tbuckley/cabot-search huggingface dataset:
Inhibitory effects of baicalein against herpes simplex virus type 1
Authors: Zhuo Luo, Xiu-Ping Kuang, Qing-Qing Zhou, Chang-Yu Yan, Wen Li, Hai-Biao Gong, Hiroshi Kurihara, Wei-Xi Li, Yi-Fang Li, Rong-Rong He
Journal: Acta Pharmaceutica Sinica B (2020)

Herpes simplex virus type 1 (HSV-1) is a ubiquitous and widespread human pathogen, which gives rise to a range of diseases, including cold sores, corneal blindness, and encephalitis. Currently, the use of nucleoside analogs, such as acyclovir and penciclovir, in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains. Therefore, new anti-herpetic drugs and strategies should be urgently developed. Here, we reported that baicalein, a naturally derived compound widely used in Asian countries, strongly inhibited HSV-1 replication in several models. Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue (an acyclovir-resistant strain) in vitro. In the ocular inoculation mice model, baicalein markedly reduced in vivo HSV-1/F replication, receded inflammatory storm and attenuated histological changes in the cornea. Consistently, baicalein was found to reduce the mortality of mice, viral loads both in nose and trigeminal ganglia in HSV-1 intranasal infection model. Moreover, an ex vivo HSV-1-EGFP infection model established in isolated murine epidermal sheets confirmed that baicalein suppressed HSV-1 replication. Further investigations unraveled that dual mechanisms, inactivating viral particles and inhibiting IκB kinase beta (IKK-β) phosphorylation, were involved in the anti-HSV-1 effect of baicalein. Collectively, our findings identified baicalein as a promising therapy candidate against the infection of HSV-1, especially acyclovir-resistant strain.
An epidemic CC1-MRSA-IV clone yields false-negative test results in molecular MRSA identification assays: a note of caution, Austria, Germany, Ireland, 2020
Authors: Stefan Monecke, Elisabeth König, Megan R Earls, Eva Leitner, Elke Müller, Gabriel E Wagner, David M Poitz, Lutz Jatzwauk, Teodora Vremerǎ, Olivia S Dorneanu, Alexandra Simbeck, Andreas Ambrosch, Ines Zollner-Schwetz, Robert Krause, Werner Ruppitsch, Wulf Schneider-Brachert, David C Coleman, Ivo Steinmetz, Ralf Ehricht
Journal: Eurosurveillance (2020)

We investigated why a clinical meticillin-resistant Staphylococcus aureus (MRSA) isolate yielded false-negative results with some commercial PCR tests for MRSA detection. We found that an epidemic European CC1-MRSA-IV clone generally exhibits this behaviour. The failure of the assays was attributable to a large insertion in the orfX /SCC mec integration site. To ensure the reliability of molecular MRSA tests, it is vital to monitor emergence of new SCC mec types and junction sites.
Oncolytic viruses for cancer immunotherapy
Authors: Otto Hemminki, João Manuel dos Santos, Akseli Hemminki
Journal: Journal of Hematology & Oncology (2020)

Abstract In this review, we discuss the use of oncolytic viruses in cancer immunotherapy treatments in general, with a particular focus on adenoviruses. These serve as a model to elucidate how versatile viruses are, and how they can be used to complement other cancer therapies to gain optimal patient benefits. Historical reports from over a hundred years suggest treatment efficacy and safety with adenovirus and other oncolytic viruses. This is confirmed in more contemporary patient series and multiple clinical trials. Yet, while the first viruses have already been granted approval from several regulatory authorities, room for improvement remains. As good safety and tolerability have been seen, the oncolytic virus field has now moved on to increase efficacy in a wide array of approaches. Adding different immunomodulatory transgenes to the viruses is one strategy gaining momentum. Immunostimulatory molecules can thus be produced at the tumor with reduced systemic side effects. On the other hand, preclinical work suggests additive or synergistic effects with conventional treatments such as radiotherapy and chemotherapy. In addition, the newly introduced checkpoint inhibitors and other immunomodulatory drugs could make perfect companions to oncolytic viruses. Especially tumors that seem not to be recognized by the immune system can be made immunogenic by oncolytic viruses. Logically, the combination with checkpoint inhibitors is being evaluated in ongoing trials. Another promising avenue is modulating the tumor microenvironment with oncolytic viruses to allow T cell therapies to work in solid tumors. Oncolytic viruses could be the next remarkable wave in cancer immunotherapy.
Emerging use of senolytics and senomorphics against aging and chronic diseases
Authors: Jan Martel, David M. Ojcius, Cheng‐Yeu Wu, Hsin‐Hsin Peng, Laurent Voisin, Jean‐Luc Perfettini, Yun‐Fei Ko, John D. Young
Journal: Medicinal Research Reviews (2020)

