tbuckley/cabot-search huggingface dataset:
Abstract 19852: When is the Ideal Time to Boost Dietary Self-Monitoring in the Prevention of Weight Regain?
Authors: Qianheng Ma, Susan M Sereika, Gary M Marsh, Lora E Burke
Journal: Circulation (2016)

Background:  Dietary self-monitoring (DSM) is a key strategy in standard behavioral treatment for weight loss and weight gain prevention. Research has demonstrated the temporal decline in DSM adherence, which precedes the onset of weight regain. Our aim was to identify the time to boost DSM adherence and prevent weight regain.   Methods:  This is a secondary analysis of daily self-weighing and daily DSM data in EMPOWER, a 12-month behavioral weight loss intervention. Weight data were collected using an in-home Wi-Fi enabled scale that uploaded data in real time. DSM was conducted using the smartphone app, Lose It! We used subject-specific piecewise linear models to detect  weight regain  onset and classified participants as  maintainers  vs.  regainers. Failure  in DSM before  weight regain  was indicated by a significant structural break (p failure  in the  weight regain  process.   Results:  Participants (N=137) were defined as  regainers  (72.3 %) vs.  maintainers  (27.7%) and 62.0% participants experienced  failure  in DSM. More  regainers  (68.4%) had failure in DSM than  maintainers  (59.6%). On average, participants began to  fail  in DSM at 126 ± 71 days, and after a mean 186 ± 79 days, participants began  weight regain .  Failure  in DSM was a more hazardous stage for  weight regain  than the initial stage without  failure  (p fail  in DSM first (hazard= 0.0039, 95% CI = (0.0031, 0.0048)) than  regain  weight without going through  failure  in DSM (hazard=0.0018, 95% CI = (0.0013, 0.0025)).  Failure in DSM  peaked (35.8%) at 195-201 days. (Figure)   Conclusions:  Participants tended to  fail  in DSM first, the hazardous stage, then to  regain  weight. We recommend booster strategies to enhance adherence to DSM at 18-20 weeks (126-140 days), which may prevent DSM  failure  and  weight regain  and thus promote cardiovascular health.   Figure.  Timeline for DSM  failure  and  weight regain
Association of Autistic Traits With Depression From Childhood to Age 18 Years
Authors: Dheeraj Rai, Iryna Culpin, Hein Heuvelman, Cecilia M. K. Magnusson, Peter Carpenter, Hannah J. Jones, Alan M. Emond, Stanley Zammit, Jean Golding, Rebecca M. Pearson
Journal: JAMA Psychiatry (2018)

Population-based studies following trajectories of depression in autism spectrum disorders (ASD) from childhood into early adulthood are rare. The role of genetic confounding and of potential environmental intermediaries, such as bullying, in any associations is unclear.
Short course of bortezomib in anemic patients with relapsed cold agglutinin disease: a phase 2 prospective GIMEMA study
Authors: Giuseppe Rossi, Doriana Gramegna, Francesca Paoloni, Bruno Fattizzo, Francesca Binda, Mariella D’Adda, Mirko Farina, Elisa Lucchini, Francesca Romana Mauro, Flavia Salvi, Monia Marchetti, Paola Fazi, Francesco Zaja, Wilma Barcellini
Journal: Blood (2018)
AB0290 Lower educational levels are associated with a higher risk of rheumatoid arthritis in a southern european nested case-control study
Authors: P. de Pablo, D. Romaguera, S. Panico, A. Mattiello, D. Gavrila, C. Navarro, C. Sacerdote, P. Vineis, R. Tumino, W. Ollier, E. Riboli, P. Venables, B. Fisher
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To investigate the association between socioeconomic status (SES) on an individual level and incident RA <h3>Methods</h3> EPIC is a multicentre, pan-European prospective cohort study of apparently healthy populations. We undertook a nested case-control study to investigate risk factors for RA, by identifying incident RA cases (pre-RA) and matched controls amongst subjects enrolled in four EPIC cohorts in Italy and Spain. The lifestyle, environmental exposure, anthropometric information and blood samples were collected at baseline. Confirmed pre-RA cases were matched with controls by age, sex, centre, and date, time and fasting status at blood collection. The exposure was SES as measured by level of educational attainment categorised as university (referent), secondary school/technical/professional school, primary school completed, and none. The primary outcome was incident RA. Conditional logistic regression (CLR) analysis was adjusted for ACPA seropositivity, smoking status, and presence of shared