tbuckley/cabot-search huggingface dataset:
Abstract 5372: Cocaine enhances HIV-1 integration by modulating the epigenetic signatures of CD4+ T cells.
Authors: Amma Addai, Chandravanu Dash
Journal: Cancer Research (2013)

Abstract Human Immunodeficiency Virus (HIV-1) has claimed the lives of over 25 million people. Illicit drug use serves as a co-factor for HIV/AIDS. Cocaine, a commonly used drug among HIV-1 positive individuals, serves as a cofactor for HIV-1 infection and progression to acquired immunodeficiency syndrome (AIDS). Previous studies suggest that cocaine increases HIV-1 replication in cell cultures, peripheral blood mononuclear cells (PBMCs) and animal models. However, the mechanism by which cocaine enhances HIV-1 replication in CD4+ T cells remains largely unknown. During HIV-1 replication, the viral genome is reverse transcribed into a double stranded DNA (dsDNA) by HIV-1 reverse transcriptase (RT). This viral dsDNA is transported into the nucleus in the form of a pre-integration complex (PICs) that contains the viral integrase (IN) and other viral and cellular proteins. Integration is a critical step in the HIV-1 life cycle. The main objective of this study is to examine the effects of cocaine on HIV-1 integration by its modulation of epigenetic signatures of CD4+ T cells. However, there are no studies on cocaine-induced integration in CD4+ T cells which serves as the main targets for HIV-1 replication in vivo. A correlation between DNA methylation and HIV-1 integration is yet to be demonstrated biochemically and mechanistic information is limited. Experimental strategy for in vitro study involves the production of infectious HIV-1 NL4.3 virus, isolation of HIV-1 PICs from SupT1 lymphoma infected cells and carrying out integration assay. Our preliminary data demonstrates cocaine and DNA demethylating agent (5-aza-2′-deoxycytidine) both enhance HIV-1 integration. The isolated PICs are active in integrating viral DNA into target DNA and integration was more efficient in unmethylated DNA than methylated DNA. To confirm integration activity, we performed quantitative nested PCR analysis using primers specific to the target and viral DNA. We propose that results from this project will help us better understand the role of cocaine in HIV-integration by modulating the epigenetic signatures of CD4+ T cells. Furthermore, understanding the molecular details of HIV-1 integration will aid in the discovery of novel targets that can synergize with integrase inhibitors as part of an approach to cure HIV/AIDS. *Amma Addai is supported by T32 grant #2T32H007735-17 from NIH/NHLBI to Dr. S. E. Adunyah Citation Format: Amma Addai, Chandravanu Dash. Cocaine enhances HIV-1 integration by modulating the epigenetic signatures of CD4+ T cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5372. doi:10.1158/1538-7445.AM2013-5372
Oncogenic Mutation of AIMP2/p38 Inhibits Its Tumor-Suppressive Interaction with Smurf2
Authors: Dae Gyu Kim, Jin Young Lee, Ji-Hyun Lee, Ha Yeon Cho, Beom Sik Kang, Song-Yee Jang, Myung Hee Kim, Min Guo, Jung Min Han, Seong-Jin Kim, Sunghoon Kim
Journal: Cancer Research (2016)

Abstract AIMP2/p38 is a multifunctional tumor suppressor that normally resides in the cytosol as a scaffold protein of the multi-tRNA synthetase complex (MSC). One of the tumor-suppressive functions of AIMP2 is to facilitate ubiquitin-mediated degradation of FUSE-binding protein (FBP, FUBP1), a transcriptional activator of c-Myc. However, the mechanism by which AIMP2 functions within this pathway and its significance in tumorigenesis are uncertain. Here, we report that Smurf2 is responsible for AIMP2-mediated ubiquitination of FBP, and a mutation in AIMP2 that inhibited its nuclear interaction with Smurf2 enhanced cellular transformation and tumorigenesis in vivo. Treatment of HeLa cells with TGFβ resulted in the phosphorylation of AIMP2 on S156, a residue that is exposed on the embedded GST domain of AIMP2. We further found that phospho-AIMP2 dissociated from the MSC and translocated to the nucleus, where it bound to Smurf2, enhancing ubiquitination of FBP. AIMP2 also inhibited nuclear export of Smurf2 to sustain TGFβ signaling. Collectively, these findings present a novel tumor-suppressive interaction between AIMP2 and Smurf2 and suggest that the disruption of this interaction can lead to oncogenic transformation. Cancer Res; 76(11); 3422–36. ©2016 AACR.