Abstract Senescence is a state of cell cycle arrest that plays an important role in embryogenesis, wound healing and protection against cancer. Senescent cells also accumulate during aging and contribute to the development of age‐related disorders and chronic diseases, such as atherosclerosis, type 2 diabetes, osteoarthritis, idiopathic pulmonary fibrosis, and liver disease. Molecules that induce apoptosis of senescent cells, such as dasatinib, quercetin, and fisetin, produce health benefits and extend lifespan in animal models. We describe here the mechanism of action of senolytics and senomorphics, many of which are derived from plants and fungi. We also discuss the possibility of using such compounds to delay aging and treat chronic diseases in humans.
IL10RA Modulates Crizotinib Sensitivity in NPM1-ALK-positive Anaplastic Large Cell Lymphoma
Authors: Nina Prokoph, Nicola Anna Probst, Liam Changwoo Lee, Jack Michael Monahan, Jamie David Matthews, Huan-Chang Liang, Klaas Bahnsen, Ivonne A Montes-Mojarro, Elif Karaca Atabay, Geeta Geeta Sharma, Vikas Malik, Hugo Larose, Sorcha Denise Forde, Stephen Paul Ducray, Cosimo Lobello, Qi Wang, Shi-Lu Luan, Sarka Pospisilova, Carlo B Gambacorti-Passerini, Amos Burke, Shahid Pervez, Andishe Attarbaschi, Andrea Janikova, Helene Pacquement, Judith Landman-Parker, Anne Lambilliotte, Gudrun Schleiermacher, Wolfram Klapper, Ralf Jauch, Wilhelm Woessmann, Gilles Vassal, Lukas Kenner, Olaf Merkel, Luca Mologni, Roberto Chiarle, Laurence Brugieres, Birgit Geoerger, Isaia Barbieri, Suzanne D Turner
Journal: Blood (2020)
Spatiotemporally tracking of nano-biofilaments inside the nuclear pore complex core
Authors: Mahmoud Shaaban Mohamed, Masaharu Hazawa, Akiko Kobayashi, Laurent Guillaud, Takahiro Watanabe-Nakayama, Mizuho Nakayama, Hanbo Wang, Noriyuki Kodera, Masanobu Oshima, Toshio Ando, Richard W. Wong
Journal: Biomaterials (2020)

