tbuckley/cabot-search huggingface dataset:
Glucosamine and O-GlcNAcylation: a novel immunometabolic therapeutic target for OA and chronic, low-grade systemic inflammation?
Authors: Gabriel Herrero-Beaumont, Raquel Largo
Journal: Annals of the Rheumatic Diseases (2020)

Osteoarthritis (OA) is a disease with a very long course and varied clinical expression in the initial stages, when it is really challenging to adequately measure disease outcomes both in clinical trials and in daily life.1 It is also very difficult to accurately study the efficacy of symptomatic slow-acting drugs for OA and that of non-pharmacological treatments.2 Although the efficacy of glucosamine (GlcN) in the treatment of OA is still a controversial issue3 4, recent high-quality epidemiological studies confirm previous data showing that prolonged GlcN intake, regardless of its effect on OA progression, could decrease cardiovascular disease (CVD) events, and the incidence of CVD-associated diseases.5–8 These data should be analysed keeping in mind that CVD is the main cause of death in patients with OA.9 Different authors suggest that this protective effect may be associated with the anti-inflammatory properties of GlcN,5 although the molecular basis has been only partially defined.

The imbalance between the mechanical loading and its absorption by the articular cartilage is the origin of joint tissue alteration in OA. While a severe overload can deteriorate any kind of cartilage, a certain load that is physiologically well tolerated by a robust cartilage could be the origin of pathological alterations for a weakened one.9 Cartilage damage begins when the load prevails over the resistance, which in the midterm activates innate immune response in the different joint tissues, and is, at least partially, responsible for joint deterioration. Unbalanced mechanical forces and damage-associated molecular patterns turn on the innate immune system through the activation of the Toll-like receptors. Once this response is activated, a secondary wave of inflammatory mediators is released, with a robust increase in the concentration of cytokines and metalloproteases, the final effectors of cartilage destruction.9 Certainly, these mediators can …
Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity
Authors: Shinya Tanaka, Wataru Ise, Takeshi Inoue, Ayako Ito, Chisato Ono, Yoshihito Shima, Shuhei Sakakibara, Manabu Nakayama, Kentaro Fujii, Ikuo Miura, Jafar Sharif, Haruhiko Koseki, Pandelakis A. Koni, Indu Raman, Quan-Zhen Li, Masato Kubo, Katsunori Fujiki, Ryuichiro Nakato, Katsuhiko Shirahige, Hiromitsu Araki, Fumihito Miura, Takashi Ito, Eiryo Kawakami, Yoshihiro Baba, Tomohiro Kurosaki
Journal: Nature Immunology (2020)
Letter to the Editor: Congenital Extrahepatic Portosystemic Shunts (Abernethy Malformation): A New Variant
Authors: Vijay Waman Dhakre, Preet Shah, Sanjay S. Nagral, Aabha Nagral
Journal: Hepatology (2020)

We read with interest the article by Baiges et al [1] which shed light on the rare entity of Abernethy malformation and gives a working algorithm for extrahepatic shunts. We commend all the authors for the effort to put together a large series and have a follow-up up to the age of 30 years, missed by previous series.
The genetic and pharmacogenomic landscape of snoRNAs in human cancer
Authors: Yaoming Liu, Hang Ruan, Shengli Li, Youqiong Ye, Wei Hong, Jing Gong, Zhao Zhang, Ying Jing, Xiulan Zhang, Lixia Diao, Leng Han
Journal: Molecular Cancer (2020)