Risk of Adverse Health and Social Outcomes Up to 50 Years After Wilms Tumor: The British Childhood Cancer Survivor Study
Authors: Kwok F. Wong, Raoul C. Reulen, David L. Winter, Joyeeta Guha, Miranda M. Fidler, Julie Kelly, Emma R. Lancashire, Kathryn Pritchard-Jones, Helen C. Jenkinson, Elaine Sugden, Gill Levitt, Clare Frobisher, Michael M. Hawkins
Journal: Journal of Clinical Oncology (2016)

Survivors of Wilms tumor (WT) are at risk for adverse health and social outcomes but risks beyond 30 years from diagnosis remain uncertain. We investigated the risks of adverse outcomes among 5-year survivors of WT, in particular, those between 30 and 50 years from diagnosis.The British Childhood Cancer Survivor Study includes 1,441 5-year survivors of WT. We investigated cause-specific mortality, risk of subsequent primary neoplasms (SPNs), and, for those who completed a questionnaire, the extent of smoking and drinking, educational achievement, health status, and health service use compared with the general population.Cumulative risk of death from all causes, excluding recurrence, increased substantially from 5.4% to 22.7% at 30 years and 50 years, respectively, after WT diagnosis-75% of excess deaths beyond 30 years from diagnosis were attributable to SPNs (50%) and cardiac diseases (25%). Digestive cancer, most frequently bowel, accounted for 41% of excess cancers beyond 30 years.Between 30 and 50 years from diagnosis, survivors of WT are at a substantially increased risk of premature mortality, and 75% of excess deaths were accounted for by SPNs and cardiac diseases. Radiotherapy exposure was a risk factor for both outcomes. The proportion of patients with WT who are exposed to radiotherapy has reduced substantially in recent decades because of initiatives such as the SIOP WT 2001 clinical trial, which sought to reduce late effects; however, the majority of current survivors, who are at least 30 years from diagnosis, received radiotherapy. Surveillance of this group should focus on SPNs, in particular, bowel and breast cancers, and cardiac conditions.
SAT0195 Is IT Worth to Include MRI of the Spine in the ASAS Classification Criteria for Axial Spondyloarthritis; Data from the Desir-Cohort
Authors: M. de Hooge, J. Pialat, A. Feydy, M. Reijnierse, P. Claudepierre, A. Saraux, M. Dougados, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Spinal MRI lesions suggestive of axial Spondyloarthritis (axSpA) are not included in the ASAS definition of a positive MRI, but do occur in the absence of affected sacroiliac joints (SIJ). It is unknown how often this happens and if it is useful to perform a MRI of the spine in patients (pts) with negative MRI-SIJ <h3>Objectives</h3> To investigate the prevalence of a positive MRI-spine in pts with short symptom duration and a negative MRI-SIJ <h3>Methods</h3> Pts aged 18-50 with inflammatory back pain (IBP) (≥3 months, ≤3 years) from 25 participating centers in France were included in the DESIR-cohort (n=708). All available baseline MRIs of the spine were independently scored by 2 well-calibrated central readers who were blind to any other data. MRIs-SI were scored according to the ASAS definition<sup>1</sup> (lesions highly suggestive of sacroiliitis plus ≥1 lesion on ≥2 consecutive slices or &gt;1 lesion on 1 slice). Inflammatory lesions on MRI-spine suggestive of spondylitis were scored when visible on ≥2 consecutive slices and according to the ASAS consensus definition<sup>2</sup> (≥3 lesions). In case of disagreement, an experienced radiologist served as adjudicator. MRI was considered positive if 2/3 readers agreed <h3>Results</h3> All pts with MRI-spine and MRI-SIJ (n=650) were included in the analyses. There were 231 pts (35,5%) with a positive MRI-SIJ and 102 pts (15.7%) with a positive MRI-spine; 67 pts (10.3%) were positive for both MRI-SIJ and MRI-spine, 384 (59.1%) were negative for both; and 35 pts (5.4%) had a positive MRI-spine but a negative MRI-SI. Thirty of these were &lt;45 years at symptom onset (entry criterion for ASAS axSpA criteria); 8 of these 30 pts fulfilled the modified