tbuckley/cabot-search huggingface dataset:
Tightly Constrained Genome Reduction and Relaxation of Purifying Selection during Secondary Plastid Endosymbiosis
Authors: Kavitha Uthanumallian, Cintia Iha, Sonja I Repetti, Cheong Xin Chan, Debashish Bhattacharya, Sebastian Duchene, Heroen Verbruggen
Journal: Molecular Biology and Evolution (2021)

Endosymbiosis, the establishment of a former free-living prokaryotic or eukaryotic cell as an organelle inside a host cell, can dramatically alter the genomic architecture of the endosymbiont. Plastids or chloroplasts, the light-harvesting organelle of photosynthetic eukaryotes, are excellent models to study this phenomenon because plastid origin has occurred multiple times in evolution. Here, we investigate the genomic signature of molecular processes acting through secondary plastid endosymbiosis-the origination of a new plastid from a free-living eukaryotic alga. We used phylogenetic comparative methods to study gene loss and changes in selective regimes on plastid genomes, focusing on green algae that have given rise to three independent lineages with secondary plastids (euglenophytes, chlorarachniophytes, and Lepidodinium). Our results show an overall increase in gene loss associated with secondary endosymbiosis, but this loss is tightly constrained by the retention of genes essential for plastid function. The data show that secondary plastids have experienced temporary relaxation of purifying selection during secondary endosymbiosis. However, this process is tightly constrained, with selection relaxed only relative to the background in primary plastids. Purifying selection remains strong in absolute terms even during the endosymbiosis events. Selection intensity rebounds to pre-endosymbiosis levels following endosymbiosis events, demonstrating the changes in selection efficiency during different origin phases of secondary plastids. Independent endosymbiosis events in the euglenophytes, chlorarachniophytes, and Lepidodinium differ in their degree of relaxation of selection, highlighting the different evolutionary contexts of these events. This study reveals the selection-drift interplay during secondary endosymbiosis and evolutionary parallels during organellogenesis.
558TiP Phase I study of effector-function enhanced monoclonal antibody (mAb), SEA-TGT, in advanced malignancies
Authors: V. Ribrag, D. Davar, E. Garralda, G. Curigliano, J. Zain, A. Mehta, A. Minchom, R.E. Sanborn, F. Foss, H.K. Oberoi, A. Forero-Torres, S. Ansell
Journal: Annals of Oncology (2021)
312P Survival of breast cancer patients with brain metastases treated with radiotherapy in Ontario, Canada: A population-based study
Authors: R. Chehade, X.Y. Wang, M.N. Rosen, A. Sahgal, S. Das, R. Saskin, B. Zhang, H. Soliman, K.K-W. Chan, K.J. Jerzak
Journal: Annals of Oncology (2021)
Beyond “consistent with” adaptation: Is there a robust test for music adaptation?
Authors: Parker Tichko, Kevin A. Bird, Gregory Kohn
Journal: Behavioral and Brain Sciences (2021)

Abstract In their article, Mehr et al. conclude that the design features of music are consistent with adaptations for credible signaling. Although appealing to design may seem like a plausible basis for identifying adaptations, probing adaptive theories of music must be done at the genomic level and will require a functional understanding of the genomic, phenotypic, and fitness properties of music.
Repurposing Colchicine for Heart Disease
Authors: Nadia Bouabdallaoui, Jean-Claude Tardif
Journal: The Annual Review of Pharmacology and Toxicology (2021)

Colchicine is one of the most ancient medications still prescribed. It is extracted from the Colchicum autumnale plant and is routinely used because of its broad anti-inflammatory properties to treat gout and familial Mediterranean fever. Colchicine has shown efficacy in various clinical settings in which inflammation is a key component, and it has become first-line therapy for acute and recurrent pericarditis. Two landmark clinical trials have recently shown that colchicine significantly improves cardiovascular outcomes on background statin and antiplatelet therapy in patients with coronary artery disease, supporting its role for the prevention of atherothrombotic events. Favorable results have also emerged in atrial fibrillation. We herein briefly review the most recent data related to the multiple cardiovascular conditions for which colchicine has been successfully repurposed.
138P Anaphylaxis and hypersensitivity in trials of intravenous pertuzumab + trastuzumab (PH IV) or the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) for HER2-positive breast cancer (BC)
Authors: S.M. Swain, A. Tan, L. Gianni, S. Kümmel, C. Dang, A. Schneeweiss, J. O'Shaughnessy, H. Liu, C. Aguila, S. Heeson, H. Macharia, E. Restuccia, S. Loibl
Journal: Annals of Oncology (2021)
328TiP Phase III study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09
Authors: S.M. Tolaney, R. Barroso-Sousa, Z. Jiang, Y.H. Park, M. Rimawi, C. Saura Manich, A. Schneeweiss, M. Toi, T. Yu, J. Shetty, P. Herbolsheimer, S. Loibl
Journal: Annals of Oncology (2021)
Violence-related distress and lung function in two longitudinal studies of youth
Authors: Kristina Gaietto, Yueh-Ying Han, Erick Forno, Leonard B. Bacharier, Wanda Phipatanakul, Theresa W. Guilbert, Michael D. Cabana, Kristie Ross, Joshua Blatter, Edna Acosta-Pérez, Gregory E. Miller, Rafael E. de la Hoz, Franziska J. Rosser, Sandy Durrani, Glorisa Canino, Stephen R. Wisniewski, Juan C. Celedón
Journal: European Respiratory Journal (2021)