Abstract Emerging evidence has revealed significant roles for small nucleolar RNAs (snoRNAs) in tumorigenesis. However, the genetic and pharmacogenomic landscape of snoRNAs has not been characterized. Using the genotype and snoRNA expression data from The Cancer Genome Atlas, we characterized the effects of genetic variants on snoRNAs across 29 cancer types and further linked related alleles with patient survival as well as genome-wide association study risk loci. Furthermore, we characterized the impact of snoRNA expression on drug response in patients to facilitate the clinical utility of snoRNAs in cancer. We also developed a user-friendly data resource, GPSno ( http://hanlab.uth.edu/GPSno ), with multiple modules for researchers to visualize, browse, and download multi-dimensional data. Our study provides a comprehensive genetic and pharmacogenomic landscape of snoRNAs, which will shed light on future clinical considerations for the development of snoRNA-based targeted therapies.
Noncompliance with surgical margin guidelines is associated with histologic margin positivity: A retrospective case-control study
Authors: Brandon T. Beal, David Xiong, Marla Rodriguez, Vamsi Varra, Hannah Cundall, Lanee Simmons, Neil Woody, Shlomo A. Koyfman, Allison T. Vidimos, Thomas J. Knackstedt
Journal: Journal of the American Academy of Dermatology (2020)
Initial Experience Prescribing Commercial Tafamidis, the Most Expensive Cardiac Medication in History
Authors: Ahmad Masri, Hongya Chen, Catherine Wong, Katherine L. Fischer, Chafic Karam, Walid F. Gellad, Stephen B. Heitner
Journal: JAMA Cardiology (2020)

This economic evaluation study examines the authors’ experience of prescribing tafamidis in terms of their cost and the insurance status of patients.
Myeloablative Conditioning for First Allogeneic Hematopoietic Stem Cell Transplantation in Children with ALL: Total Body Irradiation or Chemotherapy? - a Multicenter EBMT-PDWP Study
Authors: Andre Manfred Willasch, Christina Peters, Petr Sedlacek, Jean-Hugues Dalle, Stelios Graphakos, Akif Yesilipek, Jacek Wachowiak, Arjan Lankester, Arcangelo Prete, Amir Ali Hamidieh, Marianne Ifversen, Jochen Büchner, Gergely Krivan, Rose-Marie Hamladji, Cristina Diaz de Heredia, Elena Skorobogatova, Gerard Michel, Franco Locatelli, Alice Bertaina, Paul Veys, Sophie Dupont, Reuven Or, Tayfun Guengoer, Olga Aleinikova, Sabina Sufliarska, Mikael Sundin, Jelena Rascon, Ain Kaare, Damir Nemet, Franca Fagioli, Thomas Klingebiel, Jan Styczynski, Marc B Bierings, Kalman Nagy, Manuel Abecasis, Boris V Afanasyev, Marc Ansari, Arnaud Dalissier, Myriam Labopin, Eric Beohou, Peter Bader
Journal: Blood (2017)
Angioedema after t-PA Infusion
Authors: Miguel Leal Rato, Mariana Carvalho Dias
Journal: New England Journal of Medicine (2020)

A 78-year-old man presented to the emergency department with weakness on the left side. Fifty-four minutes after the initiation of intravenous tissue plasminogen activator, swelling developed on the left side of the tongue, a finding that was consistent with angioedema.
Telehealth in Urology: A Systematic Review of the Literature. How Much Can Telemedicine Be Useful During and After the COVID-19 Pandemic?
Authors: Giacomo Novara, Enrico Checcucci, Alessandro Crestani, Alberto Abrate, Francesco Esperto, Nicola Pavan, Cosimo De Nunzio, Antonio Galfano, Gianluca Giannarini, Andrea Gregori, Giovanni Liguori, Riccardo Bartoletti, Francesco Porpiglia, Roberto Mario Scarpa, Alchiede Simonato, Carlo Trombetta, Andrea Tubaro, Vincenzo Ficarra
Journal: European Urology (2020)
Comparison of Patient-Reported vs Physician-Estimated Angina in Patients Undergoing Elective and Urgent Percutaneous Coronary Intervention
Authors: John T. Saxon, Paul S. Chan, Andy T. Tran, Suveen Angraal, Phillip G. Jones, J. Aaron Grantham, John A. Spertus
Journal: JAMA Network Open (2020)

