tbuckley/cabot-search huggingface dataset:
Author Correction: Gut microbiome pattern reflects healthy ageing and predicts survival in humans
Authors: Tomasz Wilmanski, Christian Diener, Noa Rappaport, Sushmita Patwardhan, Jack Wiedrick, Jodi Lapidus, John C. Earls, Anat Zimmer, Gustavo Glusman, Max Robinson, James T. Yurkovich, Deborah M. Kado, Jane A. Cauley, Joseph Zmuda, Nancy E. Lane, Andrew T. Magis, Jennifer C. Lovejoy, Leroy Hood, Sean M. Gibbons, Eric S. Orwoll, Nathan D. Price
Journal: Nature Metabolism (2021)
Dipeptidyl peptidase 3, a marker of the antagonist pathway of the renin–angiotensin–aldosterone system in patients with heart failure
Authors: Eva M. Boorsma, Jozine M. ter Maaten, Kevin Damman, Dirk J. van Veldhuisen, Kenneth Dickstein, Stefan D. Anker, Gerasimos Filippatos, Chim C. Lang, Marco Metra, Karine Santos, Adriaan A. Voors
Journal: European Journal of Heart Failure (2021)
Preferred reporting items for journal and conference abstracts of systematic reviews and meta-analyses of diagnostic test accuracy studies (PRISMA-DTA for Abstracts): checklist, explanation, and elaboration
Authors: Jérémie F Cohen, Jonathan J Deeks, Lotty Hooft, Jean-Paul Salameh, Daniël A Korevaar, Constantine Gatsonis, Sally Hopewell, Harriet A Hunt, Chris J Hyde, Mariska M Leeflang, Petra Macaskill, Trevor A McGrath, David Moher, Johannes B Reitsma, Anne W S Rutjes, Yemisi Takwoingi, Marcello Tonelli, Penny Whiting, Brian H Willis, Brett Thombs, Patrick M Bossuyt, Matthew D F McInnes
Journal: BMJ (2021)

For many users of the biomedical literature, abstracts may be the only source of information about a study. Hence, abstracts should allow readers to evaluate the objectives, key design features, and main results of the study. Several evaluations have shown deficiencies in the reporting of journal and conference abstracts across study designs and research fields, including systematic reviews of diagnostic test accuracy studies. Incomplete reporting compromises the value of research to key stakeholders. The authors of this article have developed a 12 item checklist of preferred reporting items for journal and conference abstracts of systematic reviews and meta-analyses of diagnostic test accuracy studies (PRISMA-DTA for Abstracts). This article presents the checklist, examples of complete reporting, and explanations for each item of PRISMA-DTA for Abstracts.
Ensheathment and Myelination of Axons: Evolution of Glial Functions
Authors: Klaus-Armin Nave, Hauke B. Werner
Journal: Annual Review of Neuroscience (2021)

Myelination of axons provides the structural basis for rapid saltatory impulse propagation along vertebrate fiber tracts, a well-established neurophysiological concept. However, myelinating oligodendrocytes and Schwann cells serve additional functions in neuronal energy metabolism that are remarkably similar to those of axon-ensheathing glial cells in unmyelinated invertebrates. Here we discuss myelin evolution and physiological glial functions, beginning with the role of ensheathing glia in preventing ephaptic coupling, axoglial metabolic support, and eliminating oxidative radicals. In both vertebrates and invertebrates, axoglial interactions are bidirectional, serving to regulate cell fate, nerve conduction, and behavioral performance. One key step in the evolution of compact myelin in the vertebrate lineage was the emergence of the open reading frame for myelin basic protein within another gene. Several other proteins were neofunctionalized as myelin constituents and help maintain a healthy nervous system. Myelination in vertebrates became a major prerequisite of inhabiting new ecological niches.
Genetic basis of lacunar stroke: a pooled analysis of individual patient data and genome-wide association studies
Authors: Matthew Traylor, Elodie Persyn, Liisa Tomppo, Sofia Klasson, Vida Abedi, Mark K Bakker, Nuria Torres, Linxin Li, Steven Bell, Loes Rutten-Jacobs, Daniel J Tozer, Christoph J Griessenauer, Yanfei Zhang, Annie Pedersen, Pankaj Sharma, Jordi Jimenez-Conde, Tatjana Rundek, Raji P Grewal, Arne Lindgren, James F Meschia, Veikko Salomaa, Aki Havulinna, Christina Kourkoulis, Katherine Crawford, Sandro Marini, Braxton D Mitchell, Steven J Kittner, Jonathan Rosand, Martin Dichgans, Christina Jern, Daniel Strbian, Israel Fernandez-Cadenas, Ramin Zand, Ynte Ruigrok, Natalia Rost, Robin Lemmens, Peter M Rothwell, Christopher D Anderson, Joanna Wardlaw, Cathryn M Lewis, Hugh S Markus
Journal: The Lancet Neurology (2021)

