journal: Genome biology (2024)

Abstract Background The emergence of the SARS-CoV-2 virus has highlighted the importance of genomic epidemiology in understanding the evolution of pathogens and guiding public health interventions. The Omicron variant in particular has underscored the role of epistasis in the evolution of lineages with both higher infectivity and immune escape, and therefore the necessity to update surveillance pipelines to detect them early on. Results In this study, we apply a method based on mutual information between positions in a multiple sequence alignment, which is capable of scaling up to millions of samples. We show how it can reliably predict known experimentally validated epistatic interactions, even when using as little as 10,000 sequences, which opens the possibility of making it a near real-time prediction system. We test this possibility by modifying the method to account for the sample collection date and apply it retrospectively to multiple sequence alignments for each month between March 2020 and March 2023. We detected a cornerstone epistatic interaction in the Spike protein between codons 498 and 501 as soon as seven samples with a double mutation were present in the dataset, thus demonstrating the method’s sensitivity. We test the ability of the method to make inferences about emerging interactions by testing candidates predicted after March 2023, which we validate experimentally. Conclusions We show how known epistatic interaction in SARS-CoV-2 can be detected with high sensitivity, and how emerging ones can be quickly prioritized for experimental validation, an approach that could be implemented downstream of pandemic genome sequencing efforts.
Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules
Authors: Ignasi Toledano, Fran Supek, Ben Lehner
Journal: Nature Genetics (2024)

Premature termination codons (PTCs) cause ~10-20% of inherited diseases and are a major mechanism of tumor suppressor gene inactivation in cancer. A general strategy to alleviate the effects of PTCs would be to promote translational readthrough. Nonsense suppression by small molecules has proven effective in diverse disease models, but translation into the clinic is hampered by ineffective readthrough of many PTCs. Here we directly tackle the challenge of defining drug efficacy by quantifying the readthrough of ~5,800 human pathogenic stop codons by eight drugs. We find that different drugs promote the readthrough of complementary subsets of PTCs defined by local sequence context. This allows us to build interpretable models that accurately predict drug-induced readthrough genome-wide, and we validate these models by quantifying endogenous stop codon readthrough. Accurate readthrough quantification and prediction will empower clinical trial design and the development of personalized nonsense suppression therapies.
Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis
Authors: Yunli Zhao, Ya Gao, Gordon Guyatt, Timothy M Uyeki, Ping Liu, Ming Liu, Yanjiao Shen, Xiaoyan Chen, Shuyue Luo, Xingsheng Li, Rongzhong Huang, Qiukui Hao
Journal: The Lancet (2024)

Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza.
Sleep bruxism (SB) may be not associated with obstructive sleep apnea (OSA): a comprehensive assessment employing a systematic review and meta-analysis
Authors: Bartłomiej Błaszczyk, Marta Waliszewska-Prosół, Mieszko Więckiewicz, Rafał Poręba, Piotr Niemiec, Jakub Przegrałek, Helena Martynowicz
Journal: Sleep Medicine Reviews (2024)

