tbuckley/cabot-search huggingface dataset:
Evaluation of <sup>18</sup>F-IAM6067 as a sigma-1 receptor PET tracer for neurodegeneration <i>in vivo</i> in rodents and in human tissue
Authors: François-Xavier Lepelletier, Matthias Vandesquille, Marie-Claude Asselin, Christian Prenant, Andrew C Robinson, David M A Mann, Michael Green, Elizabeth Barnett, Samuel D Banister, Marco Mottinelli, Christophe Mesangeau, Christopher R McCurdy, Inga B Fricke, Andreas H. Jacobs, Michael Kassiou, Hervé Boutin
Journal: Theranostics (2020)

The sigma 1 receptor (S1R) is widely expressed in the CNS and is mainly located on the endoplasmic reticulum.The S1R is involved in the regulation of many neurotransmission systems and, indirectly, in neurodegenerative diseases.The S1R may therefore represent an interesting neuronal biomarker in neurodegenerative diseases such as Parkinson's (PD) or Alzheimer's diseases (AD).Here we present the characterisation of the S1R-specific 18 F-labelled tracer 18 F-IAM6067 in two animal models and in human brain tissue.Methods: Wistar rats were used for PET-CT imaging (60 min dynamic acquisition) and metabolite analysis (1, 2, 5, 10, 20, 60 min post-injection).To verify in vivo selectivity, haloperidol, BD1047 (S1R ligand), CM398 (S2R ligand) and SB206553 (5HT2B/C antagonist) were administrated for pre-saturation studies.Excitotoxic lesions induced by intra-striatal injection of AMPA were also imaged by 18 F-IAM6067 PET-CT to test the sensitivity of the methods in a well-established model of neuronal loss.Tracer brain uptake was also verified by autoradiography in rats and in a mouse model of PD (intrastriatal 6-hydroxydopamine (6-OHDA) unilateral lesion).Finally, human cortical binding was investigated by autoradiography in three groups of subjects (control subjects with Braak ≤2, and AD patients, Braak >2 & ≤4 and Braak >4 stages).Results: We demonstrate that despite rapid peripheral metabolism of 18 F-IAM6067, radiolabelled metabolites were hardly detected in brain samples.Brain uptake of 18 F-IAM6067 showed differences in S1R anatomical distribution, namely from high to low uptake: pons-raphe, thalamus medio-dorsal, substantia nigra, hypothalamus, cerebellum, cortical areas and striatum.Pre-saturation studies showed 79-90% blockade of the binding in all areas of the brain indicated above except with the 5HT2B/C antagonist SB206553 and S2R ligand CM398 which induced no significant blockade, indicating good specificity of 18 F-IAM6067 for S1Rs.No difference between ipsi-and contralateral sides of the brain in the mouse model of PD was detected.AMPA lesion induced a significant 69% decrease in 18 F-IAM6067 uptake in the globus pallidus matching the neuronal loss as measured by NeuN, but only a trend to decrease (-16%) in the caudate putamen despite a significant 91% decrease in neuronal count.Moreover, no difference in the human cortical binding was shown between AD groups and controls. Ivyspring
CD155 immunoregulation as a target for natural killer cell immunotherapy in glioblastoma
Authors: Kyle B. Lupo, Sandro Matosevic
Journal: Journal of Hematology & Oncology (2020)