Exposure to violence has been associated with lower lung function in cross-sectional studies.We examined whether increasing violence-related distress over time is associated with worse lung function and worse asthma control or quality of life in a secondary analysis of a 48-week randomised clinical trial in 98 youth with asthma (aged 9-16 years) treated with low-dose inhaled corticosteroids (Vitamin D Kids Asthma Study (VDKA)). We then replicated our findings for lung function in a prospective study of 232 Puerto Rican youth followed for an average of 5.4 years. Violence-related distress was assessed using the Checklist of Children's Distress Symptoms (CCDS) scale. Our outcomes of interest were percent predicted lung function measures and (in VDKA only) asthma control (assessed using the Asthma Control Test) and asthma-related quality of life (assessed using the Pediatric Asthma Quality of Life Questionnaire (PAQLQ)).In a multivariable analysis in VDKA, each 1-point increment in CCDS score was associated with decrements of 3.27% in forced expiratory volume in 1 s (FEV1) % pred (95% CI -6.44- -0.22%; p=0.04), 2.65% in forced vital capacity (FVC) % pred (95% CI -4.86- -0.45%; p=0.02) and 0.30 points in the overall PAQLQ score (95% CI -0.50- -0.10 points; p<0.01). Similar findings for FEV1 and FVC were obtained in the prospective study of Puerto Rican youth.Our findings suggest that violence-related distress may worsen lung function and quality of life in youth with asthma (even those treated with low-dose inhaled corticosteroids), and further support policies to reduce exposure to violence among children in the USA and Puerto Rico.
Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy
Authors: Tommaso Morelli, Kohei Fujita, Gil Redelman-Sidi, Paul T Elkington
Journal: Thorax (2021)

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. However, immune-related adverse events (irAEs) are a common side effect which can mimic infection. Additionally, treatment of irAEs with corticosteroids and other immunosuppressant agents can lead to opportunistic infection, which we have classed as immunotherapy infections due to immunosuppression. However, emerging reports demonstrate that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, in contrast to the majority of reported cases. These infections are characterised by a dysregulated inflammatory immune response, and so we propose they are described as immunotherapy infections due to dysregulated immunity. This review summarises the rapidly emerging evidence of these phenomena and proposes a new framework for considering infection in the context of cancer immunotherapy.
1084P PLATForM: Descriptive analysis from a randomised, phase II study of novel spartalizumab combinations in previously treated unresectable/metastatic melanoma
Authors: C. Robert, D. Schadendorf, G.V. Long, P. Ascierto, S. Intagliata, F. Meier, A.A.M. van der Veldt, A. Ribas, J.S. Weber, L. Stenson, N. Solovieff, A-L. Louveau, A.D. Boran, J.J. Grob, R. Dummer
Journal: Annals of Oncology (2021)
122MO Quality of life from the Penelope-B study on high-risk HR+/HER2- early breast cancer patients treated with endocrine therapy with or without palbociclib
Authors: J.A. García-Saenz, F. Marmé, H.S. Rugo, M. Untch, H. Bonnefoi, S-B. Kim, H.D. Bear, N. McCarthy, K. Gelmon, M. Martin, C.M. Kelly, T. Reimer, M. Toi, E.H. Law, M. Gnant, A. Makris, S. Seiler, N. Burchardi, V. Nekljudova, S. Loibl
Journal: Annals of Oncology (2021)
1790P Single-cell ex vivo drug response testing platform on fluid samples from patients with solid tumors
Authors: L. Bankel, R. Wegmann, K.J. Dedes, D. Franzen, P.K. Bode, M. Zoche, F. Arnold, H. Moch, M.G. Manz, C. Britschgi, B. Snijder
Journal: Annals of Oncology (2021)
294P Cell-free DNA (cfDNA) workflow for the risk definition of dose-limiting and recurrent neutropenia in patients treated with first-line endocrine therapy (ET) and cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) for metastatic breast cancer (MBC)
Authors: L. Palmero, R. Mazzeo, S. Buriolla, L. Bortot, A. Franzoni, A. Michelotti, G. Turra, M. Zilli, E.C. Stefani, L. Allegri, P. Di Nardo, R. Roncato, M. Bonotto, E. Cecchin, B. Belletti, G. Toffoli, G. Baldassarre, G. Damante, L. Gerratana, F. Puglisi
Journal: Annals of Oncology (2021)
Gated Versus First-Pass Radioangiography in the Evaluation of Left-to-Right Shunts
Authors: DAVOR ETEROVI??, ??ELJKO DUJI??, SLAVKO POPOVI??, DINKO MIRI??
Journal: Clinical Nuclear Medicine (1995)

