tbuckley/cabot-search huggingface dataset:
AB0819 HANDGRIP STRENGTH PREDICTS HIGH FRACTURE RISK IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Federica Bellone, Nunziata Morabito, Agostino Gaudio, Gabriella Martino, Alberto Sardella, Antonino Lasco, Antonino Catalano
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Accumulating evidence has revealed that the risk of osteoporosis related fractures is significantly increased in type 2 diabetes mellitus (T2DM) patients in comparison with healthy controls. Dual X-ray Absorptiometry (DXA) derived bone mineral density (BMD) is not completely useful to discriminate at risk patients. <h3>Objectives</h3> To find a valuable clinical tool that is helpful to identify T2DM subjects with poor bone health, finally preventing fragility fractures. <h3>Methods</h3> In a setting of Caucasian subjects with T2DM, anthropometric data and information about metabolic control and diabetic complications were recorded. Handgrip strength by dynamometer, FRAX derived 10-years probability of major osteoporotic fractures and hip fractures were also assessed. Bone evaluation was performed by a dual-energy X-ray absorptiometry (DXA) densitometer at the lumbar spine (L1-L4) and at the femoral neck; based on specific software, the trabecular bone score (TBS) was calculated. Lateral scan of thoracic and lumbar spine was assessed to investigate morphometric vertebral fractures (Vfx). <h3>Results</h3> 29 patients (female 65%) [median age 67 (60 to 70)] with T2DM were considered. Morphometric vertebral fractures were detected by DXA in 17% of patients without any gender differences (males vs. females, p=0.6). The median ten years probability of fractures was 8.1% and 2.3% as for major osteoporotic or hip fracture respectively. Median femoral neck T-score value [-1.1 SD (-1.8 to -0.5)] was indicative of a slight osteopenia while lumbar spine T-score was even in the normal range [-0.8 SD (-1.5 to -0.1)]. The median TBS value was 1.28 (1.2 to 1.31) and TBS was positively associated with BMD at lumbar spine and femoral neck. Median handgrip strength value was 22.3 kg (18.9 to 31.3). At multiple regression analysis, handgrip strength predicted both lumbar (β= 0.009, SE 0.0034, p=0.01) and femoral neck BMD values (β= 0.006, SE 0.002, p=0.01). Age (β= -0.008, SE 0.002, p=0.007) and handgrip strength (β= 0.01, SE 0.002, p=0.0001) were also independently associated with TBS score, after correcting for mean HbA1c values and time since T2DM diagnosis. <h3>Conclusion</h3> Handgrip strength may be a reliable tool to screen for bone fragility in T2DM. <h3>References</h3> [1] Napoli N, Chandran M, Pierroz DD et al. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol 2017; 13(4):208–219. [2] Russo GT, Giandalia A, Romeo EL, Nunziata M, Muscianisi M, Ruffo MC, Catalano A, Cucinotta D. Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences. Int J Endocrinol. 2016;2016:1615735. [3] Li YZ, Zhuang HF, Cai SQ, Lin CK, Wang PW, Yan LS, Lin JK, Yu HM. Low Grip Strength is a Strong Risk Factor of Osteoporosis in Postmenopausal Women. Orthop Surg. 2018 Feb;10(1):17-22. <h3>Disclosure of Interests</h3> None declared
Re: Stacy Loeb, Jacob Taylor, Mohit Butaney, et al. Twitter-based Prostate Cancer Journal Club (#ProstateJC) Promotes Multidisciplinary Global Scientific Discussion and Research Dissemination. Eur Urol 2019;75:881–2
Authors: Kaiyu Qian, Lingao Ju, Yu Xiao
Journal: European Urology (2019)
New USPSTF Guidelines for HIV Screening and Preexposure Prophylaxis (PrEP)
Authors: Rochelle P. Walensky, A. David Paltiel
Journal: JAMA Network Open (2019)

Roger Chou, MD; Christopher Evans, MD, MPH; Adam Hoverman, DO; Christina Sun, PhD; Tracy Dana, MLS; Christina Bougatsos, MPH; Sara Grusing, BA; P. Todd Korthuis, MD
BaalChIP: Bayesian analysis of allele-specific transcription factor binding in cancer genomes
Authors: Ines de Santiago, Wei Liu, Ke Yuan, Martin O’Reilly, Chandra Sekhar Reddy Chilamakuri, Bruce A. J. Ponder, Kerstin B. Meyer, Florian Markowetz
Journal: Genome biology (2017)

Allele-specific measurements of transcription factor binding from ChIP-seq data are key to dissecting the allelic effects of non-coding variants and their contribution to phenotypic diversity. However, most methods of detecting an allelic imbalance assume diploid genomes. This assumption severely limits their applicability to cancer samples with frequent DNA copy-number changes. Here we present a Bayesian statistical approach called BaalChIP to correct for the effect of background allele frequency on the observed ChIP-seq read counts. BaalChIP allows the joint analysis of multiple ChIP-seq samples across a single variant and outperforms competing approaches in simulations. Using 548 ENCODE ChIP-seq and six targeted FAIRE-seq samples, we show that BaalChIP effectively corrects allele-specific analysis for copy-number variation and increases the power to detect putative cis-acting regulatory variants in cancer genomes.
