tbuckley/cabot-search huggingface dataset:
AB0736 JUVENILE IDIOPATHIC ARTHRITIS IN ADULTHOOD: TRENDS OF THE DISEASE AND SOCIO-PROFESSIONAL FUTURE
Authors: S. Miladi, M. Yasmine, S. Mariem, A. Fazaa, K. Ouenniche, L. Souebni, S. Kassab, S. Chekili, K. Ben Abdelghani, A. Laatar
Journal: Annals of the Rheumatic Diseases (2021)

Background: Juvenile idiopathic arthritis (JIA) is the most common arthropathy of childhood that may lead to physical disability and reduced quality of life, thus hindering the ability of the patients to achieve a meaningful adult life. Objectives: The aim of this study was to assess the trends of the disease and socio-professional future. Methods: We conducted a retrospective study including adult patients aged &gt; 18 years with a history of JIA according to the International League of Associations for Rheumatology (ILAR). Collected data included age, sex, the characteristics of the disease (subtype of JIA, disease duration). The level of education, marital status as well as the profession were recorded. Results: The study included 32 patients with a female perdominance: sex ratio was 1,5. The mean age was 29,5 years old [18-64]. The mean age of onset of the disease was 6 years and 2 months [2-17]. The frequency of each JIA subset was at follows: polyarticular with rheumatoid factor (n= 14), polyarticular without rheumatoid factor (n=9), systemic (n= 2), enthesitis-related arthritis (n=7), oligoarthritis (n= 5). Four patients suffered from bilateral cataract due to corticosteroid intake. Polyarticular RF+ and RF- progressed into an authentic seropositive and seronegative RA in 71.4% and 66.7% respectively. Among oligoarticular subtype, an extension of the disease to a polyarticular FR+ form (n=1) and to a seronegative rheumatoid arthritis (n=1) was noted. Systemic JIA forms remained in remission with an articular involvement. All the patients with ERA developed spondylarthritis. Although forty–two percent of the patients were married, only half of them had children. Ten percent of patients stopped attending school because of disease flares and deformation. A university level was found in 16% of cases. Only Thirty patients had a profession. Of the patients, 74.4% had received disease-modifying anti-rheumatic drugs (DMARDs) and 36.3% of them were still taking a DMARD. Ten patients were on biologics. Severe disability was found in 20% of patients and concerned mainly the hip (57,2%), the wrist (28,5%) and the elbows (14,3%). Prosthetic joint replacement was found in 2% of cases with a revision of the latter in one patient. Conclusion: Adults with JIA often have significant levels of disability, usually related to severe joint complications. There is a clear requirement for a better transition to adulthood and a socio-professional rehabilitation. Disclosure of Interests: None declared
AB0887-HPR CHARLSON COMORBIDITY INDEX (CCI) IN RHEUMATOID ARTHRITIS: CLASSIFICATION AND CORRELATIONS
Authors: C. Flourou, S. Psarelis, A. Tofarides, E. Papanicolaou, G. Papazisis
Journal: Annals of the Rheumatic Diseases (2021)

Background: Charlson Comorbidity Index[1] is a tool including age and chronic diseases assessing the comorbidity burden. The age and the comorbidity burden in RA patients determine the morbidity and mortality. Objectives: To assess and classification of CCI in RA patients with usage of the health-care system (outpatient clinics) in a real-world setting. Methods: 327 patients with RA from a large outpatient service of a central hospital were retrospectively reviewed. Demographic characteristics, treatment for RA and comorbidities were recorded. Charlson Comorbidity Index (CCI) was measured and classified as low, intermediate and high score for 1-2, 3-4 and &gt;=5 points, respectively. Its correlation with polypharmacy and necessity of biologic DMARDs was studied. Univariable and multivariable analyses were performed. Results: Data from 327 RA patients (75,8% females, 24,2%males) with a mean±SD age of 63±11,8 years and disease duration 113±63 months, were recorded. CCI was 3±1,2 points (mean±SD) and maximum score was observed at 7 points. High score (&gt;=5points) was observed at 9,2% and in the majority the score was intermediate (3-4points) at 55%. All the RA patients with high score fulfilled the criteria of polypharmacy. Patients with high score had 9,7 times more probability of polypharmacy than the patients with low score (p=0.09, 1.4-2.5 95%CI). 70 patients were treated with biologic-DMARDs (21,7%), in the majority with TNFa inhibitors (16,5%). In RA patients receiving biologic-DMARDs was observed low or intermediate score of CCI. Τhe most likely explanation is the severity of the disease that predominated, its complications and the possible overlap with other conditions. Conclusion: The majority of RA patients had intermediate score of CCI. In patients with high score-meaning more comorbidities- polypharmacy was observed completely. Patients receiving biologic-DMARDs characterized with less comorbidities. References: [1]Charlson E M et al. A new method of classifying prognostic comorbidity in longitudinal studies:development and validation. J Chronic Dis. 1987;40(5):373-83. Disclosure of Interests: None declared
Clinical Value of Consensus Molecular Subtypes in Colorectal Cancer: A Systematic Review and Meta-Analysis
Authors: Sanne ten Hoorn, Tim R de Back, Dirkje W Sommeijer, Louis Vermeulen
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs. Methods We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized. Results In local disease, CMS4 tumors were associated with worse overall survival (OS) compared with CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval = 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33-0.55; progression-free survival HR range = 0.53-0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16-0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome compared with oxaliplatin (HR range = 0.31-0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-epidermal growth factor receptor therapy improved outcome for KRAS wild-type CMS2 patients. Conclusions The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice.
