tbuckley/cabot-search huggingface dataset:
Evolution after Whole-Genome Duplication: Teleost MicroRNAs
Authors: Thomas Desvignes, Jason Sydes, Jerôme Montfort, Julien Bobe, John H Postlethwait
Journal: Molecular Biology and Evolution (2021)

MicroRNAs (miRNAs) are important gene expression regulators implicated in many biological processes, but we lack a global understanding of how miRNA genes evolve and contribute to developmental canalization and phenotypic diversification. Whole-genome duplication events likely provide a substrate for species divergence and phenotypic change by increasing gene numbers and relaxing evolutionary pressures. To understand the consequences of genome duplication on miRNA evolution, we studied miRNA genes following the teleost genome duplication (TGD). Analysis of miRNA genes in four teleosts and in spotted gar, whose lineage diverged before the TGD, revealed that miRNA genes were retained in ohnologous pairs more frequently than protein-coding genes, and that gene losses occurred rapidly after the TGD. Genomic context influenced retention rates, with clustered miRNA genes retained more often than nonclustered miRNA genes and intergenic miRNA genes retained more frequently than intragenic miRNA genes, which often shared the evolutionary fate of their protein-coding host. Expression analyses revealed both conserved and divergent expression patterns across species in line with miRNA functions in phenotypic canalization and diversification, respectively. Finally, major strands of miRNA genes experienced stronger purifying selection, especially in their seeds and 3'-complementary regions, compared with minor strands, which nonetheless also displayed evolutionary features compatible with constrained function. This study provides the first genome-wide, multispecies analysis of the mechanisms influencing metazoan miRNA evolution after whole-genome duplication.
In vivo remodeling of human cell-assembled extracellular matrix yarns
Authors: Laure Magnan, Fabien Kawecki, Gaëlle Labrunie, Maude Gluais, Julien Izotte, Sébastien Marais, Marie-Pierre Foulc, Mickaël Lafourcade, Nicolas L'Heureux
Journal: Biomaterials (2021)

Cell-assembled extracellular matrix (CAM) has been used to produce vascular grafts. While these completely biological vascular grafts performed well in clinical trials, the in vivo remodeling and inflammatory response of this truly "bio" material has not yet been investigated. In this study, human CAM yarns were implanted subcutaneously in nude rats to investigate the innate immune response to this matrix. The impact of processing steps relevant to yarn manufacturing was evaluated (devitalization, decellularization, gamma sterilization, and twisting). We observed that yarns were still present after six months, and were integrated into a non-inflamed loose connective tissue. The CAM was repopulated by fibroblastic cells and blood vessels. While other yarns caused minor peripheral inflammation at an early stage (two weeks of implantation), gamma sterilization triggered a more intense host response dominated by the presence of M1 macrophages. The inflammatory response was resolved at six months. Yarn mechanical strength was decreased two weeks after implantation except for the more compact "twisted" yarn. While the strength of other yarns was stable after initial remodeling, the gamma-sterilized yarn continued to lose mechanical strength over time and was weaker than devitalized (control) yarns at six months. This is the first study to formally demonstrate that devitalized human CAM is very long-lived in vivo and does not trigger a degradative response, but rather is very slowly remodeled. This data supports a strategy to produce human textiles from CAM yarn for regenerative medicine applications where a scaffold with low inflammation and long-term mechanical properties are critical.
Rocket science: what spaceflight can tell us about skeletal health on Earth
Authors: Kathryn E Ackerman, Kristin L Popp, Mary L Bouxsein
Journal: British Journal of Sports Medicine (2021)