from studies such as ISCHEMIA 6 and highlight the limited benefits of revascularization in asymptomatic patients, it is increasingly important to directly elicit patients' experiences.This study has limitations.First, data were collected 9 years ago, although there is no reason to expect patterns of angina assessment would have changed substantially over time.Second, patients with unstable angina typically have recent symptom onset (eg, within 24 hours), and the SAQ is designed to assess symptoms over the last 4 weeks.Third, physicians' estimates of unstable angina may also be inaccurate in an era of Appropriate Use Criteria in which higher ratings for are assigned for unstable angina than for SIHD.Fourth, we cannot exclude the possibility that some patients had atypical presentations that were not captured by the SAQ; whether other instruments, including the Rose Dyspnea Score, may be more sensitive to atypical angina is unknown.In addition, we did not assess angina at follow-up; thus, conclusions regarding the best method of assessment at baseline could not be drawn from the context of this study.In this cohort study, 35.5% of patients undergoing PCI for SIHD and 12.3% of those undergoing PCI for unstable angina self-reported no angina.Among patients without self-reported angina, 1 in 5 undergoing elective PCI and 1 in 2 undergoing urgent PCI were assessed by physicians to have moderate-to-severe angina.These data have important implications for patient selection for coronary revascularization.
Response to: ‘Diagnostic accuracy of novel ultrasonographic halo score for giant cell arteritis: methodological issues’ by Ghajari and Sabour
Authors: Kornelis SM van der Geest, Frances Borg, Abdul Kayani, Davy Paap, Prisca Gondo, Wolfgang Schmidt, Raashid Ahmed Luqmani, Bhaskar Dasgupta
Journal: Annals of the Rheumatic Diseases (2020)

We thank Ghajari and Sabour for their interest in our work and appreciation of our study.1 We have reported that the extent of vascular inflammation on ultrasound, as quantified by the halo score, is associated with ocular ischaemia in patients with giant cell arteritis (GCA).2 Furthermore, we investigated the diagnostic accuracy of the halo score for a clinical diagnosis of GCA, as well as a positive temporal artery biopsy.2 Here, we discuss the points raised by the authors.

First, the authors propose that our study was focused on ‘test accuracy’. We fully agree with the authors on this point, as we included the term ‘diagnostic accuracy’ in our title and used it throughout our manuscript. Our definition of ‘diagnostic accuracy’ was similar to that reported in the references provided by the authors, that is, the ability of a test to discriminate between patients with the target condition and those without.3 4 It appears that the authors use a slightly distinct definition for ‘diagnostic accuracy’, that is, ‘a test’s added contribution to estimate the diagnostic probability of disease presence or absence’. This is actually the definition of ‘diagnostic yield’, as indicated by the reference provided by the authors.3 Sackett and Haynes have previously described …
Association of Impaired Spermatogenesis With the Use of Immune Checkpoint Inhibitors in Patients With Metastatic Melanoma
Authors: Jason M. Scovell, Karl Benz, Iryna Samarska, Taylor P. Kohn, Jody E. Hooper, Andres Matoso, Amin S. Herati
Journal: JAMA Oncology (2020)

Management of Immunotherapy-Related Toxicities in Patients Treated With Immune Checkpoint Inhibitor Therapy
Infographic. COFIT-19: let’s get moving through the COVID-19 pandemic!
Authors: Jane Fitzpatrick, Adam Castricum, Hugh Seward, Louise Tulloh, Elizabeth Dawson
Journal: British Journal of Sports Medicine (2020)

YES! The epidemiological data suggest that people with modifiable risks of chronic lifestyle-related diseases such as obesity, heart disease, hypertension and type 2 diabetes are profoundly more at risk of death from this virus.1 While it is also true of the elderly and those with immune deficiencies, these risks are more difficult to modify.

