tbuckley/cabot-search huggingface dataset:
Insulin-like growth factor-1 receptor (IGF-1R/CD221): A target for monoclonal antibody-based therapy to overcome drug-resistance in multiple myeloma (MM), other hematologic malignancies and solid tumors
Authors: Constantine S. Mitsiades, Nicholas Mitsiades, Ciaran J. McMullan, Reshma Shringarpure, Rajeeva Singh, Kenneth C. Anderson
Journal: Cancer Research (2004)

5331  We have shown that insulin-like growth factor-1 receptor (IGF-1R) signaling can attenuate responsiveness of multiple myeloma (MM) cells to pro-apoptotic agents, including dexamethasone (Dex), cytotoxic chemotherapy, Apo2L/TRAIL or the proteasome inhibitor bortezomib (PS-341). We have also shown that small molecule inhibitors of IGF-1R kinase activity have both in vitro and in vivo activity against MM and a broad spectrum of other hematologic malignancies and solid tumors. Due to the functional roles of IGF-1R in broad spectrum of neoplasias, we have explored diverse therapeutic approaches targeting IGF-1R function, including specific anti-human IGF-1R neutralizing monoclonal antibodies (mAb), such as EM-164 (Immunogen Inc., Boston, MA) and aIR3. Consistent with their specificity for only IGF-1R, these mAb completely abrogated IGF-1-induced IGF-1R autophosphorylation, but had no effect on phosphorylation of its more closely homologous receptor, the insulin receptor. EM-164 was active against primary MM tumor cells and a broad panel of MM cell lines (including cells resistant to cytotoxic chemotherapy, thalidomide and its immunomodulatory derivatives {IMiDs} or PS-341) and cell lines from solid tumors (e.g. breast, prostate, lung, colon, thyroid, ovarian, renal Ca, retinoblastoma, sarcoma), leukemias and lymphomas (consistent with our previous findings of cell surface IGF-1R expression in these diseases). MM cells were among the most sensitive tumor types to IGF-1R inhibition indicating a prominent role for IGF-1R signaling in MM pathophysiology. Using transcriptional and proteomic profiling, we found that EM-164 and aIR3 confer pleiotropic anti-proliferative/pro-apoptotic sequelae, including inhibition of key growth/survival cascades (e.g. PI-3K/Akt, Ras/Raf/MAPK, IKK-α/NF-κB); decreased expression of caspase inhibitors (e.g. FLIP, cIAP-2); neutralization of pro-apoptotic Forkhead transcription factors; and suppression of constitutive and IGF-induced increase in proteasome and telomerase activities. These molecular sequelae can explain why anti-IGF-1R mAb sensitized tumor cells (e.g. MM, PrCa, BrCa) to other anti-cancer drugs (e.g. Dex, cytotoxic chemotherapy or PS-341); blunted tumor cell responses to other growth factors (e.g. MM or PrCa cell response to IL-6); overcame the drug-resistance phenotype conferred by bone marrow stromal cells (BMSCs); and abrogated VEGF production in co-culture models of MM cells with BMSCs. Our current findings, coupled with our recent results on the safety and efficacy of selective IGF-1R inhibition in mouse MM models, indicate that mAb-based targeting of IGF-1R can also be part of therapeutic strategies to comprehensively abrogate the critical role of IGF-1R signaling in tumor cell proliferation and drug resistance.
A Magnetic Iron Oxide/Polydopamine Coating Can Improve Osteogenesis of 3D‐Printed Porous Titanium Scaffolds with a Static Magnetic Field by Upregulating the TGF<i>β</i>‐Smads Pathway
Authors: Zhenfei Huang, Yu He, Xiao Chang, Jieying Liu, Lingjia Yu, Yuanhao Wu, Yaqian Li, Jingjing Tian, Lin Kang, Di Wu, Hai Wang, Zhihong Wu, Guixing Qiu
Journal: Advanced Healthcare Materials (2020)