A Textile Platform Using Continuous Aligned and Textured Composite Microfibers to Engineer Tendon‐to‐Bone Interface Gradient Scaffolds
Authors: Isabel Calejo, Raquel Costa‐Almeida, Rui L. Reis, Manuela E. Gomes
Journal: Advanced Healthcare Materials (2019)

Abstract Tendon‐to‐bone interfaces exhibit a hierarchical multitissue transition. To replicate the progression from mineralized to nonmineralized tissue, a novel 3D fibrous scaffold is fabricated with spatial control over mineral distribution and cellular alignment. For this purpose, wet‐spun continuous microfibers are produced using polycaprolactone (PCL)/ gelatin and PCL/gelatin/hydroxyapatite nano‐to‐microparticles (HAp). Higher extrusion rates result in aligned PCL/gelatin microfibers while, in the case of PCL/gelatin/HAp, the presence of minerals leads to a less organized structure. Biological performance using human adipose‐derived stem cells (hASCs) demonstrates that topography of PCL/gelatin microfibers can induce cytoskeleton elongation, resembling native tenogenic organization. Matrix mineralization on PCL/gelatin/HAp wet‐spun composite microfibers suggest the production of an osteogenic‐like matrix, without external addition of osteogenic medium supplementation. As proof of concept, a 3D gradient structure is produced by assembling PCL/gelatin and PCL/gelatin/HAp microfibers, resulting in a fibrous scaffold with a continuous topographical and compositional gradient. Overall, the feasibility of wet‐spinning for the generation of continuously aligned and textured microfibers is demonsrated, which can be further assembled into more complex 3D gradient structures to mimic characteristic features of tendon‐to‐bone interfaces.
SAT0266 DIGITAL ULCER (DU) AND VENTRICULAR ARRHYTHMIAS PREDICT THE LATE GADOLINIUM ENHANCEMENT (LGE) IN CARDIAC MAGNETIC RESONANCE (CMR) IN SYSTEMIC SCLEROSIS (SSC): PROPOSAL OF CANDIDATE RED FLAGS FOR EARLY REFERRAL
Authors: Cosimo Bruni, Luna Gargani, Alessia Pepe, Antonella Meloni, Daniele De Marchi, Giancarlo Todiere, Gennaro D’angelo, Alberto Moggi Pignone, Serena Guiducci, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> in SSc, cardiac involvement either primary or secondary, is frequently subclinical. In myocardial diseases, CMR is considered the non-invasive gold standard to diagnose myocardial tissue involvement and LGE has a significant impact on prognosis. <h3>Objectives:</h3> to identify the predictors of the presence of LGE in SSc patients. Methods: patients fulfilling the 2013 ACR/EULAR classification criteria were assessed with CMR (1.5 T GE scanner) when clinically indicated. Data on demographics, clinical SSc features, laboratory and instrumental tests for cardio-pulmonary, microvascular and renal involvements were recorded at the time of CMR evaluation. Binary regression analysis was performed with SPSS version 20.0. <h3>Results:</h3> 317 SSc patients (284 women, mean age 52±14) were enrolled in the study. LGE-CMR was present in 32.9% and Myocardial edema (ME-CMR) in 6.1% of patients. On univariate regression analysis,%DLco values, NYHA functional class, history of DU (hDU), TAPSE and couples of ventricular premature beats (VPBc) were predictors of LGE-CMR or ME-CMR. At multivariate analysis,TAPSE (OR 0.832, 95% CI 0,727-0,951, p=0.007), hDU (OR 3.893, 95% CI 1.614-9.387, p=0.002) and VPBc (OR 4.238, 95%CI 0.959-18.738, p=0.057) were independent predictors for LGE-CMR. Presence of pericardial effusion was the only predictor for ME-CMR (OR 3.379, 95% CI 1.018-12.988, p=0.047). <h3>Conclusion:</h3> DU history, ventricular ectopic beats on 24 hours ECG, TAPSE impairment and pericardial effusion on echocardiography may predict myocardial LGE. More studies are necessary to further verify and validate these "red flags" to refer the patients to CMR. <h3>Disclosure of Interests:</h3> Cosimo Bruni: None declared, Luna Gargani: None declared, Alessia Pepe: None declared, Antonella Meloni: None declared, Daniele De Marchi: None declared, Giancarlo Todiere: None declared, Gennaro D'Angelo: None declared, Alberto Moggi Pignone: None declared, Serena Guiducci: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen
AB1117 DIAGNOSTIC VALUE OF ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES FOR JUVENILE IDIOPATHIC ARTHRITIS IN KOREA
