tbuckley/cabot-search huggingface dataset:
AB0388 Sleep disturbances in inflammatory rheumatic diseases
Authors: O. Addimanda, M. Burattini, L. Baldelli, G. Chiaro, E. Pignotti, F. Provini, R. Meliconi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Inflammatory rheumatic joint diseases such as Ankylosing Spondylitis (AS) and Rheumatoid Arthritis (RA) have recently been found to be associated with sleep disturbances especially obstructive sleep apnoea.<sup>1 2</sup> <h3>Objectives</h3> The aim of our study was to evaluate the occurrence of sleep disturbances, especially REM Sleep Behaviour Disorder (RBD), in inflammatory rheumatic diseases, (rheumatoid arthritis -RA and Spondyloarthritides -SpA). <h3>Methods</h3> We enrolled 103 consecutive patients affected by inflammatory rheumatic diseases [RA (64, 62.1%) or SpA (39, 37.9%)]. Patients underwent a neurologic and psychopathological assessment, including identification of sleep disorders by means of the Pittsburgh Sleep Quality Index (PSQI), the Berlin and the REM sleep behaviour disorder (RBD) questionnaires, a structured interview on sleep terrors and sleep paralysis, Beck Depression Inventory (BDI-II) and the Spielberger State-Trait Anxiety Inventory (STAI). Statistical analysis was performed utilising SPSS software. <h3>Results</h3> No significant differences were found between RA and SpA patients in age at diagnosis, disease duration, smoke habit, alcohol consumption, anamnestic comorbidities (especially metabolic diseases, anxiety or depression), disease activity/remission and biologic Disease Modifying Antirheumatic Drugs use. No differences demonstrated in BDI-II, STAI, PSQI and RBD questionnaires; only the Berlin Questionnaire showed significant differences (17.2% in RA vs 35.9% in SpA, p=0.036). No differences in sleep paralysis (10.9% in RA vs 7.7% in SpA, p=0.74) and sleep terrors (37.5% in RA vs 20.5% in SpA, p=0.0826) which were found to be increased if compared with general population (2.6%.) <h3>Conclusions</h3> Our data show an increased prevalence of sleep terrors in rheumatic patients when compared to the general population although no differences were highlighted between RA and SpA; also increased risk of sleep apnoea (Berlin Questionnaire) has been demonstrated in patients with SpA compared with RA. <h3>References</h3> [1] Aydin E, Bayraktar K, Turan Y, Omurlu I, Tastaban E, Sendur OF. Sleep quality in patients with ankylosing spondylitis. Rev Bras Reumatol2015;55:340–5. [2] Taylor-Gjevre RM, Nair BV, Gjevre JA. Obstructive sleep apnoea in relation to rheumatic disease. Rheumatology2013;52:15–21. [3] American Academy of Sleep Medicine. International Classification of Sleep Disorders, 3rd ed, American Academy of Sleep Medicine, Darien, IL 2014. <h3>Disclosure of Interest</h3> None declared
Rapid diagnostic tests for determining dengue serostatus: a systematic review and key informant interviews
Authors: R. Luo, N. Fongwen, C. Kelly-Cirino, E. Harris, A. Wilder-Smith, R.W. Peeling
Journal: Clinical Microbiology and Infection (2019)

ObjectivesVaccination for dengue with the live attenuated tetravalent CYD-TDV vaccine (Dengvaxia®) is only recommended in individuals who have had prior dengue virus (DENV) infection. Rapid diagnostic tests (RDT) for past DENV infection would offer a convenient method for pre-vaccination screening at point-of-care. A systematic review was conducted to evaluate the performance of current dengue RDTs for determining dengue serostatus, using IgG antibodies against DENV as a marker of past infection.MethodsPubMed and EMBASE databases were searched from 2000 to 2018 to identify studies evaluating dengue RDTs in individuals with known or possible previous DENV infection. Study quality was evaluated using GRADE and QUADAS-2 criteria. Semi-structured interviews were also performed with available dengue RDT manufacturers.ResultsThe performance of four dengue IgG RDTs was determined in 3137 individuals across ten studies conducted in 13 countries, with serum used in most of the studies. No studies reported data for determining dengue serostatus, and limited data were available regarding cross-reactivity with other viruses. The majority of studies demonstrated sensitivities and specificities between 80% and 100% for dengue IgG detection in samples from secondary infection or convalescent time-points after recent infection.ConclusionsAlthough current dengue IgG RDTs have shown reasonable performance compared with laboratory-based tests in secondary infection, additional research is needed to determine how RDTs would perform in relevant populations targeted for vaccination. New RDTs or modifications to current RDTs are feasible and may optimize the performance of these tests for use in a pre-vaccination screening approach.