In BJSM , Gabel and colleagues in their paper ‘Pre-flight Exercise and Bone Metabolism Predict Unloading-Induced Bone Loss due to Spaceflight’ study skeletal health in a unique population of ‘occupational athletes’: astronauts.1 Astronauts frequently experience cardiovascular deconditioning, immune suppression, balance disorders, strength deficits and bone loss as a result of space travel.2 After more than 50 years of space missions, various contributors to bone loss in astronauts have been postulated—microgravity, radiation, stress, metabolic disruption and altered calcium homeostasis all likely play a role.3 Using high-resolution three-dimensional imaging (HR-pQCT), Gabel et al report declines in bone mineral density (BMD), bone microstructure and strength at the distal tibia, although minimal changes at the distal radius.1 Their findings are broadly similar to prior reports, revealing an average rate of bone decline nearly 10-fold higher than that seen in postmenopausal women, although with remarkable interindividual variability seen in these astronauts.4 Notably, their analyses bring several new insights to our understanding of unloading-induced bone loss.

For spaceflight of 3.5–7 months, mission time predicted tibial BMD loss linearly, with accelerated trabecular bone loss in longer flights.1 …
Covid-19: Is the UK heading towards mandatory vaccination of healthcare workers?
Authors: Jacqui Wise
Journal: BMJ (2021)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Covid-19: Is the UK heading towards mandatory vaccination of healthcare workers? Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Collagen β(1-O) galactosyltransferase 2 deficiency contributes to lipodystrophy and aggravates NAFLD related to HMW adiponectin in mice
Authors: Junru Yang, Lingling He, Meixin Gao, Fan Xiao, Fuyang Zhang, Shiwei Wang, Yang Shu, Xiaohui Ye, Wenzheng Qu, Liying Li, Hongshan Wei
Journal: Metabolism (2021)
HLA Haploidentical versus Matched Unrelated Donor Transplants with Post-Transplant Cyclophosphamide based prophylaxis
Authors: Mahasweta Gooptu, Rizwan Romee, Andrew St. Martin, Mukta Arora, Monzr M. Al Malki, Joseph H. Antin, Christopher N Bredeson, Claudio G Brunstein, Saurabh Chhabra, Ephraim J Fuchs, Nilanjan Ghosh, Michael Richard Grunwald, Christopher G Kanakry, Natasha Kekre, Joseph P McGuirk, Ian McNiece, Rohtesh S. Mehta, Marco Mielcarek, Filippo Milano, Dipenkumar Modi, Ran Reshef, Scott R Solomon, Mark A Schroeder, Edmund K Waller, Yoshihiro Inamoto, Robert J. Soiffer, Mary Eapen
Journal: Blood (2021)
The LSC17 Leukemic Stem Cell Signature Predicts Outcome in Pediatric Acute Myeloid Leukemia
Authors: Jenny L. Smith, Rhonda E. Ries, Anders Kolb, Todd A Alonzo, Robert B Gerbing, Yussanne Ma, Marco A. Marra, Hamid Bolouri, Soheil Meshinchi
Journal: Blood (2017)
Bacterial and fungal respiratory co-infection among patients admitted to ICU with COVID-19: A retrospective cohort study in a UK hospital
Authors: A. May, N. Swetenham, M. Pandey, V. Taylor, H. Hughes, J. Underwood
Journal: Gut (2021)

