tbuckley/cabot-search huggingface dataset:
COVID-19 Sequelae and the Host Proinflammatory Response: An Analysis From the OnCovid Registry
Authors: Alessio Cortellini, Alessandra Gennari, Fanny Pommeret, Grisma Patel, Thomas Newsom-Davis, Alexia Bertuzzi, Margarita Viladot, Juan Aguilar-Company, Oriol Mirallas, Eudald Felip, Alvin J X Lee, Alessia Dalla Pria, Rachel Sharkey, Joan Brunet, MCarmen Carmona-García, John Chester, Uma Mukherjee, Lorenza Scotti, Saoirse Dolly, Ailsa Sita-Lumsden, Daniela Ferrante, Mieke Van Hemelrijck, Charlotte Moss, Beth Russell, Elia Seguí, Federica Biello, Marco Krengli, Javier Marco-Hernández, Gianluca Gaidano, Andrea Patriarca, Riccardo Bruna, Elisa Roldán, Laura Fox, Anna Pous, Franck Griscelli, Ramon Salazar, Clara Martinez-Vila, Anna Sureda, Angela Loizidou, Clara Maluquer, Annabelle Stoclin, Maria Iglesias, Paolo Pedrazzoli, Gianpiero Rizzo, Armando Santoro, Lorenza Rimassa, Sabrina Rossi, Nadia Harbeck, Ana Sanchez de Torre, Bruno Vincenzi, Michela Libertini, Salvatore Provenzano, Daniele Generali, Salvatore Grisanti, Rossana Berardi, Marco Tucci, Francesca Mazzoni, Matteo Lambertini, Marco Tagliamento, Alessandro Parisi, Federica Zoratto, Paola Queirolo, Raffaele Giusti, Annalisa Guida, Alberto Zambelli, Carlo Tondini, Antonio Maconi, Marta Betti, Emeline Colomba, Nikolaos Diamantis, Alasdair Sinclair, Mark Bower, Isabel Ruiz-Camps, David J Pinato, Georgina Hanbury, Chris Chung, Meera Patel, Gino Dettorre, Christopher C T Sng, Tamara Yu, Marianne Shawe-Taylor, Hamish D C Bain, Lee Cooper, Lucy Rogers, Katherine Belessiotis, Cian Murphy, Samira Bawany, Saira Khalique, Ramis Andaleeb, Eleanor Apthorp, Roxana Reyes, David Garcia-Illescas, Nadia Saoudi, Ariadna Roqué Lloveras, Ricard Mesia, Andrea Plaja, Marc Cucurull, Federica Grosso, Vittorio Fusco, Alice Baggi, Maristella Saponara, Luca Cantini
Journal: JNCI Journal of the National Cancer Institute (2022)

Fifteen percent of patients with cancer experience symptomatic sequelae, which impair post-COVID-19 outcomes. In this study, we investigated whether a proinflammatory status is associated with the development of COVID-19 sequelae.
Cardio-Oncology Drug Interactions: A Scientific Statement From the American Heart Association
Authors: Craig J. Beavers, Jo E. Rodgers, Aaron J. Bagnola, Theresa M. Beckie, Umberto Campia, Katherine E. Di Palo, Tochi M. Okwuosa, Eugene R. Przespolewski, Susan Dent
Journal: Circulation (2022)