The genetic basis of lacunar stroke is poorly understood, with a single locus on 16q24 identified to date. We sought to identify novel associations and provide mechanistic insights into the disease.
Asexual Experimental Evolution of Yeast Does Not Curtail Transposable Elements
Authors: Piaopiao Chen, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2021)

Abstract Compared with asexual reproduction, sex facilitates the transmission of transposable elements (TEs) from one genome to another, but boosts the efficacy of selection against deleterious TEs. Thus, theoretically, it is unclear whether sex has a positive net effect on TE’s proliferation. An empirical study concluded that sex is at the root of TE’s evolutionary success because the yeast TE load was found to decrease rapidly in approximately 1,000 generations of asexual but not sexual experimental evolution. However, this finding contradicts the maintenance of TEs in natural yeast populations where sexual reproduction occurs extremely infrequently. Here, we show that the purported TE load reduction during asexual experimental evolution is likely an artifact of low genomic sequencing coverages. We observe stable TE loads in both sexual and asexual experimental evolution from multiple yeast data sets with sufficient coverages. To understand the evolutionary dynamics of yeast TEs, we turn to asexual mutation accumulation lines that have been under virtually no selection. We find that both TE transposition and excision rates per generation, but not their difference, tend to be higher in environments where yeast grows more slowly. However, the transposition rate is not significantly higher than the excision rate and the variance of the TE number among natural strains is close to its neutral expectation, suggesting that selection against TEs is at best weak in yeast. We conclude that the yeast TE load is maintained largely by a transposition–excision balance and that the influence of sex remains unclear.
Coordinated methyl readers: Functional communications in cancer
Authors: Il-Geun Park, Minsol Jeon, Hyunkyung Kim, Ji Min Lee
Journal: Seminars in Cancer Biology (2021)

Methylation is a major post-translational modification (PTM) generated by methyltransferase on target proteins; it is recognized by the epigenetic reader to expand the functional diversity of proteins. Methylation can occur on specific lysine or arginine residues localized within regulatory domains in both histone and nonhistone proteins, thereby allowing distinguished properties of the targeted protein. Methylated residues are recognized by chromodomain, malignant brain tumor (MBT), Tudor, plant homeodomain (PHD), PWWP, WD-40, ADD, and ankyrin repeats by an induced-fit mechanism. Methylation-dependent activities regulate distinct aspects of target protein function and are largely reliant on methyl readers of histone and nonhistone proteins in various diseases. Methylation of nonhistone proteins that are recognized by methyl readers facilitates the degradation of unwanted proteins, as well as the stabilization of necessary proteins. Unlike nonhistone substrates, which are mainly monomethylated by methyltransferase, histones are di- or trimethylated by the same methyltransferases and then connected to other critical regulators by methyl readers. These fine-tuned controls by methyl readers are significant for the progression or inhibition of diseases, including cancers. Here, current knowledge and our perspectives about regulating protein function by methyl readers are summarized. We also propose that expanded research on the strong crosstalk mechanisms between methylation and other PTMs via methyl readers would augment therapeutic research in cancer.
Use of Telehealth by Surgical Specialties During the COVID-19 Pandemic
Authors: Grace F. Chao, Kathleen Y. Li, Ziwei Zhu, Jeff McCullough, Mike Thompson, Jake Claflin, Maximilian Fliegner, Emma Steppe, Andrew Ryan, Chad Ellimoottil
Journal: JAMA Surgery (2021)