Introduction and Objectives Bacterial and fungal co-infections contribute to mortality and morbidity to patients with Influenza  We aimed to evaluate respiratory tract flora, degree of co-infection and outcomes of patients admitted with COVID- 19 to ICU in a UK hospital  Productive cough is rare in COVID-19 and therefore identification of co-pathogens requires invasive sampling which is non-practical outside of ICU  Methods A retrospective cohort of patients admitted to ICU with confirmed SARS-CoV-2 infection was identified  Demographic data, co-morbidities, microbiology results from respiratory samples, clinical biomarkers and clinical outcomes were analysed  Respiratory samples were divided into early samples within 5 days of hospital admission that would represent community acquired organisms and late samples that would represent hospital acquired organisms  Results 77 patients were admitted to ICU with COVID-19 from February to June 2020  Respiratory samples were collected by non-directed bronchoalveolar lavage(NBL)(171 samples) and BAL from 61 patients  37/61(60 7%) patients isolated a pathogen  39 patients had an early sample with 14/ 39(35 9%) isolating a pathogen  Table 1 lists organisms isolated from early and late samples  On antimicrobial susceptibility testing of early respiratory isolates 2/7 Staphylococcus aureus were methicillin resistant and 2/5 Haemophilus influenza isolates were co-amoxiclav resistant  29/77(37 7%) patients died during their admission to hospital  There was no significant correlation between in hospital mortality and isolation of a pathogen in early or any respiratory sample (Fisher's exact test p=0 512 and p=1 0 respectively)  Conclusions A higher proportion of bacterial co-pathogens were seen in our study population compared to previously reported non-UK data1  Identifying true co-infection is complicated by fever, chest x-rays infiltrates and high CRP being characteristic of severe COVID-19  Staphylococcus aureus was commonly isolated in both early and late respiratory samples and supports empiric antibiotic regimens with staphylococcal activity for secondary bacterial pneumonia in COVID-19 as currently recommended by NICE2  However the proportion of resistant organisms isolated needs to be studied in larger cohorts to ensure guideline recommended antibiotics are appropriate
Venous and Arterial Thromboembolism in Patients With Cancer
Authors: Lorenzo Gervaso, Heloni Dave, Alok A. Khorana
Journal: JACC CardioOncology (2021)

Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Arterial thromboembolism, including myocardial infarction and stroke, is also prevalent. Risk differs in subgroups, with higher rates observed in specific cancers including pancreas, stomach, and multiple myeloma. Thromboprophylaxis is recommended for most patients with active cancer hospitalized for medical illnesses and after major cancer surgery. Outpatient thromboprophylaxis is not routinely recommended, but emerging data suggest that a high-risk population that benefits from pharmacological thromboprophylaxis can be identified using a validated risk tool. Direct oral anticoagulants are emerging as the preferred new option for the treatment of cancer-associated VTE, although low-molecular-weight heparin remains a standard for patients at high bleeding risk. Management of VTE beyond the first 6 months and challenging clinical situations including intracranial metastases and thrombocytopenia require careful management in balancing the benefits and risks of anticoagulation and remain major knowledge gaps in evidence.
A Decade of Advances in Single‐Cell Nanocoating for Mammalian Cells
Authors: Hojae Lee, Nayoung Kim, Hyeong Bin Rheem, Beom Jin Kim, Ji Hun Park, Insung S. Choi
Journal: Advanced Healthcare Materials (2021)

Abstract Strategic advances in the single‐cell nanocoating of mammalian cells have noticeably been made during the last decade, and many potential applications have been demonstrated. Various cell‐coating strategies have been proposed via adaptation of reported methods in the surface sciences and/or materials identification that ensure the sustainability of labile mammalian cells during chemical manipulation. Here an overview of the methodological development and potential applications to the healthcare sector in the nanocoating of mammalian cells made during the last decade is provided. The materials used for the nanocoating are categorized into polymers, hydrogels, polyphenolic compounds, nanoparticles, and minerals, and the corresponding strategies are described under the given set of materials. It also suggests, as a future direction, the creation of the cytospace system that is hierarchically composed of the physically separated but mutually interacting cellular hybrids.
Relating transdermal delivery plasma pharmacokinetics with in vitro permeation test (IVPT) findings using diffusion and compartment-in-series models
Authors: Xin Liu, Yuri G. Anissimov, Jeffrey E. Grice, Hanumanth Srikanth Cheruvu, Priyanka Ghosh, Sam G. Raney, Howard I. Maibach, Michael S. Roberts
Journal: Journal of Controlled Release (2021)
Abstract PO-066: Relationship between <i>KEAP1/NFE2L2</i> pathway activation and radiation resistance in oral cavity cancer
Authors: Li Guan, Hongbin Cao, Angela Hui, Shirley Kwok, Vignesh Viswanathan, Dhanya Nambiar, Rie V. Eyben, Brittany Holmes, Christina Kong, Maximilian Diehn, Quynh-Thu Le
Journal: Clinical Cancer Research (2021)