epitope (SE). A further model also adjusted for other potential confounders, including body mass index (BMI), waist circumference, physical activity, and alcohol intake. <h3>Results</h3> The study sample included 398 individuals of which 99 individuals went on to subsequently develop RA. In this analysis, time to diagnosis (defined as time between date of blood sample and date of diagnosis), was 6.71 years (SD 3.43). A significant positive association was observed with level of educational attainment and RA incidence (secondary/technical vs university: OR 5.60, 95% CI 1.59–19.7, primary school vs university: OR 5.06, 95% CI 1.45–17.6, no education vs university: 7.11, 95% CI 1.37–36.8; p for trend 0.02) independent of ACPA seropositivity, SE and smoking). A significant positive association between level of educational attainment and RA incidence was confirmed in the fully adjusted model (secondary/technical vs university: OR 5.52, 95% CI 1.53–19.9, primary school vs university: OR 4.87, 95% CI 1.38–17.1, no education vs university: OR 6.48, 95% CI 1.21–34.6; p for trend 0.02). <h3>Conclusions</h3> Lower educational levels were independently associated with higher risk of incident RA in this European Mediterranean population. <h3>Disclosure of Interest</h3> None declared
SP0169 Integration of omics data for predicting response to anti tnf treatment
Authors: L. Padyukov
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Successful development of biologics for targeting specific molecules, like TNF, was a hallmark of new era in therapy of inflammatory and rheumatic diseases. However, the approach based on interfering with TNF exceeds simple neutralisation of inflammatory cytokine and, possibly, this is why the prediction of response remains elusive. High costs of the treatment and irreversible tissue damage in non-responders have forced multiple attempts to predict response to anti TNF treatment using clinical, laboratory and molecular markers. There are several issues related to this type of studies that may include genetically heterogeneous groups of patients, different types of anti-TNF treatment, multiple types of response measures and are typically underpowered. Nowadays, an enormous amount of genetic, epigenetic and genomic data revived new expectations and stimulates producing of models for prediction of anti TNF response. We performed several studies based on different omics data in genetically homogeneous Swedish population that raises importance of disease subgrouping and interference of environmental factors on prediction values. <h3>Disclosure of Interest</h3> None declared
Cell-penetrating peptide-based nanovehicles potentiate lymph metastasis targeting and deep penetration for anti-metastasis therapy
Authors: Haiyan Hu, Jing Wang, Hong Wang, Tao Tan, Jie Li, Zhiwan Wang, Kaoxiang Sun, Yaping Li, Zhiwen Zhang
Journal: Theranostics (2018)

Lymph metastasis is a vital pathway of cancer cell dissemination, and insidious lymph node metastasis increases the risk of distant cancer metastasis.Current therapies for lymph metastasis are largely restricted by limited targeting and penetration capacity.Herein, we report that an r9 cell-penetrating peptide-based cabazitaxel nanovehicle (r9-CN) displays prominent lymph metastasis targeting and deep penetration ability after intravenous injection for effective anti-metastasis therapy.Methods: The r9-CN and CN nanovehicles were prepared by thin film dispersion, using DSPE-PEG2000 as the nano-carrier material and cabazitaxel as the model drug to fabricate r9-modified nano-micelles by self-assembly.The morphology, size, and stability in physiological solutions of r9-CN and CN were characterized.The targeting, biodistribution, deep penetration, and therapeutic efficacy of r9-CN and CN were systematically explored in vitro and in vivo.Results: The r9-CN nanovehicle consists of homogeneous particles with a mean diameter of 13 nm and zeta potential of +0.75 mV.Compared with the nanovehicle lacking the r9 peptide (CN), r9-CN exhibits long retention and deep penetration in the tumor mass, and considerably enhances accumulation and flexible permeation in metastatic lymph nodes, thereby notably suppressing primary tumor growth, lymph node metastasis, and distant lung metastasis. Conclusion:The cumulative findings reveal that r9-CN offers a promising delivery platform, enabling efficient lymph metastasis targeting and deep penetration for effective anti-metastasis therapy.