Abstract Natural killer (NK) cells are powerful immune effectors, modulating their anti-tumor function through a balance activating and inhibitor ligands on their cell surface. Though still emerging, cancer immunotherapies utilizing NK cells are proving promising as a modality for the treatment of a number of solid tumors, including glioblastoma (GBM) and other gliomas, but are often limited due to complex immunosuppression associated with the GBM tumor microenvironment which includes overexpression of inhibitory receptors on GBM cells. CD155, or poliovirus receptor (PVR), has recently emerged as a pro-tumorigenic antigen, overexpressed on GBM and contributing to increased GBM migration and aggressiveness. CD155 has also been established as an immunomodulatory receptor, able to both activate NK cells through interactions with CD226 (DNAM-1) and CD96 and inhibit them through interaction with TIGIT. However, NK cell TIGIT expression has been shown to be upregulated in cancer, establishing CD155 as a predominantly inhibitory receptor within the context of GBM and other solid tumors, and rendering it of interest as a potential target for antigen-specific NK cell-based immunotherapy. This review will explore the function of CD155 within GBM as it relates to tumor migration and NK cell immunoregulation, as well as pre-clinical and clinical targeting of CD155/TIGIT and the potential that this pathway holds for the development of emerging NK cell-based immunotherapies.
Abstract 322: Cyclooxygenase (COX) Inhibition Prior to CPR Decreases Heart Rate Variability in Pigs
Authors: Jose A Adams, Arkady Uryash, Jose R Lopez
Journal: Circulation (2018)

Background: Cyclooxygenase inhibitors (COX-1 and 2) are widely used and inhibit prostaglandin synthesis. COX inhibitors have been shown to increase overall cardiovascular risk. Heart rate variability (HRV) is a measure of the balance of autonomic nervous system and shown to be predictive of neurological outcome after cardiac arrest. Prostaglandins are cardioprotective and modulate HRV. We hypothesized that prostaglandin inhibition impacts short term CPR survival and outcomes based on HRV in swine. Methods: 24 animals (30±5kg) were randomized to pretreatment with indomethacin (I) 2mg/kg (COX-1 Inhibitor), Celecoxib (C) 2mg/kg (COX-2 inhibitor) or placebo (P). VF was induced and after 3 minutes all animals received chest compression and ventilation. After 18 minutes of VF, vasopressin given and defibrillation attempted. Electrocardiogram, echocardiogram and hemodynamic measurements done at baseline (BL), after infusions (Tx) and return of spontaneous circulation (ROSC) at 30 and 180 minutes. Results: ROSC was achieved; 3/8 (I) compared with 7/8 (C), and 7/8 (P). No differences in blood gases or hemodynamics pre, during or post CPR between groups. Echo showed decrease function post resuscitation in surviving animals but not significantly different among groups. COX-2 inhibition induced a significant decrease in linear (SDNN, RMSSD) and frequency (HF) measures of HRV towards greater sympathetic tone, post resuscitation. Compared to P, COX-2 inhibition increased Troponin I levels at 180 min after ROSC; P [84(4)] vs C [721(31)] mg/dl (p&lt; 0.001). Conclusions: COX-1 inhibition decreases ROSC, whereas COX-2 inhibition significantly increases indices of myocardial tissue damage, and decreases HRV. The impact on long term outcome is unknown. Since many adults use COX-1 or COX-2 inhibitors, studies analyzing post resuscitation outcomes of patients should consider the effects of prostaglandin synthesis inhibitors as confounding variables.
FRI0561 PRO-INFLAMMATORY DIETS ARE ASSOCIATED WITH INCREASED C-REACTIVE PROTEIN AND RHEUMATOID ARTHRITIS IN THE UK BIOBANK COHORT
Authors: J. Dainty, E. Sayers, M. Yates, A. Macgregor
Journal: Annals of the Rheumatic Diseases (2020)