Authors: Jong Gyun Ahn, Kwang Nam Kim
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Anti-cyclic citrullinated peptide(CCP) antibodies are considered to have specificity for rheumatoid arthritis(RA). However, the diagnostic value of anti-CCP antibody has not been proved in juvenile idiopathic arthritis(JIA). <h3>Objectives</h3> The purpose of this study was to access the prevalence of anti-CCP antibodies in Korean children with JIA, and to investigate the diagnostic accuracy of anti-CCP antibodies according to JIA subgroup. <h3>Methods</h3> JIA patients were recruited from Severance Children's Hospital, Seoul, Korea from 2004 to 2018. Diagnosis of JIA was made by pediatricians according to the International League of Associations for Rheumatology (ILAR) classification. Control group consisted of healthy children with anti-CCP antibodies test, who had visited the outpatient clinic of the hospital for JIA suspected symptoms, but diagnosed as not JIA. Enzyme-linked immunosorbent assay (ELISA) was used for detection and quantification of anti-CCP antibodies. <h3>Results</h3> Study subjects included 295 JIA patients and 165 controls. Among the JIA children, 14 (8.6%) patients were found to be positive for anti-CCP antibodies. 1 (0.6%) of the control group was positive for anti-CCP antibodies. The positive rates of anti-CCP were highest in rheumatoid factor (RF)-positive polyarticular JIA (n=8, 66.7%), followed by systemic JIA (n=3, 3.4%) and oligoarticular JIA (n=3, 2.2%). The sensitivity and specificity of anti-CCP antibodies in all JIA patients was 4.7% and 99.4%. <h3>Conclusion</h3> Anti-CCP antibodies have high specificity for JIA, but its sensitivity is low. Therefore, it can provide additional help for diagnosis of JIA with its high specificity. In particular, anti-CCP antibodies have the highest sensitivity in RF-positive polyarticular JIA than other subgroups, so it can be a more effective diagnostic tool in the subtype. <h3>References</h3> [1] Ferucci ED, Majka DS, Parrish LA, et al. Antibodies against cyclic citrullinated peptide are associated with HLA-DR4 in simplex and multiplex polyarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum 2005; 52:239. [2] Hamooda M, Fouad H, Galal N, et al. Anti-cyclic citrullinated peptide antibodies in children with Juvenile Idiopathic Arthritis. Electron Physician 2016; 8:2897. [3] Petty RE, Laxer RM, Wedderburn LR. Juvenile idiopathic arthritis. In : Petty RE, Laxer RM, Lindsley CB, Wedderburn LR. Textbook of Pediatric Rheumatology. 7th ed. Phliladelphia: W.B Saunders, 2016:188-204. <h3>Disclosure of Interests</h3> None declared
PB1919 EFFECT OF OCT1 GENE POLYMORPHISM ON RESPONSE TO IMATINIB MESYLATE IN CML PATIENTS
Authors: A. Sabri, M. Omran, S. Abdel Azim, R. Abdelfatah, S. Shouman
Journal: HemaSphere (2019)

Background: Imatinib mesylate (IM) has been shown to be highly efficacious in the treatment of Chronic Myeloid Leukemia (CML). Continuous and adequate dosing is essential for optimal outcomes. There is a considerable variability in the level of molecular responses achieved with IM therapy. These differences could result from variable drug level which may be due to genetic factors. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter responsible for active uptake of IM into CML cells. Aims: We hypothesized that the SNPs of this gene could predict the outcomes of IM therapy in CML patients. Methods: Fifty patients with CML at chronic phase were studied. All patients were monitored at outpatient clinic of the National Cancer Institute, Cairo University, Egypt. The study was approved by the NCI Ethical Committee for Clinical Research. Written Informed consent was obtained. The polymorphism of SLC22A1 gene was studied using PCR-RFLP technique. Imatinib mesylate level was determined using HPLC-massspectroscopy. Results: The mean IM trough plasma level in patients who achieved unfavorable response (n = 25) was 1019 ± 638 ng/mL, and in patients who achieved favorable response (n = 25) 1353 ± 611 ng/mL (p = 0.04). In regard to SLC22A1 rs(628031) gene, heterogeneous & variant allele (GA&AA) was significantly correlated to unfavorable response while wild allele GG is linked to favorable response(p = 0.0006). No