EYA2 suppresses the progression of hepatocellular carcinoma via SOCS3-mediated blockade of JAK/STAT signaling
Authors: Ze-Kun Liu, Can Li, Ren-Yu Zhang, Ding Wei, Yu-Kui Shang, Yu-Le Yong, Ling-Min Kong, Nai-Shan Zheng, Ke Liu, Meng Lu, Man Liu, Cai-Xia Hu, Xiao-Zhen Yang, Zhi-Nan Chen, Huijie Bian
Journal: Molecular Cancer (2021)

Abstract Background Somatic mutations are involved in hepatocellular carcinoma (HCC) progression, but the genetic mechanism associated to hepatocarcinogenesis remains poorly understood. We report that Eyes absent homolog 2 (EYA2) suppresses the HCC progression, while EYA2(A510E) mutation identified by exome sequencing attenuates the tumor-inhibiting effect of EYA2. Methods Whole-exome sequencing was performed on six pairs of human HCC primary tumors and matched adjacent tissues. Focusing on EYA2, expression level of EYA2 in human HCC samples was evaluated by quantitative real-time PCR, western blot and immunohistochemistry. Loss- and gain-of-function studies, hepatocyte-specific deletion of EYA2 ( Eya2 −/− ) in mice and RNA sequencing analysis were used to explore the functional effect and mechanism of EYA2 on HCC cell growth and metastasis. EYA2 methylation status was evaluated using Sequenom MassARRAY and publicly available data analysis. Results A new somatic mutation p.Ala510Glu of EYA2 was identified in HCC tissues. The expression of EYA2 was down-regulated in HCC and associated with tumor size ( P = 0.001), Barcelona Clinic Liver Cancer stage ( P = 0.016) and tumor differentiation ( P = 0.048). High level of EYA2 was correlated with a favorable prognosis in HCC patients ( P = 0.003). Results from loss-of-function and gain-of-function experiments suggested that knockdown of EYA2 enhanced, while overexpression of EYA2 attenuated, the proliferation, clone formation, invasion, and migration of HCC cells in vitro. Delivery of EYA2 gene had a therapeutic effect on inhibition of orthotopic liver tumor in nude mice. However, EYA2(A510E) mutation led to protein degradation by unfolded protein response, thus weakening the inhibitory function of EYA2. Hepatocyte-specific deletion of EYA2 in mice dramatically promoted diethylnitrosamine-induced HCC development. EYA2 was also down-regulated in HCC by aberrant CpG methylation. Mechanically, EYA2 combined with DACH1 to transcriptionally regulate SOCS3 expression, thus suppressing the progression of HCC via SOCS3-mediated blockade of the JAK/STAT signaling pathway. Conclusions In our study, we identified and validated EYA2 as a tumor suppressor gene in HCC, providing a new insight into HCC pathogenesis.
