tbuckley/cabot-search huggingface dataset:
Enhanced cytotoxic T lymphocytes recruitment targeting tumor vasculatures by endoglin aptamer and IP-10 plasmid presenting liposome-based nanocarriers
Authors: Xiaomei Yang, Jing Zhao, Siliang Duan, Xiaoqiong Hou, Xi Li, Zixi Hu, Zhuoran Tang, Fengzhen Mo, Xiaoling Lu
Journal: Theranostics (2019)

: Adequate recruitment of highly active tumor antigen-specific cytotoxic T lymphocytes (CTLs) remains a major challenge in cancer immunotherapy.
Genome sequencing analysis identifies Epstein–Barr virus subtypes associated with high risk of nasopharyngeal carcinoma
Authors: Miao Xu, Youyuan Yao, Hui Chen, Shanshan Zhang, Su-Mei Cao, Zhe Zhang, Bing Luo, Zhiwei Liu, Zilin Li, Tong Xiang, Guiping He, Qi-Sheng Feng, Li-Zhen Chen, Xiang Guo, Wei-Hua Jia, Ming-Yuan Chen, Xiao Zhang, Shang-Hang Xie, Roujun Peng, Ellen T. Chang, Vincent Pedergnana, Lin Feng, Jin-Xin Bei, Rui-Hua Xu, Mu-Sheng Zeng, Weimin Ye, Hans-Olov Adami, Xihong Lin, Weiwei Zhai, Yi-Xin Zeng, Jianjun Liu
Journal: Nature Genetics (2019)
Selective Cell Penetrating Peptide‐Functionalized Envelope‐Type Chimeric Lipopepsomes Boost Systemic RNAi Therapy for Lung Tumors
Authors: Min Qiu, Jia Ouyang, Yaohua Wei, Jian Zhang, Qing Lan, Chao Deng, Zhiyuan Zhong
Journal: Advanced Healthcare Materials (2019)

Abstract Small interfering RNA (siRNA) is considered a highly specific and potent biotherapeutic that holds tremendous potential for the treatment of various diseases. The clinical translation of siRNA is, however, greatly impeded by the lack of safe and efficient delivery vehicles in vivo. Here, the development of selective cell penetrating peptide (CPP33)‐functionalized chimeric lipopepsomes (CPP33‐CLP) for efficient encapsulation and selective delivery of polo‐like kinase 1 specific siRNA (siPLK1) to orthotopic A549 human lung tumor in vivo is reported. Interestingly, siRNA is tightly encapsulated into CPP33‐CLP with a superb encapsulation efficiency of over 95% owing to the thick strong electrostatic interactions. Notably, siPLK1‐loaded CPP33‐CLP (siPLK1‐CPP33‐CLP) is selectively internalized by A549 human lung cancer cells, efficiently escapes from endosomes, and swiftly releases siRNA into the cytoplasm, affording a significant sequence‐specific gene silencing in vitro. Moreover, siPLK1‐CPP33‐CLP exhibits prolonged blood circulation, enhanced tumor accumulation, effective suppression of tumor growth, and considerably elevated survival time of orthotopic A549 human lung tumor‐bearing nude mice. These chimeric lipopepsomes appear as an attractive and potent nanoplatform for safe and targeted siRNA delivery.
