tbuckley/cabot-search huggingface dataset:
Identification of Novel Autoantibodies Associated With Psoriatic Arthritis
Authors: Yulin Yuan, Jingyi Qiu, Zuan‐Tao Lin, Wen Li, Christopher Haley, Uyen Ngoc Mui, Jing Ning, Stephen K. Tyring, Tianfu Wu
Journal: Arthritis & Rheumatology (2019)

Objective The autoimmune etiology in psoriasis remains to be clarified. We therefore undertook this study to identify novel pathogenic autoantigens and autoantibodies in patients with psoriasis, with the aim of shedding light on the molecular and cellular basis of the pathogenesis of psoriasis and psoriatic arthritis (PsA). Methods In this study, we developed an autoantigen array system that harbors a variety of antigens, including typical autoantigens in rheumatic diseases as well as skin antigens, inflammatory mediators, and putative autoantigens in psoriasis. Serum samples from patients with psoriasis (n = 73) were used to interrogate the antigens on the array. In addition, enzyme‐linked immunosorbent assays of individual autoantibodies were used in validation studies. Results Levels of several autoantibodies were found to be elevated in the serum of patients with psoriasis compared to healthy controls; in particular, IgG autoantibodies against 2 novel antigens, LL ‐37 and ADAMTS ‐L5, were significantly increased in patients with psoriasis. Importantly, serum levels of IgG autoantibodies against LL ‐37 and ADAMTS ‐L5 were correlated with the Psoriasis Area and Severity Index, and reflected disease progression in longitudinally collected serum samples from patients with psoriasis. Importantly, both anti– ADAMTS ‐L5 and anti– LL ‐37 autoantibody levels were also significantly elevated in psoriasis patients with PsA compared to those without PsA, suggesting that these molecules may be involved in the pathogenesis of PsA. Conclusion Our findings indicate that these identified autoantibodies may be useful biomarkers and may serve as therapeutic targets in psoriasis and PsA.
Sudanese doctors appeal for support as hospitals and staff are attacked
Authors: Nigel Hawkes
Journal: BMJ (2019)

Sudanese doctors have appealed for international support as security forces in the country target hospitals and detain staff in a bid to end a month long series of demonstrations against the regime of president Omar al-Bashir.

Doctors are among professional groups to have played a major part in the insurgency, triggered initially by riots on 19 December in the town of Atareb over the price of fuel and bread. Since then, the protests have spread across the country and broadened into a campaign to oust Bashir, who came to power in a coup 29 years ago.