In the cardio-oncology population, drug interactions are of particular importance given the complex pharmacological profile, narrow therapeutic index, and inherent risk of therapies used to manage cardiovascular disease and cancer. Drug interactions may be beneficial or detrimental to the desired therapeutic effect. Clinicians in both cardiology and oncology should be cognizant of these potential drug-drug interactions that may reduce the efficacy or safety of either cardiovascular or cancer therapies. These risks can be mitigated through increased recognition of potential drug-drug interaction, use of alternative medications when possible, and careful monitoring. This scientific statement provides clinicians with an overview of pharmacodynamic and pharmacokinetic drug-drug interactions in patients with cancer exposed to common cardiovascular and cancer medications.
TCTAP C-081 Multiple Considerations of Simple PCI Stenting for CKD Patient Prior to Kidney Transplant
Authors: Riyandi Ardi Putra Fernandes, Antonia Anna Lukito, Nicolaus Novian Dwiya Wahjoepramono, Hardi Hutabarat, Sonia Chandra
Journal: Journal of the American College of Cardiology (2022)
Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection
Authors: Tania Wong Fok Lung, Daniel Charytonowicz, Kristin G. Beaumont, Shivang S. Shah, Shwetha H. Sridhar, Claire L. Gorrie, Andre Mu, Casey E. Hofstaedter, David Varisco, Thomas H. McConville, Marija Drikic, Brandon Fowler, Andreacarola Urso, Wei Shi, Dario Fucich, Medini K. Annavajhala, Ibrahim N. Khan, Irina Oussenko, Nancy Francoeur, Melissa L. Smith, Brent R. Stockwell, Ian A. Lewis, Abderrahman Hachani, Swikrity Upadhyay Baskota, Anne-Catrin Uhlemann, Danielle Ahn, Robert K. Ernst, Benjamin P. Howden, Robert Sebra, Alice Prince
Journal: Cell Metabolism (2022)

K. pneumoniae sequence type 258 (Kp ST258) is a major cause of healthcare-associated pneumonia. However, it remains unclear how it causes protracted courses of infection in spite of its expression of immunostimulatory lipopolysaccharide, which should activate a brisk inflammatory response and bacterial clearance. We predicted that the metabolic stress induced by the bacteria in the host cells shapes an immune response that tolerates infection. We combined in situ metabolic imaging and transcriptional analyses to demonstrate that Kp ST258 activates host glutaminolysis and fatty acid oxidation. This response creates an oxidant-rich microenvironment conducive to the accumulation of anti-inflammatory myeloid cells. In this setting, metabolically active Kp ST258 elicits a disease-tolerant immune response. The bacteria, in turn, adapt to airway oxidants by upregulating the type VI secretion system, which is highly conserved across ST258 strains worldwide. Thus, much of the global success of Kp ST258 in hospital settings can be explained by the metabolic activity provoked in the host that promotes disease tolerance.
Core-binding factor acute myeloid leukemia: long-term outcome of 70 patients uniformly treated with “7+3”
Authors: K. H. Begna, X. Xu, N. Gangat, H. Alkhateeb, M. M. Patnaik, A. Al-Kali, M. A. Elliott, W. J. Hogan, M. R. Litzow, C. C. Hook, A. P. Wolanskyj-Spinner, A. Mangaonkar, R. He, A. Pardanani, M. Shah, R. P. Ketterling, A. Tefferi
Journal: Blood Cancer Journal (2022)
Comparing and contrasting risk factors for heart failure in patients with and without history of myocardial infarction: data from <scp>HOMAGE</scp> and the <scp>UK</scp> Biobank
Authors: Tripti Rastogi, Frederick K. Ho, Patrick Rossignol, Thomas Merkling, Javed Butler, Andrew Clark, Timothy Collier, Christian Delles, J Wouter Jukema, Stephane Heymans, Roberto Latini, Alexandre Mebazaa, Pierpaolo Pellicori, Peter Sever, Jan A. Staessen, Lutgarde Thijs, John G. Cleland, Naveed Sattar, Faiez Zannad, Nicolas Girerd
Journal: European Journal of Heart Failure (2022)