Seven Year Follow up and Comparison of Dosing Strategies from the Pivotal Phase II Clinical Trial of Lenalidomide Plus Rituximab (R2) in Previously Untreated Follicular Lymphoma
Authors: Nathan H. Fowler, Preetesh Jain, Loretta J. Nastoupil, F. B. Hagemeister, Sheryl G Forbes, Lore Lagrone, Luis Fayad, Hun Ju Lee, R. Eric Davis, Jason R. Westin, Michael Wang, Sattva S. Neelapu, Felipe Samaniego
Journal: Blood (2018)
Lessons from negative dyspnoea studies: arguments for the multidimensional evaluation of multidirectional therapeutic approaches
Authors: Thomas Similowski, Laure Serresse
Journal: European Respiratory Journal (2019)

<b>Dyspnoea-targeted interventions should probably combine multiple approaches (multidirectional) and their evaluation should take the complex nature of dyspnoea into account (multidimensional)</b>http://ow.ly/tLaM30ndprk
Signaling Pathways of Mutant IDH1 Independent of R-2-Hydroxyglutarate
Authors: Charu Gupta, Michelle Maria Araujo Cruz, Nidhi Jyotsana, Amit Sharma, Ramya Goparaju, Kerstin Görlich, Renate Schottmann, Eduard Struys, Erwin E Jansen, Felicitas Thol, Arnold Ganser, Michael Heuser, Anuhar Chaturvedi
Journal: Blood (2018)
Trajectories of psychosocial and cognitive functioning in pediatric patients with brain tumors treated with radiation therapy
Authors: Victoria W Willard, Kristoffer S Berlin, Heather M Conklin, Thomas E Merchant
Journal: Neuro-Oncology (2019)

Pediatric patients with brain tumors who are treated with radiation therapy (RT) are at risk for neurocognitive and psychosocial late effects. Research to date has primarily examined these outcomes at a group level and in isolation. Advanced statistical techniques allow for person-centered analyses, as well as examination of relationships between domain-specific trajectories.Patients with brain tumors (craniopharyngioma, ependymoma, low-grade astrocytoma, high-grade astrocytoma) were enrolled on a phase II clinical trial of RT. Three hundred and fifty patients completed serial neurocognitive assessments as part of their treatment monitoring, including pre-RT baseline, 6 months post-RT, and then yearly for 5 years. This secondary analysis focused on outcomes of cognition (estimated IQ, parent-reported attention problems) and psychosocial effects (parent-reported socialization and social problems) post-RT.Latent growth curve modeling indicated that estimated IQ and socialization were best served by quadratic models, while attention and social problems were best served by linear models. Growth mixture modeling indicated 3-class models were the best fit for IQ and socialization, and 2-class models for attention and social problems. Baseline IQ and socialization scores were associated, but there was no association over time. Young age at diagnosis and pre-RT treatments (surgery, chemotherapy) were associated with class membership.Person-centered statistical analyses provide rich information regarding the variability in neurocognitive and psychosocial functioning following RT for pediatric brain tumor. While many patients do well over time, a subset are exhibiting significant cognitive and/or psychosocial deficits. Class membership was associated with some medical factors (eg, pre-radiation surgery/chemotherapy, age at diagnosis, shunted hydrocephalus).
HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design
Authors: Christine A. Bricault, Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, Maxwell Theiler, Peter Hraber, Jennifer P. Macke, Edward F. Kreider, Gerald H. Learn, Beatrice H. Hahn, Johannes F. Scheid, James M. Kovacs, Jennifer L. Shields, Christy L. Lavine, Fadi Ghantous, Michael Rist, Madeleine G. Bayne, George H. Neubauer, Katherine McMahan, Hanqin Peng, Coraline Chéneau, Jennifer J. Jones, Jie Zeng, Christina Ochsenbauer, Joseph P. Nkolola, Kathryn E. Stephenson, Bing Chen, S. Gnanakaran, Mattia Bonsignori, LaTonya D. Williams, Barton F. Haynes, Nicole Doria-Rose, John R. Mascola, David C. Montefiori, Dan H. Barouch, Bette Korber
Journal: Cell Host & Microbe (2019)

Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs for prophylaxis and therapeutics is being explored. We used neutralization data from four large virus panels to comprehensively map viral signatures associated with bNAb sensitivity, including amino acids, hypervariable region characteristics, and clade effects across four different classes of bNAbs. The bNAb signatures defined for the variable loop 2 (V2) epitope region of HIV-1 Env were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine, and immunization of guinea pigs with V2-SET vaccines resulted in increased breadth of NAb responses compared with Env 459C alone. These data demonstrate that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens capable of eliciting antibody responses with greater neutralization breadth.