New York criteria, 16 of these 30 pts fulfilled the clinical arm of the ASAS axSpA criteria and 6 pts did not fulfil the criteria. All these 6 pts were HLA-B27 negative. Therefore, if the MRI-spine would be considered to count for imaging for the ASAS criteria, 6 additional pts would have been classified and 16 pts would have fulfiled both the imaging and clinical arm; Two of the 5 pts with age &gt;45 years at symptom onset fulfilled the mNY criteria. Overall, only 25 pts (3.8%) had a pos MRI-spine without sacroiliitis on MRI or radiographs <h3>Conclusions</h3> In 3.8% of IBP pts aged 18-50 ≥3 spinal inflammatory lesions suggestive of axSpA are found in absence of sacroiliitis on MRI or radiograph. Therefore the yield of including MRI-spine as additional imaging criterion in the ASAS axSpA classification criteria is considered unacceptably low <h3>References</h3> Rudwaleit, ARD 2009;68:1520-7. Hermann, ARD 2012;71:1278-88. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4054
THU0433 A Study of 101 Septic Arthritis: Debridement and not Debridement.
Authors: A. Riveros, L. Mateo, M. Martínez-Morillo, B. Tejera, S. Rodríguez, J. Sanint, S. Holgado, J. Cañellas, X. Tena, A. Olivé, M. Giménez
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To describe the clinical, microbiological characteristics and evolution of pyogenic arthritis according to treatment. <h3>Methods</h3> Design retrospective (1984-2012). Hospital: academic terciary hospital. Referral area 800.000. We reviewed the medical records of patients with pyogenic arthritis from the database of the Rheumatology Department. The inclusion criterion was the isolation of bacteria in the culture of joint fluid or blood cultures. Soft tissue infection, prosthetic infection, spondylodiscitis, fungal and mycobacterial arthritis were excluded. <h3>Results</h3> We selected a total of 101 cases. Thirty four cases (33.6%) underwent surgical debridement and the remaining 67 (66.4%) were treated medically (Table 1). All patients received specific intravenous antibiotic, with an average duration of three weeks. Surgical treatment (bursectomy in 2 cases, arthrotomy in 31 cases and amputation in 1 case) was required in 34 cases (intervention before 7 days in 18 (53%) patients, arthrotomy within 48 hours in 9 patients). A second arthrotomy was required in 3 patients (9%). Moreover, articular lavages were performed daily in 35 cases (51%) of the 67 patients without arthrotomy. There were 14 deaths among the patients who were not debrided and one death in the group of patients that were surgically debrided. Of the patients who died, 5 had monoarticular involvement (knee) and 7 cases had polyarticular involvement. The causative organisms in these patients were S. Aureus (7 cases), MRSA (3 cases), Pneumococcal (1 case), E. coli (1 case), polymicrobial (1 case of S. aureus and E. coli). <h3>Conclusions</h3> The mortality of the patients with septic arthritis that were debrided was much lower than those not debrided. The history of arthroscopy or arthrocentesis before septic arthritis was more common among patients that were debrided. Patients with greater diagnostic delay needed debridement more frequently. <h3>Disclosure of Interest</h3> None Declared
CAUSES OF OUT OF HOSPITAL CARDIAC ARREST WITHOUT THE ORGANIC HEART DISEASE
Authors: Go Kawamura, Hideki Okayama, Tatsuya Shigematsu, Tatsunori Takahashi, Masaki Kinoshita, Yoshitaka Kawada, Go Hiasa, Tadakatsu Yamada, Yukio Kazatani
Journal: Journal of the American College of Cardiology (2016)
Adaptationism and intuitions about modern criminal justice
Authors: Michael Bang Petersen
Journal: Behavioral and Brain Sciences (2012)

Abstract Research indicates that individuals have incoherent intuitions about particular features of the criminal justice system. This could be seen as an argument against the existence of adapted computational systems for counter-exploitation. Here, I outline how the model developed by McCullough et al. readily predicts the production of conflicting intuitions in the context of modern criminal justice issues.