Myocardial infarction (MI) is among the commonest attributable risk factors for heart failure (HF). We compared clinical characteristics associated with the progression to HF in patients with or without a history of MI in the HOMAGE cohort and validated our results in UK Biobank.During a follow-up of 5.2 (3.5-5.9) years, 177 (2.4%) patients with prior MI and 370 (1.92%) patients without prior MI experienced HF onset in the HOMAGE cohort (n = 26 478, history of MI: n = 7241). Older age, male sex and higher heart rate were significant risk factors of HF onset in patients with and without prior MI. Lower renal function was more strongly associated with HF onset in patients with prior MI. Higher body mass index (BMI), systolic blood pressure and blood glucose were significantly associated with HF onset only in patients without prior MI (all p for interactions <0.05). In the UK Biobank (n = 500 001, history of MI: n = 4555), higher BMI, glycated haemoglobin, diabetes and hypertension had a stronger association with HF onset in participants without prior MI compared to participants with MI (all p for interactions <0.05).The importance of clinical risk factors associated with HF onset is dependent on whether the patient has had a prior MI. Diabetes and hypertension are associated with new-onset HF only in the absence of MI history. Patients may benefit from targeted risk management based on MI history.
Rab13 Sustains Breast Cancer Stem Cells by Supporting Tumor–Stroma Cross-talk
Authors: Hui Wang, Haibo Xu, Wei Chen, Mei Cheng, Li Zou, Qin Yang, Chi Bun Chan, Hao Zhu, Ceshi Chen, Jianyun Nie, Baowei Jiao
Journal: Cancer Research (2022)

Abstract Cancer stem cells (CSC) are supported by the tumor microenvironment, and non-CSCs can regain CSC phenotypes in certain niches, leading to limited clinical benefits of CSC-targeted therapy. A better understanding of the mechanisms governing the orchestration of the CSC niche could help improve the therapeutic targeting of CSCs. Here, we report that Rab13, a small GTPase, is highly expressed in breast CSCs (BCSC). Rab13 depletion suppressed breast cancer cell stemness, tumorigenesis, and chemoresistance by reducing tumor-stroma cross-talk. Accordingly, Rab13 controlled the membrane translocation of C-X-C chemokine receptor type 1/2 (CXCR1/2), allowing tumor cells to interact with tumor-associated macrophages and cancer-associated fibroblasts to establish a supportive BCSC niche. Targeting the Rab13-mediated BCSC niche with bardoxolone-methyl (C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1, 9-dien-28-oic acid; CDDO-Me) prevented BCSC stemness in vitro and in vivo. These findings highlight the novel regulatory mechanism of Rab13 in BCSC, with important implications for the development of therapeutic strategies for disrupting the BCSC niche. Significance: Targeting Rab13 perturbs formation of the breast cancer stem cell niche by inhibiting cross-talk between cancer cells and the tumor microenvironment, providing a therapeutic opportunity for niche-targeted breast cancer treatment.
High-Resolution Mass Spectrometry for the Measurement of PTH and PTH Fragments: Insights into PTH Physiology and Bioactivity
Authors: Candice Z. Ulmer, Kittrawee Kritmetapak, Ravinder J. Singh, Hubert W. Vesper, Rajiv Kumar
Journal: Journal of the American Society of Nephrology (2022)