FRI0059 SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS (SRAGE) AND RISK FOR CARDIOVASCULAR DISEASES IN FEMALES WITH RHEUMATOID ARTHRITIS
Authors: Mitra Nadali, Maria I. Bokarewa, Sofia Töyrä Silfverswärd, Malin Erlandsson, Lovisa Lyngfelt, Karin Me Andersson, Rille Pullerits
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is strongly associated with increased frequency of cardiovascular disease (CVD), which remains the major cause of mortality in these patients. Current CVD risk assessment algorithms have limited predictive value for RA patients. Soluble receptor for advanced glycation end products (sRAGE) has recently emerged as a biomarker of inflammation with an inverse correlation with traditional CVD risk factors as age, hypertension and hypercholesterolemia.<sup>1</sup> <h3>Objectives:</h3> In a cohort of female RA patients with no previous history of CVD, we assessed whether sRAGE levels were associated with increased risk of CVD during a prospective 5 years follow up. <h3>Methods:</h3> Serum sRAGE levels were measured in 171 female RA patients (median age 53; range 21-71) at the inclusion to the study. The CVD risk was estimated using the Framingham algorithm and both traditional and RA associated risk factors for CVD were measured. All the patients were prospectively followed up to 5 years for new CV events, type II diabetes and medication for hypertension and hyperlipidemia. Statistical analysis was performed to compare CVD risk and actual events in the patients with low sRAGE (&lt;1700 pg/ml). <h3>Results:</h3> The comparison of patients with low sRAGE (n=125) and normal-high sRAGE (n=46) found no significant differences in frequency of the traditional CVD risk factors including age&gt;60 years (30% vs 41%), overweight (50% vs 41%), smoking (14% vs 11%), incidental hypertension (16% vs 16%) and hypercholesterolemia (56% vs 67%) at baseline and led to similar estimated CVD risk (7.65% vs 8,45%). The RA-related CVD risk factors including disease duration &gt;10years (37% vs 39%), presence of autoantibodies (89% vs 95%), disease activity (DAS28, 46% vs 60%) were also similar in the low-and high sRAGE groups. At 5 years follow up, 11 new CVD events were registered. The events occurred with similar frequency in the low sRAGE and high sRAGE groups (5.6% vs 8.7%). Despite a lack of difference in CVD events, we did observe a significant increase in frequency of new medication for hypertension in the low sRAGE group (21.5% vs. 63%, p=0.01), but not in medication for type II diabetes or statins. <h3>Conclusion:</h3> In this study, we found no association between serum levels of sRAGE and the estimated CVD risk or actually occurred CVD events in female RA patients. <h3>Reference:</h3> [1] Santilli, F., et al. (2009). "Soluble forms of RAGE in human diseases: clinical and therapeutical implications." Curr Med Chem 16(8): 940-952. <h3>Disclosure of Interests:</h3> None declared
Sports injury and illness incidence in the PyeongChang 2018 Olympic Winter Games: a prospective study of 2914 athletes from 92 countries
Authors: Torbjørn Soligard, Debbie Palmer, Kathrin Steffen, Alexandre Dias Lopes, Marie-Elaine Grant, DooSup Kim, Sae Yong Lee, Natalia Salmina, Brett G Toresdahl, Joon Young Chang, Richard Budgett, Lars Engebretsen
Journal: British Journal of Sports Medicine (2019)

To describe the incidence of injuries and illnesses sustained during the XXIII Olympic Winter Games, hosted by PyeongChang on 9-25 February 2018.We recorded the daily number of athlete injuries and illnesses (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the PyeongChang 2018 medical staff.In total, 2914 athletes (1210 women, 42%; 1704 men, 58%) from 92 NOCs were observed for occurrence of injury and illness. NOC and PyeongChang 2018 medical staff reported 376 injuries and 279 illnesses, equalling 12.6 injuries and 9.4 illnesses per 100 athletes over the 17-day period. Altogether, 12% of the athletes incurred at least one injury and 9% at least one illness. The injury incidence was highest in ski halfpipe (28%), snowboard cross (26%), ski cross (25%), snowboard slopestyle (21%) and aerials (20%), and lowest in Nordic combined, biathlon, snowboard slalom, moguls and cross-country skiing (2%-6%). Of the 376 injuries recorded, 33% and 13% were estimated to lead to ≥1 day and >7 days of absence from sport, respectively. The highest incidences of illness were recorded in biathlon (15%), curling (14%), bobsleigh (14%) and snowboard slalom (13%). Thirty per cent of the illnesses were expected to result in time loss, and 70% affected the respiratory system. Women suffered 61% more illnesses than men.Overall, 12% of the athletes incurred at least one injury during the Games and 9% an illness, incidences that are similar to the Olympic Winter Games of 2010 and 2014.