significant correlation was detected between SLC22A1 gene polymorphism and drug level (p = 0.08). Summary/Conclusion: In patients with CML treated with IM, one of the significant factors affecting response was OCT1 polymorphism. This may influence the interindividual variation observed among Egyptian CML patients. Although a prospective study with a larger patient population is necessary to validate this finding. In patients with CML treated with IM, one of the significant factors affecting response was OCT1 polymorphism. This may influence the interindividual variation observed among Egyptian CML patients. Although a prospective study with a larger patient population is necessary to validate this finding.
PB1669 RISK FACTORS FOR THROMBOEMBOLISM IN ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: A. Boban, M. Mikulić, R. Serventi‐Seiwerth, A. Ostojić, R. Vrhovac, N. Duraković, Z. Perić, S. Bašić‐Kinda, D. Sertić, P. Rončević, D. Dujmović, I. Radman, D. Pulanić, J. Batinić, S. Zupančić‐Šalek, I. Aurer
Journal: HemaSphere (2019)

Background: Thromboembolism frequently complicates treatment of acute lymphoblastic leukemia (ALL). Aims: A single‐center retrospective study was conducted with the objective of assessing the risk factors for thromboembolism in adult patients with ALL. Methods: The study included 87 consecutive patients (aged 19–70 years; 57 males) treated for ALL; B‐cell (n = 40), T‐cell (n = 26), Ph+ (n = 13), byphenotypic (n = 3) and unclassified (n = 5) during the 10‐year period. All patients but one received intensive treatment, including L‐asparginase in 57 (65%) patients, while 23 (26%) underwent allogenic stem cell transplantation. Vast majority of patients (n = 80, 92%) had central venous catheters at least once during the treatment period, including peripherally inserted central catheter (PICC) placed in 18 (21%) patients. Results: Fourteen patients (16%) developed thrombosis during the study period. Deep venous thrombosis was described in 9(65%), pulmonary embolism in 2(14%), and cerebral sinus thrombosis in 3(21%) patients. One death was attributable to thromboembolism. The risk of thromboembolism was associated with the induction treatment, protocols including L‐asparginase, the use of central venous catheters, namely PICC, and non‐0 blood groups. Summary/Conclusion: Our results demonstrate high incidence of thromboembolic events in patients with ALL. The highest risk is attributed with the use of L‐asparginase, despite vigorous control of coagulation parameters and antithrombin substitution. Finally, our results strongly suggest against simultaneous use of L‐asparginase and PICC.
Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer
Authors: James Clarke, Bharat Panwar, Ariel Madrigal, Divya Singh, Ravindra Gujar, Oliver Wood, Serena J. Chee, Simon Eschweiler, Emma V. King, Amiera S. Awad, Christopher J. Hanley, Katy J. McCann, Sourya Bhattacharyya, Edwin Woo, Aiman Alzetani, Grégory Seumois, Gareth J. Thomas, Anusha-Preethi Ganesan, Peter S. Friedmann, Tilman Sanchez-Elsner, Ferhat Ay, Christian H. Ottensmeier, Pandurangan Vijayanand
Journal: The Journal of Experimental Medicine (2019)

High numbers of tissue-resident memory T (TRM) cells are associated with better clinical outcomes in cancer patients. However, the molecular characteristics that drive their efficient immune response to tumors are poorly understood. Here, single-cell and bulk transcriptomic analysis of TRM and non-TRM cells present in tumor and normal lung tissue from patients with lung cancer revealed that PD-1–expressing TRM cells in tumors were clonally expanded and enriched for transcripts linked to cell proliferation and cytotoxicity when compared with PD-1–expressing non-TRM cells. This feature was more prominent in the TRM cell subset coexpressing PD-1 and TIM-3, and it was validated by functional assays ex vivo and also reflected in their chromatin accessibility profile. This PD-1+TIM-3+ TRM cell subset was enriched in responders to PD-1 inhibitors and in tumors with a greater magnitude of CTL responses. These data highlight that not all CTLs expressing PD-1 are dysfunctional; on the contrary, TRM cells with PD-1 expression were enriched for features suggestive of superior functionality.