Abstract 3D‐printed porous titanium–aluminum–vanadium (Ti6Al4V, pTi) scaffolds offer surgeons a good option for the reconstruction of large bone defects, especially at the load‐bearing sites. However, poor osteogenesis limits its application in clinic. In this study, a new magnetic coating is successfully fabricated by codepositing of Fe 3 O 4 nanoparticles and polydopamine (PDA) on the surface of 3D‐printed pTi scaffolds, which enhances cell attachment, proliferation, and osteogenic differentiation of hBMSCs in vitro and new bone formation of rabbit femoral bone defects in vivo with/without a static magnetic field (SMF). Furthermore, through proteomic analysis, the enhanced osteogenic effect of the magnetic Fe 3 O 4 /PDA coating with the SMF is found to be related to upregulate the TGF β ‐Smads signaling pathway. Therefore, this work provides a simple protocol to improve the osteogenesis of 3D‐printed porous pTi scaffolds, which will help their application in clinic.
Public Attitudes, Behaviors, and Beliefs Related to COVID-19, Stay-at-Home Orders, Nonessential Business Closures, and Public Health Guidance — United States, New York City, and Los Angeles, May 5–12, 2020
Authors: Mark É. Czeisler, Michael A. Tynan, Mark E. Howard, Sally Honeycutt, Erika B. Fulmer, Daniel P. Kidder, Rebecca Robbins, Laura K. Barger, Elise R. Facer-Childs, Grant Baldwin, Shantha M.W. Rajaratnam, Charles A. Czeisler
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

This report describes a survey taken during May among adults in the United States that found widespread support for stay-at-home orders and nonessential business closures and a high degree of adherence to COVID-19 mitigation guidelines.
Trends in Pneumoconiosis Deaths — United States, 1999–2018
Authors: Jessica L. Bell, Jacek M. Mazurek
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Pneumoconioses are preventable occupational lung diseases caused by inhaling dust particles such as coal dust or different types of mineral dusts (1). To assess recent trends in deaths associated with pneumoconiosis, CDC analyzed multiple cause-of-death data*,† for decedents aged ≥15 years for the years 1999-2018, and industry and occupation data collected from 26 states§ for the years 1999, 2003, 2004, and 2007-2013. During 1999-2018, pneumoconiosis deaths decreased by 40.4%, with the exception of pneumoconiosis attributed to other inorganic dusts (e.g., aluminum, bauxite, beryllium, iron, and tin oxide), which increased significantly (p-value for time trend <0.05). The largest observed decreases in pneumoconiosis deaths were for those associated with coal workers' pneumoconiosis (69.6%) and silicosis (53.0%). Asbestosis was the most frequently reported pneumoconiosis and was associated with working in the construction industry. The ongoing occurrence of deaths associated with pneumoconiosis underscores the importance of occupational dust exposure reduction, early case detection, and continued surveillance to monitor trends.
AB0986 NT-PROBNP LEVEL IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS
Authors: T. Holovko, L. Bohmat, N. Shevchenko, A. U. Afighi
Journal: Annals of the Rheumatic Diseases (2020)

Background: The defeat of the cardiovascular system is considered a proven comorbid state in rheumatic diseases, including rheumatoid arthritis in adults. One of the markers of the cardiovascular failure formation is BNP, namely, its N-terminal inactive fragment (NT-proBNP76), which accumulates in specific granules of cardiomyocytes. Its diagnostic value increases with the appearance of minimally expressed symptoms. The long-term course of JIA is also characterized by changes in the state of the cardiovascular system, and there may be no visible clinical manifestations. For their diagnosis a 6-minute walk test is widely used, including in children. Objectives: To study the content of NT-proBNP in patients with juvenile idiopathic arthritis and compare with the level of exercise tolerance. Methods: 10 patients with JIA (9 girls, 1 boy), average age 12.78 ± 0.95 years, were examined. All children had a polyarticular RF negative subtype of JIA with a disease duration of more than three years (average disease duration 69.56 ± 17.07 months), received basic methotrexate therapy and did not have dysfunction of the lower extremities joints. The control group included 7 healthy children, comparable by sex, average age 14.25±0.73 years. An ECG, an ultrasound scan of the heart, and a 6-minute walk test (6MTX) were carried out with determining the distance traveled (6MWD) and the increase in heart rate. The level of the N-terminal polypeptide of cerebral natriuretic hormone (B-type) (NT-proBNP) was determined in the morning, after waking up, and studied by competitive immunoassay on an IMMULITE 2000 analyzer (“Siemens”). Results: In children with JIA a decrease in myocardial contractility was not detected. Left ventricular ejection fraction (62.17±0.83% (60.02 – 64.02) versus 69.84 ± 0.85% (62.3 – 80.3), p &lt;0.05) in children with JIA were within normal limits, but significantly lower than in the control group. According to the results 6MTX indicator 6MWD in JIA-patients was 490.51 ± 11.40 m and in the control group 516.85 ± 8.84 m (p &lt;0.05) and heart rate growth was 27.75 ± 2.30% versus in the control group (37.38 ± 3.86%), p &lt;0.05. A negative correlation between the increase in heart rate and the duration of the disease was found (r = -0.7, p = 0.05). The level of NT-proBNP in patients with JIA was within physiological values and amounted to 47.5 ± 14.09 pg / ml (20 – 128 pg/ml), but this was higher than in children of the control group (20.29 ± 0.29 pg / ml (20-22 pg/ml), p &lt;0.05). A high correlation was found between 6 MWD and NT-proBNP level (r = 0.8, p &lt;0.03). Conclusion: In children with JIA there is a decrease of the exercise tolerance that increases with the duration of JIA on the background of preserved myocardial contractility. This is accompanied by a higher basal NT-proBNP level than in healthy children. Disclosure of Interests: None declared
A pragmatic randomized waitlist-controlled effectiveness and cost-effectiveness trial of digital interventions for depression and anxiety
Authors: Derek Richards, Angel Enrique, Nora Eilert, Matthew Franklin, Jorge Palacios, Daniel Duffy, Caroline Earley, Judith Chapman, Grace Jell, Sarah Sollesse, Ladislav Timulak
Journal: npj Digital Medicine (2020)