Excluding regurgitant ventricles and multiple shunting, left-to-right shunts of the central circulation can be evaluated from the difference between the right ventricular stroke counts (SCRV) and the left ventricular stroke counts (SCLV), which are obtained from gated radioangiography. The pulmonary-to-systemic flow ratio (QP/Qs) is equated to SCRV/SCLV in atrial shunts and to SCLV/SCRV in ventricular and ductal shunts. In this paper, the potentials of the stroke count method have been compared to the gamma fit first-pass technique, incorporating the recent refinements in ductal shunts and deconvolution of the pulmonary curve. In 17 patients with left-to-right shunt, the stroke count method and the gamma fit method correlated moderately with oximetry (r = .71 and .87), respectively. The gamma variate method appeared superior in the detection and estimation of small shunts, whereas when QP/Qs was two or larger, the stroke count method yielded closer agreement with oximetry data.
Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial
Authors: Niels Jongs, Tom Greene, Glenn M Chertow, John J V McMurray, Anna Maria Langkilde, Ricardo Correa-Rotter, Peter Rossing, C David Sjöström, Bergur V Stefansson, Robert D Toto, David C Wheeler, Hiddo J L Heerspink
Journal: The Lancet Diabetes & Endocrinology (2021)
Dynamic self-assembly of mannosylated-calix[4]arene into micelles for the delivery of hydrophobic drugs
Authors: Padincharapad Sreedevi, Jyothi B. Nair, Manu M. Joseph, Vishnu Priya Murali, Cherumuttathu H. Suresh, R. Luxmi Varma, Kaustabh Kumar Maiti
Journal: Journal of Controlled Release (2021)
Prostate Cancer Early Detection
Authors: _ _
Journal: Journal of the National Comprehensive Cancer Network (2007)

Prostate cancer is the most commonly diagnosed cancer in American men and the third leading cause of cancer-related deaths. However, the decision whether to pursue early detection of prostate cancer is complex; because not all men with prostate cancer will die of this disease, treatment is not necessary for some. These guidelines are intended to help men and clinicians choose a program for early detection of prostate cancer and make decisions about the need for prostate biopsy. For the most recent version of the guidelines, please visit NCCN.org
Race, Lung Function, and Long-Term Mortality in the National Health and Nutrition Examination Survey III
Authors: Meredith C. McCormack, Aparna Balasubramanian, Elizabeth C. Matsui, Roger D. Peng, Robert A. Wise, Corinne A. Keet
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Race, Lung Function, and Long-Term Mortality in the National Health and Nutrition Examination Survey III." American Journal of Respiratory and Critical Care Medicine, 205(6), pp. 723–724
HRT supplies are increasing, but access is still a problem for many, says charity
Authors: Elisabeth Mahase
Journal: BMJ (2021)

A combination of difficulty in accessing healthcare during the pandemic and ongoing shortages of certain drugs has led to many patients with menopausal symptoms still struggling to get hormone replacement therapy, the British Menopause Society (BMS) has warned.1

Before the pandemic, years of HRT shortages had left patients frustrated and clinicians and pharmacists unable to fulfil patients’ needs.2 However, despite an improvement in supplies since the beginning of 2020, some still remain unavailable.