FRI0552 Sm04690, a wnt pathway inhibitor: anti-inflammatory and cartilage protective effects in preclinical oa models
Authors: V. Deshmukh, T. Seo, C. Swearingen, Y. Yazici
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoarthritis (OA) is characterised by pain, swelling, and reduced function in the knee joint. Upregulated Wnt signalling drives OA through synovial inflammation, increased subchondral bone, and thinning cartilage. <h3>Objectives</h3> SM04690, a small molecule Wnt pathway inhibitor that demonstrated chondrogenic and anti-inflammatory properties preclinically<sup>1</sup>, was further evaluated to determine its potential to reduce inflammation, protect cartilage, improve joint health and modify pain in OA. <h3>Methods</h3> Cytokine secretion (IL-6 and TNF-α) from IL-1β-stimulated and SM04690-treated synovial fibroblasts was measured by ELISA. A single intra-articular injection of SM04690 or vehicle was evaluated in an<i> in vivo</i> rat knee monosodium iodoacetate (MIA) OA model. Joint inflammation was evaluated by H and E staining, inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α and IFN-γ) by qPCR, and cartilage protection by qPCR for matrix metalloproteinases (MMPs). Histological evaluation of cartilage health was performed using OARSI score and thickness by Safranin-O staining. Pain was measured as paw withdrawal threshold using Von Frey apparatus and weight distribution using incapacitance metre and analysed using generalised estimating equation regression. <h3>Results</h3> SM04690 dose-dependently inhibited IL-1β-induced cytokine secretion in synovial fibroblasts (EC<sub>50 ~</sub>30 nM; figure 1). In the rat MIA OA model, compared to vehicle, SM04690 injection reduced visible knee swelling, inflammatory cells, and proinflammatory cytokine and MMP production (p&lt;0.05). SM04690 increased (p&lt;0.01) paw withdrawal threshold from day 6 and improved weight distribution to the affected limb in treated rats, at multiple timepoints, compared to vehicle (figure 2). SM04690 increased Safranin-O stained cartilage thickness and decreased OARSI score (p&lt;0.05) compared to vehicle. <h3>Conclusions</h3> In a rat MIA OA model, SM04690 injection reduced inflammation, protease production, and pain, with improved cartilage and joint health, compared to vehicle. Previously demonstrated regenerative effects in nonclinical studies<sup>1</sup>, along with anti-inflammatory properties, show SM04690 may improve symptoms and potentially provide disease modification in OA. Clinical studies are ongoing. <h3>Reference</h3> [1] Deshmukh V, et al. Osteoarthritis Cartilage2018;26:18–27. <h3>Disclosure of Interest</h3> V. Deshmukh Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, T. Seo Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, C. Swearingen Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Y. Yazici Shareholder of: Samumed, LLC, Employee of: Samumed, LLC
Sisu—The Ability to Keep Fighting After Most Would Quit
Authors: Justine V. Cohen
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
CAR T Cells with Enhanced Sensitivity to B Cell Maturation Antigen for the Targeting of B Cell Non-Hodgkin’s Lymphoma and Multiple Myeloma
Authors: Julia Bluhm, Elisa Kieback, Stephen F. Marino, Felix Oden, Jörg Westermann, Markus Chmielewski, Hinrich Abken, Wolfgang Uckert, Uta E. Höpken, Armin Rehm
Journal: Molecular Therapy (2018)

Autologous T cells genetically modified with a chimeric antigen receptor (CAR) redirected at CD19 have potent activity in the treatment of B cell leukemia and B cell non-Hodgkin's lymphoma (B-NHL). Immunotherapies to treat multiple myeloma (MM) targeted the B cell maturation antigen (BCMA), which is expressed in most cases of MM. We developed a humanized CAR with specificity for BCMA based on our previously generated anti-BCMA monoclonal antibody. The targeting single-chain variable fragment (scFv) domain exhibited a binding affinity in the low nanomolar range, conferring T cells with high functional avidity. Redirecting T cells by this CAR allowed us to explore BCMA as an alternative target for mature B-NHLs. We validated BCMA expression in diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia. BCMA CAR T cells triggered target cell lysis with an activation threshold in the range of 100 BCMA molecules, which allowed for an efficient eradication of B-NHL cells in vitro and in vivo. Our data corroborate BCMA is a suitable target in B cell tumors beyond MM, providing a novel therapeutic option for patients where BCMA is expressed at low abundance or where anti-CD19 immunotherapies have failed due to antigen loss.