Security forces have used tear gas and live rounds of ammunition against the demonstrators, pursuing them into hospitals where they had sought protection and treatment. The Sudan Doctors’ Syndicate reports that Omdurman …
Influence of the Gut Microbiome on Clinical Outcomes in the CPIT-001 Trial, a Phase Ib-IIA Study of Combined Checkpoint Inhibition with Nivolumab and Ipilimumab after Autologous Hematopoietic Stem Cell Transplantation in Patients at High-Risk for Post-Transplant Recurrence
Authors: Rena Feinman, Tracy Andrews, Iriana Colorado, Joshua Zenreich, Suzanne Kosky, Themba Nyirenda, Noa Biran, David S Siegel, David H. Vesole, Michele L. Donato, Scott D. Rowley, Pashna N. Munshi, Michael B Atkins, Tatyana A. Feldman, Lori A. Leslie, Andre Goy, Robert Korngold, Alan P Skarbnik, Andrew L. Pecora
Journal: Blood (2018)
AB0126 Low prevalence of antibodies against malondialdehyde-acetaldehyde adducts in spanish patients with rheumatoid arthritis
Authors: L. Rodriguez-Martinez, E. Perez-Pampin, A. Mera-Varela, C. Conde, A. Gonzalez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) present increased oxidative stress that leads to lipid peroxidation and the formation of malondialdehyde (MDA) and acetaldehyde (AA). These two compounds under oxidative stress form malondialdehyde-acetaldehyde (MAA) adducts with proteins, which are highly immunogenic. Recently, Thiele <i>et al.</i><sup>1</sup> described the presence of antibodies against human albumin MAA adducts in patients with established RA from the Veterans Affairs Rheumatoid Arthritis (VARA) registry. Of particular relevance was the reported presence of IgG anti-MAA antibodies in 92% of the patients, including 88% of the anti-CCP negative patients. These results suggest MAA adducts could contribute to the pathogenesis of RA and the anti-MAA antibodies could drastically reduce the number of patients with seronegative RA. <h3>Objectives</h3> To replicate the association of anti-MAA antibodies with RA and explore their value as biomarkers. <h3>Methods</h3> Sera from 515 Spanish patients with established RA that fulfilled the 1987 ACR classification criteria and from 274 healthy controls were included. Available information included history of smoking, anti-CCP status, and genotype of HLA-DRB1 and PTPN22 rs2476601. Human serum albumin MAA adducts and hexyl-MAA standard were chemically synthesised. Anti-MAA antibodies against the albumin MAA adducts were determined by indirect ELISA using isotype-specific secondary antibodies for IgG, IgM and IgA. <h3>Results</h3> Anti-MAA antibodies were detected in a small fraction of the RA patients, who had slightly increased antibody titers compared to healthy controls, 6.4% were positive for IgG, 15.7% for IgM and 8.0% for IgA. The low prevalence of anti-MAA antibodies persisted in spite of multiple variations in the ELISA protocols including the use of different albumin sources, albumin MAA adducts produced in two different laboratories, and various secondary antibodies. IgM anti-MAA antibody titers were increased in smokers compared to non-smokers. Moreover, the presence of IgM and of IgA anti-MAA antibodies were associated with anti-CCP and RF positivity. <h3>Conclusions</h3> Anti-MAA antibodies were detected in a small fraction of the Spanish RA patients, but their low sensitivity questions the value of these antibodies as biomarkers of RA. Due to the contradictory findings, additional studies should be performed that will need to address also the role of MAA adducts on RA pathogenesis. <h3>Reference</h3> [1] Thiele GM, et al. Arthritis Rheumatol2015;67(3):645–55. <h3>Acknowledgements</h3> Supported by grants PI14/01651 and RD16/0012/0014 of the Instituto de Salud Carlos III (Spain) that are partially financed by the ERDF <h3>Disclosure of Interest</h3> None declared
AB1212 Analytical validation of an interferon-inducible gene expression kit as a potential diagnostic test for anifrolumab
Authors: P.K. Brohawn, B.W. Higgs, S. Patel, A. Moody, P. Cooper, K. Ranade
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Anifrolumab, a fully human monoclonal antibody that binds to the type I interferon receptor, is in Phase III development for moderate to severe systemic lupus erythematosus (SLE). Patients with greater interferon-inducible gene signatures (IFNGS) have enhanced response to anifrolumab treatment.<sup>1</sup> AstraZeneca and QIAGEN developed an <i>in-vitro</i> diagnostic test for interferon-inducible gene expression (IFIGx). Efficacy of anifrolumab will be evaluated in patients with high and low IFNGS. <h3>Objectives</h3> We aimed to analytically validate the IFIGx kit for use in a pivotal clinical study and potentially to support future regulatory submission. <h3>Methods</h3> The IFIGx kit measures expression of four interferon-inducible genes (IF127, IF114, IF114L and RSAD2) compared with three housekeeping genes. Measurements were performed on mRNA extracted from whole blood from adults with SLE. A score was generated that identified patients as "IFNGS test–high" or "IFNGS test–low." Analytical validation involved six studies measuring lot interchangeability, linearity, repeatability, reproducibility, cross contamination, and system verification. <h3>Results</h3> Repeatability was 100%. Reproducibility was &gt;96%. No cross contamination was observed. Results of all studies validated the IFIGx kit (table 1). <h3>Conclusions</h3> The IFIGx kit was shown to be a robust, reproducible diagnostic test for IFNGS. The IFIGx kit has demonstrated value in prior anifrolumab studies,<sup>1</sup> and will be used both for patient stratification in Phase III studies and to support anifrolumab regulatory filings. <h3>Reference</h3> [1] Furie, et al. <i>Arthritis Rheumatol</i>. 2017;69:376–86. <h3>Disclosure of Interest</h3> P. Brohawn Employee of: MedImmune LLC, B. Higgs Employee of: MedImmune LLC, S. Patel Employee of: AstraZeneca, A. Moody Employee of: QIAGEN Manchester Ltd, P. Cooper Employee of: QIAGEN Manchester Ltd, K. Ranade Employee of: MedImmune LLC
Secondhand smoke alters arachidonic acid metabolism and inflammation in infants and children with cystic fibrosis
Authors: Benjamin T Kopp, Rohan Thompson, Jeeho Kim, Robert Konstan, Alejandro Diaz, Bennett Smith, Chandra Shrestha, Lynette K Rogers, Don Hayes, Dmitry Tumin, Frederick W Woodley, Octavio Ramilo, Don B Sanders, Judith A Groner, Asuncion Mejias
Journal: Thorax (2019)