Abstract Radiotherapy (RT) is one of the primary treatment modalities for head and neck squamous cell carcinoma (HNSCC) either in the definitive or the adjuvant setting. Unfortunately, despite therapeutic and technological advances in radiotherapy, some patients will have persistence tumor or develop locoregional failure, resulting in significant morbidity and mortality. Presently, there is no biomarker that can reliably identify HNSCC that is resistant to RT. Recent genomic sequencing studies show that mutations in the KEAP1/NFE2L2 pathway exist in HNSCC. However, very little data is available with regards to the relationship between RT resistance and activating mutation or pathway hyperactivation of this pathway in HNSCC. Moreover, the mechanism by which dysregulation of this pathway can lead to RT resistance in HNSCC is poorly understood. Therefore, the project is aimed to study the relationship between KEAP1/NFE2L2 mutations and patient outcomes in HNSCC. To address this aim, DNA sequencing strategies and tissue microarray (TMA) are used to identify mutations and/or a hyperactivation protein signature of the KEAP1/NFE2L2 oxidative stress pathway in an oral cavity cancer patient cohorts (N = 69[MOU1]) treated with surgery and adjuvant RT. In addition, identified mutations are introduced into HNSCC cell lines and mouse xenografts to study the effect of these mutations on radiation response and to identify the mechanism by which they mediate radiation resistance. Here we find that 6% of oral cavity cancer patients harbor mutation in this pathway, primarily in a hotspot in the NFE2L2 gene. NFE2L2 mutation is associated with 100% in-field recurrence after radiotherapy. Strong co-expression of two downstream targets of this pathway (HO1 and NQO1) in tumor cells on the TMA strongly correlates with NFE2L2 mutation and in-field recurrence after RT. Finally, overexpression of the mutated NFE2L2 gene in HNC cell lines lead to increased ROS and radioresistance. Our findings suggest oral cavity cancers harboring activating mutation or a hyperactivation protein signature of the KEAP1/NFE2L2 pathway are more radioresistant. Work is ongoing to validate these findings in other types of HNSCC and to determine how to enhance radiation effectiveness in mutated tumors. Citation Format: Li Guan, Hongbin Cao, Angela Hui, Shirley Kwok, Vignesh Viswanathan, Dhanya Nambiar, Rie V. Eyben, Brittany Holmes, Christina Kong, Maximilian Diehn, Quynh-Thu Le. Relationship between KEAP1/NFE2L2 pathway activation and radiation resistance in oral cavity cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-066.
Effect of Corneal Cross-linking versus Standard Care on Keratoconus Progression in Young Patients
Authors: Daniel F.P. Larkin, Kashfia Chowdhury, Jennifer M. Burr, Mathew Raynor, Matthew Edwards, Stephen J. Tuft, Catey Bunce, Emilia Caverly, Caroline Doré, Susmito Biswas, Catey Bunce, Jennifer Burr, Emilia Caverly, Kashfia Chowdhury, Caroline Doré, Matthew Edwards, Lisa French, Stephen Kaye, Anne Klepacz, Dimitra Kopsini, Frank Larkin, Mathew Raynor, Stephen Tuft, Sue Webber, Colin Willoughbys
Journal: Ophthalmology (2021)