While telehealth use in surgery has shown to be feasible, telehealth became a major modality of health care delivery during the COVID-19 pandemic.To assess patterns of telehealth use across surgical specialties before and during the COVID-19 pandemic.Insurance claims from a Michigan statewide commercial payer for new patient visits with a surgeon from 1 of 9 surgical specialties during one of the following periods: prior to the COVID-19 pandemic (period 1: January 5 to March 7, 2020), early pandemic (period 2: March 8 to June 6, 2020), and late pandemic (period 3: June 7 to September 5, 2020).Telehealth implementation owing to the COVID-19 pandemic in March 2020.(1) Conversion rate defined as the rate of weekly new patient telehealth visits divided by mean weekly number of total new patient visits in 2019. This outcome adjusts for a substantial decrease in outpatient care during the pandemic. (2) Weekly number of new patient telehealth visits divided by weekly number of total new patient visits.Among 4405 surgeons in the cohort, 2588 (58.8%) performed telehealth in any patient care context. Specifically for new patient visits, 1182 surgeons (26.8%) used telehealth. A total of 109 610 surgical new outpatient visits were identified during the pandemic. The median (interquartile range) age of telehealth patients was 46.8 (34.1-58.4) years compared with 52.6 (38.3-62.3) years for patients who received care in-person. Prior to March 2020, less than 1% (8 of 173 939) of new patient visits were conducted through telehealth. Telehealth use peaked in April 2020 (week 14) and facilitated 34.6% (479 of 1383) of all new patient visits during that week. The telehealth conversion rate peaked in April 2020 (week 15) and was equal to 8.2% of the 2019 mean weekly new patient visit volume. During period 2, a mean (SD) of 16.6% (12.0%) of all new patient surgical visits were conducted via telehealth (conversion rate of 5.1% of 2019 mean weekly new patient visit volumes). During period 3, 3.0% (2168 of 71 819) of all new patient surgical visits were conducted via telehealth (conversion rate of 2.5% of 2019 new patient visit volumes). Mean (SD) telehealth conversion rates varied by specialty with urology being the highest (14.3% [7.7%]).Results from this study showed that telehealth use grew across all surgical specialties in Michigan in response to the COVID-19 pandemic. While rates of telehealth use have declined as in-person care has resumed, telehealth use remains substantially higher across all surgical specialties than it was prior to the pandemic.
P01.24 Ramucirumab + Docetaxel (DOC) vs PBO + DOC for Stage IV NSCLC after Disease Progression (REVEL): Indian Sub-Group Analysis
Authors: K. Prabhash, D. Doval, B. Rangarajan, N. Somani, A. Pruthi, Y. D'Yachova, T. Puri
Journal: Journal of Thoracic Oncology (2021)
PS01.05 Surgical and Clinical Outcomes With Neoadjuvant Atezolizumab in Resectable Stage IB–IIIB NSCLC: LCMC3 Trial Primary Analysis
Authors: J. Lee, J. Chaft, A. Nicholas, A. Patterson, S. Waqar, E. Toloza, E. Haura, D. Raz, K. Reckamp, R. Merritt, D. Owen, D. Finley, C. Mcnamee, J. Blasberg, E. Garon, J. Mitchell, R. Doebele, F. Baciewicz, M. Nagasaka, H. Pass, K. Schulze, S. Phan, A. Johnson, P. Bunn, B. Johnson, M. Kris, D. Kwiatkowski, I. Wistuba, D. Carbone, V. Rusch
Journal: Journal of Thoracic Oncology (2021)
MA11.10 Lung Master Protocol (Lung-MAP) Next Generation Sequencing Analysis of Advanced Squamous Cell Cancers (SWOG S1400)
Authors: D. Kozono, X. Hua, M. Wu, K. Tolba, S. Waqar, K. Dragnev, H. Cheng, F. Hirsch, P. Mack, K. Kelly, R. Herbst, D. Gandara, M. Redman
Journal: Journal of Thoracic Oncology (2021)
Leveraging microenvironmental synthetic lethalities to treat cancer
Authors: Kevin J. Metcalf, Alaa Alazzeh, Zena Werb, Valerie M. Weaver
Journal: Journal of Clinical Investigation (2021)

Treatment resistance leads to cancer patient mortality. Therapeutic approaches that employ synthetic lethality to target mutational vulnerabilities in key tumor cell signaling pathways have proven effective in overcoming therapeutic resistance in some cancers. Yet, tumors are organs composed of malignant cells residing within a cellular and noncellular stroma. Tumor evolution and resistance to anticancer treatment are mediated through a dynamic and reciprocal dialogue with the tumor microenvironment (TME). Accordingly, expanding tumor cell synthetic lethality to encompass contextual synthetic lethality has the potential to eradicate tumors by targeting critical TME circuits that promote tumor progression and therapeutic resistance. In this Review, we summarize current knowledge about the TME and discuss its role in treatment. We outline the concept of tumor cell–specific synthetic lethality and describe therapeutic approaches to expand this paradigm to leverage TME synthetic lethality to improve cancer therapy.
P01.01 HERTHENA-Lung01: A Randomized Phase 2 Study of Patritumab Deruxtecan (HER3-DXd; U3-1402) in Previously Treated Metastatic EGFR-mutated NSCLC
Authors: P. Janne, M. Johnson, Y. Goto, J.C. Yang, S. Karam, S. Chen, Y. Qiu, H. Yu, C. Yu
Journal: Journal of Thoracic Oncology (2021)
P09.13 Bone Metastases and Overall Survival in Patients with Metastatic Non-Small Cell Lung Cancer Treated with Pembrolizumab
Authors: P. Das, S. Zhao, L. Wei, A. Miah, M. Li, G. Lopez, S. Patel, A. Johns, M. Grogan, E. Bertino, K. He, P. Shields, D. Carbone, G. Otterson, C. Presley, D. Owen
Journal: Journal of Thoracic Oncology (2021)
Cardiovascular Risk Factors Are Associated With Future Cancer
Authors: Emily S. Lau, Samantha M. Paniagua, Elizabeth Liu, Manol Jovani, Shawn X. Li, Katherine Takvorian, Navin Suthahar, Susan Cheng, Greta L. Splansky, James L. Januzzi, Thomas J. Wang, Ramachandran S. Vasan, Bernard Kreger, Martin G. Larson, Daniel Levy, Rudolf A. de Boer, Jennifer E. Ho
Journal: JACC CardioOncology (2021)