Full-length parathyroid hormone (PTH 1–84) is crucial for the regulation of calcium and phosphate homeostasis and bone remodeling. PTH 1–84 is metabolized into various PTH fragments, which are measured with varying levels of efficiency by PTH immunoassays. These PTH fragments, which increase in serum as CKD progresses, could potentially modulate the effects of PTH 1–84 and contribute to CKD-associated bone disorders. To obtain a true biologic representation of total PTH bioactivity, it is necessary to measure not only PTH 1–84 but also PTH fragments that are present in circulation. Traditional second-generation PTH immunoassays collectively measure PTH 1–84, PTH fragments, and post-translationally modified PTH 1–84, making it difficult to accurately predict the character of underlying renal osteodystrophy. This review highlights current advances in methods available for PTH measurement and the clinical relevance of PTH fragments in CKD. We emphasize the usefulness of mass spectrometry as a potential reference method for PTH measurement.
TCTAP A-027 Impact of Left Ventricular Ejection Fraction (EF) on 10-Year Mortality After PCI or CABG in the SYNTAXES Trial: CABG Safer Than PCI in Reduced Ejection Fraction (rEF)
Authors: Shinichiro Masuda, Kai Ninomiya, Shigetaka Kageyama, Michael J. Mack, A. Pieter Kappetein, Marie-Claude Morice, Yoshinobu Onuma, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2022)
Cohort design and natural language processing to reduce bias in electronic health records research
Authors: Shaan Khurshid, Christopher Reeder, Lia X. Harrington, Pulkit Singh, Gopal Sarma, Samuel F. Friedman, Paolo Di Achille, Nathaniel Diamant, Jonathan W. Cunningham, Ashby C. Turner, Emily S. Lau, Julian S. Haimovich, Mostafa A. Al-Alusi, Xin Wang, Marcus D. R. Klarqvist, Jeffrey M. Ashburner, Christian Diedrich, Mercedeh Ghadessi, Johanna Mielke, Hanna M. Eilken, Alice McElhinney, Andrea Derix, Steven J. Atlas, Patrick T. Ellinor, Anthony A. Philippakis, Christopher D. Anderson, Jennifer E. Ho, Puneet Batra, Steven A. Lubitz
Journal: npj Digital Medicine (2022)

Electronic health record (EHR) datasets are statistically powerful but are subject to ascertainment bias and missingness. Using the Mass General Brigham multi-institutional EHR, we approximated a community-based cohort by sampling patients receiving longitudinal primary care between 2001-2018 (Community Care Cohort Project [C3PO], n = 520,868). We utilized natural language processing (NLP) to recover vital signs from unstructured notes. We assessed the validity of C3PO by deploying established risk models for myocardial infarction/stroke and atrial fibrillation. We then compared C3PO to Convenience Samples including all individuals from the same EHR with complete data, but without a longitudinal primary care requirement. NLP reduced the missingness of vital signs by 31%. NLP-recovered vital signs were highly correlated with values derived from structured fields (Pearson r range 0.95-0.99). Atrial fibrillation and myocardial infarction/stroke incidence were lower and risk models were better calibrated in C3PO as opposed to the Convenience Samples (calibration error range for myocardial infarction/stroke: 0.012-0.030 in C3PO vs. 0.028-0.046 in Convenience Samples; calibration error for atrial fibrillation 0.028 in C3PO vs. 0.036 in Convenience Samples). Sampling patients receiving regular primary care and using NLP to recover missing data may reduce bias and maximize generalizability of EHR research.
TCTAP C-132 Incidentally Detected Overlooked Coarctation of Aorta During Cerebral Angiography
Authors: Yusuf Ziya Sener, Ahmet Hakan Ateş, Mehmet Levent Sahiner, Ergün Baris Kaya, Enver Atalar, Tevfik Karagöz, Kudret Aytemir
Journal: Journal of the American College of Cardiology (2022)
Atrial fibrillation
Authors: Bianca J. J. M. Brundel, Xun Ai, Mellanie True Hills, Myrthe F. Kuipers, Gregory Y. H. Lip, Natasja M. S. de Groot
Journal: Nature Reviews Disease Primers (2022)

Atrial fibrillation (AF) is the most common cardiac arrhythmia despite substantial efforts to understand the pathophysiology of the condition and develop improved treatments. Identifying the underlying causative mechanisms of AF in individual patients is difficult and the efficacy of current therapies is suboptimal. Consequently, the incidence of AF is steadily rising and there is a pressing need for novel therapies. Research has revealed that defects in specific molecular pathways underlie AF pathogenesis, resulting in electrical conduction disorders that drive AF. The severity of this so-called electropathology correlates with the stage of AF disease progression and determines the response to AF treatment. Therefore, unravelling the molecular mechanisms underlying electropathology is expected to fuel the development of innovative personalized diagnostic tools and mechanism-based therapies. Moreover, the co-creation of AF studies with patients to implement novel diagnostic tools and therapies is a prerequisite for successful personalized AF management. Currently, various treatment modalities targeting AF-related electropathology, including lifestyle changes, pharmaceutical and nutraceutical therapy, substrate-based ablative therapy, and neuromodulation, are available to maintain sinus rhythm and might offer a novel holistic strategy to treat AF. Atrial fibrillation (AF) is the most common cardiac arrhythmia and is increasing in prevalence as populations age. This Primer provides an overview of AF epidemiology, the mechanisms underlying electropathology in AF, and the diagnostic approaches and treatments, and highlights important directions to improve understanding and management of AF in co-creation with patients.
Sounding the Alarm on Leiomyosarcoma Recurrence: Role of Circulating Tumor DNA
Authors: Bernd Kasper, Breelyn A. Wilky
Journal: Clinical Cancer Research (2022)