Associations between obstructive sleep apnea (OSA) and sleep bruxism (SB) are the subject of discussion but have not been confirmed definitively. Therefore, the objective of this meta-analysis was to examine the relationship between OSA and SB. This systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed, Embase and Web of Science were screened up to February 2024. The risk of bias was assessed with the Joanna Briggs Institute tool. 2260 records were identified, but only 14 studies were included. The odds of SB presence in OSA did not differ from the control group (OR: 1.23, 95 % CI: 0.47-3.20). The chance of SB compared to controls also did not differ in mild OSA (OR: 1.56, 95 % CI: 0.76-3.18), in moderate OSA (OR: 1.51, 95 % CI: 0.77-2.94) and in severe OSA (OR: 1.50, 95 % CI: 0.68-3.29). Additionally, the odds of SB were not increased in moderate OSA in comparison to mild OSA (OR: 1.14, 95 % CI: 0.63-2.94), in severe OSA compared to moderate OSA (OR: 1.31, 95 % CI: 0.61-2.79) or in severe OSA compared to mild OSA (OR = 1.42, 95 % CI: 0.69-2.93). The presence of SB in OSA did not differ between genders (OR: 2.14, 95 % CI: 0.65-7.05). The quality of the major studies included is low; therefore, the noted lack of correlation between OSA and SB may require further research. The relationship between OSA and SB seems to be multi-faceted. Presented results should not exempt clinicians from exact diagnosis of concomitant sleep conditions in OSA subjects.
A community engagement framework to accelerate the uptake of malaria vaccines in Africa
Authors: Nebiyu Dereje, Mosoka Papa Fallah, Nicaise Ndembi, Alemayehu Duga, Tamrat Shaweno, Merawi Aragaw, Mohammed Abdulaziz, Ngashi Ngongo, Tajudeen Raji, Jean Kaseya
Journal: Nature Medicine (2024)
Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial
Authors: John Deanfield, Subodh Verma, Benjamin M Scirica, Steven E Kahn, Scott S Emerson, Donna Ryan, Ildiko Lingvay, Helen M Colhoun, Jorge Plutzky, Mikhail N Kosiborod, G Kees Hovingh, Søren Hardt-Lindberg, Ofir Frenkel, Peter E Weeke, Søren Rasmussen, Assen Goudev, Chim C Lang, Miguel Urina-Triana, Mikko Pietilä, A Michael Lincoff
Journal: The Lancet (2024)

Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure.
Resolution of chronic inflammation and cancer
Authors: Gulcin Tezcan, Nil Yakar, Hatice Hasturk, Thomas E. Van Dyke, Alpdogan Kantarci
Journal: Periodontology 2000 (2024)

Abstract Chronic inflammation poses challenges to effective cancer treatment. Although anti‐inflammatory therapies have shown short‐term benefits, their long‐term implications may be unfavorable because they fail to initiate the necessary inflammatory responses. Recent research underscores the promise of specialized pro‐resolving mediators, which play a role in modulating the cancer microenvironment by promoting the resolution of initiated inflammatory processes and restoring tissue hemostasis. This review addresses current insights into how inflammation contributes to cancer pathogenesis and explores recent strategies to resolve inflammation associated with cancer.
COVID-19 diagnosis, vaccination during pregnancy, and adverse pregnancy outcomes of 865,654 women in England and Wales: a population-based cohort study
Authors: Elena Raffetti, Thomas Bolton, John Nolan, Luisa Zuccolo, Rachel Denholm, Gordon Smith, Ashley Akbari, Katie Harron, Gwenetta Curry, Elias Allara, Deborah A Lawlor, Massimo Caputo, Hoda Abbasizanjani, Tim Chico, Angela M Wood
Journal: The Lancet Regional Health - Europe (2024)
Genomic and Epigenomic Analysis of Plasma Cell-Free DNA Identifies Stemness Features Associated with Worse Survival in Lethal Prostate Cancer
Authors: Pradeep S. Chauhan, Irfan Alahi, Savar Sinha, Elisa M. Ledet, Ryan Mueller, Jessica Linford, Alexander L. Shiang, Jace Webster, Lilli Greiner, Breanna Yang, Gabris Ni, Ha X. Dang, Debanjan Saha, Ramandeep K. Babbra, Wenjia Feng, Peter K. Harris, Faridi Qaium, Dzifa Y. Duose, Sanchez E. Alexander, Alexander D. Sherry, Ellen B. Jaeger, Patrick J. Miller, Sydney A. Caputo, Jacob J. Orme, Fabrice Lucien, Sean S. Park, Chad Tang, Russell K. Pachynski, Oliver Sartor, Christopher A. Maher, Aadel A. Chaudhuri
Journal: Clinical Cancer Research (2024)

Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSI) is often lethal. Liquid biopsy biomarkers for this deadly form of disease remain under investigation, and underpinning mechanisms remain ill-understood.
Antivirals for treatment of severe influenza: a systematic review and network meta-analysis of randomised controlled trials
Authors: Ya Gao, Gordon Guyatt, Timothy M Uyeki, Ming Liu, Yamin Chen, Yunli Zhao, Yanjiao Shen, Jianguo Xu, Qingyong Zheng, Zhifan Li, Wanyu Zhao, Shuyue Luo, Xiaoyan Chen, Jinhui Tian, Qiukui Hao
Journal: The Lancet (2024)

The optimal antiviral drug for treatment of severe influenza remains unclear. To support updated WHO influenza clinical guidelines, this systematic review and network meta-analysis evaluated antivirals for treatment of patients with severe influenza.
The Role of Technology-based Dance Intervention for Enhancing Wellness - A Systematic Scoping Review and Meta-synthesis
Authors: Dan Tao, Roger Awan-Scully, Garrett I Ash, Alistair Cole, Pei Zhong, Yang Gao, Yan Sun, Shuai Shao, Huw Wiltshire, Julien S Baker
Journal: Ageing Research Reviews (2024)
Effect of long-term physical exercise and multidomain interventions on cognitive function and the risk of mild cognitive impairment and dementia in older adults: a systematic review with meta-analysis
Authors: Imanol Reparaz-Escudero, Mikel Izquierdo, Heike A Bischoff-Ferrari, P Martínez-Lage, Mikel L Sáez de Asteasu
Journal: Ageing Research Reviews (2024)
Feasibility of Image-guided Navigation with Electromagnetic Tracking During Robot-assisted Sentinel Node Biopsy: A Prospective Study
Authors: Laura Aguilera Saiz, Wouter J Heerink, Harald C Groen, Marijn A J Hiep, Henk G van der Poel, Esther M K Wit, Jakko A Nieuwenhuijzen, Ton A Roeleveld, André N Vis, Maarten L Donswijk, Pim J van Leeuwen, Theo J M Ruers
Journal: European Urology (2024)

Image-guided surgical navigation (IGSN) can enhance surgical precision and safety. The expansion of minimally invasive surgery has increased the demand for integration of these navigation systems into robot-assisted surgery. Our objective was to evaluate the integration of electromagnetic tracking with IGSN in robot-assisted sentinel lymph node biopsy (SLNB).
Antivenom treatment for snakebite envenoming
Authors: Jin-Long Wang
Journal: Nature Reviews Disease Primers (2024)

Antivenom treatment for snakebite envenoming V enomous snakes are widely distri buted in the world and snakebite envenoming is a medical emergency with high fatality and disability rates 1,2 .Rapid identification and assessment of the patients affected by venomous snakebite, and accurate and timely medical decisionmaking are crucial to save the lives of these patients.In their article, Gutiérrez and colleagues have comprehensively elaborated the epidemiol ogy, clinical manifestations, assessment and treatment strategies of snakebite envenoming (Gutiérrez, J. M. et al.Snakebite envenom ing.Nat.Rev. Dis.Primers 3, 17063 (2017)) 3 .However, after careful literature review, I believe that some supplements need to be made in terms of the indication of antivenom treatment [1][2][3] .Antivenom is the only specific treatment for snakebite envenoming.Monovalent serums are often given to victims of venomous snakebites of known species, and polyvalent
Integration of multiomics features for blood-based early detection of colorectal cancer
Authors: Yibo Gao, Dandan Cao, Mengfan Li, Fuqiang Zhao, Pei Wang, Shiwen Mei, Qianqian Song, Pei Wang, Yanli Nie, Wei Zhao, Sizhen Wang, Hai Yan, Xishan Wang, Yuchen Jiao, Qian Liu
Journal: Molecular Cancer (2024)

