tbuckley/cabot-search huggingface dataset:
Identification of the skeletal progenitor cells forming osteophytes in osteoarthritis
Authors: Anke J Roelofs, Karolina Kania, Alexandra J Rafipay, Meike Sambale, Stephanie T Kuwahara, Fraser L Collins, Joanna Smeeton, Maxwell A Serowoky, Lynn Rowley, Hui Wang, René Gronewold, Chrysa Kapeni, Simón Méndez-Ferrer, Christopher B Little, John F Bateman, Thomas Pap, Francesca V Mariani, Joanna Sherwood, J Gage Crump, Cosimo De Bari
Journal: Annals of the Rheumatic Diseases (2020)

Objectives Osteophytes are highly prevalent in osteoarthritis (OA) and are associated with pain and functional disability. These pathological outgrowths of cartilage and bone typically form at the junction of articular cartilage, periosteum and synovium. The aim of this study was to identify the cells forming osteophytes in OA. Methods Fluorescent genetic cell-labelling and tracing mouse models were induced with tamoxifen to switch on reporter expression, as appropriate, followed by surgery to induce destabilisation of the medial meniscus. Contributions of fluorescently labelled cells to osteophytes after 2 or 8 weeks, and their molecular identity, were analysed by histology, immunofluorescence staining and RNA in situ hybridisation. Pdgfrα-H2BGFP mice and Pdgfrα-CreER mice crossed with multicolour Confetti reporter mice were used for identification and clonal tracing of mesenchymal progenitors. Mice carrying Col2-CreER , Nes-CreER , LepR-Cre , Grem1-CreER , Gdf5-Cre, Sox9-CreER or Prg4-CreER were crossed with tdTomato reporter mice to lineage-trace chondrocytes and stem/progenitor cell subpopulations. Results Articular chondrocytes, or skeletal stem cells identified by Nes , LepR or Grem1 expression, did not give rise to osteophytes. Instead, osteophytes derived from Pdgfrα -expressing stem/progenitor cells in periosteum and synovium that are descendants from the Gdf5 -expressing embryonic joint interzone. Further, we show that Sox9 -expressing progenitors in periosteum supplied hybrid skeletal cells to the early osteophyte, while Prg4 -expressing progenitors from synovial lining contributed to cartilage capping the osteophyte, but not to bone. Conclusion Our findings reveal distinct periosteal and synovial skeletal progenitors that cooperate to form osteophytes in OA. These cell populations could be targeted in disease modification for treatment of OA.
AB0004 Molecular analysis of hla-b27 haplotypes in the croatian population
Authors: Z Grubic, P Peric, V Kerhin-Brkljacic, E Cecuk-Jelicic, R Zunec, A Kastelan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> HLA-B27 is strongly associated with ankylosing spondylitis (AS) and most studies in the last years suggest that B27 molecule itself could be directly involved in the aetiology of AS. On the other hand, some studies suppose existence of additional gene involved in AS. That gene could also be located inside the HLA region. <h3>Objectives</h3> The aim of this study was to analyse the polymorphism at neighbouring HLA-loci in the group of B27 positive AS patients and B27 positive unrelated healthy individuals. <h3>Methods</h3> All 52 B27 positive AS patients and 32 B27 positive controls were DNA typed for B27 subtypes, Cw and DRB1 alleles by PCR-SSP method. <h3>Results</h3> Three different ancestral haplotypes were found in the patient group: B*2705-Cw*0202 (82.3%), B*2705-Cw*0102 (13.8%), and B*2705-Cw*0202 (6.9%). Comparison between patients and controls did not show any significant differences. Analysis of distribution of DRB1 alleles revealed that DRB1*01 allele was the most present allele among B*27 positive individuals (21.5% in AS group and 23.4% in control group). DRB1*0301 allele was significantly more frequent in patients than in controls (9.6% vs. 1.6%; p = 0.03), while lower frequency of DRB1*0701 allele among patients is marginally significant (1.9% vs 7.8%; p = 0.055). Furthermore, the linkage disequilibrium between observed between second most frequent allele (DRB1*16) and B*27 has to be noted as characteristic for our population. <h3>Conclusion</h3> Our results suggest that HLA-Cw alleles are not involved in aetiology of AS. The possible role of some DRB1 alleles, as well as non HLA markers around HLA-B locus in necessary to confirm on a larger group of B27 positive individuals.
Associations of a Metal Mixture Measured in Multiple Biomarkers with IQ: Evidence from Italian Adolescents Living near Ferroalloy Industry
Authors: Julia A. Bauer, Katrina L. Devick, Jennifer F. Bobb, Brent A. Coull, David Bellinger, Chiara Benedetti, Giuseppa Cagna, Chiara Fedrighi, Stefano Guazzetti, Manuela Oppini, Donatella Placidi, Thomas F. Webster, Roberta F. White, Qiong Yang, Silvia Zoni, Robert O. Wright, Donald R. Smith, Roberto G. Lucchini, Birgit Claus Henn
Journal: Environmental Health Perspectives (2020)