FRI0053 ACCELERATED ATHEROSCLEROSIS IN PREMENOPAUSAL WOMEN WITH RHEUMATOID ARTHRITIS (15 YEARS PROSPECTIVE STUDY)
Authors: Metka Koren Krajnc, Radovan Hojs, Iztok Holc, Artur Pahor
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is chronic inflammatory disease, associated with increased mortality and morbidity due to higher cardiovascular risk in these patients. <h3>Objectives:</h3> Traditional risk factors are not the only answer for accelerated atherosclerosis. In long term prospective study, we investigated the relationship between asymptomatic atherosclerosis and traditional risk factors as well inflammatory markers in patients with RA and matched healthy controls. <h3>Methods:</h3> In 60 RA premenopausal women and 34 matched controls values of laboratory test results, concentrations of inflammatory mediators, matrix metalloproteases (MMP) and markers of inflammation were measured. Using B-mode ultrasonography carotid intima-media thickness (cIMT) and plaques occurrence (markers of asymptomatic atherosclerosis) at baseline and after 15 years of observation were defined in both groups. The differences in concentrations of inflammatory mediators, MMPs and markers of inflammation were compared. The relationship of inflammatory mediators and markers, MMPs and markers of asymptomatic atherosclerosis was examined using regression models. <h3>Results:</h3> After the follow up statistically significant higher values of inflammatory markers like selective adhesion molecules ICAM &amp; VCAM, interleukin 6 (IL-6), tumour necrosis factor alpha (TN alpha) and MMP-3 in patient`s group was found. Among traditional risk factors only sedimentation rate and CRP levels were statistically higher in patient`s group. More plaques were found in patients' group (12.9% vs. 42.4%; p=0.005), patients had also higher values of cIMT (p&lt;0.0001). Using multiple linear regression analysis only VCAM was found as independent prognostic factor for plaques occurrence (p=0.016), but not for cIMT (p=0.314) in RA patients after the follow up. <h3>Conclusion:</h3> Asymptomatic atherosclerosis is accelerated in premenopausal women with RA patients. The results of our study showed the association between the inflammation and accelerated atherosclerosis, VCAM was found as independent risk factor for plaques occurrence in these patients. <h3>References:</h3> [1] Dalbeni A, et al. Traditional cardiovascular risk factors or inflammation: Which factors accelerate atherosclerosis in arthritis patients?. International J Cardial 2017; 236: 488-492. [2] Mahmoudi M, Aslani S and Jamshidi AR. New insights to the mechanisms underlying atherosclerosis in rheumatoid arthritis. International Journal of Rheumatic diseases 2017; 20: 287-297. [3] Johnson JL. Metalloproteinases in atherosclerosis. Eur J Pharmacol. 2017;816:93-106. [4] Agca R, Heslinga SC, Rollefstad S e tal. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann rheum Dis 2017; 76: 17-28. <h3>Disclosure of Interests:</h3> None declared
S1623 INTESTINAL MICROBIOTA CAN PREDICT AGVHD FOLLOWING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: L. Han, H. Zhang, S. Chen, K. Zhao, F. Huang, Z. Fan, H. Jin, Z. Jiang, Q.‐F. Liu
Journal: HemaSphere (2019)

Background: The intestinal microbiome plays an important role in the development of acute graft‐versus‐host disease (aGVHD), and loss of microbiota diversity is associated with aGVHD. However, it has been rarely reported whether the intestinal microbiota at neutrophil engraftment could predict the occurrence and grades of aGVHD. Aims: We collected stool and blood samples from 141 patients undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT) at pre‐conditioning, day 0 and day 15 post‐transplantation. The microbiota in stool were detected by 16S rRNA gene sequencing; the inflammatory factors in blood were detected by multiplex immunoassays and dynamic turbidimetric methods; and T lymphocyte subsets were tested by flow cytometry. Methods: The microbiota diversity was lower in the aGVHD group compared with non‐aGVHD group at day 0 and day 15 ± 1 ( P = 0.018 and 0.009, respectively). Diversity was associated with conditioning ( P = 0.017, day 0 and P = 0.045, day 15) and β‐lactam antibiotics ( P = 0.004, day 15). The Treg/Th17 ratio in blood was positively correlated with microbial diversity (r = 0.216, P = 0.010), while it was negatively correlated with the levels of TNF‐α, IL‐17A, IL‐1β and LPS in plasma (r = −0.226, −0.225, −0.335, −0.291; P = 0.007, 0.010, &lt; 0.001, &lt; 0.001, respectively) at day 15 post‐transplantation. In addition, the accumulated intestinal microbiota (AIM) score at day 15 could be a predictor for the development of aGVHD (II‐IV aGVHD: AUC = 0.75, P &lt; 0.001; III‐IV aGVHD: AUC = 0.84, P &lt; 0.001). The AIM score was also correlated with aGVHD grades (r = 0.481, P &lt; 0.001). Results: These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and influence the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment can predict the subsequent development and grades of aGVHD. Summary/Conclusion: These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and influence the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment can predict the subsequent development and grades of aGVHD.