Summary Recent work confirms a bench-to-bedside approach that circulating tumor DNA is associated with outcome and objective response to chemotherapy in patients with advanced leiomyosarcoma. Liquid biopsies may be used for risk stratification in future trials guiding treatment decisions by identifying patients who are likely to benefit from chemotherapy. See related article by Madanat-Harjuoja et al., p. 2579
Genetic variation and intestinal cholesterol absorption in humans: A systematic review and a gene network analysis
Authors: Fatma B.A. Mokhtar, Jogchum Plat, Ronald P. Mensink
Journal: Progress in Lipid Research (2022)

Intestinal cholesterol absorption varies widely between individuals, which may translate into differences in responsiveness to cholesterol-lowering drugs or diets. Therefore, understanding the importance of genetic variation on cholesterol absorption rates and the complex intestinal cholesterol network is important. Based on a systematic review, genetic variants in seven genes (ABCG5, ABCG8, ABO, APOE, MTTP, NPC1L1, and LDLR) were identified that were associated with intestinal cholesterol absorption. No clear associations were found for variants in APOA4, APOB, CETP, CYP7A1, HMGCR, SCARB1, SLCO1B1, and SREBF1. The seven genes were used to construct an intestinal cholesterol absorption network. Finally, a network with fifteen additional genes (APOA1, APOA4, APOB, APOC2, APOC3, CETP, HSPG2, LCAT, LDLRAP1, LIPC, LRP1, OLR1, P4HB, SAR1B, and SDC1) was generated. The constructed network shows that cholesterol absorption is complex. Further studies are needed to validate and improve this network, which may ultimately lead to a better understanding of the wide inter-individual variability in intestinal cholesterol absorption and the development of personalized interventions.
Structure, Dynamics, and Impact of Replication Stress–Induced Structural Variants in Hepatocellular Carcinoma
Authors: Quentin Bayard, Pierre Cordier, Camille Péneau, Sandrine Imbeaud, Theo Z. Hirsch, Victor Renault, Jean-Charles Nault, Jean-Frédéric Blanc, Julien Calderaro, Chantal Desdouets, Jessica Zucman-Rossi, Eric Letouzé
Journal: Cancer Research (2022)

Abstract Oncogene activation leads to replication stress and promotes genomic instability. Here we combine optical mapping and whole-genome sequencing (WGS) to explore in depth the nature of structural variants (SV) induced by replication stress in cyclin-activated hepatocellular carcinomas (CCN-HCC). In addition to classical tandem duplications, CCN-HCC displayed frequent intra-chromosomal and interchromosomal templated insertion cycles (TIC), likely resulting from template switching events. Template switching preferentially involves active topologically associated domains that are proximal to one another within the 3D genome. Template sizes depend on the type of cyclin activation and are coordinated within each TIC. Replication stress induced continuous accumulation of SVs during CCN-HCC progression, fostering the acquisition of new driver alterations and large-scale copy-number changes at TIC borders. Together, this analysis sheds light on the mechanisms, dynamics, and consequences of SV accumulation in tumors with oncogene-induced replication stress. Significance: Optical mapping and whole-genome sequencing integration unravels a unique signature of replication stress–induced structural variants that drive genomic evolution and the acquisition of driver events in CCN-HCC.
Direct Cardiac Compression Devices to Augment Heart Biomechanics and Function
Authors: Jean Bonnemain, Pedro J. del Nido, Ellen T. Roche
Journal: Annual Review of Biomedical Engineering (2022)