Background: Several individual dietary components have been associated with the risk of rheumatoid arthritis (RA) and recent studies have suggested that dietary indices, which account for the consumption of multiple foods, can be used as more complete measures of risk. Objectives: In this study we aimed to use the Dietary Inflammatory Index (DII), an independent index of dietary variable associated with inflammatory biomarkers, to evaluate potential associations between pro-inflammatory exposures in the diet, an inflammation biomarker (C-reactive protein) and RA onset using the UK Biobank cohort. Methods: The DII was calculated from data obtained in 24-hour dietary recall questionnaires collected on healthy participants on four separate occasions over an approximate annual period between Feb 2011 and April 2012. Cases of RA in the UK Biobank cohort were identified from the participants with appropriate ICD10 codes and compared against a randomly selected subsample of controls matched (20:1) for age, sex, smoking status and BMI. Results: Among the 502,519 subjects enrolled in Biobank, 141,769 had completed 24-hour dietary recall questionnaires and had full data for the 18 dietary variables that were required to create the DII (mean=0.03, range: -3.88, 4.22). Higher (positive) DII values indicate more pro-inflammatory diets. This index was positively correlated (p&lt;0.001) with C-reactive protein (CRP), attesting to the validity of this index for assessing dietary inflammatory potential. A total of 1,423 participants were classified as having RA (1% prevalence in ‘dietary’ cohort of 141,769) according to their ICD10 codes that were last updated in 2018. Their mean age at enrolment (2006-10) was 59 years. There was a significant association between DII and RA: OR 1.05 [1.01-1.09]; p=0.028) that suggested RA cases were more likely to be consuming a pro-inflammatory diet. Conclusion: These data show a significant association between diet, inflammation (CRP) and RA in the UK Biobank population. The findings are consistent with a recent analysis of the US Nurse’s Health Study which was based on data only from females, indicating that these findings are likely to be robust and generalisable. Diet is one of the few modifiable factors that has the potential to reduce the risk of future RA onset. These results open the way to providing evidence-based health advice and for designing clinical interventions. References: [1] Shivappa N, Steck SE, Hurley TG, Hussey JR, Hebert JR. Designing and developing a literature-derived, population-based dietary inflammatory index. Public health nutrition 2014;17:1689-96. Acknowledgments: This research has been conducted using the UK Biobank Resource under Application Number ‘33557’ Disclosure of Interests: None declared
Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits (vol 38, pg 1456, 2015)
Authors: H.S. Dashti, J.L. Follis, C.E. Smith, T. Tanaka, M. Garaulet, D.J. Gottlieb, A. Hruby, P.F. Jacques, J.C. Kiefte-de Jong, S. Lamon-Fava, F.A.J.L. Scheer, T.M. Bartz, L. Kovanen, M.K. Wojczynski, A.C. Frazier-Wood, T.S. Ahluwalia, M.M. Perala, A. Jonsson, T. Muka, I.P. Kalafati, V. Mikkila, J.M. Ordovas, Charge Nutr Study Grp
Journal: Diabetes Care (2017)
THU0491 HYALURONIC ACID INJECTION IN PLANTER FASCIITIS: CAN WE USE?
Authors: A. Zakria, A. Hafez, A. Abdel-Nasser
Journal: Annals of the Rheumatic Diseases (2020)

Background: Plantar fasciitis is the most common cause of hind foot pain. Treatment is aimed at pain reduction and maintaining or improving function. Several types of injected materials are used including corticosteroids, hyaluronic acid and Platelet-rich plasma. Objectives: The aim of this study was to evaluate the efficacy of hyaluronic acid injection in comparison to corticosteroid injection for the treatment of degenerative plantar fasciitis. Methods: This study included forty patients with degenerative plantar fasciitis diagnosed according to clinical examination and ultrasound findings. They were divided into two groups. Group one included twenty patients who were injected with Methylprednisolone (MP). Group two included another twenty patients who were injected with hyaluronic acid (HA). Clinical assessment was done including morning heel pain, localized heel tenderness, patient assessment of heel pain using the numerical rating scale (NRS), Functional assessment using the Manchester-Oxford foot questionnaire (MOXFQ) and musculoskeletal ultrasound assessment including planter fascia thickness, echogenicity, power Doppler signals, erosions and calcification. Patients were injected and a follow up was done at two and six weeks for each group. Results: The two groups MP &amp;HA showed no significant baseline differences in clinical and sonographic variables, while they both significantly improved from baseline after two &amp;six weeks injection (P&lt;0.001).The MP group achieved a significant improvement in NRS, MOXFQ, plantar fascial thickness and echogenicity in the first follow up after two weeks better than the second follow up after six weeks (P&lt;0.001). The HA group achieved significant improvement in NRS, MOXFQ, plantar fascial thickness and echogenicity in the second follow up after six weeks better than the first follow up after two weeks (P&lt;0.001). Over all, MP group had significant improvement clinically and sonographically than HA group after two weeks (P&lt;0.001), while HA group had significant improvement clinically and sonographically in comparison with MP group after six weeks. Conclusion: Our study supports the use of a single injection of hyaluronic acid as therapy for plantar fasciitis in preference to methylprednisolone acetate injections, while MP offers short term improvement (after two weeks). HA injection offers better therapeutic advantages in the intermediate-term follow up (after six weeks). Moreover, it has a longer duration of action and enables better tissue healing and can therefore be used as an effective alternative treatment for plantar fasciitis. Disclosure of Interests: : None declared
Covid-19 communication aids
Authors: Nathan A Gray, Anthony L Back
Journal: BMJ (2020)