Hyperparathyroidism and Hungry Bone Syndrome Revisited
Authors: Rajeev Varma, Yeonsoo James Kim, Kareen Garjian, David Barank
Journal: Clinical Nuclear Medicine (2014)

A 36-year-old woman presented with a calcium level of 15.7 mg/dL (normal, 8.5-11.0 mg/dL) and an extremely elevated parathyroid hormone level of 1549.6 pg/mL (normal, 10.0-65.0 pg/ mL). She subsequently underwent a parathyroid scan and ultrasound evaluation, which suggested parathyroid carcinoma. Biopsy of a lytic lesion in her left iliac bone was performed because of concern for metastatic disease but revealed a brown tumor. The patient then underwent parathyroidectomy. The patient's postsurgical course was complicated by protracted symptomatic hypocalcemia consistent with hungry bone syndrome.
RT-39 * CONTROL OF BRAIN METASTASES FROM RADIORESISTANT TUMORS TREATED BY GAMMA KNIFE RADIOSURGERY
Authors: A. Yaeh, T. Nanda, T. Rozenblat, Y. Qureshi, S. Saad, S. Isaacson, M. Sisti, J. Bruce, G. McKhann, A. Lassman, A. Jani, T. Wang
Journal: Neuro-Oncology (2014)

BACKGROUND: Renal cell carcinoma, sarcoma, and melanoma are considered to be “radioresistant” tumor histologies. Brain metastases (BM) from these tumors are unlikely to be controlled using the relatively low doses used in whole brain radiotherapy (WBRT). This study was designed to analyze the efficacy of Gamma Knife Radiosurgery (GKRS) on local control of BM from radioresistant primary tumors. METHODS: We reviewed all patients who received GKRS for BM at Columbia University Medical Center between January 2009 and April 2014. All patients were treated using the Gamma Knife Perfexion System. Dosimetric data was collected from treatment plans and metastases were categorized as radioresistant or not. Response was assessed by reviewing follow-up brain imaging studies and classified according to the Response Evaluation Criteria in Solid Tumors. Local control was calculated using the Kaplan-Meier method. RESULTS: In total, 373 tumors were analyzed. Of these, 49 (13.1%) originated from radioresistant cancers. Median follow up was 6 months in the radioresistant cohort and 5 months in the non-radioresistant cohort. The overall local control rate in the radioresistant cohort was 89.8% and 90.1% in the non-radioresistant cohort. Local control of radioresistant tumors at 6-, 12-, and 18- months was 97.2%, 91.5%, and 69.7%, respectively. Local control of non-radioresistant tumors at 6-, 12-, and 18- months was 94.2%, 83.0%, and 79.6%, respectively. Univariate and multivariate analyses demonstrated that radioresistance status of the primary tumor had no significant effect on local control with hazard ratios of 1.0 (p = 1.0, 95% CI: 0.388-2.576) and 0.954 (p = 0.926, 95% CI: 0.349-2.603) respectively. CONCLUSIONS: There was no significant difference in local control of BM from radioresistant and non-radioresistant primary tumors treated with GKRS. Both cohorts showed excellent response and local control, suggesting that GKRS upfront or in addition to WBRT may be an appropriate strategy in the treatment of BM from radioresistant cancers.
AB0697 Correlation between Sleep Disturbance, Fatigue and Psychological Features in Patients with Ankylosing Spondylarthritis: Table 1.