Refining How We Identify High-Value Surgical Care
Authors: Misty D. Humphries
Journal: JAMA Surgery (2019)

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Interferon regulatory factor 1 eliminates mycobacteria by suppressing p70 S6 kinase via mechanistic target of rapamycin signaling
Authors: Xinying Zhou, Jiahui Yang, Zelin Zhang, Lijie Zhang, Linmiao Lie, Bo Zhu, Lei Xu, Yuchi Gao, Xialin Du, Yingqi Huang, Ruining Wang, Honglin Liu, Yanfen Li, Shengfeng Hu, Chaoying Zhou, Qian Wen, Qiuwei Pan, Li Ma
Journal: Journal of Infection (2019)
AB0715 ASSESSMENT OF BODY COMPOSITION IN LEAN MASS AND FAT MASS IN SPONDYLOARTHRITIS
Authors: Dhia Kaffel, selma bouden, Kaouther Maatallah, Nahaline Abaza, Hend Riahi, Wafa Hamdi, Mohamed Montacer Kchir
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Mohamed Montacer Kchir bsorptiometry absorptiometer (DEXA) is the gold standard for the study of body composition. It allows to sepMohamed Montacer Kchirarate the 2 compartments lean mass (LM) and fat mass (FM), and to study their distribution at the android and gynoid level <h3>Objectives:</h3> Evaluate the change in total body composition measured the DEXA in patients with spondyloarthritis (SpA) compared to a control group. Evaluate the distribution of LM/FM at the android and gynoid levels. Study the influence of disease activity and bone mass on body composition. <h3>Methods:</h3> This was a case-control study involving 50 patients with SpA compared to 50 controls. Each control was comparable in age and sexe to the matched patient. <h3>Results:</h3> The mean age was 36 years in the SpA group and 35,5 years in the control group. Eighty per cent of the patients with SpA were male. The mean BASDAI was 4,64 ± 2,5. The mean ESR rate was 32,37 ± 20,95, the mean CRP rate was 18,05 ± 27,22 [0-141]. The mean body mass index (BMI) was 25,4 Kg/m² (25,74 Kg/m² in the control group). The mean bone mineral density (BMD) at the lumbar spine was 1.033 g/cm² (with a mean T score of -1.5 DS and Z score -1.3 DS) while it was 0.956 g/cm² at upper end of the femur level (with a mean T score of -0.8 and a mean Z score of -1.2 DS). In controls, the mean BMD was 1.055 g/cm² and 1.013 g/cm² at the lumbar spine and upper end of the femur respectively (with a mean T score of -1.4 DS and -0.5 SD and a mean Z score of -1.4 and -0.3 respectively at the lumbar and superior femoral sites). In the SpA group, the mean value of whole body FM was 31.6%, whereas this average was around 36% in controls. FM was distributed as follows: 39.2% at the android level versus 37.7% at the gynoid level. For LM, the whole body average was 68.4%, while the average was 60.8% at the android level and 62.3% at the gynoid level. The 2 groups (patients and controls) were comparable in terms of BMD, T score and Z score measurements at different lumbar and superior femoral sites. The SpA group and their healthy controls were comparable in terms of FM and LM measurements and their distributions. We found a significant correlation between the rate of CRP and the measurements of FM at the android level (r = -0.358, p = 0.023) (and conversely the LM at the android level). However, we found no association between disease activity (BASDAI) and body composition. <h3>Conclusion:</h3> Changes in body composition (MM/MG) related to chronic inflammatory status may occur during chronic inflammatory diseases. However, few studies in the world have focused on changes in the bodily compartments and their distribution in SpA. <h3>Disclosure of interests:</h3> None declared