Illness related to the novel coronavirus has driven a global crisis, and many clinicians are facing unexpected and challenging conversations.This guide is a graphic medicine adaptation of text that was created to provide a practical introduction on how to talk about difficult topics related to covid-19.During early spread of the pandemic, the written text and subsequent illustrations were created to promote rapid sharing of communication skills with clinicians across diverse disciplines.The primary text was produced by non-profit organisation VitalTalk, which gives training to support conversations around serious illness.This guide is not meant to be comprehensive, but it is a starting place for improving conversations with those facing this illness.
Phase II trial of CPX-351 in patients with acute myeloid leukemia at high risk for induction mortality
Authors: Ghayas C. Issa, Hagop M. Kantarjian, Lianchun Xiao, Jing Ning, Yesid Alvarado, Gautam Borthakur, Naval Daver, Courtney D. DiNardo, Elias Jabbour, Prithviraj Bose, Nitin Jain, Tapan M. Kadia, Kiran Naqvi, Naveen Pemmaraju, Koichi Takahashi, Srdan Verstovsek, Micheal Andreeff, Steven M. Kornblau, Zeev Estrov, Alessandra Ferrajoli, Guillermo Garcia-Manero, Maro Ohanian, William G. Wierda, Farhad Ravandi, Jorge E. Cortes
Journal: Leukemia (2020)
Four point-of-care lateral flow immunoassays for diagnosis of COVID-19 and for assessing dynamics of antibody responses to SARS-CoV-2
Authors: Jhong-Lin Wu, Wen-Pin Tseng, Chien-Hao Lin, Tai-Fen Lee, Ming-Yi Chung, Chien-Hua Huang, Shey-Ying Chen, Po-Ren Hsueh, Shyr-Chyr Chen
Journal: Journal of Infection (2020)
Development of the highly sensitive chemosensitivity testing using ATP bioluminescence assay
Authors: Mika Hoshino, Masanori Terashima, Seigo Kashimura, Norio Kanzaki, Takuro Saitoh, Mitsukazu Gotoh, Shigeya Suzuki, Yasuhiro Harada
Journal: Cancer Research (2004)