Authors: I. Cherif, W. Hamdi, D. Kaffel, I. Zouch, M.M. Kchir
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Sleep disturbance in patients with Ankylosing Spondylarthritis (AS) seems to be multifactorial. In fact inflammatory pain, depression and anxiety could have a negative impact on sleep quality in patients with AS. <h3>Objectives</h3> The aim of this study was to evaluate sleep quality and its relationship with psychological features and fatigue in patients with AS. <h3>Methods</h3> We conduct a cross sectional prospective study including patients with AS fulfilling the New York modified criteria. The MOS sleep Questionnaire was used for the assessment of sleep disturbance. It is a 12-item questionnaire exploring 6 domains of sleep: sleep adequacy, sleep disturbance, sleep quantity, daytime sleepiness, and shortness of breath or headache. It leads to two sleep problem indexes (SP1 and SP2). Beck depression and anxiety inventories (BDI, BAI) were used to evaluate psychological features and Chalder scale was used to evaluate the fatigue. <h3>Results</h3> Fifty patients with AS patients were included. The mean age was 42±12.1 years (range 18 to 65) with a male to ratio female about 3.5. The mean VAS for joint pain was 49.85±25.17 [range 0.5 to 90]. The mean BDI score was 16.2±11.8 [0-43] and the mean BAI score was 14.7±10.5 [0-36]. The mean somatic fatigue score was 5.9±2.3 [0-8] and the mean mental fatigue score was 1.8±2 [0-6].The results of the MOS sleep questionnaire and the correlations of its items with BDI, BAI and Chalder scale was presented in Table 1. <h3>Conclusions</h3> Our study showed that the poor sleep quality in AS is highly associated with depression anxiety and fatigue except for snoring which is related to BMI. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6033
MYOCARDIAL EXTRACELLULAR MATRIX VOLUME HAS INDEPENDENT PROGNOSTIC VALUE IN PATIENTS WITH NON-ISCHEMIC CARDIOMYOPATHY
Authors: Tomas Vita, Siddique Abbasi, Ethan Rowin, Gokturk Ipek, Neilan Tomas, Hoshang Farhad, Eri Watanabe, Francois-Pierre Mongeon, Michael Givertz, Ron Blankstein, Michael Steigner, Marcelo Di Carli, Michael Jerosch-Herold, Raymond Kwong
Journal: Journal of the American College of Cardiology (2016)
Bleeding from gastroduodenal metastases as the first manifestation of lung adenocarcinoma
Authors: Charlotte Bouzbib, Ulriikka Chaput, Irène Jarrin, Anne Lavergne-Slove, Philippe Marteau, Xavier Dray
Journal: Endoscopy (2014)

Gastrointestinal metastases from lung cancer are rarely symptomatic [1]. They can cause gastrointestinal bleeding [2] [3], acute abdominal pain [4], and perforation [5]. We describe herein a case of acute anemia secondary to gastroduodenal metastases, revealing a lung adenocarcinoma.
OUTCOMES OF PATIENTS WITH NEW OR PRESUMED NEW LEFT BUNDLE-BRANCH BLOCK COMPARED WITH ST-ELEVATION MYOCARDIAL INFARCTION: INSIGHTS FROM THE SECOND GULF REGISTRY OF ACUTE CORONARY EVENTS
Authors: Amar Salam, Khalid AlHabib, Kadhim Sulaiman, Wael Almahmeed, Alawi Alsheikh-Ali, Haitham Amin, Jawad Al-Lawati, Ahmed Al-Motarreb, Rajvir Singh, Jassim Al Suwaidi
Journal: Journal of the American College of Cardiology (2014)
FRI0154 The Spondyloarthritis Research Consortium of Canada MRI Sacroiliac Joint Structural Score: Reliable Detection of Structural Progression Even over One Year: Table 1.