BACKGROUND: Research on the health effects of chemical mixtures has focused mainly on early life rather than adolescence, a potentially important developmental life stage.OBJECTIVES: We examined associations of a metal mixture with general cognition in a cross-sectional study of adolescents residing near ferromanganese industry, a source of airborne metals emissions.METHODS: We measured manganese (Mn), lead (Pb), copper (Cu), and chromium (Cr) in hair, blood, urine, nails, and saliva from 635 Italian adolescents 10-14 years of age.Full-scale, verbal, and performance intelligence quotient (FSIQ, VIQ, PIQ) scores were assessed using the Wechsler Intelligence Scale for Children-III.Multivariable linear regression and Bayesian kernel machine regression (BKMR) were used to estimate associations of the metal mixture with IQ.In secondary analyses, we used BKMR's hierarchical variable selection option to inform biomarker selection for Mn, Cu, and Cr.RESULTS: Median metal concentrations were as follows: hair Mn, 0:08 lg=g; hair Cu, 9:6 lg=g; hair Cr, 0:05 lg=g; and blood Pb, 1:3 lg=dL.Adjusted models revealed an inverted U-shaped association between hair Cu and VIQ, consistent with Cu as an essential nutrient that is neurotoxic in excess.At low levels of hair Cu (10th percentile, 5:4 lg=g), higher concentrations (90th percentiles) of the mixture of Mn, Pb, and Cr (0:3 lg=g, 2:6 lg=dL, and 0:1 lg=g, respectively) were associated with a 2.9 (95% CI: -5:2, -0:5)-point decrease in VIQ score, compared with median concentrations of the mixture.There was suggestive evidence of interaction between Mn and Cu.In secondary analyses, saliva Mn, hair Cu, and saliva Cr were selected as the biomarkers most strongly associated with VIQ score.DISCUSSION: Higher adolescent levels of Mn, Pb, and Cr were associated with lower IQ scores, especially at low Cu levels.Findings also support further investigation into Cu as both beneficial and toxic for neurobehavioral outcomes.
Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier &amp; targeting ligand
Authors: Ahmed O. Elzoghby, Mona A. Abdelmoneem, Islam A. Hassanin, Mahmoud M. Abd Elwakil, Manar A. Elnaggar, Sarah Mokhtar, Jia-You Fang, Kadria A. Elkhodairy
Journal: Biomaterials (2020)
The global response to the COVID-19 pandemic: how have immunology societies contributed?
Authors: Faith Osier, Jenny P. Y. Ting, John Fraser, Bart N. Lambrecht, Marta Romano, Ricardo T. Gazzinelli, Karina R. Bortoluci, Dario S. Zamboni, Arne N. Akbar, Jennie Evans, Doug E. Brown, Kamala D. Patel, Yuzhang Wu, Ana B. Perez, Oliver Pérez, Thomas Kamradt, Christine Falk, Mira Barda-Saad, Amiram Ariel, Angela Santoni, Francesco Annunziato, Marco A. Cassatella, Hiroshi Kiyono, Valeriy Chereshnev, Alioune Dieye, Moustapha Mbow, Babacar Mbengue, Maguette D. S. Niang, Melinda Suchard
Journal: Nature reviews. Immunology (2020)

