tbuckley/cabot-search huggingface dataset:
PB2418 CLINICAL PRESENTATION AND MOLECULAR IDENTIFICATION OF ALPHA GLOBIN VARIANTS
Authors: Z. Salcioglu, G. Aydoğan, F. Akıcı, C. Bayram, G. N. Özdemir
Journal: HemaSphere (2019)

Background: Alpha thalassemia is the most common genetic disease inthe world with the prevalence of carriers ranging from 5–50% in several populations. Alpha thalassemia, characterized by variable degrees of α‐globin chain deficit is highly prevalent throughout the world. Alpha thalassemia syndromes are caused by mutations on one or more of the four α‐globin genes. Aims: The aim of this study was to determine alpha thalassemia mutations in our patients and to evaluate types of mutations. Methods: In a retrospective review of 52 patients with alpha thalassemia. followed at our centre from 1990 to 2018. Information of patients were retrieved from patient files and from the records contained in the electronic information processing environment created after 2005. The samples were investigated for α‐thalassemia mutations. Results: Presending ages of our patients ranged between one year and 13 years of age (5 ± 4.3 year). Twenty four of them were girls and 28 were boys. Fourteen patients (27%) were asymptomatic at the time of diagnosis, 32 (61.5%) of whom were diagnosed in patients with unsolved hypochromic microcytic anemia and 6 (11.5%) by family history. Thirteen different mutations were determined in patients. The most common mutation was the 3.7 gene deletion and was found in 23 patients (44.2%). Others common mutations were the 20.5 kb gene deletion (18; 34.6%), MED gene deletion (2;3.8%), α2 polyA2 (2;3.8%). Double gen mutations were determined in 27 patients (51.9%). The most common double gen mutation was the 3.7 gene deletion and was found in 8 patients (29.6%). Summary/Conclusion: Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and b‐thalassemia carrier state. Genetic testing should be performed for the suspicious cases. We also recommend that a national database with all mutations in Turkey.
Abstract P128: The Epigenomic Signature of Life's Simple 7
Authors: Niranjan Gowda, Marguerite R Irvin, Bertha A Hidalgo, Hemant K Tiwari, Devin M Absher, Donna K Arnett, Stella W Aslibekyan
Journal: Circulation (2018)

Introduction: Life’s Simple 7 (LS7) comprises seven health factors and behaviors promoted by the American Heart Association to reduce cardiovascular morbidity and mortality. Despite compelling evid...
Abstract P271: The Association of Lifestyle Factors with Circulating Levels of the Soluble Receptor for Advanced Glycation End Products (sRAGE): The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Julie K Bower, Brad C Astor, James S Pankow, Cheryl A Anderson, Mariana Lazo, Pamela L Lutsey, Jennifer A Nettleton, Bruce B Duncan, Maria I Schmidt, Ron C Hoogeveen, Marc K Halushka, Elizabeth Selvin
Journal: Circulation (2013)

Introduction. Accumulation of advanced glycation end products (AGEs) is hypothesized to contribute to oxidative stress, vascular inflammation, and atherosclerosis. The soluble form of the receptor ...
Rapid Decomposition of 99mTc-MAA Complex During Lung Perfusion Imaging
Authors: Sadegh Ebrahim Ajdari, Mohsen Qutbi
Journal: Clinical Nuclear Medicine (2019)