Nuclear pore complex (NPC) is a gating nanomachine with a central selective barrier composed mainly of Nups, which contain intrinsically disordered (non-structured) regions (IDRs) with phenylalanine-glycine (FG) motifs (FG-NUPs). The NPC central FG network dynamics is poorly understood, as FG-NUPs liquid-liquid phase separation (LLPS) have evaded structural characterization. Moreover, the working mechanism of single FG-NUP-biofilaments residing at the central lumen is unknown. In general, flexible biofilaments are expected to be tangled and knotted during their motion and interaction. However, filament knotting visualization in real-time and space has yet to be visualized at the nanoscale. Here, we report a spatiotemporally tracking method for FG-NUP organization with nanoscale resolution, unveiling FG-NUP conformation in NPCs of colorectal cells and organoids at timescales of ~150 ms using high-speed atomic force microscopy (HS-AFM). Tracking of FG-NUP single filaments revealed that single filaments have a heterogeneous thickness in normal and cancer models which in turn affected the filament rotation and motion. Notably, FG-NUPs are overexpressed in various cancers. Using the FG-NUP inhibitor, trans-1,2-cyclohexanediol, we found that central plug size was significantly reduced and incompletely reversible back to filamentous structures in aggressive colon cancer cells and organoids. These data showed a model of FG-NUPs reversible self-assembly devolving into the central plug partial biogenesis. Taken together, HS-AFM enabled the tracking and manipulation of single filaments of native FG-NUPs which has remained evasive for decades.
Transporters (OATs and OATPs) contribute to illustrate the mechanism of medicinal compatibility of ingredients with different properties in yuanhuzhitong prescription
Authors: Ze Wang, Haihua Shang, Yazhuo Li, Chen Zhang, Yan Dong, Tao Cui, Hongbing Zhang, Xiaoyan Ci, Xiulin Yi, Tiejun Zhang, Fengying Yan, Yaping Zhang, Xing Huang, Weidang Wu, Changxiao Liu
Journal: Acta Pharmaceutica Sinica B (2020)

Various medicinal ingredients with different tastes are combined according to the theory of compatibility in Chinese materia medica to achieve a better efficacy, while the mechanism was not very clear. Here, the authors studied the interaction between ingredients and human transporters such as the kidney transporters OAT1 and OAT3, the liver transporters OATP1B1 and OATP1B3, and the intestine transporter OATP2B1 to discern the compatibility mechanism of ingredients with different tastes in the Yuanhuzhitong preparation (YHP) comprising Corydalis yanhusuo (CYH) and Angelica dahurica (AD), which could relieve pain by restraining the central system. The results show that tetrahydropalmatine (TDE), the major component of CYH, could be transported by OAT3 into kidney, OATP1B1 and OATP1B3 into liver, while imperatorin (IPT) and isoimperatorin (ISP), the two key components of AD, and AD extract showed strong inhibition to OAT1 and OAT3. What's more, AD extract also exerted strongly inhibition to human transporters OATP1B1 and OATP1B3. It was also detected that IPT, ISP, and AD extract significantly downregulated the expression of Oatp1a1, Oatp1a4, and Oatp1b2 of liver in mice. The in vivo results show that the concentration of TDE in liver and kidney significantly decreased, while the TDE concentration in blood and brain were both significantly enhanced in the presence of IPT, ISP, and AD extract. These results suggest that the ingredients in AD with pungent taste could enhance the exposure of TDE in blood and brain by inhibiting the uptake of TDE in liver and kidney. That is to say, TDE with bitter taste could "flood up" into the central nervous system to play its therapeutic effect by the cut-off of that into liver and kidney in the presence of ingredients within AD. This paper not only proves the meridian distribution of CYH in liver and kidney with the role of OAT3, OATP1B1, and OATP1B3, but also illustrates how to improve the efficacy of CYH by reasonable compatibility with AD. This study may offer a valuable clue to illustrate the mechanism of compatibility theory.
Senescence of fibroblastic reticular cells in draining lymph nodes: immunoregulation following transplantation
Authors: Zhaoli Sun, James Burdick
Journal: Journal of Clinical Investigation (2020)

The lymph node (LN) is an intriguing site not only for inducing protective effector immunity but also for inducing tolerance against peripherally encountered antigens such as tissue-specific self-antigens that are regionally drained and through draining lymph nodes (DLNs). The dual functions of DLNs in immunity are attributable at least in part to fibroblastic reticular cells (FRCs), which are a major population of the nonhematopoietic compartment in the LN. In this issue of the JCI, Li, Zhao, and colleagues investigated DLNs in the transplantation setting. The authors demonstrated that, following skin transplantation, the donor mast cell-mediated senescence in FRCs was associated with collagen 1 deposition in DLNs. Systemic administration to mice of FRCs that were expanded ex vivo decreased DLN fibrosis and strengthened the effect of anti-CD40L in prolonging heart allograft survival. These data implicate the DLN as a target for immunomodulatory therapy of transplant rejection.
Modifiable Lifestyle Factors in Alzheimer Disease
Authors: Timothy J. Hohman, Catherine C. Kaczorowski
Journal: JAMA Neurology (2020)