The COVID-19 pandemic is shining a spotlight on the field of immunology like never before. To appreciate the diverse ways in which immunologists have contributed, Nature Reviews Immunology invited the president of the International Union of Immunological Societies and the presidents of 15 other national immunology societies to discuss how they and their members responded following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this Viewpoint, Nature Reviews Immunology asked the presidents of 16 immunology societies from around the world to discuss how their society and its members responded to the COVID-19 pandemic. Their answers highlight the incredible contributions that immunologists around the globe have made following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
TIGIT in cancer immunotherapy
Authors: Joe-Marc Chauvin, Hassane M Zarour
Journal: Journal for ImmunoTherapy of Cancer (2020)

Tumors evade immune-mediated recognition through multiple mechanisms of immune escape. On chronic tumor antigen exposure, T cells become dysfunctional/exhausted and upregulate various checkpoint inhibitory receptors (IRs) that limit T cells' survival and function. During the last decade, immunotherapies targeting IRs such as programmed cell death receptor 1 (PD-1) and anticytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have provided ample evidence of clinical benefits in many solid tumors. Beyond CTLA-4 and PD-1, multiple other IRs are also targeted with immune checkpoint blockade in the clinic. Specifically, T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is a promising new target for cancer immunotherapy. TIGIT is upregulated by immune cells, including activated T cells, natural killer cells, and regulatory T cells. TIGIT binds to two ligands, CD155 (PVR) and CD112 (PVRL2, nectin-2), that are expressed by tumor cells and antigen-presenting cells in the tumor microenvironment. There is now ample evidence that the TIGIT pathway regulates T cell-mediated and natural killer cell-mediated tumor recognition in vivo and in vitro. Dual PD-1/TIGIT blockade potently increases tumor antigen-specific CD8
Subclinical Hypothyroidism
Authors: Robin P Peeters
Journal: New England Journal of Medicine (2017)

I agree with Rosario’s comment that ultrasonographic examination of the thyroid can provide additional evidence of thyroid autoimmunity. However, this examination is associated with a risk of incidental findings. A large proportion of diagnoses of thyroid cancer in the past two decades were probably due to diagnostic changes after the introduction of ultrasonographic examination of the neck in the 1980s. This is best illustrated by data from South Korea, where a large-scale introduction of ultrasonographic examination of the thyroid (ultrasonographic examination of the neck was offered at a low cost in addition to organized screening programs for other cancers) resulted in a rate of thyroid-cancer diagnoses in 2011 that was 15 times that observed in 1993.3 Despite this dramatic increase in incidence, thyroid cancer–specific mortality remained stable; this clearly suggests overdiagnosis of indolent thyroid cancers.  
It is estimated that overdiagnosis accounts for the majority of cases of thyroid cancer in many Western countries.4 In the context of guidelines from professional societies that emphasize avoidance of both overdiagnosis and overtreatment of thyroid cancer,5 ultrasonographic examination of the neck should not be performed routinely in the management of subclinical hypothyroidism unless there are additional clinical indications.
Engineering of tissue constructs using coaxial bioprinting
Authors: Andrew Kjar, Bailey McFarland, Keetch Mecham, Nathan Harward, Yu Huang
Journal: Bioactive Materials (2020)

Bioprinting is a rapidly developing technology for the precise design and manufacture of tissues in various biological systems or organs. Coaxial extrusion bioprinting, an emergent branch, has demonstrated a strong potential to enhance bioprinting's engineering versatility. Coaxial bioprinting assists in the fabrication of complex tissue constructs, by enabling concentric deposition of biomaterials. The fabricated tissue constructs started with simple, tubular vasculature but have been substantially developed to integrate complex cell composition and self-assembly, ECM patterning, controlled release, and multi-material gradient profiles. This review article begins with a brief overview of coaxial printing history, followed by an introduction of crucial engineering components. Afterward, we review the recent progress and untapped potential in each specific organ or biological system, and demonstrate how coaxial bioprinting facilitates the creation of tissue constructs. Ultimately, we conclude that this growing technology will contribute significantly to capabilities in the fields of in vitro modeling, pharmaceutical development, and clinical regenerative medicine.
Neuron specific enolase and matrix metaloproteinase 9 signal silent brain infarction associated with TAVI
Authors: Jonathon P. Fanning, See Louise E. Hoe, Margaret R. Passmore, Adrian G. Barnett, Nchafatso G. Obonyo, Jonathan E. Millar, Jacky Y. Suen, John F. Fraser
Journal: Circulation (2018)
Pharmacologic Treatment of Attention Deficit–Hyperactivity Disorder
Authors: Samuele Cortese
Journal: New England Journal of Medicine (2020)