Abstract A 30-year-old woman with a recent episode of dyspnea was presented. The lung perfusion scan using 99m Tc-MAA (macro-aggregated albumin) initially revealed an acceptable lung-to-background activity ratio implying a proper radiopharmaceutical preparation and radiolabeling efficiency. Unexpectedly, later during the scan, rapidly increasing concentration of activity was observed in salivary glands, thyroid and stomach. Rapid breakdown of 99m Tc-MAA complexes was considered as a likely explanation for the increase in the circulatory level of the free pertechnetate.
Cancer nanotechnology: Enhancing tumor cell response to chemotherapy for hepatocellular carcinoma therapy
Authors: Yongbing Sun, Wen Ma, Yuanyuan Yang, Mengxue He, Aimin Li, Lei Bai, Bin Yu, Zhiqiang Yu
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Hepatocellular carcinoma (HCC) is one of the deadliest cancers due to its complexities, reoccurrence after surgical resection, metastasis and heterogeneity. In addition to sorafenib and lenvatinib for the treatment of HCC approved by FDA, various strategies including transarterial chemoembolization, radiotherapy, locoregional therapy and chemotherapy have been investigated in clinics. Recently, cancer nanotechnology has got great attention for the treatment of various cancers including HCC. Both passive and active targetings are progressing at a steady rate. Herein, we describe the lessons learned from pathogenesis of HCC and the understanding of targeted and non-targeted nanoparticles used for the delivery of small molecules, monoclonal antibodies, miRNAs and peptides. Exploring current efficacy is to enhance tumor cell response of chemotherapy. It highlights the opportunities and challenges faced by nanotechnologies in contemporary hepatocellular carcinoma therapy, where personalized medicine is increasingly becoming the mainstay. Overall objective of this review is to enhance our understanding in the design and development of nanotechnology for treatment of HCC.
THU0605 SHEAR WAVE ELASTOGRAPHY MUSCLE STIFFNESS MAY DIMINISH AFTER CORTICOSTEROID TREATMENT
Authors: Abdulrahman M. Alfuraih, Ai Lyn Tan, Philip O’connor, Paul Emery, Richard Wakefield
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The use of corticosteroids is associated with several adverse effects including corticosteroid-induced myopathy (CIM). CIM may cause structural alterations to the myofibres, which support the hypothesis of altered muscle stiffness as seen in histological and preclinical studies [1,2]. Shear wave elastography is an ultrasound technology that can quantify tissue stiffness non-invasively. <h3>Objectives:</h3> To investigate the changes in muscle stiffness as measured by SWE and muscle strength tests in giant cell arteritis (GCA) patients exposed to high doses (40–60 mg/day) of corticosteroid treatment. <h3>Methods:</h3> Fourteen GCA patients (4 males, mean age 68.2±4.3 years) were recruited and evaluated at baseline, after 3 months and 6 months on prednisolone. Shear wave velocity (SWV), as a surrogate for tissue stiffness, and muscle strength were evaluated at each visit. Baseline data were compared to frequency-matched healthy controls. Linear mixed models were used to analyse the longitudinal data. <h3>Results:</h3> The patients did not have a significantly different muscle SWV to healthy controls (all <i>p</i> &gt;0.05) at baseline. However, after 3 months, the quadriceps and hamstrings SWV decreased on average by 14% (range 8.3%–17.3%; <i>p</i>=0.001) and after 6 months decreased by 18% (range 10.2%–25.3%<i> p</i>&lt;0.001). The biceps brachii SWV did not change with time (<i>p</i>=0.92) (Fig 1). The baseline, 3-months and 6-months mean SWV for the vastus lateralis were 1.62 m/s, 1.40 m/s and 1.31 m/s respectively (p&lt;0.001). Muscle strength was generally preserved at follow-up. However, there were moderate to strong correlations (r= 0.54–0.96) between weaker muscle strength at follow-up and greater reduction in SWV. <h3>Conclusion:</h3> The GCA patients showed a significant loss of muscle stiffness after 3 and 6 months of corticosteroid treatment. With further validation in larger samples, shear wave elastography may be useful for detecting subclinical CIM. <h3>References:</h3> [1] -Alev, K., et al., Glucocorticoid-Induced Changes in Rat Skeletal Muscle Biomechanical and Viscoelastic Properties: Aspects of Aging. J Manipulative Physiol Ther, 2018. 41(1): p.19-24. [2] - Schakman, O., et al., Glucocorticoid-induced skeletal muscle atrophy. The International Journal of Biochemistry &amp; Cell Biology, 2013. 45(10): p.2163-2172. <h3>Disclosure of Interests:</h3> Abdulrahman M. Alfuraih: None declared, Ai Lyn Tan: None declared, Philip O'Connor: None declared, Paul Emery Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, Roche, Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Gilead,Samsung, Sandoz and Lilly, Richard Wakefield: None declared
The burden of illness in metastatic renal cell carcinoma (mRCC) patients after two targeted therapies: A review of the literature.
Authors: Giuseppe Di Lorenzo, John Coombs, Roman Casciano, Lee Stern
Journal: Journal of Clinical Oncology (2012)

