tbuckley/cabot-search huggingface dataset:
PARE0023 ORAL HEALTH IN RHEUMATOID ARTHRITIS: LISTENING TO PATIENTS
Authors: J. Protudjer, C. Billedeau, C. Stavropoulou, A. Cholakis, R. Schroth, C. Hitchon
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rates of periodontal disease and tooth loss are increased in rheumatoid arthritis (RA). Periodontal disease may exacerbate RA inflammation and complicate RA care. Understanding factors that contribute to the increased burden of periodontal disease in RA is critical to improving oral health and possibly arthritis outcomes. People with RA may have unique needs and/or barriers to maintain oral health. Objectives: To determine from people with RA what are their experiences and perceptions about their oral health, their most important questions relating to oral health, and how they wish to receive oral health information. Methods: Semi-structured interviews were conducted with RA patients. Recorded interview transcripts underwent iterative content analysis. Transcripts were initially reviewed to develop a coding guide. Latent content, or larger themes, were then applied to the transcripts. Constructs were considered saturated when no new themes were identified with subsequent interviews. We report identified themes with representative quotes. Results: Interviews with 11 RA (10[91%] female; all on RA medication) averaged 19 minutes (range 8-31 minutes) and were mostly conducted face-to-face. Many believed RA medication contributed to dry mouth. Most participants had not previously considered other links between oral health and RA. Themes identified included the need for complicated oral health routines, barriers of cost and access to dental care, and shame relating to oral health (Table 1). Participants preferred to receive oral health education from their rheumatologists or dentists over printed or online resources. Conclusion: RA patients have unique needs relating to oral health and report poor oral quality of life. Strategies to optimize oral health in RA may include educational tools for optimizing oral self-care appropriate for RA, and improved access to oral care professionals who are aware of the needs of arthritis patients. Disclosure of Interests: Jennifer Protudjer: None declared, Corrie Billedeau: None declared, Chrysi Stavropoulou: None declared, Anastasia Cholakis: None declared, Robert Schroth: None declared, Carol Hitchon Grant/research support from: UCB Canada; Pfizer Canada
Novel Long Non-coding RNA lncAMPC Promotes Metastasis and Immunosuppression in Prostate Cancer by Stimulating LIF/LIFR Expression
Authors: Wei Zhang, Xiaolei Shi, Rui Chen, Yasheng Zhu, Shihong Peng, Yifan Chang, Xinwen Nian, Guang’an Xiao, Ziyu Fang, Yaoming Li, Zhexu Cao, Lin Zhao, Guang Liu, Yinghao Sun, Shancheng Ren
Journal: Molecular Therapy (2020)

Long non-coding RNAs (lncRNAs) participate in the development and progression of prostate cancer (PCa). We aimd to identify a novel lncRNA, named lncRNA activated in metastatic PCa (lncAMPC), and investigate its mechanisms and clinical significance in PCa. First, the biological capacity of lncAMPC in PCa was demonstrated both in vitro and in vivo. The lncAMPC was overexpressed in tumor tissue and urine of metastatic PCa patients and promoted PCa tumorigenesis and metastasis. Then, a mechanism study was conducted to determine how the lncAMPC-activated pathway contributed to PCa metastasis and immunosuppression. In the cytoplasm, lncAMPC upregulated LIF expression by sponging miR-637 and inhibiting its activity. In the nucleus, lncAMPC enhanced LIFR transcription by decoying histone H1.2 away from the upstream sequence of the LIFR gene. The lncAMPC-activated LIF/LIFR expressions stimulated the Jak1-STAT3 pathway to simultaneously maintain programmed death-ligand 1 (PD-L1) protein stability and promote metastasis-associated gene expression. Finally, the prognostic value of the expression of lncAMPC and its downstream genes in PCa patients was evaluated. High LIF/LIFR levels indicated shorter biochemical recurrence-free survival among patients who underwent radical prostatectomy. Therefore, the lncAMPC/LIF/LIFR axis plays a critical role in PCa metastasis and immunosuppression and may serve as a prognostic biomarker and potential therapeutic target.
Geoffrey Patrick Ridsdill Smith
Authors: William Ridsdill Smith
Journal: BMJ (2020)

Geoffrey Patrick Ridsdill Smith, known as Patrick, chose to follow a medical career in his early thirties having worked as an economist for Fisons plc. He went on to have over 25 years as a GP. He never became disillusioned. He treasured both the variety and security of the job. He was a great advocate for medicine as a second career.