The treatment of end-stage heart failure has evolved substantially with advances in medical treatment, cardiac transplantation, and mechanical circulatory support (MCS) devices such as left ventricular assist devices and total artificial hearts. However, current MCS devices are inherently blood contacting and can lead to potential complications including pump thrombosis, hemorrhage, stroke, and hemolysis. Attempts to address these issues and avoid blood contact led to the concept of compressing the failing heart from the epicardial surface and the design of direct cardiac compression (DCC) devices. We review the fundamental concepts related to DCC, present the foundational devices and recent devices in the research and commercialization stages, and discuss the milestones required for clinical translation and adoption of this technology.
Association of Cumulative Blood Pressure With Cognitive Decline, Dementia, and Mortality
Authors: Chenglong Li, Yidan Zhu, Yanjun Ma, Rong Hua, Baoliang Zhong, Wuxiang Xie
Journal: Journal of the American College of Cardiology (2022)

Elevated blood pressure (BP) has been linked to impaired cognition and dementia in older adults. However, few studies have accounted for long-term cumulative BP exposure. The aim of this study was to test whether long-term cumulative BP was independently associated with subsequent cognitive decline, incident dementia, and all-cause mortality among cognitively healthy adults. This study used data from the HRS (Health and Retirement Study) and ELSA (English Longitudinal Study of Ageing). Cumulative BP was calculated as the area under the curve using measurements from wave 0 (1998-1999) to wave 4 (2008-2009) in ELSA and wave 8 (2006-2007) to wave 10 (2010-2011) in the HRS. Outcomes included cognitive decline, incident dementia, and all-cause mortality. A total of 7,566 and 9,294 participants from ELSA and the HRS were included (44.8% and 40.2% men and median age 62.0 years [IQR: 55.0-70.0 years] and 65.0 years [IQR: 58.0-72.0 years], respectively). The median follow-up duration was 8.0 years (IQR: 4.0-8.0 years) and 8.0 years (IQR: 6.0-8.0 years), respectively. Elevated cumulative systolic BP and pulse pressure were independently associated with accelerated cognitive decline (P < 0.001 for both), elevated dementia risk (P < 0.001 for both), and all-cause mortality (P < 0.001 for both), while a significant inverse association was observed for diastolic BP. Strong dose-response relationships were identified, with similar results for the 2 cohorts. Long-term cumulative BP was associated with subsequent cognitive decline, dementia risk, and all-cause mortality in cognitively healthy adults aged ≥50 years. Efforts are required to control long-term systolic BP and pulse pressure and to maintain adequate diastolic BP.
Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia
Authors: Duncan S. Palmer, Daniel P. Howrigan, Sinéad B. Chapman, Rolf Adolfsson, Nick Bass, Douglas Blackwood, Marco P. M. Boks, Chia-Yen Chen, Claire Churchhouse, Aiden P. Corvin, Nicholas Craddock, David Curtis, Arianna Di Florio, Faith Dickerson, Nelson B. Freimer, Fernando S. Goes, Xiaoming Jia, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, Mikael Landén, Adam E. Locke, Andrew M. McIntosh, Andrew McQuillin, Derek W. Morris, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Nancy L. Pedersen, Danielle Posthuma, Andreas Reif, Neil Risch, Catherine Schaefer, Laura Scott, Tarjinder Singh, Jordan W. Smoller, Matthew Solomonson, David St. Clair, Eli A. Stahl, Annabel Vreeker, James T. R. Walters, Weiqing Wang, Nicholas A. Watts, Robert Yolken, Peter P. Zandi, Benjamin M. Neale
Journal: Nature Genetics (2022)