To examine the efficacy and safety of corneal cross-linking (CXL) for stabilization of progressive keratoconus.Observer-masked, randomized, controlled, parallel-group superiority trial.Sixty participants 10 to 16 years of age with progressive keratoconus, one eye of each deemed the study eye.The study eye was randomized to either CXL plus standard care or standard care alone, with spectacle or contact lens correction as necessary for vision.The primary outcome was steep keratometry (K2) in the study eye as a measure of the steepness of the cornea at 18 months. Secondary outcomes included keratoconus progression defined as a 1.5-diopter (D) increase in K2, visual acuity, keratoconus apex corneal thickness, and quality of life.Of 60 participants, 30 were randomized to CXL and standard care groups. Of these, 30 patients in the CXL group and 28 patients in the standard care group were analyzed. Mean K2 in the study eye 18 months after randomization was 49.7 D (standard deviation [SD], 3.8 D) in the CXL group and 53.4 D (SD, 5.8 D) in the standard care group. The adjusted mean difference in K2 in the study eye was -3.0 D (95% confidence interval [CI], -4.9 to -1.1 D; P = 0.002), favoring CXL. Adjusted differences between groups in uncorrected and corrected vision favored eyes receiving CXL: -0.31 logarithm of the minimum angle of resolution (logMAR; 95% CI, -0.50 to -0.11 logMAR; P = 0.002) and -0.51 logMAR (95% CI, -1.37 to 0.35 logMAR; P = 0.002). Keratoconus progression in the study eye occurred in 2 patients (7%) randomized to CXL compared with 12 patients (43%) randomized to standard care. The unadjusted odds ratio suggests that on average, patients in the CXL arm had 90% (odds ratio, 0.1; 95% CI, 0.02-0.48; P = 0.004) lower odds of experiencing progression compared with those receiving standard care.CXL arrests progression of keratoconus in the majority of young patients. CXL should be considered as a first-line treatment in progressive disease. If the arrest of keratoconus progression induced by CXL is sustained in longer follow-up, particular benefit may be derived from avoiding a later requirement for contact lens wear or corneal transplantation.
Inhibition of mammalian target of rapamycin (mTOR) induces phosphatidylinositol 3 kinase-dependent and Mnk-mediated eIF4E phosphorylation
Authors: Xuerong Wang, Ping Yue, Haian Fu, Fadlo Khuri, Shi-Yong Sun
Journal: Cancer Research (2007)

3735  The initiation factor eukaryotic translation initiation factor 4E (eIF4E) plays a key regulatory role in initiating translation of mRNAs, including those encoding oncogenic proteins. Thus, eIF4E is considered a survival protein involved in cell cycle progression, cell transformation and apoptotic resistance. Phosphorylation of eIF4E (usually at Ser209) increases its affinity for the cap of mRNA, and may also favor its entry into initiation complexes. The best candidate for eIF4E phosphorylation is the MAPK-activated protein kinase Mnk1, which physically associates with eIF4F and directly phosphorylates eIF4E at Ser209. Mammalian target of rapamycin (mTOR) inhibitors suppress cap-dependent translation through inhibition of phosphorylation of eIF4E-binding protein 1 (4E-BP1). Paradoxically, we have shown that inhibition of mTOR signaling by mTOR inhibitors increases eIF4E phosphorylation in cancer cells (Sun et al. Cancer Research, 2005). In this study, we focused on revealing the mechanism by which mTOR inhibition increases eIF4E phosphorylation. Silencing of either mTOR or raptor could mimic mTOR inhibitors’ effects in increasing eIF4E phosphorylation. Moreover, knockdown of mTOR but not p70S6K abrogated rapamycin’s ability to increase eIF4E phosphorylation. Thus, these results indicate that mTOR inhibitor-induced eIF4E phosphorylation is secondary to mTOR/raptor inhibition and independent of p70S6K. mTOR inhibitors failed to increase eIF4E phosphorylation in phosphatidylinositol 3 kinase (PI3K) deficient cells, furthering the notion that mTOR inhibitors induce a PI3K-dependent eIF4E phosphorylation. We noted that mTOR inhibitors lost their activity in increasing eIF4E phosphorylation only in cells where both Mnk1 and Mnk2 are knocked out, indicating that mTOR inhibitors increase eIF4E phosphorylation through a Mnk-dependent mechanism. Since PI3K deficiency also inhibited rapamycin-induced Mnk phosphorylation, we conclude that mTOR inhibition increases eIF4E phosphorylation through a PI3K-dependent and Mnk-mediated mechanism. (Supported by GCC Distinguished Cancer Scholar award, NIH grant RO1 CA118450-01 and DOD grant W81XWH-05-0027-IMPACT).
Systematic Assessment of Online Health Information for Coronary Revascularization
Authors: Irbaz Hameed, N. U. Farrukh Hameed, Christian T. Oakley, Ivancarmine Gambardella, Claudio Bravo, Dominick J. Angiolillo, Mario Gaudino
Journal: JAMA Internal Medicine (2021)