5329  Objective: Chemosensitivity testing is thought to be a useful method for selecting susceptive agents or eliminating resistant agents prior to treatment. However, one unsolved problem is that these assays require a relatively large amount of tumor tissue, which hampers wide clinical application. For example, conventional MTT assay usually requires 50,000 cells /well for determining chemosensitivity. In order to minimize the sample size for chemosensitivity testing, we have developed a highly sensitive assay using ATP bioluminescence methods. Materials and Methods: Human gastric cancer cell line MKN-45 was used for the basic experiment. Cells were plated onto 96-well microplates at a concentration of 2,000, 1,000, 500, 250 cells / well and then anti-cancer drugs were added at various concentrations, and were cultured for 72 hrs. Cell viability was determined by ATP bioluminescence assay using highly sensitive synthetic firefly luciferase and compared with that in MTT assay. In clinical samples, obtained from 64 patients with various kinds of cancers, cells were plated at 20,000, 10,000, 5,000cells /well, and drug sensitivity was determined by the ATP assay in a similar manner. Results: In the basic examination using gastric cancer cell line, intracellular ATP levels showed significant linear correlation with the number of cells ranging from 10 to 1,000,000 cells/ml. The ATP assay could detect drug sensitivity regardless number of cells applied, while MTT assay failed to do so. Minimal number of cells for MTT assay were considered to be >50,000 cells /well. In clinical samples, chemosensitivity testing was evaluable at any concentration of cells applied in 47 of 64 samples (73%), and the results were always consistent regardless of cell concentration. Consideration: ATP bioluminescence assay enables reproducible chemosensitivity testing for a much smaller size of cancer cells as compared to MTT assay, suggesting a wide clinical application for chemosensitivity testing with small sample such as biopsy specimen.
Biomimetic osteogenic peptide with mussel adhesion and osteoimmunomodulatory functions to ameliorate interfacial osseointegration under chronic inflammation
Authors: Jiaxiang Bai, Huaiyu Wang, Hao Chen, Gaoran Ge, Miao Wang, Ang Gao, Liping Tong, Yaozeng Xu, Huiling Yang, Guoqing Pan, Paul K. Chu, Dechun Geng
Journal: Biomaterials (2020)
Abstract 15419: Comparison Between Del Nido Cardioplegia and Conventional Blood Cardioplegia in Pediatric Cardiopulmonary Bypass Surgery
Authors: Shubhadeep Das, Maruti Haranal, Osami Honjo, Chun-Po S Fan, Peter C Laussen, Lynn Crawford, Luc L Mertens, Alejandro A Floh
Journal: Circulation (2019)

Introduction: Del Nido cardioplegia (cDN) is a hyperpolarizing agent designed for superior myocardial protection during cardiopulmonary bypass (CPB). Following its introduction in August 2015, we c...
Resuming liver transplantation amid the COVID-19 pandemic
Authors: Hanns Lembach, Angus Hann, Siobhan C McKay, Hermien Hartog, Suresh Vasanth, Phillip El-Dalil, Nick Murphy, Katherine Snelson, Jaimin K Patel, John L Isaac, Matthew J Armstrong, James Ferguson, Andrew Holt, Davinia Bennett, Ian Sharp, Paul Cockwell, Darius F Mirza, John R Isaac, M Thamara P R Perera
Journal: The Lancet. Gastroenterology & hepatology (2020)

the largest deceased-donor liver transplantation programmes in Europe, with 230 adult and 25-30 paediatric transplants per annum (average 4-5 transplants per week).At the peak of the pandemic, the West Midlands region, where our unit is based, was one of the worst affected regions in the UK, with 15 632 (265 per 100 000 population) confirmed cases by mid-May, 2020.Rapid community spread of SARS-CoV-2 meant demand for mechanical ventilation exceeded pre-pandemic supply. 5Our institution re-allocated staff and mechanical ventilators to accommodate for around 150 ventilated patients with SARS-CoV-2 pneumonia, an increase of 200%.All liver transplant activity (except for extremely urgent cases) was temporarily suspended on March 27, 2020, because of a surge in hospital admissions, ICU bed shortage, and organ procurement restrictions implemented by the organ donation authority. 6Emergency surgery was continued, with an individualised risk assessment approach.At the peak of the pandemic, the ICU had 97 patients within four dedicated SARS-CoV-2 units and 25 additional patients without SARS-CoV-2 in a COVID-19-free clean ICU.204 patients with suspected or proven SARS-CoV-2 infection were treated in ICU between March 11 and May 13, 2020.On April 6, 2020, following a detailed assessment of ICU and theatre resources, liver transplant activity was resumed in steps (appendix).A SARS-CoV-2-free pathway was established, including a physically separate clean ICU and hospital ward (step 1).To prevent SARS-CoV-2 infection, all wait-listed patients were instructed to strictly selfisolate (step 2).A rapid protocol for SARS-CoV-2 screening began as soon as an organ was available; the chosen recipient was screened via telephone for symptoms of COVID-19 and adequacy of self-isolation.On arrival at hospital, both nasopharyngeal SARS-CoV-2 RNA RT-PCR and screening 3
Calcium-mineralized polypeptide nanoparticle for intracellular drug delivery in osteosarcoma chemotherapy
Authors: Ke Li, Di Li, Li Zhao, Yonghe Chang, Yi Zhang, Yan Cui, Zhiyu Zhang
Journal: Bioactive Materials (2020)