Haitham Hamoda, chair of the society and a …
711P Outcomes according to genomic characteristics of patients with metastatic urothelial carcinoma in phase I/II trials
Authors: C.J. Pobel, D. Teyssonneau, A. Procureur, L. Verlingue, F. Facchinetti, G. Roubaud, M. Cabart, M. Ningarhari, A. Geraud, L. Friboulet, J-C. Soria, C. Massard, Y. Loriot, A. Italiano
Journal: Annals of Oncology (2021)
304P Incidence and resolution of eribulin-induced peripheral neuropathy (IRENE) in patients with locally advanced or metastatic breast cancer
Authors: M. Schmidt, C. Jackisch, T. Hesse, O. Hoffmann, B.J. Heinrich, T-W. Park-Simon, E-M. Grischke, R. Weide, H. Müller-Huesmann, M. Welslau, J. Wu, H. Schmitz, C. Engelbrecht, H-J. Lück
Journal: Annals of Oncology (2021)
Targeting the IL-6–Yap–Snail signalling axis in synovial fibroblasts ameliorates inflammatory arthritis
Authors: Rebecca A Symons, Fabio Colella, Fraser L Collins, Alexandra J Rafipay, Karolina Kania, Jessica J McClure, Nathan White, Iain Cunningham, Sadaf Ashraf, Elizabeth Hay, Kevin S Mackenzie, Kenneth A Howard, Anna H K Riemen, Antonio Manzo, Susan M Clark, Anke J Roelofs, Cosimo De Bari
Journal: Annals of the Rheumatic Diseases (2021)

We aimed to understand the role of the transcriptional co-factor Yes-associated protein (Yap) in the molecular pathway underpinning the pathogenic transformation of synovial fibroblasts (SF) in rheumatoid arthritis (RA) to become invasive and cause joint destruction.Synovium from patients with RA and mice with antigen-induced arthritis (AIA) was analysed by immunostaining and qRT-PCR. SF were targeted using Pdgfrα-CreER and Gdf5-Cre mice, crossed with fluorescent reporters for cell tracing and Yap-flox mice for conditional Yap ablation. Fibroblast phenotypes were analysed by flow cytometry, and arthritis severity was assessed by histology. Yap activation was detected using Yap-Tead reporter cells and Yap-Snail interaction by proximity ligation assay. SF invasiveness was analysed using matrigel-coated transwells.Yap, its binding partner Snail and downstream target connective tissue growth factor were upregulated in hyperplastic human RA and in mouse AIA synovium, with Yap detected in SF but not macrophages. Lineage tracing showed polyclonal expansion of Pdgfrα-expressing SF during AIA, with predominant expansion of the Gdf5-lineage SF subpopulation descending from the embryonic joint interzone. Gdf5-lineage SF showed increased expression of Yap and adopted an erosive phenotype (podoplanin+Thy-1 cell surface antigen-), invading cartilage and bone. Conditional ablation of Yap in Gdf5-lineage cells or Pdgfrα-expressing fibroblasts ameliorated AIA. Interleukin (IL)-6, but not tumour necrosis factor alpha (TNF-α) or IL-1β, Jak-dependently activated Yap and induced Yap-Snail interaction. SF invasiveness induced by IL-6 stimulation or Snail overexpression was prevented by Yap knockdown, showing a critical role for Yap in SF transformation in RA.Our findings uncover the IL-6-Yap-Snail signalling axis in pathogenic SF in inflammatory arthritis.
Abstract 13076: Impact of Haptoglobin Genotype and Diabetes Status on Anacetrapib-Mediated Increase in Cholesterol Efflux Capacity
Authors: Jaskeerat Gulati, Mark Metzinger, Suzanne Saldanha, Ayea El-Ghazali, Sneha Deodhar, Aseruchi Chindah, Colby R Ayers, Anand Rohatgi
Journal: Circulation (2019)