This cross-sectional study examines the readability, accuracy, content, quality, and suitability of online health information on coronary artery bypass grafting or percutaneous coronary intervention for patients.
Recommendations for respiratory syncytial virus surveillance at the national level
Authors: Anne C. Teirlinck, Eeva K. Broberg, Are Stuwitz Berg, Harry Campbell, Rachel M. Reeves, AnnaSara Carnahan, Bruno Lina, Gatis Pakarna, Håkon Bøås, Hanna Nohynek, Hanne-Dorthe Emborg, Harish Nair, Janine Reiche, Jesus Angel Oliva, Joanne O’Gorman, John Paget, Karol Szymanski, Kostas Danis, Maja Socan, Manuel Gijon, Marie Rapp, Martina Havlíčková, Ramona Trebbien, Raquel Guiomar, Siddhivinayak S. Hirve, Silke Buda, Sylvie van der Werf, Adam Meijer, Thea K. Fischer
Journal: European Respiratory Journal (2021)

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections and hospitalisations among young children and is globally responsible for many deaths in young children, especially in infants aged &lt;6 months. Furthermore, RSV is a common cause of severe respiratory disease and hospitalisation among older adults. The development of new candidate vaccines and monoclonal antibodies highlights the need for reliable surveillance of RSV. In the European Union (EU), no up-to-date general recommendations on RSV surveillance are currently available. Based on outcomes of a workshop with 29 European experts in the field of RSV virology, epidemiology and public health, we provide recommendations for developing a feasible and sustainable national surveillance strategy for RSV that will enable harmonisation and data comparison at the European level. We discuss three surveillance components: active sentinel community surveillance, active sentinel hospital surveillance and passive laboratory surveillance, using the EU acute respiratory infection and World Health Organization (WHO) extended severe acute respiratory infection case definitions. Furthermore, we recommend the use of quantitative reverse transcriptase PCR-based assays as the standard detection method for RSV and virus genetic characterisation, if possible, to monitor genetic evolution. These guidelines provide a basis for good quality, feasible and affordable surveillance of RSV. Harmonisation of surveillance standards at the European and global level will contribute to the wider availability of national level RSV surveillance data for regional and global analysis, and for estimation of RSV burden and the impact of future immunisation programmes.
Abstract 16568: Risk Factors for Prolonged Length of Stay Following Stage II procedure in the Single Ventricle Reconstruction Trial
Authors: Steven M Schwartz, Minmin Lu, Richard G Ohye, Kevin D Hill, Andrew M Atz, Maryam Naim, Ismee Williams, Caren Goldberg, Alan Lewis, Frank Pigula, Peter Manning, Christian Pizarro, Paul Chai, Phillip Burch, Carolyn Dunbar-Masterson, Jonathan Kaltman, Kirk Kanter, Lynn A Sleeper, Julie Schonbeck, Nancy Ghanayem
Journal: Circulation (2012)

Background: The Single Ventricle Reconstruction trial randomized patients with single right ventricle lesions to a modified Blalock-Taussig shunt (MBTS) or Right Ventricle to Pulmonary Artery Shunt...