Background Mechanisms that facilitate early infection and inflammation in cystic fibrosis (CF) are unclear. We previously demonstrated that children with CF and parental-reported secondhand smoke exposure (SHSe) have increased susceptibility to bacterial infections. SHSe hinders arachidonic acid (AA) metabolites that mediate immune function in patients without CF, and may influence CF immune dysfunction. We aimed to define SHSe’s impact on inflammation mediators and infection in children with CF. Methods Seventy-seven children with CF &lt;10 years of age ( 35 infants &lt;1 year; 42 children 1–10 years) were enrolled and hair nicotine concentrations measured as an objective surrogate of SHSe. AA signalling by serum and macrophage lipidomics, inflammation using blood transcriptional profiles and in vitro macrophage responses to bacterial infection after SHSe were assessed. Results Hair nicotine concentrations were elevated in 63% of patients. Of the AA metabolites measured by plasma lipidomics, prostaglandin D 2 (PGD 2 ) concentrations were decreased in children with CF exposed to SHSe, and associated with more frequent hospitalisations (p=0.007) and worsened weight z scores (p=0.008). Children with CF exposed to SHSe demonstrated decreased expression of the prostaglandin genes PTGES3 and PTGR2 and overexpression of inflammatory pathways. These findings were confirmed using an in vitro model, where SHSe was associated with a dose-dependent decrease in PGD 2 and increased methicillin-resistant Staphylococcus aureus survival in human CF macrophages. Conclusions Infants and young children with CF and SHSe have altered AA metabolism and dysregulated inflammatory gene expression resulting in impaired bacterial clearance. Our findings identified potential therapeutic targets to halt early disease progression associated with SHSe in the young population with CF.
<scp>EAACI</scp> position paper: Comparing insect hypersensitivity induced by bite, sting, inhalation or ingestion in human beings and animals
Authors: Isabella Pali‐Schöll, Simon Blank, Kitty Verhoeckx, Ralf S. Mueller, Jozef Janda, Eliane Marti, Ahmed A. Seida, Claudio Rhyner, Douglas J. DeBoer, Erika Jensen‐Jarolim
Journal: Allergy (2019)