He was born on St Patrick’s Day in his uncle’s house in Wellington Park, Belfast. His uncle, Sir Ian Fraser, a surgeon at Queens Hospital, carried out the first field trials of penicillin with Howard Florey in North Africa. Ian was a source of inspiration for Patrick.

He spent the war years in Newcastle, County Down, Ireland, while his father, Geoff, served in the Home Guard in England. Geoff had suffered extensive facial burns in a plane crash during training in the Royal Flying Corps in 1917, and had a series of operations under Sir Harold Gillies at Queen Mary’s Sidcup, including a new nose, cheek, and eyelids.

Patrick was educated at Windlesham School, East Sussex, and then Haileybury College, Hertford, where his father taught history. He became head boy and developed a love of sailing in the naval section of the cadet corps. The family and their corgi, Taffy, lived in Southfield, an idyllic house with a grass tennis court.

Patrick joined up with the Royal Navy for national service. He won a short service commission and was posted to Hong Kong, where he met his wife to be, Diana, daughter of the acting attorney general, Arthur Hooton. …
Abstract 14939: Clinical Characteristics and Outcomes of Atrial Fibrillation Patients With Thrombocytopenia: The Fushimi AF Registry
Authors: Kenjiro Ishigami, Yuya Aono, Syuhei Ikeda, Kosuke Doi, Yoshimori An, Mitsuru Ishii, Moritake Iguchi, Nobutoyo Masunaga, Hisashi Ogawa, Hiromichi Wada, Koji Hasegawa, Mitsuru Abe, Masaharu Akao
Journal: Circulation (2019)

Introduction: The clinical impact of thrombocytopenia and use of anti-thrombotic drugs has not been fully determined in patients with atrial fibrillation (AF). Methods: The Fushimi AF Registry was ...
Lysophosphatidylserine induces eosinophil extracellular trap formation and degranulation: Implications in severe asthma
Authors: Hye Jeong Kim, Myeong Seong Sim, Dong Hyun Lee, Chun Kim, Youngwoo Choi, Hae‐Sim Park, Il Yup Chung
Journal: Allergy (2020)

Recent evidence demonstrates that activated eosinophils undergo a distinct form of lytic cell death, accompanied by formation of DNA-based eosinophil extracellular trap (EET) and degranulation, enhancing inflammatory immune responses in asthmatic airways. We previously showed that human blood eosinophils undergo degranulation in response to lysophosphatidylserine (LysoPS), an inflammatory lipid mediator, and strongly express P2Y10, a LysoPS receptor.We evaluated EET, degranulation, and cell death of eosinophils in response to various concentrations of LysoPS. We also compared responsiveness to LysoPS between eosinophils from severe and nonsevere asthmatics.Extensive EET formation was elicited from a substantial fraction of stimulated eosinophils in response to 50 μmol/L LysoPS. Analyses for LDH and eosinophil-derived neurotoxin release showed that both lytic cell death and degranulation accompanied EET formation in response to LysoPS. Cytological analyses demonstrated that citrullinated histone 3 was present in the extracellular, filamentous DNA structure embedded with eosinophil granules. The LysoPS-induced EET was independent of ROS production and irrelevant to several signaling pathways examined, but dependent on protein arginine deiminase 4. A low concentration of LysoPS (5 μmol/L) did not induce EET or degranulation, but significantly increased platelet-activating factor-induced degranulation. Eosinophils from severe asthmatics exhibited greater degranulation, but not EET formation, in response to LysoPS (50 μmol/L), than those from nonsevere asthmatics, along with great expression of surface P2Y10.We identified a novel function of LysoPS, namely induction of EET in association with cytolysis and degranulation. LysoPS-dependent EET or degranulation plays a potential role in eosinophilic inflammation of severe asthma.
Long-term Outcomes of Primary Endoscopic Resection vs Surgery for T1 Colorectal Cancer: A Systematic Review and Meta-analysis
Authors: Jen-Hao Yeh, Cheng-Hao Tseng, Ru-Yi Huang, Chih-Wen Lin, Ching-Tai Lee, Po-Jen Hsiao, Tsung-Chin Wu, Liang-Tseng Kuo, Wen-Lun Wang
Journal: Clinical Gastroenterology and Hepatology (2020)
Using circular questions to explore individual family member experiences of youth gender dysphoria in Australia
Authors: Jason J. Westwater, Elizabeth Riley, Gregory M. Peterson
Journal: International Journal of Transgender Health (2020)