Authors: W.P. Maksymowych, S. Wichuk, P. Chiowchanwisawakit, R.G. Lambert, S.J. Pedersen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> With increasing focus on effective treatment intervention in early spondyloarthritis (SpA), there is an unmet need for reliable assessment of structural progression in the sacroiliac joints (SIJ) but radiography is unreliable for detecting change and lacks responsiveness. There has been limited validation of MRI-based scores for structural lesions in the SIJ but it is unclear whether change in structural progression can be reliably detected, especially over a time frame shorter than 2 years. <h3>Objectives</h3> To assess the reliability of a new MRI-based scoring method for detecting change in structural damage in the sacroiliac joints of patients with SpA. <h3>Methods</h3> The SPARCC SIJ Structural Score (SSS) method for assessment of structural lesions on T1WSE MRI scans is based on: 1. Validated definitions of structural lesions, 2. Anatomical matching of all time points according to the transitional SIJ slice, defined as the first slice in the cartilaginous portion that has a visible portion of the ligamentous joint, 3. Dichotomous scoring (present/absent) of lesions in SIJ quadrants (fat, erosion) or halves (backfill, ankylosis), 4. Assessment of 5 consecutive slices from the transitional slice anteriorly through the cartilaginous portion of the joint. Scoring ranges are: fat metaplasia (0-40), erosion (0-40), backfill (0-20), ankylosis (0-20). We progressively conducted 3 validation exercises with 2-4 readers according to the Outcome Measures in Rheumatology (OMERACT) filter on baseline and either 2-year (exercises 1 and 2) or 1 year (exercise 3) scans from 147 patients with SpA assessed blinded to time point. Inter-observer reliability was assessed by intra-class correlation coefficient (ICC3,1). The smallest detectable change (SDC) was calculated using the Bland-Altman 80% levels of agreement. <h3>Results</h3> Change &gt;0 in SSS score in patients after one year of follow up was recorded in 51 to 69% for fat metaplasia, 60 to 90% for erosion, 48 to 85% for backfill, and 35 to 53% for ankylosis for the 3 exercises. Mean change scores were 0.21 to 0.73, -0.63 to -1.32, -0.03 to 0.5, and 0.15 to 0.58 for fat, erosion, backfill and ankylosis, respectively. The SDC was comparable for structural lesion scores at 5-7% of the scoring range with the exception of backfill (14%). For status scores, excellent reliability was observed for ankylosis and good reliability for fat metaplasia and erosion. For change scores at 1 and 2 years, fair reliability was observed for all SSS scores despite the small degree of change. <h3>Conclusions</h3> The SPARCC MRI SSS method is a reliable scoring method for detecting structural progression in the sacroiliac joints, especially ankylosis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3755
Increased Bone Mineral Density in Dual X-ray Densitometry Due to Gluteal Implants
Authors: MARCELA RIVERA, PAMELA HUMERES, PATRICIO GONZÁLEZ
Journal: Clinical Nuclear Medicine (1999)

The results of dual x-ray bone densitometry in a patient with bilateral gluteal implants are presented. The patient underwent three measurements of the spine and hips, and one of them was before surgery. A baseline study showed mild osteopenia. After surgery, bone mineral density increased in both femoral necks, because of the superimposition of the implants. A spine phantom with and without a similar implant reproduced the findings in the patient. It is important to consider this type of surgery as a cause of potential bone mineral density artifact.
Cytomegalovirus-associated gastric ulcers in a patient with dermatomyositis treated with steroid and cyclophosphamide pulse therapy
Authors: K. Hoshino, D. Shibata, T. Miyagi, Y. Yamamoto, S. Arakaki, T. Maeshiro, A. Hokama, F. Kinjo, K. Takahashi, J. Fujita
Journal: Endoscopy (2011)

A 63-year-old woman presented with epigastric pain and melena. She had been diagnosed as having dermatomyositis and treated with immunosuppression therapy, including three courses of steroid pulse therapy, intravenous immunoglobulin, and two courses of double-filtration plasmapheresis. She presented with symptoms 5 days after additional cyclophosphamide pulse therapy. Her hemoglobin level had dropped from 9.1 to 6.3 g/dL in 2 days. Serum cytomegalovirus (CMV) pp65 antigenemia was strongly positive (1150/1.5 × 105 leukocytes), and CMV-DNA was remarkably elevated to 2.5 × 105 copy/106 leukocytes. Endoscopy revealed multiple deep, punched-out ulcers with blood vessels, in the antrum of the stomach ([Fig. 1]). Histopathological examinations of the biopsy specimen showed large epithelial cells with enlarged nuclei and peripheral halos (“owl’s-eye” cells) ([Fig. 2]). Immunochemical staining was positive for CMV ([Fig. 3]).