tbuckley/cabot-search huggingface dataset:
Characterization of Gene Expression Phenotype in Amyotrophic Lateral Sclerosis Monocytes
Authors: Weihua Zhao, David R. Beers, Kristopher G. Hooten, Douglas H. Sieglaff, Aijun Zhang, Shanker Kalyana-Sundaram, Christopher M. Traini, Wendy S. Halsey, Ashley M. Hughes, Ganesh M. Sathe, George P. Livi, Guo-Huang Fan, Stanley H. Appel
Journal: JAMA Neurology (2017)

Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by selective loss of upper and lower motor neurons. Patients with ALS have persistent peripheral and central inflammatory responses including abnormally functioning T cells and activated microglia. However, much less is known about the inflammatory gene profile of circulating innate immune monocytes in these patients.To characterize the transcriptomics of peripheral monocytes in patients with ALS.Monocytes were isolated from peripheral blood of 43 patients with ALS and 22 healthy control individuals. Total RNA was extracted from the monocytes and subjected to deep RNA sequencing, and these results were validated by quantitative reverse transcription polymerase chain reaction.The differential expressed gene signatures of these monocytes were identified using unbiased RNA sequencing strategy for gene expression profiling.The demographics between the patients with ALS (mean [SD] age, 58.8 [1.57] years; 55.8% were men and 44.2% were women; 90.7% were white, 4.65% were Hispanic, 2.33% were black, and 2.33% were Asian) and control individuals were similar (mean [SD] age, 57.6 [2.15] years; 50.0% were men and 50.0% were women; 90.9% were white, none were Hispanic, none were black, and 9.09% were Asian). RNA sequencing data from negative selected monocytes revealed 233 differential expressed genes in ALS monocytes compared with healthy control monocytes. Notably, ALS monocytes demonstrated a unique inflammation-related gene expression profile, the most prominent of which, including IL1B, IL8, FOSB, CXCL1, and CXCL2, were confirmed by quantitative reverse transcription polymerase chain reaction (IL8, mean [SE], 1.00 [0.18]; P = .002; FOSB, 1.00 [0.21]; P = .009; CXCL1, 1.00 [0.14]; P = .002; and CXCL2, 1.00 [0.11]; P = .01). Amyotrophic lateral sclerosis monocytes from rapidly progressing patients had more proinflammatory DEGs than monocytes from slowly progressing patients.Our data indicate that ALS monocytes are skewed toward a proinflammatory state in the peripheral circulation and may play a role in ALS disease progression, especially in rapidly progressing patients. This increased inflammatory response of peripheral immune cells may provide a potential target for disease-modifying therapy in patients with ALS.
Lenalidomide, adriamycin, dexamethasone for induction followed by stem-cell transplant in newly diagnosed myeloma
Authors: S Knop, C Langer, M Engelhardt, L-O Mügge, A Reichle, W Rösler, F Bassermann, B Hertenstein, A Kunitz, C Röllig, H Ostermann, K Schäfer-Eckart, M Ringhoffer, A Günther, C Junghanss, H Biersack, M Schreder, A Liebert, S Held, H Einsele, R C Bargou
Journal: Leukemia (2017)
OS08.1 TERT promoter mutations in Meningiomas drive tumor aggressiveness and cellular immortalization
Authors: S. Spiegl-Kreinecker, None Loetsch, None Laaber, None Neumayer, None Pichler, None Weis, None Webersinke, None Gruber, None Berger
Journal: Neuro-Oncology (2017)