The acidic microenvironments of tumor tissue and cells provide an opportunity for the development of pH-responsive drug delivery systems in cancer therapy. In this work, we designed a calcium carbonate (CaCO3)-core-crosslinked nanoparticle of methoxy poly(ethylene glycol)-block-poly(l-glutamic acid) through mineralization for intracellular delivery of doxorubicin (DOX), referred to as CaNP/DOX. CaNP/DOX exhibited high drug loading capability, uniform nanoparticle size, and pH-dependent DOX release. In the meantime, the enhanced cell uptake, superior cytotoxicity toward mouse osteosarcoma K7 cells, extended circulation half-life, and improved accumulation of DOX in K7 allograft tumor from CaNP/DOX were also demonstrated. More interestingly, CaNP/DOX displayed improved antitumor effect and reduced side effects against the K7 osteosarcoma-allografted mouse model and the 143B orthotopic osteosarcoma mouse model. Given the superior properties of Ca-mineralized polypeptide nanoparticle for intracellular drug delivery, the smart drug delivery system showed strong competitiveness in clinical chemotherapy of cancers.
SARS‐CoV‐2 infection: the same virus can cause different cutaneous manifestations
Authors: F. Drago, G. Ciccarese, A. Rebora, S.I. Muzic, A. Parodi
Journal: British Journal of Dermatology (2020)

Linked Article:Galván Casas et al. Br J Dermatol 2020; 183:71–77.
Anna A Artaryan: paediatric neurosurgeon who created the first chair in the specialty
Authors: Boleslav Lichterman
Journal: BMJ (2020)

<h3>Background</h3> Multiple Sclerosis (MS) is the most common demyelinating disorder. Still today its pathogenesis is not well known, but there are several drugs to slow down disease progression. Interferon-B (IFN-B) drugs are useful to initiate treatment quickly after diagnosis. But treatment response to IFN-B is highly variable between individuals. There are recent investigations demonstrating genetic polymorphisms associated with the response to INF-B. <h3>Purpose</h3> To determine the main genetic polymorphisms evaluated for possible clinical utility in MS. <h3>Material and methods</h3> A literature review focused on genetic polymorphisms associated with IFN-B treatment responses in MS published in 2004 or later. <h3>Results</h3> Twenty-seven articles were reviewed. Different genes have been studied as a possible cause of inter-individual response. HLA genes have been associated with development of neutralising antibodies (NAbs) to interferon: rs4961252-GG, rs9272105-GG, HLA-DRB1*04:01, DRB1*04:08 and DRB1*16:01 polymorphisms were associated with higher risk of appearance of NAbs. In the CD46 gene the polymorphism rs2724385-AT was significantly lower and the TT genotype was higher in responders to interferon compared to non-responding patients. Other genes for pro and anti-inflammatory cytokines (IFNG, TNF, IFNB1, TGFB1) and receptors (IFNAR1, CCR5 and IL7RA) have been studied due to the inflammatory component of MS; Only the single alleles TGFB1*C and CCR5*d were associated with optimal IFN-B response. Another study associated one polymorphism (rs2542109-AA) from the ubiquitin-specific peptidase-18 gene with a better response to IFN-B. Another important gene studied was myxovirus resistance A (MXA) because previous studies demonstrated different gene expression in IFN-B patients treated. But in one study of two promoter region single nucleotide polymorphisms (rs2071430; rs17000900) no association was found with the clinical course. <h3>Conclusion</h3> Although individual genetic polymorphisms are relatively poor predictors, combinations of these will possibly be useful to guide therapeutic decision-making given the variety of different treatments now available with varying mechanisms of action and risks. <h3>Reference</h3> Baranzini SE, Madireddy LR, Cromer A, <i>et al</i>. Prognostic biomarkers of IFNb treatment in multiple sclerosis patients. Mult Scler 2014 No conflict of interest.