Abstract Adverse reactions to insects occur in both human and veterinary patients. Systematic comparison may lead to improved recommendations for prevention and treatment in all species. In this position paper, we summarize the current knowledge on insect allergy induced via stings, bites, inhalation or ingestion, and compare reactions in companion animals to those in people. With few exceptions, the situation in human insect allergy is better documented than in animals. We focus on a review of recent literature and give overviews of the epidemiology and clinical signs. We discuss allergen sources and allergenic molecules to the extent described, and aspects of diagnosis, prophylaxis, management and therapy.
THU0724-HPR Investigation of immediate effect of cervical stabilisation exercises on proprioception in patients with neck pain
Authors: E. Tonga, T. Özen, E. Timurtaş, G.M. Polat
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Reduced ability to maintain and upright posture, may reflect impaired muscle endurance and proprioceptive accuracy required to control the postural position in patients with neck pain. A recent study investigated the effect of cervical stabilisation exercises on proprioception of neck pain patients. But in mentioned study the joint position change was evaluated for only cervical flexion movement. <h3>Objectives</h3> The aim of our study is determine the acute effect of cervical stabilisation exercises on joint position sense in all ranges of neck movement in patients with idiopathic chronic neck pain. <h3>Methods</h3> 20 patients (27–45 ages, 80%female and 4 men 20% male) with neck pain for more than 3 months were participated in this study. Exercise training was performed only one session. Patients with any neurological deficits, any recent injuries to neck and were excluded from the study Training included craniocervical flexion, deep cervical extensor muscle activation, isometric flexion-extension exercises in upright position and shoulder flexion with neutral cervical position in upright position. Each exercise were performed five times. The measured variables included joint repositioning errors in the sagittal and horizontal directions. Visual Analogue Scale (VAS), Neck Disability Index (NDI) were implemented for determining the personal characteristics of patients. Cervical joint repositioning error was evaluated by laser pointer in flexion, extension, rotation and lateral flexion of cervical movement directions at sitting position before and after exercise session. Wilcoxon test was used to compare to differences between repeated assessments <h3>Results</h3> VAS values for pain intensity were (mean ±SD) 5.56±3.17, NDI values were 14.06±6.83 and HADS scores were 18.27±2.23. In comparison to baseline values, joint position error was significantly lower in flexion, extension, rotation and lateral flexion directions at horizontal and sagittal planes (p&lt;0.001) except right lateral flexion at sagittal plane (p&gt;0.05) (table 1). <h3>Conclusions</h3> The immediate effects of neck stabilisation exercises on proprioceptive function of neck may reflect that these exercises, may enhance postural awareness and control while in motion. <h3>References</h3> [1] Stanton TR, et al. Evidence of Impaired Proprioception in Chronic, Idiopathic Neck Pain: Systematic Review and Meta-Analysis. Phys Ther2016;96(6). [2] Rupesh P, Immediate Effect of Neck Stabilization Exercise on Neck Repositioning Accuracy in Chronic Neck Pain Patients. International Journal of Clinical Skills2017:2. <h3>Disclosure of Interest</h3> None declared
VDJH Gene Repertoire Analysis in Multiple Myeloma (MM) Patients: Correlation with Clinical Data
Authors: Alejandro Medina, Cristina Jiménez, Maria E Sarasquete, Noemi Puig, Ana Balanzategui, Miguel Alcoceba, Veronica Gonzalez De La Calle, Maria Garcia-Alvarez, Isabel Prieto-Conde, Carmen Chillon, Enrique M. Ocio, Norma C. Gutierrez, Maria-Victoria Mateos, Joaquin Martínez-López, Juan Jose Lahuerta, Jesús F San-Miguel, Marcos González, Ramon García-Sanz
Journal: Blood (2018)
Evaluation of [<sup>11</sup>C]NMS-E973 as a PET tracer for <i>in vivo</i> visualisation of HSP90
Authors: Koen Vermeulen, Evelyne Naus, Muneer Ahamed, Bala Attili, Maxime Siemons, Kaat Luyten, Sofie Celen, Joost Schymkowitz, Frederic Rousseau, Guy Bormans
Journal: Theranostics (2019)

Heat shock protein 90 is an ATP-dependent molecular chaperone important for folding, maturation and clearance of aberrantly expressed proteins and is abundantly expressed (1-2% of all proteins) in the cytosol of all normal cells.In some tumour cells, however, strong expression of HSP90 is also observed on the cell membrane and in the extracellular matrix and the affinity of tumoural HSP90 for ATP domain inhibitors was reported to increase over 100-fold compared to that of HSP90 in normal cells.Here, we explore [ 11 C]NMS-E973 as a PET tracer for in vivo visualisation of HSP90 and as a potential tool for in vivo quantification of occupancy of HSP90 inhibitors.Methods: HSP90 expression was biochemically characterized in a panel of established cell lines including the melanoma line B16.F10.B16.F10 melanoma xenograft tumour tissue was compared to non-malignant mouse tissue.NMS-E973 was tested in vitro for HSP90 inhibitory activity in several tumour cell lines.HSP90-specific binding of [ 11 C]NMS-E973 was evaluated in B16.F10 melanoma cells and B16.F10 melanoma, prostate cancer LNCaP and PC3, SKOV-3 xenograft tumour slices and in vivo in a B16.F10 melanoma mouse model.Results: Strong intracellular upregulation and abundant membrane localisation of HSP90 was observed in the different tumour cell lines, in the B16.F10 tumour cell line and in B16.F10 xenograft tumours compared to non-malignant tissue.NMS-E973 showed HSP90-specific inhibition and reduced proliferation of cells.[ 11 C]NMS-E973 showed strong binding to B16.F10 melanoma cells, which was inhibited by 200 µM of PU-H71, a non-structurally related HSP90 inhibitor.HSP90-specific binding was observed by in vitro autoradiography of murine B16.F10 melanoma, LNCaP and PC3 prostate cancer and SKOV-3 ovary carcinoma tissue slices.Further, B16.F10 melanoma-inoculated mice were subjected to a µPET study, where the tracer showed fast and persistent tumour uptake.Pretreatment of B16.F10 melanoma mice with PU-H71 or Ganetespib (50 mg/kg) completely blocked tumour accumulation of [ 11 C]NMS-E973 and confirmed in vivo HSP90 binding specificity.HSP90-specific binding of [ 11 C]NMS-E973 was observed in blood, lungs and spleen of tumour-bearing animals but not in control animals.Conclusion: [ 11 C]NMS-E973 is a PET tracer for in vivo visualisation of tumour HSP90 expression and can potentially be used for quantification of HSP90 occupancy.Further translational evaluation of [ 11 C]NMS-E973 is warranted.
Tafenoquine — A Radical Improvement?
Authors: Nicholas J White
Journal: New England Journal of Medicine (2019)