Utilization of internet-delivered cognitive behavioural therapy (iCBT) for treating depression and anxiety disorders in stepped-care models, such as the UK's Improving Access to Psychological Therapies (IAPT), is a potential solution for addressing the treatment gap in mental health. We investigated the effectiveness and cost-effectiveness of iCBT when fully integrated within IAPT stepped-care settings. We conducted an 8-week pragmatic randomized controlled trial with a 2:1 (iCBT intervention: waiting-list) allocation, for participants referred to an IAPT Step 2 service with depression and anxiety symptoms (Trial registration: ISRCTN91967124). The primary outcomes measures were PHQ-9 (depressive symptoms) and GAD-7 (anxiety symptoms) and WSAS (functional impairment) as a secondary outcome. The cost-effectiveness analysis was based on EQ-5D-5L (preference-based health status) to elicit the quality-adjust life year (QALY) and a modified-Client Service Receipt Inventory (care resource-use). Diagnostic interviews were administered at baseline and 3 months. Three-hundred and sixty-one participants were randomized (iCBT, 241; waiting-list, 120). Intention-to-treat analyses showed significant interaction effects for the PHQ-9 (b = -2.75, 95% CI -4.00, -1.50) and GAD-7 (b = -2.79, 95% CI -4.00, -1.58) in favour of iCBT at 8-week and further improvements observed up to 12-months. Over 8-weeks the probability of cost-effectiveness was 46.6% if decision makers are willing to pay £30,000 per QALY, increasing to 91.2% when the control-arm's outcomes and costs were extrapolated over 12-months. Results indicate that iCBT for depression and anxiety is effective and potentially cost-effective in the long-term within IAPT. Upscaling the use of iCBT as part of stepped care could help to enhance IAPT outcomes. The pragmatic trial design supports the ecological validity of the findings.
Scaffold‐Mediated Static Transduction of T Cells for CAR‐T Cell Therapy
Authors: Pritha Agarwalla, Edikan A. Ogunnaike, Sarah Ahn, Frances S. Ligler, Gianpietro Dotti, Yevgeny Brudno
Journal: Advanced Healthcare Materials (2020)