Structure-activity relationship, physicochemical and pharmacokinetic properties of AZD2171: A highly potent inhibitor of VEGF receptor tyrosine kinases
Authors: Fortunato Ciardiello, Marco Romano, Concetta Tuccillo, Rosa Caputo, Vincenzo Damiano, Teresa Troiani, Ferdinando De Vita, Sabino De Placido, A. R. Bianco, Giampaolo Tortora
Journal: Cancer Research (2004)

4542  ZD6474 is an orally available, vascular endothelial cell growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor with additional activity against epidermal growth factor receptor (EGFR) tyrosine kinase. VEGF is a major regulator of angiogenesis, endothelial cell growth and vascular permeability while the EGFR autocrine pathway plays a key role in cancer development and progression. The antitumor efficacy of ZD6474 has been investigated in combination with SC-236, a selective cyclooxygenase-2 (COX-2) inhibitor, as enhanced COX-2 expression has been linked to cancer cell proliferation, EGFR pathway activation, VEGF secretion and tumor-induced angiogenesis. The combination of ZD6474 and SC-236 resulted in a supra-additive, dose-dependent growth inhibition of soft agar colony formation in a range of human cancer cell lines (lung adenocarcinoma [A549], pancreatic carcinoma [MiaPaca2], colon carcinoma [GEO] and gastric carcinoma [MKN-28]). The effect of this combination on EGFR and COX-2 pathways was also evaluated in GEO and A549 cells. While ZD6474 resulted in partial inhibition of activated phosphorylated, mitogen-activated protein kinase (MAPK) and AKT expression (40–60% inhibition), COX-2 had no significant effect on these proteins. Combined treatment however, resulted in an almost complete suppression of phosphorylated MAPK and AKT. Furthermore, the combination of ZD6474 and SC-236 treatment led to a significant reduction in the expression of COX-2, VEGF and the anti-apoptotic protein bcl-xL in both GEO and A549 cell lines. In vivo evaluation of this combination has also been conducted in nude mice bearing established GEO or A549 cancer xenografts (approximately 0.2–0.3 cm3), treated with ZD6474 (75 mg/kg/dose) and/or SC-236 (6 mg/kg/dose) p.o. 5 days/week for 3 weeks. Although tumor growth inhibition was seen with both ZD6474 and SC-236 therapy alone (approx. 70% and 50%, respectively) prolonged growth inhibition resulted from a combination of the two agents (approx. 90%, persisting for 3–5 weeks from the end of treatment; P=0.01). Immunohistochemical analysis of the tumor vasculature revealed that the combination had significant antiangiogenic activity. In a long-term (10-week) study of the same schedule of ZD6474/SC-236 treatment in mice bearing established GEO xenografts, assessment of tumor growth showed that tumors in the combined treatment group took an average of 182 ± 6 days to reach a size of 2.5 cm3, compared with 28 ± 3 days in the control animals, 91 ± 4 days with ZD6474 alone and 77 ± 5 days with SC-236 alone. In conclusion, this study provides a strong scientific rationale for evaluating the simultaneous blockade of EGFR, COX-2 and VEGF signaling in cancer patients.