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PKCλ/ι Loss Induces Autophagy, Oxidative Phosphorylation, and NRF2 to Promote Liver Cancer Progression
Authors: Yotaro Kudo, Masayuki Sugimoto, Esperanza Arias, Hiroaki Kasashima, Thekla Cordes, Juan F. Linares, Angeles Duran, Yuki Nakanishi, Naoko Nakanishi, Antoine L'Hermitte, Alex Campos, Nadia Senni, Tarmo Rooslid, Lewis R. Roberts, Ana Maria Cuervo, Christian M. Metallo, Michael Karin, Maria T. Diaz-Meco, Jorge Moscat
Journal: Cancer Cell (2020)
Guidelines for wrist-worn consumer wearable assessment of heart rate in biobehavioral research
Authors: Benjamin W. Nelson, Carissa A. Low, Nicholas Jacobson, Patricia Areán, John Torous, Nicholas B. Allen
Journal: npj Digital Medicine (2020)

Abstract Researchers have increasingly begun to use consumer wearables or wrist-worn smartwatches and fitness monitors for measurement of cardiovascular psychophysiological processes related to mental and physical health outcomes. These devices have strong appeal because they allow for continuous, scalable, unobtrusive, and ecologically valid data collection of cardiac activity in “big data” studies. However, replicability and reproducibility may be hampered moving forward due to the lack of standardization of data collection and processing procedures, and inconsistent reporting of technological factors (e.g., device type, firmware versions, and sampling rate), biobehavioral variables (e.g., body mass index, wrist dominance and circumference), and participant demographic characteristics, such as skin tone, that may influence heart rate measurement. These limitations introduce unnecessary noise into measurement, which can cloud interpretation and generalizability of findings. This paper provides a brief overview of research using commercial wearable devices to measure heart rate, reviews literature on device accuracy, and outlines the challenges that non-standardized reporting pose for the field. We also discuss study design, technological, biobehavioral, and demographic factors that can impact the accuracy of the passive sensing of heart rate measurements, and provide guidelines and corresponding checklist handouts for future study data collection and design, data cleaning and processing, analysis, and reporting that may help ameliorate some of these barriers and inconsistencies in the literature.
Mailed fecal immunochemical test outreach for colorectal cancer screening: Summary of a Centers for Disease Control and Prevention–sponsored Summit
Authors: Samir Gupta, Gloria D. Coronado, Keith Argenbright, Alison T. Brenner, Sheila F. Castañeda, Jason A. Dominitz, Beverly Green, Rachel B. Issaka, Theodore R. Levin, Daniel S. Reuland, Lisa C. Richardson, Douglas J. Robertson, Amit G. Singal, Michael Pignone
Journal: CA A Cancer Journal for Clinicians (2020)