e15043 Background: MRCC poses a substantial burden in terms of morbidity, mortality, impaired quality of life (QoL), and costs. Despite the emergence of targeted therapies (VEGF-TKIs and mTORs) in this setting, considerable unmet medical needs remain. Methods: A comprehensive literature search was performed to systematically review available data on the burden of mRCC. Included articles focused on the efficacy, toxicity, guidelines, therapy sequencing, and overall disease burden of mRCC patients who have failed multiple targeted therapies. Of the 933 articles mRCC articles identified, 83 met the criteria for data extraction. Results: An extensive amount of literature is published on targeted therapies in the treatment of patients with mRCC. Recently approved therapies report improved outcomes in 1 st and 2 nd line treatment; however, there are minimal data on the efficacy and safety of treatments following failure of 2 sequential targeted therapies. Specifically, two studies report OS in 2nd line failures: one prospective study of capecitabine as 3 rd line treatment (OS: 7.2 months [CI: 4.6-8.8]) and one retrospective single arm study of 3 rd line sorafenib use after failure of both VEGF-TKIs and mTORs (OS: 7 months [range: 6-10]). Consequently, of the six current practice guidelines, none recommend a specific treatment for patients who fail 2 targeted therapies. As highlighted in over 20 articles on therapy sequencing, the treatment population failing 2 targeted therapies represents an extremely heterogeneous group with a variety of prior therapies, for whom data are lacking. QoL and economic data focusing on patients in this setting were not identified. However, based upon evaluations in 1 st and 2 nd line patients, treatment toxicity and disease progression are expected to have a negative impact on QoL while increasing costs due to the associated need for additional treatment, hospitalizations, and other management. Conclusions: Despite significant advances in the treatment options for patients with mRCC, many patients inevitably progress and are left with few options. There is substantial unmet need for safe and effective 3 rd line treatment options that can provide clinical benefit.
Alterations of gut microbiome in autoimmune hepatitis
Authors: Yiran Wei, Yanmei Li, Li Yan, Chunyan Sun, Qi Miao, Qixia Wang, Xiao Xiao, Min Lian, Bo Li, Yong Chen, Jun Zhang, You Li, Bingyuan Huang, Yikang Li, Qin Cao, Zhuping Fan, Xiaoyu Chen, Jing-Yuan Fang, Merrill Eric Gershwin, Ruqi Tang, Xiong Ma
Journal: Gut (2019)

Objective The significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls. Design We performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy. Results The gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p&lt;0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including Veillonella were associated with disease status. Of note, Veillonella dispar , the most strongly disease-associated taxa (p=8.85E–8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites. Conclusion Our study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.
THU0600 QUANTITATIVE INDEXES TO ASSESS THE INTERSTITIAL LUNG DISEASE, AND ITS EXTENSION, IN SJÖGREN’S SYNDROME
Authors: Pablo Guisado-Vasco, Mario Silva, Miguel Angel Duarte-Millán, Gianluca Sambataro, Chiara Bertolazzi, Mauro Pavone, Isabel Martín-Garrido, Oriol Martín-Segarra, José Manuel Luque-Pinilla, Daniele Santilli, Domenico Sambataro, Sebastiano Emanuele Torrisi, Vancheri Ada, Marwin Gutierrez, Mayra Mejia, Stefano Palmucci, Flavio Mozzani, Jorge Rojas-Serrano, Carlo Vanchieri, Nicola Sverzellati, Alarico Ariani
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Interstitial lung disease (ILD) is the most frequent pulmonary impairment in Sjögren's syndrome (SS). The diagnosis is challenging, as there are not specific tests (i.e. autoantibodies or pulmonary function tests) or symptoms. Chest CT is the gold standard. Semiquantitative visual scores (SQCT) estimate ILD extent, though burdened by relevant intra-, inter-rater variability. Quantitative chest CT (QCT) is a promising method to assess ILD severity Objectives: to verify if QCT assessment could identify SS subjects affected by ILD and to identify those SS patients with an extensive lung disease. Methods: in this multi-center, cross-sectional, and retrospective study, subjects affected by SS and with a chest CT were enrolled. A blind and centralized SQCT assessment was carried out in order to calculate both Goh and Taouli scores. An operator-independent analysis of all CTs with an open-source software (i.e. Horos), provided the QCT indexes. Patients were clustered in cohorts according to ILD extent. Differences in QCT indexes distribution were analyzed using non-parametric tests. <h3>Results</h3> 102 consecutive SS patients were enrolled. ILD prevalence was 36% (36/102). There was a difference in QCT indexes' distribution in SS-ILD versus SS without ILD (p &lt; 0.001). Moreover, SS-ILD patients with an ILD &gt;20% (according to Goh score) had QCT indexes statistically different from those with a limited ILD extension (p&lt;0.001). QCT indexes have a moderate to good correlation with Goh and Taouli scores (from 0.44 to 0.65; absolute numbers, +/-; p &lt; 0.001). To value its potential of diagnosis, ROC curves were calculated, achieving several of them values of AUC &gt; 0.7; the best QTC index was: tSkew AUC 0.87 (95CI 0.78-0.95), p&lt; 0.001; cut-off ≤ 2.72 - sensitivity 0.81 (95CI 0.65-0.9), specificity 0.82 (95CI 0.7-0.89). <h3>Conclusion</h3> QCT indexes are a serious alternative to visual scorings in ILD related to autoimmune diseases. This innovative tool will open up a potential research area in SS as it appears able to select ILD patients with an extensive lung impairment and likewise a worse prognosis. We are confident that in the next future, QCT will have a pivotal role in the diagnosis, monitoring and treatment pathway of ILD associated to SS. <h3>References</h3> [1] Silva M, Milanese G, Seletti V, Ariani A, Sverzellati N. Pulmonary quantitative CT imaging in focal and diffuse disease: current research and clinical applications. Br J Radiol2018; 91: 20170644. <h3>Disclosure of Interests</h3> None declared
Fast and accurate single-cell RNA-seq analysis by clustering of transcript-compatibility counts
Authors: Vasilis Ntranos, Govinda M. Kamath, Jesse M. Zhang, Lior Pachter, David N. Tse
Journal: Genome biology (2016)