AB0690 Diagnostic values of endothelin-1 in patients with systemic necrotizing vasculitis
Authors: L. Petelytska, O. Iaremenko, K. Iaremenko
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic necrotizing vasculitis (SNV) is characterised by destructive and inflammatory changes in the vessels. Binding of autoantibodies and immune complexes on the surface of endothelial cells stimulates the synthesis of endothelin-1 (ET-1), which leads to activation of macrophages and adhesion of neutrophils, remodelling of the vascular wall and its damage. <h3>Objectives</h3> To evaluate the serum level of ET-1 in patients with SNV and the possibility of its using for the diagnosis of SNV and involvement of individual organs. <h3>Methods</h3> The study included 36 patients with SNV (polyarthritis nodosa – 8, ANCA – associated vasculitis – 28) and healthy controls (n=26). Clinical activities of patients were calculated according to the Birmingham Vasculitis Activity Score (BVAS). All patients had active disease (BVAS &gt;11). The serum levels of ET-1 (pmol/L) were determined by immunoassay analysis using the kits of Biomedica. The outcomes of this study were the differences in marker levels between patients with active SNV and healthy controls, patients with different forms of vasculitis, with varying degrees of BVAS activity, with involvement different organs and systems estimated by analysis of the absolute changes in marker levels and the areas under receiver operating characteristic (ROC) curves (AUC). <h3>Results</h3> The level of ET-1 (M±σ) in the general group of patients with SNV was 0.31±0.24 and did not differ significantly from the control group (0.27±0.10, p&gt;0.05). At the same time, in patients who did not receive at screening glucocorticoids and cytotoxic agents (n=9), it was significantly elevated (0.62±0.58, p=0.03). However, ROC analysis indicated the moderate sensitivity (67%) and the low specificity (48%) of ET-1 for diagnosis of SNV. There were no significant differences in the levels of ET-1 between patients with different forms of vasculitis and with varying degrees of BVAS activity. In the analysis of the values of the ET-1 depending on the involvement of different organs and systems, it was found that only in patients with kidney involvement (n=15) its level (0.40±0.33) was significantly higher compared with patients without kidney involvement (0.28±0.22, p=0.04) and control group (p&lt;0.01). ROC analysis showed that the AUC for ET-1 is 0.75±0.10 (p=0.004), which indicates acceptable capacity for ET-1 differentiate groups of patients with kidney involvement and patients without kidney involvement (sensitivity – 80.0%, specificity – 78.3%). <h3>Conclusions</h3> The serum levels of ET-1 were elevated in patients with SNV with kidney involvement (48% compared to healthy controls and 43% compared with patients without kidney involvement), which can be used for diagnostic purposes. <h3>Disclosure of Interest</h3> None declared
OP0183 Association between hfe genotypes and clinical severity characteristics of calcium pyrophosphate crystal arthritis
Authors: F. Perez-Ruiz, S.P. Chinchilla, J. Atxotegi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Several metabolic disturbances that reduce the activity of pyrophosphatases have been associated with development of calcium pyrophosphate crystal arthritis (CPPCA), but there is scarce data on their influence on clinical manifestations, as such disease-specific variables are not recorded in most available databases. <h3>Objectives</h3> To evaluate factors associated to severity of clinical joint involvement in patients with definite CPPCA. <h3>Methods</h3> Transversal study with prospective recruitment of cases (patients with CPPCA diagnosis confirmed by microscopy showing CPP crystals within leucocytes in synovial fluid plus presence of X-ray chondrocalcinosis in at least one joint) and controls (patients with synovial effusion shown to have no CPP crystals and no chondrocalcinosis in hands and knee X-rays), paired by age and gender. Patients with hemochromatosis or primary hyperparathyroidsm were not included. General variables were included along with plausible metabolic variables (Ca, P, Mg, iPth, iron saturation [satFe%], ferritin, diuretics and type of diuretic, and HFE genotype), and distributon of joint involvement (mono-oligo-polyarticular) and clinical manifestations (acute [A-CPPCA] and chronic inflammatory [CI-CPPCA]), as in EULAR recommendations. <h3>Results</h3> 340 patients and 316 controls were recruited, 53% were men, age at inclusion was 67±10 year (IC range 62–75), time from onset of symptoms 5.2±5.3 year (IC range 1–8). Regarding cases, A-CPPCA was present in 147 (43.2%), CI-CPPCA in 193 (56.8%), with monoarticular involvement in 102 (30.0%), oligoarticular in 176 (51.8%), and polyarticular in 62 (18.2%). Patients showed higher serum ferritine levels and lower Mg levels than controls (253 and 2.00 vs 204 and 2.08, respectively), along with higher rate of HFE gene mutations (Odds ratio 2.30, 95% CI: 1.66 to 3.20). Genotypes including homozygotic mutations of H63D allele, heterozygotic mutations for C282Y allele, and double heterozygotic mutations for C282Y and H63D were statistically associated with higher frequency of polyarticular involvement and with CI-PPA (figure 1). Clinical variables were also associated with higher SatFe% levels, but not Mg or ferritin levels. S65C gene mutations were not increased in patients compared to controls and did not show any association with clinical phenotype. <h3>Conclusions</h3> Patients with definite CPPCA show differences in serum Mg and Ferritin levels compared to that of controls, and may contribute, along with other factors, to development of CPPCA. Nevertheless, only presence of some HFE genotypes involving C282Y and H63D genes were associated with more severe phenotype of clinical involvement. <h3>Disclosure of Interest</h3> None declared