Abstract Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow‐up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high‐quality, 1‐sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented.
Author Correction: Introducing PIONEER: a project to harness big data in prostate cancer research
Authors: Muhammad Imran Omar, Monique J. Roobol, Maria J. Ribal, Thomas Abbott, Paul-Michael Agapow, Sonia Araujo, Alex Asiimwe, Charles Auffray, Irina Balaur, Katharina Beyer, Chiara Bernini, Anders Bjartell, Alberto Briganti, John-Edward Butler-Ransohoff, Riccardo Campi, Marinel Cavelaars, Bertrand De Meulder, Zsuzsanna Devecseri, Marc Dietrich Voss, Konstantinos Dimitropoulos, Susan Evans-Axelsson, Billy Franks, Louise Fullwood, Denis Horgan, Emma Jane Smith, Amit Kiran, Kati Kivinummi, Mark Lambrecht, Doron Lancet, Peter Lindgren, Sara MacLennan, Steven MacLennan, Maria Manuela Nogueira, Fredrik Moen, Maxim Moinat, Kishore Papineni, Christian Reich, Kristin Reiche, Stijn Rogiers, Claudio Sartini, Kees van Bochove, Femke van Diggelen, Mieke Van Hemelrijck, Hein Van Poppel, Jihong Zong, James N’Dow, Emelie Andersson, Heidi Arala, Anssi Auvinen, Chris Bangma, Danny Burke, Antonella Cardone, Joaquin Casariego, Guido Cuperus, Saeed Dabestani, Francesco Esperto, Nicola Fossati, Adam Fridhammar, Giorgio Gandaglia, Delila Gasi Tandefelt, Friedemann Horn, Johannes Huber, Jonas Hugosson, Henkjan Huisman, Andreas Josefsson, Olavi Kilkku, Markus Kreuz, Michael Lardas, Joe Lawson, Florence Lefresne, Stephane Lejeune, Elaine Longden-Chapman, Gordon McVie, Lisa Moris, Nicolas Mottet, Teemu Murtola, Charlie Nicholls, Karl H. Pang, Katie Pascoe, Marta Picozzi, Karin Plass, Pasi Pohjanjousi, Matthew Reaney, Sebastiaan Remmers, Paul Robinson, Jack Schalken, Max Schravendeel, Thomas Seisen, Angela Servan, Kirill Shiranov, Robert Snijder, Carl Steinbeisser, Nesrine Taibi, Kirsi Talala, Derya Tilki, Thomas Van den Broeck, Zdravko Vassilev, Olli Voima, Eleni Vradi, Reg Waldeck, Ward Weistra, Peter-Paul Willemse, Manfred Wirth, Russ Wolfinger, Nazanin Zounemat Kermani
Journal: Nature Reviews Urology (2020)
Criteria for academic promotion in medicine
Authors: Harold C Sox, Mark A Schuster
Journal: BMJ (2020)

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 Criteria for academic promotion in medicine Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Changes in treatment for multidrug-resistant tuberculosis according to national income
Authors: Nakwon Kwak, Nicholas Winters, Jonathon R. Campbell, Edward D. Chan, Medea Gegia, Christoph Lange, Myungsun Lee, Vladimir Milanov, Dick Menzies, Jae-Joon Yim
Journal: European Respiratory Journal (2020)

The aim of this study was to analyse temporal changes in treatments for and outcomes of multidrug-resistant (MDR)/rifampin-resistant (RR)-tuberculosis (TB) in the context of national economic status. We analysed data collected by the Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB Treatment on MDR/RR-TB patients from 37 countries. The data were stratified by three national income levels (low-/lower-middle, upper-middle and high) and grouped by time of treatment initiation (2001–2003, 2004–2006, 2007–2009, 2010–2012 and 2013–2015). Temporal trends over the study period were analysed. The probability of treatment success in different income groups over time was calculated using generalised linear mixed models with random effects. In total, 9036 patients were included in the analysis. Over the study period, use of group A drugs (levofloxacin/moxifloxacin, bedaquiline and linezolid) recommended by the World Health Organization increased and treatment outcomes improved in all income groups. Between 2001–2003 and 2013–2015, treatment success rates increased from 60% to 78% in low-/lower-middle-income countries, from 40% to 67% in upper-middle-income countries, and from 73% to 81% in high-income countries. In earlier years, the probability of treatment success in upper-middle-income countries was lower than that in low-/lower-middle-income countries, but no difference was observed after 2010. However, high-income countries had persistently higher probability of treatment success compared to upper-middle income countries. Improved treatment outcomes and greater uptake of group A drugs were observed over time for patients with MDR/RR-TB at all income levels. However, treatment outcomes are still unsatisfactory, especially in upper-middle-income countries.