Freeze‐Casting with 3D‐Printed Templates Creates Anisotropic Microchannels and Patterned Macrochannels within Biomimetic Nanofiber Aerogels for Rapid Cellular Infiltration
Authors: Johnson V. John, Alec McCarthy, Hongjun Wang, Zeyu Luo, Hongbin Li, Zixuan Wang, Feng Cheng, Yu Shrike Zhang, Jingwei Xie
Journal: Advanced Healthcare Materials (2021)

A new approach is described for fabricating 3D poly(ε-caprolactone) (PCL)/gelatin (1:1) nanofiber aerogels with patterned macrochannels and anisotropic microchannels by freeze-casting with 3D-printed sacrificial templates. Single layer or multiple layers of macrochannels are formed through an inverse replica of 3D-printed templates. Aligned microchannels formed by partially anisotropic freezing act as interconnected pores between templated macrochannels. The resulting macro-/microchannels within nanofiber aerogels significantly increase preosteoblast infiltration in vitro. The conjugation of vascular endothelial growth factor (VEGF)-mimicking QK peptide to PCL/gelatin/gelatin methacryloyl (1:0.5:0.5) nanofiber aerogels with patterned macrochannels promotes the formation of a microvascular network of seeded human microvascular endothelial cells. Moreover, nanofiber aerogels with patterned macrochannels and anisotropic microchannels show significantly enhanced cellular infiltration rates and host tissue integration compared to aerogels without macrochannels following subcutaneous implantation in rats. Taken together, this novel class of nanofiber aerogels holds great potential in biomedical applications including tissue repair and regeneration, wound healing, and 3D tissue/disease modeling.
AB0672 PSYCHOLOGIC STATE OF PATIENTS WITH RHEUMATIC DISEASES AFTER THE OUTBREAK OF SARS-COV2
Authors: M. Yasmine, S. Mariem, S. Miladi, A. Fazaa, L. Souebni, K. Ouenniche, S. Kassab, S. Chekili, K. Ben Abdelghani, A. Laatar
Journal: Annals of the Rheumatic Diseases (2021)

Background: The ongoing Coronavirus-19 disease epidemic is a public health emergency of international concern which could pose a challenge to psychological resilience. This is mainly the case of patients with rheumatic diseases (RD). Objectives: The aim of this study was to establish the prevalence of psychiatric symptoms in patients with RD and to identify factors associated with psychological stress. Methods: A cross-sectional study was conducted among patients with RD. They were invited to respond to a survey designed to assess their psychological response after the outbreak of the SARS-COV2 pandemic. Mental health status after the Covid-19 was evaluated using the Depression and Anxiety Scale (DASS-21). The total depression subscale score was divided into normal (0–9), mild depression (10–12), moderate depression (13–20), severe depression (21–27), and extremely severe depression (28–42). The total anxiety subscale score was divided into normal (0–6), mild anxiety (7–9), moderate anxiety (10–14), severe anxiety (15–19), and extremely severe anxiety (20–42).The Impact of Event Scale-Revised (IES-R) is a 22-item self-administered questionnaire that assesses the post-traumatic state (PTS). A cut-off point of 33 provided the best diagnostic accuracy for PTS. The level of significance was fixed at 0.05. Results: Sixty patients were included (42 with rheumatoid arthritis and 18 with spondylarthritis) with a mean age of 51.3 ± 13.1 years [18-75]. The majority of patients were women (63.3%), married (81.7%), with a household size of 3–5 people (67.9%). The mean disease duration was 11.9 ±5.6 [1-23] years. According to DASS depression score almost half of the patients (47%) suffered from depression, which was classified as severe in 10% of cases. The mean DASS anxiety subscale was 12.6 ± 8.2 [1-35]. The level of anxiety was mild in 23% of cases, moderate in 25% of cases, and severe in 23.3% of cases. The mean ILES-R score was 20.4 ± 10.2 [20-38]. Women experienced more PTS than men (26.3% vs 22.7%) without reaching a statistically significant correlation (p=0.9). Patients with higher education had lower IES-R, depression, and anxiety subscale scores as compared to those who were