Plasmodium vivax is a major cause of malaria in the Americas, the Horn of Africa, and Asia. P. vivax malaria has a propensity to recur (relapse), often multiple times, after resolution of the initial illness. This may cause substantial medical complications and contribute to death.1 Relapses arise from the dormant parasite stage in the liver (the hypnozoite). The only available drug that clears hypnozoites, thereby providing “radical cure,” is the 8-aminoquinoline primaquine. In this issue of the Journal, two studies report on the radical curative efficacy of tafenoquine, a newly registered, slowly eliminated, single-dose 8-aminoquinoline.2,3 It’s been a long time . . .
Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18 seasons
Authors: Larisa V Gubareva, Vasiliy P Mishin, Mira C Patel, Anton Chesnokov, Ha T Nguyen, Juan De La Cruz, Sarah Spencer, Angela P Campbell, Mallory Sinner, Heather Reid, Rebecca Garten, Jackie M Katz, Alicia M Fry, John Barnes, David E Wentworth
Journal: Eurosurveillance (2019)

The anti-influenza therapeutic baloxavir targets cap-dependent endonuclease activity of polymerase acidic (PA) protein. We monitored baloxavir susceptibility in the United States with next generation sequencing analysis supplemented by phenotypic one-cycle infection assay. Analysis of PA sequences of 6,891 influenza A and B viruses collected during 2016/17 and 2017/18 seasons showed amino acid substitutions: I38L (two A(H1N1)pdm09 viruses), E23G (two A(H1N1)pdm09 viruses) and I38M (one A(H3N2) virus); conferring 4-10-fold reduced susceptibility to baloxavir.
Malignant primary brain and other central nervous system tumors diagnosed in Canada from 2009 to 2013
Authors: Emily V Walker, Faith G Davis, Amanda Shaw, Rabia Louchini, Lorrains Shack, Ryan Woods, Carol Kruchko, John Spinelli, Marie-Christine Guiot, James Perry, Beatrice Melin, Jill Barnholtz-Sloan, Donna Turner, MaryJane King, Heather Hannah, Heather Bryant
Journal: Neuro-Oncology (2018)

We present a national surveillance report on malignant primary brain and other central nervous system (CNS) tumors diagnosed in the Canadian population in 2009–2013. Patients were identified through the Canadian Cancer Registry, an administrative dataset that includes cancer incidence data from all provinces/territories in Canada. Tumor types were classified by site and histology using the definitions from the Central Brain Tumor Registry of the United States (CBTRUS). Incidence rates (IRs) and 95% confidence intervals (CIs) were calculated per 100000 person-years (py) and age-standardized to the 2011 Canadian population for comparisons within Canada and to the 2000 United States population for comparisons with the US. Overall, 12515 malignant brain and other CNS tumors were diagnosed in the Canadian population in 2009–2013 (IR: 8.71/100000 py; 95% CI: 8.56, 8.86); 7085 were among males (IR: 10.06/100000 py; 95% CI: 9.82, 10.29) and 5430 among females (IR: 7.41/100000 py; 95% CI: 7.22, 7.61). Of these, 12115 were classifiable according to histological subgroups defined by CBTRUS. The most common histology was glioblastoma (IR: 4.06/100000 py; 95% CI: 3.95, 4.16). Among those aged 0–19 years, 1130 malignant brain and CNS tumors were diagnosed in 2009–2013 (IR: 3.36/100000 py; 95% CI: 3.16, 3.56). The most common histology among the pediatric population was embryonal tumor (IR: 0.74/100000 py; 95% CI: 0.65, 0.84). These data represent an initial detailed report on the frequency and distribution of primary malignant brain and other CNS tumors diagnosed in the Canadian population in 2009–2013. The reported distributions of tumor diagnoses by sex and age reflected expected patterns based on the literature from similar populations. A report incorporating data on nonmalignant primary brain tumors is forthcoming.