Current approaches to single-cell transcriptomic analysis are computationally intensive and require assay-specific modeling, which limits their scope and generality. We propose a novel method that compares and clusters cells based on their transcript-compatibility read counts rather than on the transcript or gene quantifications used in standard analysis pipelines. In the reanalysis of two landmark yet disparate single-cell RNA-seq datasets, we show that our method is up to two orders of magnitude faster than previous approaches, provides accurate and in some cases improved results, and is directly applicable to data from a wide variety of assays.
The association between maternal body mass index and child obesity: A systematic review and meta-analysis
Authors: Nicola Heslehurst, Rute Vieira, Zainab Akhter, Hayley Bailey, Emma Slack, Lem Ngongalah, Augustina Pemu, Judith Rankin
Journal: PLoS Medicine (2019)

Background There is a global obesity crisis, particularly among women and disadvantaged populations. Early-life intervention to prevent childhood obesity is a priority for public health, global health, and clinical practice. Understanding the association between childhood obesity and maternal pre-pregnancy weight status would inform policy and practice by allowing one to estimate the potential for offspring health gain through channelling resources into intervention. This systematic review and meta-analysis aimed to examine the dose–response association between maternal body mass index (BMI) and childhood obesity in the offspring. Methods and findings Searches in MEDLINE, Child Development & Adolescent Studies, CINAHL, Embase, and PsycInfo were carried out in August 2017 and updated in March 2019. Supplementary searches included hand-searching reference lists, performing citation searching, and contacting authors. Two researchers carried out independent screening, data extraction, and quality assessment. Observational studies published in English and reporting associations between continuous and/or categorical maternal and child BMI or z-score were included. Categorical outcomes were child obesity (≥95th percentile, primary outcome), overweight/obesity (≥85th percentile), and overweight (85th to 95th percentile). Linear and nonlinear dose–response meta-analyses were conducted using random effects models. Studies that could not be included in meta-analyses were summarised narratively. Seventy-nine of 41,301 studies identified met the inclusion criteria (n = 59 cohorts). Meta-analyses of child obesity included 20 studies (n = 88,872); child overweight/obesity, 22 studies (n = 181,800); and overweight, 10 studies (n = 53,238). Associations were nonlinear and there were significantly increased odds of child obesity with maternal obesity (odds ratio [OR] 3.64, 95% CI 2.68–4.95) and maternal overweight (OR 1.89, 95% CI 1.62–2.19). Significantly increased odds were observed for child overweight/obesity (OR 2.69, 95% CI 2.10–3.46) and for child overweight (OR 1.80, 95% CI 1.25, 2.59) with maternal obesity. A limitation of this research is that the included studies did not always report the data in a format that enabled inclusion in this complex meta-analysis. Conclusions This research has identified a 264% increase in the odds of child obesity when mothers have obesity before conception. This study provides substantial evidence for the need to develop interventions that commence prior to conception, to support women of childbearing age with weight management in order to halt intergenerational obesity.
Interstitial nephritis in immune checkpoint inhibitor therapy
Authors: Sandhya Manohar, Robert C. Albright
Journal: Kidney International (2019)