Even before COVID-19, the medical world was aware of the public health emergency created by a lack of physical activity.2 The increase in hypertension, type 2 diabetes and obesity in the western world has been profound. We have developed a population ‘at risk’ due to underlying comorbidities, many of which can be improved with exercise. The reality, however, is that …
Coating doxycycline on titanium-based implants: Two in vivo studies
Authors: Maryam Rahmati, Ståle Petter Lyngstadaas, Janne E. Reseland, Ingrid Andersbakken, Heidi Straume Haugland, Mónica López-Peña, Antonio Gonzalez Cantalapiedra, Fernando Maria Guzon Muñoz, Håvard Jostein Haugen
Journal: Bioactive Materials (2020)

Regardless of the substantial progress in designing titanium-based dental implants and aseptic techniques, infection remains as the most common complication after implantation surgeries. Although, having a weakened immune system or systematic diseases is not seen as contraindicated for dental implants anymore, controlling the immune system is required to avoid surgical site infections after implantation. These patients have to control the surgical site infections by taking a high daily dose of oral antibiotics after dental implantation. The antibiotics oral administration has many side effects such as gastrointestinal symptoms, skin rashes and thrush. Coating antibiotics on the biomaterials surface could be a promising solution to reduce these disadvantages through locally releasing antibiotics in a controlled manner. The aim of this study was to investigate the effects of doxycycline coating layer on titanium-zirconium alloy surfaces in vitro and in vivo. In our previous studies, we demonstrated the chemical presence of doxycycline layer in vitro. In this study, we examined its physical presence using field emission scanning electron microscope and confocal microscope. We also analyzed its controlled released manner using Nano-Drop UV Vis spectrometer. After in vitro characterization of the coating layer, we evaluated its effects on the implant osseointegration in dogs and rabbits. The histological and histomorphometrical results exhibited no significant difference between doxycycline coated and uncoated groups regarding the implants osseointegration and biocompatibility for dental applications. Therefore, coating a doxycycline layer on TiZr implants could be favorable for reducing or removing the antibiotics oral administration after the implantation surgery.
Multi-omic analysis reveals significantly mutated genes and DDX3X as a sex-specific tumor suppressor in cutaneous melanoma
Authors: Rached Alkallas, Mathieu Lajoie, Dan Moldoveanu, Karen Vo Hoang, Philippe Lefrançois, Marine Lingrand, Mozhdeh Ahanfeshar-Adams, Kevin Watters, Alan Spatz, Jonathan H. Zippin, Hamed S. Najafabadi, Ian R. Watson
Journal: Nature Cancer (2020)
99mTc-MIP-1404 SPECT/CT for Assessment of Whole-Body Tumor Burden and Treatment Response in Patients With Biochemical Recurrence of Prostate Cancer
Authors: Christian Schmidkonz, Theresa Ida Götz, Armin Atzinger, Philipp Ritt, Olaf Prante, Torsten Kuwert, Tobias Bäuerle, Peter Goebell, Michael Cordes
Journal: Clinical Nuclear Medicine (2020)