FRI0529 Preoperative pain seems to modify the effect of radiographic osteoarthiritis severity on postoperative pain and function 1 year after total knee arthroplasty
Authors: R. van de Water, C. Leichtenberg, R. Nelissen, H. Kroon, H. Kaptijn, R. Onstenk, S. Verdegaal, T. Vliet Vlieland, M. Gademan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Radiographic osteoarthritis (OA) severity and pain play an important role in the indication for total knee arthroplasty (TKA). It is however unkonw whether preoperative self-reported clinical pain modifies the effect of radiographic OA severity on postoperative pain and function in OA patients after TKA. <h3>Objectives</h3> To investigate whether preoperative self-reported clinical pain modified the effect of radiographic OA severity on postoperative pain and function in OA patients 1 year after TKA. <h3>Methods</h3> Data from the Longitudinal Leiden Orthopaedics Outcomes of Osteoarthritis Study (LOAS), a multicentre cohort study on outcomes after TKA were used. Radiographic OA severity was assessed with the Kellgren and Lawrence (KL) score (0–4). Pain and function were evaluated with the Knee Injury and Osteoarthritis Outcome Score (KOOS). After adjustment for confounders (BMI, age, gender and Mental Health Component Scores from the Short Form-12), multivariate linear regression analyses with an interaction term between KL-score and preoperative pain were performed. <h3>Results</h3> 560 patients were included. Both KL-score and preoperative pain were associated with postoperative pain (β:6.1, 95% CI: 1.7–10.5 and β:0.4, 95% CI 0.1–0.7)) and function (β:8.0, 95% CI: 3.7–12.3 and β 0.5, 95% CI 0.2–0.8). A trend towards effect modification of preoperative pain on the association between KL-score and postoperative pain (β −0.1, 95% CI −0.2–0.0) and function (β −0.1, 95% CI −0.2–0.0) was found indicating that effect of preoperative pain on postoperative pain and function seems to become less important when more severe radiographic severity is present. <h3>Conclusions</h3> Patients with less preoperative pain and higher KL grades have better function and pain outcomes 12 months after TKA. However preoperative pain seems less importance in patients with more severe radiographic OA. <h3>Acknowledgements</h3> This study was supported by the Dutch Arthritis Association [grant number LLP13]. <h3>Disclosure of Interest</h3> None declared
Acetylation of CCAR2 Establishes a BET/BRD9 Acetyl Switch in Response to Combined Deacetylase and Bromodomain Inhibition
Authors: Praveen Rajendran, Gavin Johnson, Li Li, Ying-Shiuan Chen, Mohaiza Dashwood, Nhung Nguyen, Ahmet Ulusan, Furkan Ertem, Mutian Zhang, Jia Li, Deqiang Sun, Yun Huang, Shan Wang, Hon-Chiu Leung, David Lieberman, Laura Beaver, Emily Ho, Mark Bedford, Kyle Chang, Eduardo Vilar, Roderick Dashwood
Journal: Cancer Research (2019)

There continues to be interest in targeting epigenetic "readers, writers, and erasers" for the treatment of cancer and other pathologies. However, a mechanistic understanding is frequently lacking for the synergy observed when combining deacetylase and bromodomain inhibitors. Here we identify cell cycle and apoptosis regulator 2 (CCAR2) as an early target for acetylation in colon cancer cells treated with sulforaphane. N-terminal acetylation of CCAR2 diminished its interactions with histone deacetylase 3 and β-catenin, interfering with Wnt coactivator functions of CCAR2, including in cells harboring genetically encoded CCAR2 acetylation. Protein domain arrays and pull-down assays identified acetyl "reader" proteins that recognized CCAR2 acetylation sites, including BRD9 and members of the bromodomain and extraterminal domain (BET) family. Treatment with the BET inhibitor JQ1 synergized with sulforaphane in colon cancer cells and suppressed tumor development effectively in a preclinical model of colorectal cancer. Studies with sulforaphane+JQ1 in combination implicated a BET/BRD9 acetyl switch and a shift in the pool of acetyl "reader" proteins in favor of BRD9-regulated target genes. SIGNIFICANCE: These results highlight the competition that exists among the "readers" of acetylated histone and nonhistone proteins and provide a mechanistic basis for potential new therapeutic avenues involving epigenetic combination treatments.