Amphetamines and methylphenidate and, less often, nonstimulants (atomoxetine, clonidine, and guanfacine) are used to treat ADHD. Inattentiveness and restlessness are improved more than quality-of-life measures in short-term trials.
Cancer Risk Associated with Lorcaserin — The FDA’s Review of the CAMELLIA-TIMI 61 Trial
Authors: John Sharretts, Ovidiu Galescu, Shanti Gomatam, Eugenio Andraca-Carrera, Christian Hampp, Lisa Yanoff
Journal: New England Journal of Medicine (2020)

In early 2020, the FDA requested that the manufacturer of lorcaserin voluntarily withdraw the drug from the market because of a signal of increased cancer risk. The FDA concluded that the drug's benefits don't outweigh its risks for any identifiable patient population.
Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells
Authors: May Daher, Rafet Basar, Elif Gokdemir, Natalia Baran, Nadima Uprety, Ana Karen Nunez Cortes, Mayela Mendt, Lucila Nassif Kerbauy, Pinaki P. Banerjee, Mayra Shanley, Nobuhiko Imahashi, Li Li, Francesca Lorraine Wei Inng Lim, Mohsen Fathi, Ali Rezvan, Vakul Mohanty, Yifei Shen, Hila Shaim, Junjun Lu, Gonca Ozcan, Emily Ensley, Mecit Kaplan, Vandana Nandivada, Mustafa Bdiwi, Sunil Acharya, Yuanxin Xi, Xinhai Wan, Duncan Mak, Enli Liu, Xin Ru Jiang, Sonny Ang, Luis Muniz-Feliciano, Ye Li, Jing Wang, Shahram Kordasti, Nedyalko Petrov, Navin Varadarajan, David Marin, Lorenzo Brunetti, Richard J. Skinner, Shangrong Lyu, Leiser Silva, Rolf Turk, Mollie S. Schubert, Garrett R. Rettig, Matthew S. McNeill, Gavin Kurgan, Mark A. Behlke, Heng Li, Natalie W. Fowlkes, Ken Chen, Marina Konopleva, Richard E. Champlin, Elizabeth J. Shpall, Katayoun Rezvani
Journal: Blood (2020)
Peter Byass: global health specialist, epidemiologist, and teacher
Authors: Chris Mahony
Journal: BMJ (2020)

Epidemiologist Peter Byass was contributing to covid-19 research—including for the World Health Organization—right up to his sudden death from a heart attack in August.

A specialist in measuring health outcomes in low and middle income countries (LMICs) in Africa and Asia, Byass published more than 300 papers, led work on the health impact of climate change, and campaigned for the election of Tedros Adhanom Ghebreyesus as WHO director general in 2017. He had kept in touch with Tedros since supervising the Ethiopian’s doctoral degree when the latter was a student at the University of Nottingham 17 years earlier.

At the daily WHO covid-19 media briefing, days after Byass died, Tedros paid tribute to “my dear friend and mentor who was a committed and talented servant of global health who helped many people shine around the world.”

Tedros was one of dozens of scientists and doctors from LMICs supported by Byass, who believed strongly in building local capacity rather than having health initiatives driven from Western universities and non-governmental organisations. While he has the highest profile, Tedros is just one of several former students now in senior clinical, research, or administrative positions across Africa and south east Asia.