Background: The number of young people reporting gender dysphoria is increasing worldwide, with gender dysphoria known to affect everyone in the family in unique ways. Previous research has highlighted the importance of family support and understanding; however, much less is known about individual and collective family member experiences, particularly for siblings under the age of 18 years. Aims: This study sought to identify, describe and interpret individual family member experiences of youth gender dysphoria using semi-structured interviews, incorporating circular questioning, within a whole of family, clinical and wider social context. Methods: Thirty-five individual family members living in Australia (nine young people aged 12-17 years experiencing gender dysphoria, 10 mothers, eight fathers, and eight siblings aged 11-17 years) were interviewed, exploring positive and negative experiences of youth gender dysphoria, within and outside of the family. Family relationships, support and healthcare experiences were also explored. Results: All participants reported a mixture of positive and negative experiences of youth gender dysphoria. Levels of acceptance tended to change with the duration of transition, with most family members adapting with time. Siblings reported mixed experiences within the same family, with some struggling to adapt. Most family members felt that including the whole family in the healthcare of the young person was important, although dependent on individual circumstances and family context. Specialist gender care experiences were unanimously positive, although services were considered difficult to access. Discussion: Family members reported shared and individual positive and negative experiences of youth gender dysphoria across social contexts. Accepting and facilitating gender transition for young people appeared to improve individual and family functioning. Most participants valued a whole of family approach within specialist healthcare. The use of circular questioning in the study helped dispel assumptions and facilitated curiosity for others' experiences in the family.
GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study
Authors: Giacomo De Luca, Giulio Cavalli, Corrado Campochiaro, Emanuel Della-Torre, Piera Angelillo, Alessandro Tomelleri, Nicola Boffini, Stefano Tentori, Francesca Mette, Nicola Farina, Patrizia Rovere-Querini, Annalisa Ruggeri, Teresa D'Aliberti, Paolo Scarpellini, Giovanni Landoni, Francesco De Cobelli, John F Paolini, Alberto Zangrillo, Moreno Tresoldi, Bruce C Trapnell, Fabio Ciceri, Lorenzo Dagna
Journal: The Lancet Rheumatology (2020)
World leaders in covid-19 control
Authors: Mun-Keat Looi
Journal: BMJ (2020)

As the pandemic has spread around the world much has been made of the rising numbers-more than 7.2 million cases and at least 400 000 deaths.But at least 3.6 million people have recovered from infection, and lessons are emerging from countries that have been successful in stemming transmission, notably by taking early action with a strong emphasis on test, track, and trace.
Abstract 16019: Worsening Renal Function During Intensive Volume Removal is Driven by Renin-Angiotensin-Aldosterone System Activation
Authors: Matthew Griffin, Juan Ivey-Miranda, Veena Rao, James Fleming, Nicole Gomez, Joslyn Barnett, Megan Pattoli, Emily Wycallis, Devin Mahoney, Anvin Thomas, Griffin Struyk, Jeffrey M Testani
Journal: Circulation (2019)