Abstract 202: Engineering Artificial Sinus Node by Reprogrammed Cardiomyocytes
Authors: Hu Yufeng, Shih-Ann Chen
Journal: Circulation Research (2017)

The lack of clinically relevant sinoatrial node (SAN) disease model makes the pathophysiological investigation and therapeutic development stagnant. We hypothesize that engineering SAN by TBX18 somatic-reprogrammed cardiomyocytes on the three-dimension (3D) scaffold could create an in vitro SAN model, sharing similar features with a native SAN. Methods: In addition to neonatal rat ventricular cardiomyocytes (NRVMs) alone, we chose cardiosphere-derived cells (CDCs), or fibroblasts as supportive cells with different mixing ratios to construct engineered SAN. Hydrogel scaffolds including matrigels or platelet gels were used and compared. The engineered tissue was reprogrammed by TBX18 over-expression. Results: The over-expression of TBX18 increased HCN4 and CX45 transcriptions in cardiomyocytes. A stable spontaneous beating rate could be created in TBX18-reprogrammed engineered tissue, made of NRVMs and fibroblasts with matrigel scaffold (beating rate, TBX18 vs. control: 105.0 ± 10.7 bpm vs. 35.5±7.1 bpm, n=12, P&lt;0.001). Although spontaneous beating could be observed in reprogrammed engineered tissues by NRVM alone, NRVM with CDCs, or NRVMs with CDCs and fibroblasts, the beating rates were not stable and slower. The beating rate in engineered tissue did not differ between scaffolds of matrigel and platelet gel. However, inter-experimental variation is higher in platelet gels, compared to matrigels. By immunofluorescent staining, an unique spatial distribution of NRVMs and fibroblasts was identified. NRVMs formed the central core of engineered tissues, encapsulated by fibroblasts, which was similar to a native SAN. The application of a sympathomimetic drug (epinephrine) doubled the beating rate of reprogrammed engineered tissue (P=0.02, n=6-8). Conclusions: A pilot model of engineered SAN was established by TBX18-reprogrammed cardiomyocytes. The supportive cells such as fibroblasts played an important role in tissue engineering of SAN.
AB0265 ASSOCIATION OF CUMULATIVE ANTI-CYCLIC CITRULLINATED PROTEIN ANTIBODIES WITH RADIOGRAPHIC PROGRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Young Bin Joo, Yune-Jung Park, Kyung-Su Park, Ki-Jo Kim
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Antibody against cyclic citrullinated proteins (ACPA) is counted as one of the most important biomarkers in diagnosis, classification, and prognosis of rheumatoid arthritis (RA). The clinical implications of change in ACPA level over time remain undetermined. <h3>Objectives</h3> We examined the evolution of ACPA during disease course and assess predictive value of time-weighted cumulative ACPA titer on radiographic progression in patients with RA. <h3>Methods</h3> A group of 734 patients with RA was followed longitudinally over 2 years, with annual measurements of IgM rheumatoid factor (RF) and ACPA. Radiographs of the hands were scored with the modified Sharp score (SHS). Cumulative ACPA antibody titers were calculated using the trapezoidal rule. <h3>Results</h3> The patients with radiographic progression had a higher SHS at baseline; and smoking status, diabetes, RF positivity, and use of biologic DMARDs were independently associated with radiographic progression (all <i>P</i>&lt;0.05). As for ACPA, reversion happened more commonly in men and was associated with younger onset age and lower titer at baseline, but it had no direct relevance to radiographic outcome. In multivariable regression analysis, only high cumulative or baseline titer of ACPA had a predictive power for rapid radiographic progression (all <i>P</i>&lt;0.05), and cumulative ACPA titer was superior in terms of statistical significance (Cohen's d, 0.637 versus 0.583). <h3>Conclusion</h3> High cumulative ACPA titer was an independent predictor for accelerated radiographic progression, especially with initiation of joint damage. Serial measurement of ACPA titer can provide information about its dynamics over the clinical course and can facilitate an additional assessment of radiographic progression. <h3>Acknowledgement</h3> Nothing specified. <h3>Disclosure of Interests</h3> None declared
CLINICAL AND MOLECULAR CHARACTERISTICS OF SRSF2-MUTATED NEOPLASMS
Authors: G. Todisco, M. Creignou, P. Guglielmelli, E. Rumi, Y. Nannya, A. Galli, D. Pietra, C. Elena, E. Bono, M. Dimitriou, J. Ungerstedt, A. Vannucchi, E. Hellström-Lindberg, M. Cazzola, S. Ogawa, L. Malcovati
Journal: HemaSphere (2019)
PB2232 THE NATURAL ANTICOAGULANTS IN PATIENTS WITH PHILADELPHIA‐NEGATIVE MYELOPROLIFERATIVE NEOPLASMS
Authors: E. Efremova, N. Korsakova, O. Matvienko, M. Fominykh, N. Silina, O. Golovina, L. Papayan, I. Martynkevich, A. Samorodova, L. Polushkina, S. Voloshin, V. Shuvaev
Journal: HemaSphere (2019)