Introduction: TERT promoter mutations in meningiomas were recently found to be strongly prognostic and associated with risk of recurrence. However, the impact of these genomic alterations on telomere-associated parameters namely TERT mRNA expression, telomerase activity and telomere lengths was not yet studied. MATERIAL AND METHODS: For this purpose meningioma cases of WHO grades I-III (n=101) were analysed for the TERT promoter mutations C228T and C250T by direct sequencing. Telomerase activity and TERT mRNA expression were investigated by the TRAP assay and RT-PCR, respectively. Lengths of telomeres were measured by a quantitative PCR approach. Additionally, in vitro chemosensitivity testing (MTT) was performed using the telomerase inhibitors BIBR-1532 and MST-312 in meningioma cells TERT promoter wt as compared to mutant background. Results: Mutations in the TERT promoter were found in 7% (7/101) of all samples analysed and exclusively in meningiomas of higher grade, WHOII and WHO III. Out of the patients suffering from progressive recurrence (18/101), 17% (3/18) harbored a TERT mutation (one C250T and two C228T mutations). In meningiomas with non-progressive recurrences one (1/15; 7%) C228T mutation was detected. Positivity for TERT promoter mutations was found in 7% (3/68) of meningiomas without recurrences. TERT promoter mutations were accompanied by a significant upregulation of TERT mRNA and telomerase activity (p<0.0001) and significantly worse overall survival of patients (p=0.042). Telomere lengths on average were longer in wt as compared to mut tumors, but this trend failed to reach significance. Interestingly, telomerase activity was also found occasionally in TERT wt meningiomas (n=8/94), indicating other factors driving telomerase reactivation in these rare cases. TERT promoter methylation, known to be associated with telomerase reactivation, was scored positive in 75% of telomerase-positive TERT promoter wt meningiomas exhibiting telomerase activity in TRAP assay. Focusing on telomerase expression and cell immortalization in vitro we dissected meningiomas according to TERT promoter wt and mut background. Stable immortalized meningioma cell lines were obtained exclusively from cases harboring a TERT promoter hot spot mutation. In contrast, none of the TERT promoter wt tumors even when exhibiting telomerase activity in the malignant tissue developed into a stable immortal cell line. Sensitivity towards telomerase inhibitors did not differ between TERT promoter mutant and wt meningioma primary cells cultures. SUMMARY AND CONCLUSION: Summing up, TERT promoter mutations are main characteristics of aggressiveness and tumor progression in meningiomas. This is corroborated by the fact that TERT promoter mutation- but not methylation-associated telomerase upregulation drives tumor cell immortalization allowing cell line propagation in vitro.
Comparison of Corneal Biomechanical Properties between Indian and Chinese Adults
Authors: Jacqueline Chua, Monisha E. Nongpiur, Wanting Zhao, Yih Chung Tham, Preeti Gupta, Charumathi Sabanayagam, Tin Aung, Tien Yin Wong, Ching-Yu Cheng
Journal: Ophthalmology (2017)
OS07.9 Standard of care temozolomide chemotherapy ± tumor treating fields (TTFields) in newly diagnosed glioblastoma. Final results of the phase III EF-14 clinical trial
Authors: R. Stupp, Z. Ram
Journal: Neuro-Oncology (2017)

BACKGROUND: Tumor Treating Fields (TTFields) is an established, frequency-tuned, anti-mitotic, physical treatment modality that acts in metaphase, anaphase and telophase. TTFields are delivered to the brain by a patient operated, portable medical device (Optune™, Novocure Ltd.). This multicenter, prospective, randomized phase 3 trial (EF-14) tested the efficacy and safety of combining TTFields with maintenance temozolomide (TMZ) compared to TMZ alone in patients with newly diagnosed GBM (Stupp et al. JAMA 2015). Here we report the outcomes of all 695 patients enrolled with a mature minimum follow-up of 18 month (median follow-up 36 months, range 19–80 months). METHODS: Within 7 weeks after the end of TMZ/RT and stratification for extent of resection and MGMT status patients were randomized (at a 1:2 ratio) to either standard adjuvant TMZ alone (150–200 mg/m2/d x 5d) or TMZ and continuous administration of TTFields. Eligible patients had a newly diagnosed GBM, non-progressive after concomitant chemoradiotherapy, a performance status of ≥70%, and adequate hematological, liver and renal function. The primary endpoint of the study is progression free survival (PFS) as determined by blinded central radiology review; overall survival (OS) is a powered secondary endpoint. Results: A total of 695 patients were randomized from 7/2009 - 11/2014. Patient characteristics are balanced, median age was 56 years (range 19–83), 87 % had undergone prior tumor resection and 13 % a biopsy only. The median number of adjuvant TMZ cycles were 6 and 5 cycles, for the TTFields and the TMZ alone control arm, respectively. Progression-free survival was 4 months (mo) and 6.7 months, with a hazard ratio of 0.63 (95% CI 0.52 - 0.76, p= 0.00005); this ultimately translated into a benefit in overall survival (calculated from the date of randomization) of 20.8 mo compared to 16.0 mo (HR 0.65 (CI 0.54 - 0.79; p=0.0006), and at 2 years of 43% compared to 30% for the experimental and standard arm, respectively. Updated results with additional data on molecular markers, quality of life and correlative analyses will be presented. Conclusions: Tumor treating fileds (TTFields) combined with standard maintenance (adjuvant) TMZ chemotherapy significantly improves both progression-free and overall survival in newly diagnosed GBM. Toxicity was generally mild and easily manageable. Adjuvant/maintenance TMZ chemotherapy n combination with TTFields has been established as the new standard of care for patients with a newly diagnosed GBM who completed initial chemoradiotherapy.
INJURY AND ILLNESS PATTERNS IN COMPETITIVE SAILORS OF THE INTERNATIONAL SAILING FEDERATION SAILING WORLD CHAMPIONSHIPS 2014 – A 12-MONTH RETROSPECTIVE STUDY
Authors: Darren Leong, Ben Tan, Carmen Vaz Pardal, Cindy Lin, Jia Wen Kam
Journal: British Journal of Sports Medicine (2017)