Abstract Chimeric antigen receptor T (CAR‐T) cell therapy has produced impressive clinical responses in patients with B‐cell malignancies. Critical to the success of CAR‐T cell therapies is the achievement of robust gene transfer into T cells mediated by viral vectors such as gamma‐retroviral vectors. However, current methodologies of retroviral gene transfer rely on spinoculation and the use of retronectin, which may limit the implementation of cost‐effective CAR‐T cell therapies. Herein, a low‐cost, tunable, macroporous, alginate scaffold that transduces T cells with retroviral vectors under static condition is described. CAR‐T cells produced by macroporous scaffold‐mediated viral transduction exhibit &gt;60% CAR expression, retain effector phenotype, expand to clinically relevant cell numbers, and eradicate CD19 + lymphoma in vivo. Efficient transduction is dependent on scaffold macroporosity. Taken together, the data show that macroporous alginate scaffolds serve as an attractive alternative to current transduction protocols and have high potential for clinical translation to genetically modify T cells for adoptive cellular therapy.
AB0159 INTERLEUKIN-16 PLAYS A ROLE IN THE PATHOGENESIS OF SYSTEMIC SCLEROSIS
Authors: J. Luo, A. Kerstein-Staehle, S. Comduehr, T. Dreyer, A. Müller, S. Schinke, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic sclerosis (SSc) is an autoimmune disorder with chronic and persistent inflammation. Interleukin-16 was originally described as a factor that could attract activated T cells in humans [1]. Elevated amounts of IL-16 have been demonstrated in SSc [2]. Objectives: This study was undertaken to find out if IL-16 is associated with clinical characteristics of SSc. Methods: IL-16 was measured by Elisa in serum of patients with SSc (n=119) and healthy controls (n=50). Further, the presence of active IL-16 in mononuclear cells from peripheral blood of SSc patients (n=10) was examined by Western blot. Statistical analyses were done employing Graph Pad prism software (v 8). Patients with SSc were characterized based upon epidemiological and clinical parameters. Results: The serum concentration of IL-16 was higher in patients with SSc than in healthy controls (272.7±165.4 vs 172.8±64.84 pg/ml, p&lt;0.0001). Further, the difference in the IL-16 serum concentration was more prominent in females (265.6±174.2 vs 160.1±53.37 pg/ml, p=0.0002) than in males (287.1±144.1 vs 187.6±74.64 pg/ml, p=0.0034). In addition, the concentration of IL-16 was elevated in patients with diffuse SSc compared to limited SSc (p=0.0206). The concentration of IL-16 in serum of SSc patients positively correlated with CRP (n=115, r=0.49, p&lt;0.0001). There was a weak positive correlation between IL-16 in serum of SSc patients and the mRSS (n=112, r=0.22, p=0.0175). Noteworthy, the concentration of IL-16 was heightened in SSc patients with lung fibrosis compared to SSc patients without lung fibrosis (p=0.009). The ROC value of SSc patients with lung fibrosis was 0.64 (95%CI: 0.58-0.83). Moreover, active IL-16 derived from peripheral blood mononuclear cells (PBMC) of SSc patients with lung fibrosis was present in higher amounts compared to PBMC of SSc patients without lung fibrosis (5 vs 5, p=0.0557). Conclusion: Our results confirm and extend previous data by showing not only an increased concentration of IL-16 in the circulation of SSc patients, but new findings pointing towards a role of IL-16 for contributing to lung fibrosis in SSc. References: [1]Cruikshank, W. and D.M. Center, Modulation of lymphocyte migration by human lymphokines. II. Purification of a lymphotactic factor (LCF). J Immunol, 1982. 128(6): p. 2569-74. [2]Kawabata, K., et al., IL-16 expression is increased in the skin and sera of patients with systemic sclerosis. Rheumatology (Oxford), 2019. Disclosure of Interests: Jiao Luo: None declared, Anja Kerstein-Staehle: None declared, Sara Comduehr: None declared, TatjanaKathleen Dreyer: None declared, Antje Müller: None declared, Susanne Schinke Speakers bureau: Pfizer, Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer
Interleukin-6 as prognosticator in patients with COVID-19
Authors: Elisa Grifoni, Alice Valoriani, Francesco Cei, Roberta Lamanna, Anna Maria Grazia Gelli, Benedetta Ciambotti, Vieri Vannucchi, Federico Moroni, Lorenzo Pelagatti, Roberto Tarquini, Giancarlo Landini, Simone Vanni, Luca Masotti
Journal: Journal of Infection (2020)
Measuring Patient Activation as Part of Kidney Disease Policy: Are We There Yet?
Authors: Devika Nair, Kerri L. Cavanaugh
Journal: Journal of the American Society of Nephrology (2020)

Optimal care occurs when patients possess the skills, knowledge, and confidence needed to effectively manage their health. Promoting such patient activation in kidney disease care is increasingly being prioritized, and patient activation has recently emerged as central to kidney disease legislative policy in the United States. Two options of the Centers for Medicare and Medicaid Services Kidney Care Choices model-the Kidney Care First option and the Comprehensive Kidney Care Contracting option-now include patient activation as a quality metric; both models specifically name the patient activation measure (PAM) as the patient-reported outcome to use when assessing activation in kidney disease. Because nephrology practices participating in these models will receive capitated payments according to changes in patients' PAM scores, it is time to more critically evaluate this measure as it applies to patients with kidney disease. In this review, we raise important issues related to the PAM's applicability to kidney health, review and summarize existing literature that applies this measure to patients with kidney disease, and outline key elements to consider when implementing the PAM into practice and policy. Our aim is to spur further dialogue regarding how to assess and address patient activation in kidney disease to facilitate best practices for supporting patients in the successful management of their kidney health.
FRI0477 SYSTEMIC TREATMENT IN SARCOIDOSIS. STUDY OF 377 PATIENTS FROM A SINGLE UNIVERSITY HOSPITAL
Authors: M. Calderón-Goercke, R. Fernández-Ramón, J. L. Martín-Varillas, L. Sanchez-Bilbao, D. Martínez-López, I. González-Mazón, J. J. Gaitán-Valdizán, R. Demetrio-Pablo, M. A. González-Gay, R. Blanco
Journal: Annals of the Rheumatic Diseases (2020)