Abstract P185: Hypertensive Disorders of Pregnancy in Women With Gestational Diabetes Mellitus on Overweight Status of Their Children
Authors: Shuang Zhang, Leishen Wang, Junhong Leng, Huikun Liu, Weiqin Li, Tao Zhang, Nan Li, Wei Li, Huiguang Tian, Gang Hu
Journal: Circulation (2017)

Background: Hypertensive disorders of pregnancy (HDP) as a group of medical complications in pregnancy are believed to be associated with an increased risk of poor fetal growth, but the influence on offspring’s body composition is not clear. Aims: To evaluate the association between maternal hypertensive disorders of pregnancy and overweight status in the offspring of mothers with gestational diabetes mellitus (GDM). Methods: A cross-sectional study among 1263 GDM mother-child pairs was performed in Tianjin, China. General linear models and logistic regression models were used to assess the associations of maternal hypertension in pregnancy with anthropometry and overweight status in the offspring from birth to 1-5 years old. Results: Offspring of GDM mothers who were diagnosed with hypertensive disorders during pregnancy had higher mean values of Z scores for birth weight for gestational age and birth weight for length, and higher mean values of Z scores for weight for age, weight for length/height, and body mass index for age at 1-5 years old than those of GDM mothers with normal blood pressure during pregnancy. Maternal hypertensive disorders of pregnancy were associated with increased risks of large for gestational age (OR 1.74, 95%CI 1.08-2.79) and macrosomia (OR 2.02, 95%CI 1.23-3.31) at birth and childhood overweight/obesity at 1-5 years old age (OR 1.88, 95%CI 1.16-3.04). Conclusion: For offspring of mothers with GDM, maternal hypertension during pregnancy was a risk factor for macrosomia at birth and childhood overweight and obesity.
Suicide mortality and natural environments – Authors' reply
Authors: Marco Helbich, Derek de Beurs, Mei-Po Kwan, Rory C O'Connor, Peter P Groenewegen
Journal: The Lancet Planetary Health (2019)

We welcome the comments from Bence Mátyás concerning our Article about the associations between suicide mortality and green and blue space.1Helbich M Beurs DD Kwan MP O'Connor RC Groenewegen PP Natural environments and suicide mortality in the Netherlands: a cross-sectional, ecological study.Lancet Planet Health. 2018; 2: e134-e139Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar Here, we would like to respond to his two observations. First, Mátyás commented that our study was not “the first of its kind” and corroborated this statement with a reference to Nutsford and colleague's 2016 retrospective study.2Nutsford D Pearson AL Kingham S Reitsma F Residential exposure to visible blue space (but not green space) associated with lower psychological distress in a capital city.Health Place. 2016; 39: 70-78Crossref PubMed Scopus (191) Google Scholar After careful deliberation, we concluded that his observation is only partly valid because, as he correctly states in their Correspondence, Nutsford and colleague's study correlates blue space with psychological stress, but not with suicide mortality. We acknowledge, as we do in the Article, that evidence about the potential salutogenic effects of blue space on mental health is mounting. However, we stress that whether this evidence applies to suicide mortality, remains an open question. Second, Mátyás queries the absence from our models of psychological wellbeing. His observation is correct and, as in any ecological study with official statistics, the difficulty is that such important personal level variables are often absent. Indeed, as a result of such limitations, we did not attempt to draw final conclusions on these matters, although we did raise them as topics for further research to understand the underlying mechanisms. We declare no competing interests. This research received funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreement number 714993). Natural environments and suicide mortality in the Netherlands: a cross-sectional, ecological studyOur findings support the notion that exposure to natural environments, particularly to greenery, might have a role in reducing suicide mortality. If confirmed by future studies on an individual level, the consideration of environmental exposures might enrich suicide prevention programmes. Full-Text PDF Open AccessSuicide mortality and natural environmentsMarco Helbich and colleagues' important Article1 investigated the correlation between suicide mortality and natural outdoor environments, such as green (grass, forests, and parks) and blue (visible bodies of lakes, rivers, and seas) spaces. One of their findings contradicted their hypothesis, which stated that coastal proximity is negatively associated with suicide mortality. When discussing their study, the authors found that blue space visibility did not necessarily correlate with mental health. Full-Text PDF Open Access