Introduction: Worsening renal function (WRF) in the setting of aggressive diuresis may carry a neutral or even beneficial prognosis for patients with acute decompensated heart failure (ADHF). Prior...
Corrigendum to “Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial”
Authors: K. Behringer, I. Thielen, H. Mueller, H. Goergen, A.D. Eibl, J. Rosenbrock, T. Halbsguth, D.A. Eichenauer, M. Fuchs, K.S. Reiners, J.H. Renno, K. van der Ven, M. Kuehr, M. von Wolff, V. Diehl, A. Engert, P. Borchmann
Journal: Annals of Oncology (2020)
Up-regulation of hypoxia-inducible factor antisense as a novel approach to treat ovarian cancer
Authors: Tiangong Lu, Jianming Tang, Binita Shrestha, Blake R. Heath, Li Hong, Yu L. Lei, Mats Ljungman, Nouri Neamati
Journal: Theranostics (2020)

Ovarian cancer (OC) is estimated to kill ~14,000 women in the United States in 2019.Current chemotherapies to treat OC initially show therapeutic efficacy but frequently drug resistance develops, at which point therapies with alternative targets are needed.Herein, we are describing a novel approach to sensitize these tumors to standard chemotherapies by increasing the transcription of hypoxia-inducible factor antisense.Methods: Genome-wide Bru-seq analysis was performed to fully capture the nascent transcriptional signature of OC cells treated with the gp130 inhibitor, SC144.In vitro and in vivo analysis, including characterization of hypoxia and select protein expression, combination with standard of care chemotherapy and antitumor efficacy were performed to assess the biological activity of SC144 on induction of hypoxia in OC cells.Results: Bru-seq analysis of OVCAR8 cells treated with SC144 shows upregulation of hypoxia related genes.In addition, transcription of hypoxia-inducible factor antisense (HIF1A-AS2) was induced that in turn reduced expression of HIF-1α and simultaneously increased expression of NDRG1.Furthermore, we observed decreased protein levels of EGFR, Met, c-Myc, cyclin D1, MMP-2, MMP-9 and TF, and phosphorylation of Src and P130-cas.SC144-induced alterations of HIF-1α and NDRG1 were also confirmed in prostate cancer cells.Ciclopirox olamine (CPX) induces a cellular transcriptional profile comparable to SC144, suggesting a similar cellular mechanism of action between these two compounds.In addition, SC144 sensitized OC cells to olaparib, carboplatin and cisplatin, and shows better in vivo efficacy than CPX.Conclusion: Induction of hypoxic stress responses through inhibition of gp130 represents a novel approach to design effective anticancer treatments in combination with standard-of-care chemotherapy in OC and the efficacy reported here strongly supports their clinical development.
AB0349 EFFICACY OF TOFACITINIB THERAPY, DEPENDING ON THE USE OF DMARDS IN PATIENTS WITH RHEUMATOID ARTHRITIS IN A REAL CLINICAL PRACTICE IN RUSSIAN FEDERATION.
Authors: A. Misiyuk, A. Lila, A. Gordeev, E. Galushko
Journal: Annals of the Rheumatic Diseases (2020)