illiterate without a statistically significant correlation (p=0.5, p=0.2, p=0.4 respectively). A positive correlation was found between anxiety score and IES-R (p=0.00). Other sociodemographic variables including disease duration, parental status, marital status, and household size were not associated with IES-R and DASS subscale scores (p&gt;0.05). Conclusion: Our study showed that many of our patients with RD experienced anxiety, depression, and PTS after the outbreak of Covid-19. Professional status as well as other sociodemographic data was not associated with psychological stress. Disclosure of Interests: None declared
First-Line Afatinib plus Cetuximab for <i>EGFR</i>-Mutant Non–Small Cell Lung Cancer: Results from the Randomized Phase II IFCT-1503 ACE-Lung Study
Authors: Alexis B. Cortot, Anne Madroszyk, Etienne Giroux-Leprieur, Olivier Molinier, Elisabeth Quoix, Henri Bérard, Josiane Otto, Isabelle Rault, Denis Moro-Sibilot, Judith Raimbourg, Elodie Amour, Franck Morin, José Hureaux, Lionel Moreau, Didier Debieuvre, Hugues Morel, Aldo Renault, Eric Pichon, Benjamin Huret, Sandrine Charpentier, Marc G. Denis, Jacques Cadranel
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Double inhibition of epidermal growth factor receptor (EGFR) using a tyrosine kinase inhibitor plus a monoclonal antibody may be a novel treatment strategy for non–small cell lung cancer (NSCLC). We assessed the efficacy and toxicity of afatinib + cetuximab versus afatinib alone in the first-line treatment of advanced EGFR-mutant NSCLC. Patients and Methods: In this phase II, randomized, open-label study, patients with stage III/IV EGFR-positive NSCLC were randomly assigned (1:1) to receive afatinib (group A) or afatinib + cetuximab (group A + C). Oral afatinib 40 mg was given once daily; cetuximab 250 mg/m² was administered intravenously on day 15 of cycle 1, then every 2 weeks at 500 mg/m² for 6 months. The primary endpoint was time to treatment failure (TTF) rate at 9 months. Exploratory analysis of EGFR circulating tumor DNA in plasma was performed. Results: Between June 2016 and November 2018, 59 patients were included in group A and 58 in group A + C. The study was ended early after a futility analysis was performed. The percentage of patients without treatment failure at 9 months was similar for both groups (59.3% for group A vs. 64.9% for group A + C), and median TTF was 11.1 (95% CI, 8.5–14.1) and 12.9 (9.2–14.5) months, respectively. Other endpoints, including progression-free survival and overall survival, also showed no improvement with the combination versus afatinib alone. There was a slight numerical increase in grade ≥3 adverse events in group A + C. Allele frequency of the EGFR gene mutation in circulating tumor DNA at baseline was associated with shorter PFS, regardless of the treatment received. Conclusions: These results suggest that addition of cetuximab to afatinib does not warrant further investigation in treatment-naïve advanced EGFR-mutant NSCLC.
Receptor activator of NF-κB mediates podocyte injury in diabetic nephropathy
Authors: Guibao Ke, Xueqin Chen, Ruyi Liao, Lixia Xu, Li Zhang, Hong Zhang, Sujuan Kuang, Yue Du, Juan Hu, Zhiwen Lian, Caoshuai Dou, Qianmei Zhang, Xingchen Zhao, Fengxia Zhang, Shuangshuang Zhu, Jianchao Ma, Zhuo Li, Sijia Li, Chaosheng He, Xia Chen, Yingzhen Wen, Zhonglin Feng, Minghao Zheng, Ting Lin, Ruizhao Li, Bohou Li, Wei Dong, Yuanhan Chen, Wenjian Wang, Zhiming Ye, Chunyu Deng, Houqin Xiao, Jie Xiao, Xinling Liang, Wei Shi, Shuangxin Liu
Journal: Kidney International (2021)
Genomic Profiling of Blast Phase in Philadelphia-Negative Myeloproliferative Neoplasms
Authors: Elisa Roncoroni, Jelena D. Milosevic Feenstra, Elisa Rumi, Daniela Pietra, Virginia Valeria Ferretti, Marta Bellini, Chiara Cavalloni, Ilaria Carola Casetti, Roland Jäger, Edith Bogner, Michele Ciboddo, Patrizia Zappasodi, Cristina Picone, Laura Vanelli, Cesare Astori, Robert Kralovics, Mario Cazzola
Journal: Blood (2017)
AB0860-HPR IS THERE A RELATIONSHIP BETWEEN PHYSICAL ACTIVITY, SLEEP QUALITY, ANXIETY AND DEPRESSION IN PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER?