Byass’s passion for Africa began during a whirlwind three months in 1978, when he completed his BSc in Nottingham in July; married his wife, Margaret, in August; and began a three year stint teaching (with Margaret) at a Methodist missionary school in Sierra Leone in September. Religion played a central part throughout his …
Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia
Authors: Marie E. Faughnan, Johannes J. Mager, Steven W. Hetts, Valerie A. Palda, Kelly Lang-Robertson, Elisabetta Buscarini, Erik Deslandres, Raj S. Kasthuri, Andrea Lausman, David Poetker, Felix Ratjen, Mark S. Chesnutt, Marianne Clancy, Kevin J. Whitehead, Hanny Al-Samkari, Murali Chakinala, Miles Conrad, Daniel Cortes, Claudia Crocione, Jama Darling, Els de Gussem, Carol Derksen, Sophie Dupuis-Girod, Patrick Foy, Urban Geisthoff, James R. Gossage, Adrienne Hammill, Ketil Heimdal, Katharine Henderson, Vivek N. Iyer, Anette D. Kjeldsen, Masaki Komiyama, Kevin Korenblatt, Jamie McDonald, Jack McMahon, Justin McWilliams, Mary E. Meek, Meir Mei-Zahav, Scott Olitsky, Sara Palmer, Rose Pantalone, Jay F. Piccirillo, Beth Plahn, Mary E.M. Porteous, Marco C. Post, Ivan Radovanovic, Paul J. Rochon, Josanna Rodriguez-Lopez, Carlo Sabba, Marcelo Serra, Claire Shovlin, Dennis Sprecher, Andrew J. White, Ingrid Winship, Roberto Zarrabeitia
Journal: Annals of Internal Medicine (2020)

Description: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. Methods: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. Recommendations: The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.
EZH2 Regulates Pancreatic Cancer Subtype Identity and Tumor Progression via Transcriptional Repression of <i>GATA6</i>
Authors: Shilpa Patil, Benjamin Steuber, Waltraut Kopp, Vijayalakshmi Kari, Laura Urbach, Xin Wang, Stefan Küffer, Hanibal Bohnenberger, Dimitra Spyropoulou, Zhe Zhang, Lennart Versemann, Mark Sebastian Bösherz, Marius Brunner, Jochen Gaedcke, Philipp Ströbel, Jin-San Zhang, Albrecht Neesse, Volker Ellenrieder, Shiv K. Singh, Steven A. Johnsen, Elisabeth Hessmann
Journal: Cancer Research (2020)

Recent studies have thoroughly described genome-wide expression patterns defining molecular subtypes of pancreatic ductal adenocarcinoma (PDAC), with different prognostic and predictive implications. Although the reversible nature of key regulatory transcription circuits defining the two extreme PDAC subtype lineages "classical" and "basal-like" suggests that subtype states are not permanently encoded but underlie a certain degree of plasticity, pharmacologically actionable drivers of PDAC subtype identity remain elusive. Here, we characterized the mechanistic and functional implications of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in controlling PDAC plasticity, dedifferentiation, and molecular subtype identity. Utilization of transgenic PDAC models and human PDAC samples linked EZH2 activity to PDAC dedifferentiation and tumor progression. Combined RNA- and chromatin immunoprecipitation sequencing studies identified EZH2 as a pivotal suppressor of differentiation programs in PDAC and revealed EZH2-dependent transcriptional repression of the classical subtype defining transcription factor Gata6 as a mechanistic basis for EZH2-dependent PDAC progression. Importantly, genetic or pharmacologic depletion of EZH2 sufficiently increased GATA6 expression, thus inducing a gene signature shift in favor of a less aggressive and more therapy-susceptible, classical PDAC subtype state. Consistently, abrogation of GATA6 expression in EZH2-deficient PDAC cells counteracted the acquisition of classical gene signatures and rescued their invasive capacities, suggesting that GATA6 derepression is critical to overcome PDAC progression in the context of EZH2 inhibition. Together, our findings link the EZH2-GATA6 axis to PDAC subtype identity and uncover EZH2 inhibition as an appealing strategy to induce subtype-switching in favor of a less aggressive PDAC phenotype. SIGNIFICANCE: This study highlights the role of EZH2 in PDAC progression and molecular subtype identity and suggests EZH2 inhibition as a strategy to recalibrate GATA6 expression in favor of a less aggressive disease. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/21/4620/F1.large.jpg.
Should We Simplify Computed Tomography Angiography Reporting as Black or White vs Describing All Shades of Gray?—Reply
Authors: Angela Lowenstern, Karen P. Alexander, Pamela S. Douglas
Journal: JAMA Cardiology (2020)

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Exosome-mediated RNAi of PAK4 prolongs survival of pancreatic cancer mouse model after loco-regional treatment
Authors: Lizhou Xu, Farid N. Faruqu, Yau M. Lim, Kee Y. Lim, Revadee Liam-Or, Adam A. Walters, Paul Lavender, David Fear, Claire M. Wells, Julie Tzu-Wen Wang, Khuloud T. Al-Jamal
Journal: Biomaterials (2020)