Background: Objectives: To evaluate how disease-modifying antirheumatic drugs (DMARDs) affects efficacy of tofacitinib (TOFA) therapy in patients with rheumatoid arthritis (RA). Methods: We analyzed the history of 107 patients (mean age 51,4±12,1 yrs) with RA according to the 2010 ACR/EULAR criteria, from 11 regions Russian Federation, including patients who were treated at the V.A. Nasonova Research Institute of Rheumatology. These patients were non-responders to DMARDs, previously biologic therapy and were treated with TOFA in combination with DMARDs or without. 107 patients (77 woman (72%),tested positive for ACCP (76.5%)/RF (87.3%), the median disease duration was 7,5±6,6 years; the mean DAS28 score was 5,8±1,0, mean SDAI and CDAI score was 35,6±13,4 and 32,1±12,4 respectively) received TOFA for 12 months. TOFA therapy was started in all patients in dose 5 mg BID per os with escalation to 10 mg BID in 17,6% pts. Results: The use of TOFA was accompanied by a decrease in the disease activity after 6 and 12 months of therapy. All patients were divided into 3 groups, depending on DMARDs therapy: TOFA+ methotrexate (MTX), TOFA+ another DMARDs (leflunomide, hydroxychloroquine, azathioprine), mono-therapy of TOFA. The dynamic of the disease activity in 3 groups is presenting on the table below: Table 1. A Outcome of contributory AEs/SAE at close of follow-up. B SAEs classified as ‘expected’. DLT: dose limiting toxicity; N+V: nausea, vomiting. Parameters Weeks TOFA+MTX (n=69) TOFA+ another DMARDs (n=20) TOFA monotherepy (n=18) DAS28 (ESR) baseline 5,9 ±1,0 5,6±1,1 6,0±0,8 6 months 3,5±1,2* 4,1±1,1* 4,2±1,6* 12 months 3,3±1,0* 3,5±1,3* 3,8±1,2* SDAI baseline 36,2±14,2 32,6±9,5 35,3± 10,3 6 months 14,4± 10,7* 16,7± 10,2* 27,3±19,1* 12 months 9,5±8,0* 12,9± 8,6* 15,3±10,2* CDAI baseline 32,4±12,1 29,7±8,9 33,2±9,8 6 months 13,3±10,2* 15,6±9,8* 22,4±16,8* 12 months 8,7±7,6* 12,6±8,2* 14,4±9,6* *p&lt;0,05 Patients who received TOFA with MTX had lower disease activity during the therapy. Patients on mono-therapy of TOFA had higher disease activity according to DAS28, SDAI, CDAI. Conclusion: Tofacitinib is effective ts-DMARDs for active rheumatoid arthritis on the Russian population. It shows better efficacy in combination with methotrexate, than in combination with another DMARDs (leflunomide and other) or in mono-therapy. Disclosure of Interests: None declared
THU0487 DIAGNOSTIC DILEMMA: WHICH CLINICAL TEST IS MOST ACCURATE FOR DIAGNOSING SUPRASPINATUS MUSCLE TEARS AND TENDINOSIS?
Authors: E. Balevi Batur, Z. Bekin Sarikaya, M. E. Kaygisiz, İ. Albayrak Gezer, F. Levendoğlu
Journal: Annals of the Rheumatic Diseases (2020)

Background: Supraspinatus tears and tendinosis are the most common pathology that cause shoulder pain to approximately half of the patients presenting clinically. 1 Objectives: To investigate the diagnostic accuracy of five clinical tests in the diagnosis of supraspinatus tears and tendinosis compared with magnetic resonance imaging (MRI). Methods: A total of 116 painful shoulders of 106 consecutive patients were examined. Patients were assessed using the most commonly used special clinical tests including the Jobe test (empty can), Neer test, drop arm test, Hawkins test and full can tests to identify supraspinatus tears and tendinosis. A visual analogue scale (VAS) was used for pain detection, and the Shoulder Pain and Disability Index (SPADI) questionnaire was administered. MRI examinations were performed on 1.5 Tesla MR system and images were assessed by a blinded radiologist. The primary outcomes were to determine the sensitivity, specificity, and accuracy of the five clinical tests, and to establish their correlation with MRI for supraspinatus tears and tendinosis. Results: The mean age was 55.10 ± 10.20 years, and 32.08% of the patients were female. The Hawkins test had a higher sensitivity and accuracy in tears (sensitivity 89.66%, accuracy 56.03%, respectively) and higher sensitivity in tendinosis (79.07%). The drop arm test had a lower sensitivity but higher specificity in both tendinosis and tears (sensitivity 0%, 12.07%, respectively, and specificity 87.67%, 96.5%, respectively Conclusion: The Hawkins test was the most sensitive in both supraspinatus tendinosis and tears compared with MRI findings. References: [1]Yamaguchi K, Ditsios K, Middleton WD, Hildebolt CF, Galatz LM, Teefey SA,The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders. J Bone Joint Surg Am, 2006. 88(8): p. 1699-704. Disclosure of Interests: : None declared
3D model of harlequin ichthyosis reveals inflammatory therapeutic targets
Authors: Florence Enjalbert, Priya Dewan, Matthew P. Caley, Eleri M. Jones, Mary A. Morse, David P. Kelsell, Anton J. Enright, Edel A. O’Toole
Journal: Journal of Clinical Investigation (2020)