Abstract Background Early detection of colorectal cancer (CRC) significantly enhances patient outcomes. Conventional CRC screening tools, like endoscopy and stool-based tests, have constraints due to their invasiveness or suboptimal patient adherence. Recently, liquid biopsy employing plasma cell-free DNA (cfDNA) has emerged as a potential noninvasive screening technique for various malignancies. Methods In this research, we harnessed the Mutation Capsule Plus (MCP) technology to profile an array of genomic characteristics from cfDNA procured from a single blood draw. This profiling encompassed DNA methylation, the 5’ end motif, copy number variation (CNV), and genetic mutations. An integrated model built upon selected multiomics biomarkers was trained using a cohort of 93 CRC patients and 96 healthy controls. Results This model was subsequently validated in another cohort comprising 89 CRC patients and 95 healthy controls. Remarkably, the model achieved an area under the curve (AUC) of 0.981 (95% confidence interval (CI), 0.965–0.998) in the validation set, boasting a sensitivity of 92.1% (95% CI, 84.5%-96.8%) and a specificity of 94.7% (95% CI, 88.1%-98.3%). These numbers surpassed the performance of any single genomic feature. Importantly, the sensitivities reached 80% for stage I, 89.2% for stage II, and were 100% for stages III and IV. Conclusion Our findings underscore the clinical potential of our multiomics liquid biopsy test, indicating its prospective role as a noninvasive method for early-stage CRC detection. This multiomics approach holds promise for further refinement and broader clinical application.
Evolution of T-cell fitness through AML progression: enhanced bispecific T-cell engager-mediated function of bone marrow T cells at remission compared to initial diagnosis and relapse
Authors: Maryam Kazerani, Anetta Marcinek, Nora Philipp, Bettina Brauchle, Jonathan Jonas Taylor, Helena Domínguez Moreno, Andrea Terrasi, Benjamin Tast, Lisa Rohrbacher, Yingshuai Wang, Maximilian Warm, Alica-Joana Emhardt, Giulia Magno, Karsten Spiekermann, Tobias Herold, Tobias Straub, Sebastian Theurich, Gunnar Schotta, Roman Kischel, Veit L. Bücklein, Marion Subklewe
Journal: Leukemia (2024)

In acute myeloid leukemia (AML), the anti-leukemic potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and post-transplant donor lymphocyte infusion (DLI) hinges on the activity of T cells [1].Bispecific antibodies, including bispecific T-cellengager (BiTE ® ) molecules, redirect endogenous T cells against neoplastic cells for eradication by CD3-dependent T-cell activation.In B-lymphoid malignancies, high clinical efficacy has led to the approval of several T-cell-recruiting constructs [2, 3].In AML, several bispecific antibodies have been developed and have shown strong preclinical efficacy [4, 5].However, albeit early-phase I/II clinical trials in heavily pre-treated patients with R/R AML have yielded promising, dose-dependent results, sustained responses were not observed [6-8].We hypothesize that T-cell dysfunction contributes to BiTE resistance and a lack of long-term responses in AML.Evidence for the relevance of T-cell fitness to BiTE-mediated activity is derived from patients with B-cell precursor acute lymphoblastic leukemia in whom a predominance of T cells with an exhausted phenotype was associated with failure of blinatumomab treatment [9].Additionally, transcriptional profiles associated with T-cell dysfunction were found in nonresponding patients [10].Further evidence of an association between T-cell fitness and BiTE activity was found in a preclinical model of T-cell exhaustion after continuous BiTE exposure [11].So far, attempts to characterize T-cell phenotype and function in AML patients have yielded variable and sometimes contradictory results.Studies suggest that BM T cells in contrast to peripheral blood T cells better reflect the immune state and are the main mediators of BiTE-mediated cytotoxicity [12, 13].Hence, characterizing BM T cells at different time points during the course of the disease might help to guide the optimal clinical application of T-cell-based immunotherapies in AML.
Endothelial to mesenchymal transition enhances permissiveness to AAV vectors in cardiac endothelial cells
Authors: Nina Volf, Roman Vuerich, Andrea Colliva, Maria Concetta Volpe, Margherita Marengon, Lorena Zentilin, Mauro Giacca, Nadja Anneliese Ruth Ring, Simone Vodret, Luca Braga, Serena Zacchigna
Journal: Molecular Therapy (2024)