Objective This study aims to investigate the value of 99m Tc-MIP-1404 SPECT/CT for assessment of whole-body tumor burden and treatment response in patients with biochemical recurrence of prostate cancer who undergo androgen deprivation therapy (ADT) or external beam radiation therapy (EBRT). Methods A total of 125 patients with biochemical recurrence of prostate cancer underwent 99m Tc-MIP-1404 SPECT/CT. All 364 prostate-specific membrane antigen (PSMA)–positive lesions in the field of view were assessed quantitatively to calculate PSMA-derived metabolic tumor parameters, including whole-body PSMA tumor volume and whole-body total lesion PSMA. These metrics were correlated with serum prostate-specific antigen (PSA) levels and Gleason scores. In a subset of 50 patients who underwent 99m Tc-MIP-1404 SPECT/CT before the initiation of ADT or EBRT, TL-PSMA and SUV max were compared with radiographic response assessment by CT based on RECIST 1.1 and to biochemical response (BR) determined by changes in serum PSA levels. Results Serum PSA levels correlated with SUV max , whole-body PSMA tumor volume, and whole-body total lesion PSMA in patients with 1 and in those with more than 1 PSMA-positive lesion ( P &lt; 0.05). The correlations were significant for both well-differentiated (Gleason score ≤7) and poorly differentiated tumors (Gleason score ≥8) ( P &lt; 0.05). The agreement between TL-PSMA derived from SPECT and BR in patients who underwent 99m Tc-MIP-1404 SPECT/CT before and after initiation of ADT was 80% (95% confidence interval [CI], 0.43–0.91; Cohen κ = 0.68; P &lt; 0.05); in these patients, the agreement between TL-PSMA and CT was 60% (95% CI, 0.20–0.72; Cohen κ = 0.46; P &lt; 0.05) and the agreement between BR and CT was 52% (0.07–0.61; Cohen κ = 0.34; P &lt; 0.05). Comparable results were found for patients who underwent SPECT/CT before and after initiation of EBRT, with the strongest agreement between TL-PSMA and BR (80%; 95% CI, 0.38–0.93; Cohen κ = 0.66; P &lt; 0.05) compared with the agreement between TL-PSMA and CT (60%; 95% CI, 0.13–0.69; Cohen κ = 0.69; P &lt; 0.05) and between BR and CT (48%; 95% CI, 0–0.54; Cohen κ = 0.26; P = 0.11). Discordant findings between SPECT and CT were most likely due to limitations in the assessment of small lymph node metastases and bone involvement, which were detectable on SPECT but not on CT. Conclusions The results of our study show that 99m Tc-MIP-1404 SPECT/CT is a promising method for the evaluation of treatment response in patients with biochemical recurrence of prostate cancer who undergo either ADT or EBRT. TL-PSMA for assessment of treatment response has the strongest correlation with serum PSA levels, superior to SUV max -based evaluation and response assessment based on CT data and RECIST 1.1.
Abstract 15317: The Effects of a Single Session Education With Telephone Follow-Up on Mortality, Disease Knowledge, Self-Care, and Health-Related Quality of Life in Patients With Heart Failure
Authors: Boyoung Hwang, Hyun-jai Cho, Hae-young Lee
Journal: Circulation (2019)

Introduction: Self-care is essential in the management of heart failure (HF). However, the evidence on the effects of educational programs remains inconsistent, especially on health-related quality...
Effects of Vitamin D Supplementation on Prevention of Type 2 Diabetes in Patients With Prediabetes: A Systematic Review and Meta-analysis
Authors: Yu Zhang, Huiwen Tan, Jingjing Tang, Jing Li, Weelic Chong, Yang Hai, Yuning Feng, L. Dade Lunsford, Ping Xu, Desheng Jia, Fang Fang
Journal: Diabetes Care (2020)

While observational studies have shown an association between vitamin D insufficiency and diabetes, it is unclear whether intervention with vitamin D supplements can lower the risk of type 2 diabetes mellitus (T2DM).To assess whether vitamin D supplementation reduces the risk of T2DM in people with prediabetes.We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 5 July 2019.We included randomized controlled trials assessing vitamin D supplementation versus placebo in relation to new-onset T2DM in people with prediabetes.We screened studies and extracted data from published trials independently.We identified eight eligible trials with a total of 4,896 subjects. Vitamin D supplementation significantly reduced the risk of T2DM (risk ratio [RR] 0.89 [95% CI 0.80-0.99]; I2 = 0%). Benefit was found in nonobese subjects (RR 0.73 [95% CI 0.57-0.92]) but not in obese subjects (RR 0.95 [95% CI 0.84-1.08]) (Pinteraction = 0.048). The reversion of prediabetes to normoglycemia occurred in 116 of 548 (21.2%) participants in the vitamin D group and 75 of 532 (14.1%) in the control group. Vitamin D supplementation increased reversion rate of prediabetes to normoglycemia (RR 1.48 [95% CI 1.14-1.92]; I2 = 0%.) LIMITATIONS: Definitions of prediabetes and new-onset diabetes in eligible studies were different, and long-term data on outcomes of T2DM prevention were lacking.In persons with prediabetes, vitamin D supplementation reduces the risk of T2DM and increases the reversion rate of prediabetes to normoglycemia. The benefit of the prevention of T2DM could be limited to nonobese subjects. Individual participant data meta-analyses are needed to confirm these findings.
Abstract B04: Using PSA dynamics to forecast individual responses to intermittent androgen deprivation
Authors: Renee Brady, Heiko Enderling
Journal: Clinical Cancer Research (2020)