AB1328 Flares in spondyloarthritis: prevalence and related factors
Authors: J. Eddarami, L. Ichchou
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Spondylaoarthritis is a chronic condition characterised by alternated periods of flares and stable disease. <h3>Objectives</h3> The aim of this study is to assess the prevalence of patient-reported flares and the validity of this concept through its related factors. <h3>Methods</h3> We have conducted a cross-sectional study over two months in our department of rheumatology. All SpA patients fulfilled <sup>ASAS 2009</sup> criteria. Current and past flares over the last 3 months were recorded. Disease activity and functional status were assessed by the BASDAI score (0–10) and the Bath Ankylosing Spondylitis Functional Index (BASFI; 0–100), respectively. Data analysis was carried out using the SPSS Statistics 20 software. Univaried and multivariate regressions were performed to identify the factors associated with current flare. <h3>Results</h3> We included ninety tow patients with SpA, 61 (66.3%) were men. The mean age was 37.34±12.77 years old. The mean disease duration was 10.59±7.63 year. The mean BASDAI was 2.7±1.99 and the median BASFI was 14 (IQR 0–100). Thirty-five patients (38%) received antitumor necrosis factor alpha (anti-TNF-α). Twenty-nine patients (31.5%) were currently in flare, and 6 patients (6.5%) reported only past flares. In univariate analysis, patients reporting current flares had a current enthesitis (OR=3.14 [1.250–7.923], p=0.015) and higher values of BASDAI, ASDAS VS and ASDAS CRP (OR=2.17 [1.085–4.362], p=0.029; 2.20 [1.448–3.359], p=0.0001; 2.23 [1.495–3.340], p=2.235, respectively). These patients had also more extra-articular manifestations (OR=3.37 [1.326–8.601], p=0.011). In multivariate analysis, the following factors were associated with current flare: higher BASFI (OR=1.05 [1.013–1.098], p=0.010), protein c-reactive (OR=1.087 [1.016–1.163], p=0.016), ASDAS VS (OR=10.99 [1.921–62.873], p=0.007), current enthesitis (OR=25.00 [2.185–286.146], p=0.01), the presence of extra-articular manifestations (OR=30.66 [1.709–550.049], p=0.02) and the use of non steroidal anti-inflammatory drugs during the last 3 months (OR=125.064 [3.33–4491.0], p=0.009). <h3>Conclusions</h3> Our study shows that assessment of flares may provide a good estimation of disease activity. <h3>References</h3> [1] Jacquemin C, et al. Patient-reported Flares in Ankylosing Spondylitis: A Cross-sectional Analysis of 234 Patients. J Rheumatol2017;44:425–30. [2] Cooksey R, et al. Severe flare as a predictor of poor outcome in ankylosing spondylitis: a cohort study using questionnaire and routine data linkage. Rheumatology2015;54:1563–72. [3] Stone MA, et al. Assessment of the impact of flares in ankylosing spondylitis disease activity using the Flare Illustration. Rheumatology2008;47:1213–8. <h3>Disclosure of Interest</h3> None declared
Effectiveness of low-dose radiation therapy on symptoms in patients with knee osteoarthritis
Authors: Xiang-Dong Wu, Ke-Jia Hu, Bing-Yan Xiang, Wei Huang
Journal: Annals of the Rheumatic Diseases (2018)

We read with interest the milestone work in the Annals of the Rheumatic Diseases by Mahler and colleagues1 on the effectiveness of low-dose radiation therapy (LDRT) on symptoms in patients with knee osteoarthritis (OA). The authors have conducted a series of studies to investigate the effects of LDRT on OA, which compensate the lack of high-level evidence in the medical literature, and inevitably forcing us to re-examine the true effectiveness of LDRT on OA in real-world clinical practice.1–3 The group should be applauded for their accomplishments. In this well-designed and well-conducted randomised, double-blinded, sham-controlled trial, they found no substantial beneficial effect on symptoms and …