Background: Sarcoidosis is a multisystemic disease characterized by the formation of non-necrotizing granulomas. The most frequently affected organs are lungs, skin and eyes. Systemic corticosteroids are the most used drugs in the treatment of this disease. Conventional and biological immunosuppressants (IS) may also be used (1-3). Objectives: To evaluate the systemic treatment of sarcoidosis according to clinical domains. Methods: Study of all consecutive patients diagnosed with sarcoidosis between 1/1/1999 and 1/1/2019 in a tertiary university hospital. The diagnosis was established following the ATS/ERS/WASOG criteria (Eur Respir J. 1999;14(4):735-737): compatible clinical and radiological presentation, evidence of non-caseifying granulomas and exclusion of other granulomatous diseases. Results: We studied 377 patients (188 men/189 women), mean age at diagnosis of 46.0±14.8 years. After a mean follow-up of 13.0±9.3 years, 161 (42.7%) patients did not require treatment. The remaining 216 (57.3%) received oral glucocorticoids (206, 54.6%) with a maximum mean dose of 43.2±19.0 mg/day, conventional IS (60, 16.2%), biological therapy (28, 7.4%) and/or endovenous methylprednisolone (15, 4.0%). Biological therapy was indicated by pulmonary (9, 32.1%), ocular (9, 32.1%), neurological (3, 10.7%), muskuloeskeletal (3, 10.7%), cutaneous (2, 7.1%), nephrological involvement (1, 3.6%); and Heerfordt’s syndrome (1, 3.6%). Adalimumab and Infliximab were the biologics used more frequently ( Table ). TABLE Systemic treatment of sarcoidosis according to clinical domains. Conclusion: Compared to other studies, the high percentage of patients who required systemic treatment is remarkable. It also highlights the frequency of the use of biological drugs in more severe organ involvement (ocular and neurological), which is consistent with the trend in recent years. References: [1]Riancho-Zarrabeitia L, et al. Semin Arthritis Rheum. 2015; 45:361-8. [2]Vegas-Revenga N, et al. Am J Ophthalmol. 2019; 200:85-94. [3]Calvo-Río V, et al.. Clin Exp Rheumatol. 2014;32(4 Suppl 84): S54-7. Disclosure of Interests: Monica Calderón-Goercke: None declared, Raúl Fernández-Ramón: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Janssen and Celgene, Speakers bureau: Pfizer and Lilly, Lara Sanchez-Bilbao Grant/research support from: Pfizer, David Martínez-López: None declared, Iñigo González-Mazón: None declared, Jorge Javier Gaitán-Valdizán: None declared, Rosalía Demetrio-Pablo: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD
Novel biomarkers for the management of chronic hepatitis B
Authors: Takako Inoue, Yasuhito Tanaka
Journal: Clinical and Molecular Hepatology (2020)

Hepatitis B virus (HBV) cannot be eliminated completely from infected hepatocytes because of the presence of intrahepatic covalently closed circular DNA (cccDNA). As chronic hepatitis B (CHB) can progress to cirrhosis and hepatocellular carcinoma (HCC), it is important to manage CHB to prevent HCC development in high-risk patients with high viral replicative activity or advanced fibrosis. Serum biomarkers are noninvasive and valuable for the management of CHB. Hepatitis B core-related antigen (HBcrAg) correlates with serum HBV DNA and intrahepatic cccDNA. In CHB patients with undetectable serum HBV DNA or loss of HBsAg, HBcrAg still can be detected and the decrease in HBcrAg levels is significantly associated with hopeful outcomes. Therefore, HBcrAg can predict HCC occurrence or recurrence. Measurement of the Mac-2 binding protein glycosylation isomer (M2BPGi) has been introduced for the evaluation of liver fibrosis. Because elevated M2BPGi in CHB is related to liver fibrosis and the prediction of HCC development, monitoring its progression is essential. Because alpha fetoprotein (AFP) has insufficient sensitivity and specificity for early-stage HCC, a combination of AFP plus protein induced by vitamin K absence factor II, or AFP plus Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein might improve the diagnosis of HCC development. Additionally, Dickkopf-1 and circulating immunoglobulin G antibodies are the novel markers to diagnose HCC or assess HCC prognosis. This review provides an overview of novel HBV biomarkers used for the management of intrahepatic viral replicative activity, liver fibrosis, and HCC development.