Abstract Intermittent androgen-deprivation therapy (IADT) is an attractive treatment approach for biochemically recurrent prostate cancer (PCa), whereby cycling treatment on and off has been shown to limit toxicities and reduce cumulative dose. While IADT has been shown to delay the development of treatment resistance, underlying mechanisms and actionable biomarkers are required to accurately predict when resistance will emerge and how to maximally delay time to progression. We developed a quantitative framework to simulate the enrichment of prostate cancer stem cell dynamics during treatment as a plausible mechanism of resistance evolution. Using simulated dynamics of cancer stem cells and nonstem cancer cells, we derive longitudinal blood serum prostate-specific antigen (PSA) concentrations that were calibrated to and validated with data of 70 patients undergoing multiple cycles of IADT. Model analysis suggests that cancer stem cell proliferation patterns correlate with PSA dynamics and patient outcomes. Learning these dynamics adaptively from the earlier treatment cycles in individual patients can predict the evolution of resistance in subsequent IADT cycles with a predictive power of 90%, which warrants prospective evaluation in a clinical setting. The model is used to simulate and predict alternative treatment options. In particular, simulations show that response dynamics from the first IADT cycle can be used to identify patients who would benefit from concurrent docetaxel. Citation Format: Renee Brady, Heiko Enderling. Using PSA dynamics to forecast individual responses to intermittent androgen deprivation [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B04.
The two languages of science
Authors: Itai Yanai, Martin Lercher
Journal: Genome biology (2020)

If we allow ourselves the license of talking about genes as if they had conscious aims, always reassuring ourselves that we could translate our sloppy language back into respectable terms if we wanted to, we can ask the question, what is a single selfish gene trying to do?"-Richard Dawkins, The Selfish Gene: p. 88 "I've made agents out of system 1 and system 2 because everybody finds it easier to think about agentswith propensities and traitsthan about abstract categories.Agents make powerful subjects because they're active and they do things."-DanielKahneman, personal communication In no small part, the amazing success of modern science in learning about our world is rooted in its rigorous structure: scientists clearly lay out assumptions, design conclusive experiments with the appropriate controls, and use statistical methods to assess our confidence in the results.These processes form the core of what Francois Jacob called day science [1, 2].To utilize these strengths, we speak in a highly precise and metaphor-free language when we describe our work in manuscripts and at conferences.Acquiring this language is an important part of our formal training as day scientists.But there is an equally important second language of science, which is rarely taught explicitly and often overlooked.This is the language of night science-the creative part of our work, where we come up with the first, hazy versions of the very ideas to be tested by day science [1,2].In night science, insistence on precision becomes a hindrance, while metaphors and anthropomorphizing-the personification of nonhuman objects such as cells, proteins, and genes-impart us with powerful intuitions about the unknowns we explore.Once we have identified an idea in our night science explorations, we can translate it into respectable day science language, so that an experiment can be designed and executed using the rigorous day science tools at our disposal.To avoid misunderstandings, the distinct language of night science must be clearly labeled when we speak.But developing it as a complement to the formal day science language is an important step in our development as a creative scientist.Do not anthropomorphize genes, they do not like it "We are survival machinesrobot vehicles blindly programmed to preserve the selfish molecules known as genes" [3].