The extent to which co-occurrence of cardiovascular disease (CVD) and cancer is due to shared risk factors or other mechanisms is unknown.We investigated the association of standard CVD risk factors, CVD biomarkers, preexisting CVD, and ideal CV health metrics with the development of future cancer.We prospectively followed Framingham Heart Study and PREVEND participants free of cancer at baseline, and ascertained histology-proven cancer. We studied the association of baseline CV risk factors, 10-year atherosclerotic CVD risk score, established CVD biomarkers, prevalent CVD, and AHA Life's Simple 7 CV health score with incident cancer using multivariable Cox models. Analyses of interim CVD events with incident cancer used time-dependent covariates.Among 20,305 participants (mean age 50 ± 14 years, 54% women), 2,548 incident cancer cases occurred over a median follow-up of 15.0 (13.3-15.0) surveillance years. Traditional CVD risk factors including age, sex, and smoking status were independently associated with cancer (P <0.001 for all). Estimated 10-year atherosclerotic CVD risk was also associated with future cancer (HR 1.16 per 5% increase in risk, 95% CI 1.14-1.17, P<0.001). We found that natriuretic peptides (NP) (tertile 3 vs 1: HR 1.40, 95% CI 1.03-1.91, p=0.035) was associated with incident cancer, but not high sensitivity troponin (hs-cTn) (p=0.47). Prevalent CVD and the development of interim CV events were not associated with higher risk of subsequent cancer. However, ideal CV health was associated with lower future cancer risk (HR 0.95 per 1-point increase in AHA health score, 95% CI 0.92-0.99, p=0.009).CVD risk as captured by traditional CVD risk factors, 10-year atherosclerotic CVD risk score, and NP concentrations are associated with increased risk of future cancer. Conversely, a heart healthy lifestyle is associated with a reduced risk of future cancer. Our data suggest that the association between CVD and future cancer is attributable to shared risk factors.
Abstract 16878: Cardiac Overexpression of RXFP1 via AAV9 Gene Therapy Sensitizes Myocardial Inotropic Response to Serelaxin
Authors: Siva Teja Devarakonda, Adolfo G Mauro, Chad Cain, Fadi N Salloum
Journal: Circulation (2020)

Background: The pleiotropic hormone relaxin has been shown to mediate physiologic responses during pregnancy by facilitating increases in vascular compliance and cardiac output. While relaxin signaling has been attributed to increases in atrial inotropy, the hormonal effects on ventricular contractility have not been explored in vivo . In this study, we investigated the dose-response effects of recombinant human relaxin (serelaxin) on ventricular mechanics. Methods and Results: Adult male CD1 mice were anesthetized and mechanically ventilated prior to Millar cardiac catheterization. A pressure-volume catheter was advanced into the left ventricle (LV), and baseline systolic and diastolic pressure/volume (PV) loops were recorded (Pre). Mice were injected with either saline, 10 μg/kg (low dose) or 1 mg/kg (high dose) of serelaxin, and PV loops were obtained after stabilization (Post) . Mice injected with 1 mg/kg demonstrated significantly higher LV contractility ( Fig A ) independent of preload ( Fig B ). These responses were not observed with low dose. In order to further examine the role of RXFP1 in modulating these responses, healthy CD1 were injected with AAV9-RXFP1 or empty vector as control and receptor overexpression was confirmed four weeks later via qPCR ( Fig C ). PV loop analysis showed an increased inotropic response [ΔP Max , Δ(dP/dt) Max ] and improved relaxation kinetics [Δ(dP/dt) Min , Δτ] in RXFP1-overexpressing mice at a lower dose of serelaxin, when compared to empty vector mice ( Fig D ). Conclusions: Our data show a novel, dose-dependent correlation between serelaxin and ventricular inotropic and lusitropic responses in mice. These responses were observed at a lower drug dose in cardiac RXFP1-overexpressing mice. We propose that further investigation of this phenomenon could advance the therapeutic, cardioprotective effects associated with relaxin therapy in different etiologies of heart failure that may exhibit changes in RXFP1 expression.
The genetic architecture of structural left–right asymmetry of the human brain
Authors: Zhiqiang Sha, Dick Schijven, Amaia Carrion-Castillo, Marc Joliot, Bernard Mazoyer, Simon E. Fisher, Fabrice Crivello, Clyde Francks
Journal: Nature Human Behaviour (2021)