Authors: T. Civi Karaaslan, S. Ugurlu, E. Tarakci
Journal: Annals of the Rheumatic Diseases (2021)

Background: Maintenance of regular physical activity is associated with better physical and mental health (1). In addition, sleep disturbances and mood disorders are common in chronic inflammatory diseases (2). Objectives: The aim of this study was to determine the relationship between physical activity, sleep quality, anxiety and depression in patients with FMF. Methods: A total of 56 patients (30 female, 26 male) with Familial Mediterranean Fever (FMF) were enrolled in the study. They were diagnosed with FMF based on the Livneh diagnostic criteria (3). International Physical Activity Questionnaire - Short Form (IPAQ) was used to evaluate health-related physical activity. Patient-reported sleep quality was evaluated with the Pittsburgh Sleep Quality Index (PSQI). Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety and depression in FMF patients. Patients who were 20-55 years old was included in the study. Results: The mean age was 32.23±9.87 years. The mean disease duration of the patients was 12.24±7.61 years. The education level of 51.8% (n=29) of the participants was undergraduate and above. The rate of those who did not work was 32.1% (n=18) and 48.2% (n=27) of the participants were married. The mean of scores of IPAQ was 2333.99±2640.29, the mean of PSQI was 6.14±3.66, the mean of HADS-Anxiety was 7.89±5.03 and HADS-Depression was 7.01±4.44. The patients were classified according to physical activity categories as low (25.0%, n=14), moderate (41,1% n=23) and high (33.9%, n=19). Physical activity categories were not found associated with PSQI (p=0.437), HADS-Anxiety (p=0.363) and HADS-Depression (p=0.861). The relationships of scores of IPAQ, PSQI and HADS were demonstrated Table 1. Conclusion: This study confirmed that patients with FMF suffer from sleep disturbances, anxiety and depression. In addition, sleep disturbances, anxiety and depression were not associated with physical activity category. References: [1]Sokka, Tuulikki, et al. Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study. Arthritis Care &amp; Research: Official Journal of the American College of Rheumatology, 2008, 59.1: 42-50. [2]Kucuksahin, Orhan, et al. Incidence of sleep disturbances in patients with familial Mediterranean fever and the relation of sleep quality with disease activity. International journal of rheumatic diseases, 2018, 21.10: 1849-1856. [3]Bashardoust, Bahman. Familial Mediterranean fever; diagnosis, treatment, and complications. Journal of nephropharmacology, 2015, 4.1: 5. Table 1. The correlations of IPAQ, PSQI and HADS scores. HADS-Depression HADS-Anxiety PSQI IPAQ r -0.091 -0.142 -0.002 p 0.505 0.295 0.990 PSQI r 0.689 0.615 p 0.001 0.001 HADS-Anxiety r 0.681 p 0.001 -Pearson Correlation Disclosure of Interests: None declared
In Situ Construction of Functional Assemblies in Living Cells for Cancer Therapy
Authors: Xuejiao Yang, Zeyuan Cao, Honglei Lu, Huaimin Wang
Journal: Advanced Healthcare Materials (2021)

Abstract Peptide‐based materials hold great promise for various biomedical applications and have drawn increasing attention over the past five years. Despite the progress in fabrication and handling peptide materials in vitro, manipulating assemblies of peptides in living cells (or animals) is still in its infancy. In this contributing review, recent work is summarized using endogenous triggers to construct functional assemblies of peptides in vivo. After introducing the triggers for inducing peptide assemblies, the recent progress is highlighted of the in situ construction of assemblies for biomedical applications with emphasis on cancer therapy. Finally, a brief perspective is provided to discuss the future promises and challenges of this emerging area of supramolecular chemistry.
PGC-1α deficiency reveals sex-specific links between cardiac energy metabolism and EC-coupling during development of heart failure in mice
Authors: Nikolay Naumenko, Maija Mutikainen, Lari Holappa, Jorge L Ruas, Tomi Tuomainen, Pasi Tavi
Journal: Cardiovascular Research (2021)

Biological sex has fundamental effects on mammalian heart physiology and pathogenesis. While it has been established that female sex is a protective factor against most cardiovascular diseases (CVDs), this beneficial effect may involve pathways associated with cardiac energy metabolism. Our aim was to elucidate the role of transcriptional coactivator PGC-1α in sex dimorphism of heart failure (HF) development.Here, we show that mice deficient in cardiac expression of the peroxisome proliferator-activated receptor gamma (PPAR-γ) coactivator-1α (PGC-1α) develop dilated HF associated with changes in aerobic and anaerobic metabolism, calcium handling, cell structure, electrophysiology, as well as gene expression. These cardiac changes occur in both sexes, but female mice develop an earlier and more severe structural and functional phenotype associated with dyssynchronous local calcium release resulting from disruption of t-tubular structures of the cardiomyocytes.These data reveal that the integrity of the subcellular Ca2+ release and uptake machinery is dependent on energy metabolism and that female hearts are more prone to suffer from contractile dysfunction in conditions with compromised production of cellular energy. Furthermore, these findings suggest that PGC-1α is a central mediator of sex-specific differences in heart function and CVD susceptibility.