A major obstacle in inducing therapeutic angiogenesis in the heart is inefficient gene transfer to endothelial cells (ECs). Here, we identify compounds able to enhance the permissiveness of cardiac ECs to adeno-associated virus (AAV) vectors, which stand as ideal tools for in vivo gene delivery. We screened a library of >1,500 US Food and Drug Administration (FDA)-approved drugs, in combination with AAV vectors, in cardiac ECs. Among the top drugs increasing AAV-mediated transduction, we found vatalanib, an inhibitor of multiple tyrosine kinase receptors. The increased AAV transduction efficiency by vatalanib was paralleled by induction of the endothelial-to-mesenchymal transition, as documented by decreased endothelial and increased mesenchymal marker expression. Induction of the endothelial-to-mesenchymal transition by other strategies similarly increased EC permissiveness to AAV vectors. In vivo injection of AAV vectors in the heart after myocardial infarction resulted in the selective transduction of cells undergoing the endothelial-to-mesenchymal transition, which is known to happen transiently after cardiac ischemia. Collectively, these results point to the endothelial-to-mesenchymal transition as a mechanism for improving AAV transduction in cardiac ECs, with implications for both basic research and the induction of therapeutic angiogenesis in the heart.
One hundred years of EEG for brain and behaviour research
Authors: Faisal Mushtaq, Dominik Welke, Anne Gallagher, Yuri G. Pavlov, Layla Kouara, Jorge Bosch-Bayard, Jasper J. F. van den Bosch, Mahnaz Arvaneh, Amy R. Bland, Maximilien Chaumon, Cornelius Borck, Xun He, Steven J. Luck, Maro G. Machizawa, Cyril Pernet, Aina Puce, Sidney J. Segalowitz, Christine Rogers, Muhammad Awais, Claudio Babiloni, Neil W. Bailey, Sylvain Baillet, Robert C. A. Bendall, Daniel Brady, Maria L. Bringas-Vega, Niko A. Busch, Ana Calzada-Reyes, Armand Chatard, Peter E. Clayson, Michael X. Cohen, Jonathan Cole, Martin Constant, Alexandra Corneyllie, Damien Coyle, Damian Cruse, Ioannis Delis, Arnaud Delorme, Damien Fair, Tiago H. Falk, Matthias Gamer, Giorgio Ganis, Kilian Gloy, Samantha Gregory, Cameron D. Hassall, Katherine E. Hiley, Richard B. Ivry, Karim Jerbi, Michael Jenkins, Jakob Kaiser, Andreas Keil, Robert T. Knight, Silvia Kochen, Boris Kotchoubey, Olave E. Krigolson, Nicolas Langer, Heinrich R. Liesefeld, Sarah Lippé, Raquel E. London, Annmarie MacNamara, Scott Makeig, Welber Marinovic, Eduardo Martínez-Montes, Aleya A. Marzuki, Ryan K. Mathew, Christoph Michel, José d. R. Millán, Mark Mon-Williams, Lilia Morales-Chacón, Richard Naar, Gustav Nilsonne, Guiomar Niso, Erika Nyhus, Robert Oostenveld, Katharina Paul, Walter Paulus, Daniela M. Pfabigan, Gilles Pourtois, Stefan Rampp, Manuel Rausch, Kay Robbins, Paolo M. Rossini, Manuela Ruzzoli, Barbara Schmidt, Magdalena Senderecka, Narayanan Srinivasan, Yannik Stegmann, Paul M. Thompson, Mitchell Valdes-Sosa, Melle J. W. van der Molen, Domenica Veniero, Edelyn Verona, Bradley Voytek, Dezhong Yao, Alan C. Evans, Pedro Valdes-Sosa
Journal: Nature Human Behaviour (2024)