Introduction: Impaired cholesterol efflux (CEC) from macrophages to apolipoprotein A-I is linked to coronary heart disease (CHD). Haptoglobin (Hp) binds to apolipoprotein A-I, and the Hp copy numbe...
Birth Volume and Geographic Distribution of US Hospitals With Obstetric Services From 2010 to 2018
Authors: Sara C. Handley, Molly Passarella, Heidi M. Herrick, Julia D. Interrante, Scott A. Lorch, Katy B. Kozhimannil, Ciaran S. Phibbs, Elizabeth E. Foglia
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Timely access to clinically appropriate obstetric services is critical to the provision of high-quality perinatal care. <h3>Objective</h3> To examine the geographic distribution, proximity, and urban adjacency of US obstetric hospitals by annual birth volume. <h3>Design, Setting, and Participants</h3> This retrospective population-based cohort study identified US hospitals with obstetric services using the American Hospital Association (AHA) Annual Survey of Hospitals and Centers for Medicare &amp; Medicaid provider of services data from 2010 to 2018. Obstetric hospitals with 10 or more births per year were included in the study. Data analysis was performed from November 6, 2020, to April 5, 2021. <h3>Exposure</h3> Hospital birth volume, defined by annual birth volume categories of 10 to 500, 501 to 1000, 1001 to 2000, and more than 2000 births. <h3>Main Outcomes and Measures</h3> Outcomes assessed by birth volume category were percentage of births (from annual AHA data), number of hospitals, geographic distribution of hospitals among states, proximity between obstetric hospitals, and urban adjacency defined by urban influence codes, which classify counties by population size and adjacency to a metropolitan area. <h3>Results</h3> The study included 26 900 hospital-years of data from 3207 distinct US hospitals with obstetric services, reflecting 34 054 951 associated births. Most infants (19 327 487 [56.8%]) were born in hospitals with more than 2000 births/y, and 2 528 259 (7.4%) were born in low-volume (10-500 births/y) hospitals. More than one-third of obstetric hospitals (37.4%; 10 064 hospital-years) were low volume. A total of 46 states had obstetric hospitals in all volume categories. Among low-volume hospitals, 18.9% (1904 hospital-years) were not within 30 miles of any other obstetric hospital and 23.9% (2400 hospital-years) were within 30 miles of a hospital with more than 2000 deliveries/y. Isolated hospitals (those without another obstetric hospital within 30 miles) were more frequently low volume, with 58.4% (1112 hospital-years) located in noncore rural areas. <h3>Conclusions and Relevance</h3> In this cohort study, marked variations were found in birth volume, geographic distribution, proximity, and urban adjacency among US obstetric hospitals from 2010 to 2018. The findings related to geographic isolation and rural-urban distribution of low-volume obstetric hospitals suggest the need to balance proximity with volume to optimize effective referral and access to high-quality perinatal care.
Expansion of a SARS-CoV-2 Delta variant with an 872 nt deletion encompassing ORF7a, ORF7b and ORF8, Poland, July to August 2021
Authors: Natalia Mazur-Panasiuk, Lukasz Rabalski, Tomasz Gromowski, Grzegorz Nowicki, Michal Kowalski, Witold Wydmanski, Piotr Szulc, Maciej Kosinski, Karolina Gackowska, Natalia Drweska-Matelska, Jakub Grabowski, Anna Piotrowska-Mietelska, Boguslaw Szewczyk, Krystyna Bienkowska-Szewczyk, Jakub Swadzba, Pawel Labaj, Maciej Grzybek, Krzysztof Pyrc
Journal: Eurosurveillance (2021)

Routine genomic surveillance on samples from COVID-19 patients collected in Poland during summer 2021 revealed the emergence of a SARS-CoV-2 Delta variant with a large 872 nt deletion. This change, confirmed by Sanger and deep sequencing, causes complete loss of ORF7a , ORF7b , and ORF8 genes. The index case carrying the deletion is unknown. The standard pipeline for sequencing may mask this deletion with a long stretch of N’s. Effects of this deletion on phenotype or immune evasion needs further study.
Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people
Authors: Joshua Elliott, Matthew Whitaker, Barbara Bodinier, Oliver Eales, Steven Riley, Helen Ward, Graham Cooke, Ara Darzi, Marc Chadeau-Hyam, Paul Elliott
Journal: PLoS Medicine (2021)

Background Rapid detection, isolation, and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and investigated whether predictive symptoms differ between the B.1.1.7 (Alpha) lineage (predominating as of April 2021 in the US, UK, and elsewhere) and wild type. Methods and findings We obtained throat and nose swabs with valid SARS-CoV-2 PCR test results from 1,147,370 volunteers aged 5 years and above (6,450 positive cases) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This study involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%–27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR-positive samples with N-gene cycle threshold value &lt; 34 ( N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least 1 symptom identified 7 symptoms as jointly and positively predictive of PCR positivity in rounds 2–7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss, and muscle aches. The resulting model (rounds 2–7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same 7 symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although when comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. The main limitations of our study are (i) potential participation bias despite random sampling of named individuals from the National Health Service register and weighting designed to achieve a representative sample of the population of England and (ii) the necessary reliance on self-reported symptoms, which may be prone to recall bias and may therefore lead to biased estimates of symptom prevalence in England. Conclusions Where testing capacity is limited, it is important to use tests in the most efficient way possible. We identified a set of 7 symptoms that, when considered together, maximize detection of COVID-19 in the community, including infection with the B.1.1.7 lineage.