The biology of harlequin ichthyosis (HI), a devastating skin disorder caused by loss-of-function mutations in the gene ABCA12, is poorly understood, and to date, no satisfactory treatment has been developed. We sought to investigate pathomechanisms of HI that could lead to the identification of new treatments for improving patients' quality of life. In this study, RNA-Seq and functional assays were performed to define the effects of loss of ABCA12 using HI patient skin samples and an engineered CRISPR/Cas9 ABCA12 KO cell line. The HI living skin equivalent (3D model) recapitulated the HI skin phenotype. The cytokines IL-36α and IL-36γ were upregulated in HI skin, whereas the innate immune inhibitor IL-37 was strongly downregulated. We also identified STAT1 and its downstream target inducible nitric oxide synthase (NOS2) as being upregulated in the in vitro HI 3D model and HI patient skin samples. Inhibition of NOS2 using the inhibitor 1400W or the JAK inhibitor tofacitinib dramatically improved the in vitro HI phenotype by restoring the lipid barrier in the HI 3D model. Our study has identified dysregulated pathways in HI skin that are feasible therapeutic targets.
Usefulness of mean number of adenomas per positive screenee for identifying meticulous endoscopists among those who achieve acceptable adenoma detection rates
Authors: Satimai Aniwan, Kunvadee Vanduangden, Stephen J. Kerr, Naruemon Wisedopas, Natanong Kongtab, Pinit Kullavanijaya, Rungsun Rerknimitr
Journal: Endoscopy (2020)

Abstract Background Adenoma detection rate (ADR) is a quality indicator for colonoscopy. However, many missed adenomas have subsequently been identified after colonoscopies performed by endoscopists with ADR ≥ 25 %. Adenomas per positive participant (APP; mean number of adenomas detected by an endoscopist among screenees with positive findings) correlates well inversely with adenoma miss rate. This study aimed to evaluate whether APP added additional information on the detection rate for advanced adenomas (AADR) and proximal adenomas (pADR) and among endoscopists with acceptable ADRs (≥ 25 %). Methods A total of 47 endoscopists performed 7339 screening colonoscopies that were retrospectively reviewed. Using a cutoff APP value of 2.0, endoscopist performance was classified as high or low APP. Endoscopist ADRs were also classified as acceptable (25 % – 29 %), high standard (30 % – 39 %) and aspirational (≥ 40 %). Generalized linear models were used to assess the relationship between AADR or pADR, and ADR and APP, after adjusting for potential confounders. Results After adjusting for endoscopist performance and patient characteristics, endoscopists with high APP had a significant 2.1 percentage point increase in AADR (95 %CI 0.3 to 3.9; P = 0.02) and a 2.1 percentage point increase in pADR (95 %CI – 0.8 to 5.1; P = 0.15) compared to endoscopists with low APP. In total, 11 (24 %), 18 (38 %), and 18 (38 %) endoscopists were classified as having acceptable, high standard, and aspirational ADRs, respectively. APP values higher than the cutoff were found in 18 %, 44 %, and 72 % of endoscopists with acceptable, high standard, and aspirational ADRs, respectively (P = 0.02). Conclusion APP is helpful for identifying more meticulous endoscopists who can detect a greater number of advanced adenomas. Endoscopists who achieved an only acceptable ADR had the lowest APP.
ボウマン層ジストロフィー(Thiel-BehnkeおよびReis-Buckler角膜ジストロフィー)のレーザー生体共焦点顕微鏡所見 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Kobayashi A, Sugiyama K
Journal: Ophthalmology (2007)