Left-right hemispheric asymmetry is an important aspect of healthy brain organization for many functions including language, and it can be altered in cognitive and psychiatric disorders. No mechanism has yet been identified for establishing the human brain's left-right axis. We performed multivariate genome-wide association scanning of cortical regional surface area and thickness asymmetries, and subcortical volume asymmetries, using data from 32,256 participants from the UK Biobank. There were 21 significant loci associated with different aspects of brain asymmetry, with functional enrichment involving microtubule-related genes and embryonic brain expression. These findings are consistent with a known role of the cytoskeleton in left-right axis determination in other organs of invertebrates and frogs. Genetic variants associated with brain asymmetry overlapped with those associated with autism, educational attainment and schizophrenia. Comparably large datasets will likely be required in future studies, to replicate and further clarify the associations of microtubule-related genes with variation in brain asymmetry, behavioural and psychiatric traits.
COVID-19: angiotensin II in development of lung immunothrombosis and vasculitis mimics – Author's reply
Authors: Dennis McGonagle, Charlie Bridgewood, Athimalaipet V Ramanan, James F M Meaney, Abdulla Watad
Journal: The Lancet Rheumatology (2021)

We thank Graham Lloyd-Jones and Matthijs Oudkerk for their comments on our recent Viewpoint on vasculitis and novel vasculitis mimics in COVID-19.1McGonagle D Bridgewood C Ramanan A Meaney J Watad A COVID-19 vasculitis and novel vasculitis mimics.Lancet Rheumatol. 2021; 3: e224-e233Summary Full Text Full Text PDF PubMed Scopus (124) Google Scholar In our Viewpoint, we mentioned several mechanisms, including pulmonary microembolisation, systemic RNAaemia with arteriolar and venous thrombosis, and other factors contributing to the thrombotic phenotypes that can mimic vasculitis. The authors point out that angiotensin II might play a role in this immunothrombotic process, and they point to one animal model in particular in which angiotensin II was implicated and associated with accelerated arteriolar thrombus formation and leukocyte recruitment in venules. Thus, the authors propose that, after the initial viral-angiotensin-converting enzyme 2 (ACE2) receptor interaction, increased angiotensin II concentrations can further trigger endothelial inflammation and more extensive in situ immunothrombosis. Of course, there are several other studies incriminating ACE2 in cardiovascular physiology, and a multiplicity of mechanisms consequent to its dysregulation might facilitate viral entry into cells and also concomitantly block generation of the anti-inflammatory angiotensin-(1–7).2Abassi Z Higazi AAR Kinaneh S Armaly Z Skorecki K Heyman SN ACE2, COVID-19 infection, inflammation, and coagulopathy: missing pieces in the puzzle.Front Physiol. 2020; 11574753Crossref PubMed Scopus (50) Google Scholar Indeed, following this line of enquiry, a recent small study showed that recombinant ACE2 reduces systemic concentrations of angiotensin II in patients with severe COVID-19, with a hint that this might be a helpful therapeutic strategy.3Khan A Benthin C Zeno B et al.A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome.Crit Care. 2017; 21: 234Crossref PubMed Scopus (488) Google Scholar Further studies will clarify this approach, but we believe that the predominant mechanism of pulmonary intravascular coagulopathy4McGonagle D O'Donnell JS Sharif K Emery P Bridgewood C Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia.Lancet Rheumatol. 2020; 2: e437-e445Summary Full Text Full Text PDF PubMed Scopus (589) Google Scholar is likely to be due to immunothrombosis resulting from the juxtaposition of the large alveolar and capillary surface areas in the context of severe viral pneumonia, and it is the SARS-CoV-2 tropism for ACE2 on pneumocytes, rather than the systemic factors suggested by Lloyd-Jones and Oudkerk, that determines the outcome of severe infection. Further clinical trials will clarify this. COVID-19 vasculitis and novel vasculitis mimicsCOVID-19: angiotensin II in development of lung immunothrombosis and vasculitis mimics