A 67-year-old woman with a history of metastatic melanoma on therapy presented to the oncology clinic with worsening fatigue for 2 weeks. She had subjective fevers, chills, and a pruritic rash. Her melanoma had progressed on pembrolizumab and so she had recently been started on combination therapy with ipilimumab and nivolumab about 3 months previously. Because of concerns for disease progression, she underwent a positron emission tomography–computed tomography (PET-CT) before being seen in the clinic. Her PET-CT scan demonstrated an interval decrease in fludeoxyglucose F-18 update in her prior liver and gastroesophageal lesions suggestive of a partial response to therapy.
AB1259 EVALUATION OF ENALAPRIL ON ARTERIAL STIFFNESS IN RHEUMATOID ARTHRITIS IN A RANDOMISED CLINICAL TRIAL
Authors: Felipe Perez-Vazquez, Sergio Duran Barragan, Eduardo Gomez-Bañuelos, Efrain Chavarria Avila, Carlos Ramos Becerra, Gustavo-Ignacio Diaz-Rubio, Mario Salazar-Paramo, Fernando Grover Páez, Arnulfo Hernán Nava-Zavala, Ernesto G. Cardona-Muñoz, David Cardona Müller, Rosa E. Navarro-Hernández, Valeria-Nicole Mera-Riofrio, Natalia Prado-Bachega, Monica Vazquez-Del-Mercado
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> This is the first study where suboptimal doses of enalapril proved to be successful for the reduction of arterial stiffness in in a clinical trial of rheumatoid arthritis (RA) patients. <h3>Objectives:</h3> The aim of this study was to analyze the effect of enalapril on arterials stiffness through the evaluation of subclinical parameters in RA patients without traditional cardiovascular risk factors or previous comorbidities. <h3>Methods:</h3> Fifty three patients were enrolled in a clinical, randomized, closed-label trial. The subjects were randomly assigned into two groups: One receiving 5 mg of enalapril (27) and 5 mg of placebo (26), both twice a day. Clinical assessment included a structured questionnaire to gather demographic and clinical variables, including disease duration, treatment, disease activity, laboratory, anthropometric measurements and determination of cardiovascular parameters [carotid femoral pulse wave velocity (cfPWV) (1), cardio-ankle vascular index (CAVI) (2), carotid intima media thickness (cIMT), carotid artery distensibility (3), Young's incremental elastic modulus (Einc)]. The whole set of evaluations were analyzed at the baseline and at the end of 12 weeks of intervention. <h3>Results:</h3> A significant reduction in delta CAVI of 0.21 in the enalapril intervention group was found. In contrast, an increase of 0.39 was observed in the placebo group. The delta CAVI reduction was not influenced by age or peripheral systolic blood pressure (pSBP). <h3>Conclusion:</h3> Enalapril seems to be effective in CAVI reduction in RA patients. The effect of enalapril intervention on arterial stiffness translated to the clinical context, might be interpreted as a reduction of 6.4 years of arterial aging. <h3>References</h3> [1] Vazquez-Del Mercado, M., et al., Disease duration of rheumatoid arthritis is a predictor of vascular stiffness: a cross-sectional study in patients without known cardiovascular comorbidities: A STROBE-compliant article. Medicine (Baltimore), 2017. 96(33): p. e7862. [2] Saiki, A., et al., The Role of a Novel Arterial Stiffness Parameter, Cardio-Ankle Vascular Index (CAVI), as a Surrogate Marker for Cardiovascular Diseases. J Atheroscler Thromb, 2016. 23(2): p. 155-68. [3] Vazquez-Del Mercado, M., et al., Subclinical parameters of arterial stiffness and arteriosclerosis correlate with QRISK3 in systemic lupus erythematosus. PLoS One, 2018. 13(12): p. e0207520. <h3>Disclosure of Interests:</h3> None declared