Background: Myeloproliferative neoplasms (MPNs) are characterized by an increased frequency of thrombotic complications. Patients with MPNs show little or no abnormalities in traditional coagulation tests. Chronic inflammation associated with pathological secretion of several inflammatory cytokines leads to activation of endothelial cells and imbalance between coagulation and anticoagulation systems. Aims: To estimate the natural anticoagulants activity and activated protein C resistance in MPNs patients. Methods: The study included 99 MPNs patients (aged 25 – 86 years, median = 55) and 43 healthy controls (aged 30‐73 years, median = 46). There were 65 female and 34 male in the study group. 75 (76%) patients were JAK2V617F positive, 24 (24%) were JAK2 V617F negative. Antithrombin (AT), protein C (PC) activities and free protein S level (PS) estimation was performed by standard techniques. Thrombin generation was assessed by calibrated automated thrombinography (CAT) according to Hemker et al. Measurement was conducted in platelet poor plasma with or without thrombomodulin (TM). Such parameters as endogenous thrombin potential (ETP, nM∗min) and peak thrombin (Peak, nM) were evaluated. ETP and Peak sensitivity for TM were calculated as percent of these parameters decrease after TM adding to assay (S ETP, % and S Peak, % respectively). STATISTICA 6.0 package was used for data analysis. Parameter results were presented as median (Me) with 95% confidence intervals (CI), p&lt;0.05 was considered statistically significant. Results: Protein C and protein S activity, Peak and ETP decrease were lower in patients with MPN than controls. Patients with Jak2V617F‐ had a tendency to lower sensitivity for TM in comparison with Jak2V617F+ patients. This fact could have a significant role in thrombotic complication development. Summary/Conclusion : Our results showed presence of activated protein C resistance probably caused by anticoagulant protein C system dysfunction. Jak2V617F influence on hemostatic parameters demands further investigations. image
PF283 A RETROSPECTIVE STUDY OF MYELOID LEUKAEMIA IN CHILDREN WITH DOWN SYNDROME IN IRELAND
Authors: G.P. Dowling, A. Piccin, A. O’Marcaigh, K.T. Gavin, A. Malone, D. Betts, M. Cotter, O.P. Smith
Journal: HemaSphere (2019)

Background: Children with trisomy 21 have several clinical complications such as a variety of dysmorphic features, congenital malformations and endocrine abnormalities for example. An important complication of Down Syndrome (DS) is that they may also develop leukaemia. Acute myeloid leukaemia (AML) is the type of haematological malignancy most commonly reported in this population. A subtype of AML called M7 leukaemia (as classified by FAB system) has an incidence nearly 200 times greater compared to children without DS. This is a type of leukaemia otherwise very rare in both adults and children. M7 leukaemia is often preceded by a transient neonatal pre-leukaemic syndrome, called Transient Abnormal Myelopoiesis (TAM). TAM is unique as it has the ability to resolve spontaneously. However, 20–30% of these patients may develop M7 leukaemia over time. This is most likely to occur within the first 4 years of life. Aims: A retrospective national audit of all documented cases of childhood TAM and M7 leukaemia referred from 1990–2018 to the National Paediatric Hematology/Oncology Centre at Our Lady's Children's Hospital Crumlin (OLCHC) Ireland. We also aimed to compare our demographic and outcome findings with the recent medical literature and make recommendations for future research. Methods: All consecutive charts of the children with a diagnosis of M7 leukaemia treated at (OLCHC) between the years 1990 – 2019 were sourced from medical records. The hospital database and charts were reviewed and information including date and age of diagnosis of AML, comorbidities, previous history of TAM, treatment regime and outcome was noted. Cytogenetic information was obtained by accessing a dedicated database. Kaplan-Meier survival curves were constructed. Results: Twenty-seven patients with M7 leukaemia were treated in OLCHC. A prior neonatal diagnosis of TAM was described in 10 patients (37%). Patients had a low platelet count (<50 × 109 /L) at presentation. Nineteen patients (70%) are alive and well, in complete remission, at a median follow up of 11.4 years. Overall survival (OS) of this cohort has risen from 54% from those treated between the years 1990 – 2004 (n = 13) to 93% for those treated between the years 2005 – 2019 (n = 14). Summary/Conclusion: Overall an excellent outcome is observed in M7 leukaemia when treated with current poly-chemotherapy protocols. In general children with DS have a much better response to the cytotoxic-chemotherapy than constitutionally normal children. Our finding of a low platelet count at diagnosis is in accordance with the current knowledge that M7 leukaemia is a condition affecting platelet precursors. GATA-1 is mutated universally in M7 leukaemia and therefore appears to be an interesting molecular target.