Background Olympic Sailing events have evolved to include quicker and more physically demanding boats, stirring interest in the injury patterns and associations amongst sailors of these boats. Objective To characterise sailing-related injuries and illnesses among sailors participating in the ISAF 2014 World Championships. Design Retrospective descriptive study. Setting The International Sailing Federation (ISAF) World Championships is a top tier competition bringing together 1167 sailors in all 10 Olympic classes. The Sailing World Championships 2014 were held in Santander, Spain. Patients (or Participants) Sailors registered for the 2014 ISAF World Championships were surveyed via an interviewer-administered questionnaire from June to September 2014 (off-site prior to competition; and on-site during competition). This was a 12-month recall questionnaire on sailing-related injuries and illnesses. Interventions (or Assessment of Risk Factors) Gender, position (helm, crew), sailing class, training volume, part of boat contributing to injury, and actions performed during sailing. Main Outcome Measurements The occurrence or non-occurrence of sailing-related injuries and illnesses; the number of injuries; injury site, type, cause/mechanism; injury prevalence and severity; and contributing factors to injury. Results There were 760 respondents (65% of all participants) for the 12-month recall questionnaire (58% male, 42% female), of whom 244 participants reported 299 injuries (0.59 injuries per 1000 h of sailing). Injuries were most prevalent in the 49erFX (64%), RS:X Women (39%), 49er (37%) and Nacra 17 (36%). Lower back (29% of sailors), knee (13%), shoulder (12%) and ankle (10%) injuries were most prevalent; most (58% of all injuries) were overuse injuries; and 56% of sailors lost sailing time. Most illnesses (40%) were infections, primarily of the respiratory system (43%). Conclusions The Olympic classes introduced since 2000 (49erFX, 49er, Nacra 17) report more injuries. These injuries were mainly traumatic events, compared with overuse injuries in the other classes.
Suicide Prevention in an Emergency Department Population
Authors: Ivan W. Miller, Carlos A. Camargo, Sarah A. Arias, Ashley F. Sullivan, Michael H. Allen, Amy B. Goldstein, Anne P. Manton, Janice A. Espinola, Richard Jones, Kohei Hasegawa, Edwin D. Boudreaux
Journal: JAMA Psychiatry (2017)

Suicide is a leading cause of deaths in the United States. Although the emergency department (ED) is an opportune setting for initiating suicide prevention efforts, ED-initiated suicide prevention interventions remain underdeveloped. To determine whether an ED-initiated intervention reduces subsequent suicidal behavior. This multicenter study of 8 EDs in the United States enrolled adults with a recent suicide attempt or ideation and was composed of 3 sequential phases: (1) a treatment as usual (TAU) phase from August 2010 to December 2011, (2) a universal screening (screening) phase from September 2011 to December 2012, and (3) a universal screening plus intervention (intervention) phase from July 2012 to November 2013. Screening consisted of universal suicide risk screening. The intervention phase consisted of universal screening plus an intervention, which included secondary suicide risk screening by the ED physician, discharge resources, and post-ED telephone calls focused on reducing suicide risk. The primary outcome was suicide attempts (nonfatal and fatal) over the 52-week follow-up period. The proportion and total number of attempts were analyzed. A total of 1376 participants were recruited, including 769 females (55.9%) with a median (interquartile range) age of 37 (26-47) years. A total of 288 participants (20.9%) made at least 1 suicide attempt, and there were 548 total suicide attempts among participants. There were no significant differences in risk reduction between the TAU and screening phases (23% vs 22%, respectively). However, compared with the TAU phase, patients in the intervention phase showed a 5% absolute reduction in suicide attempt risk (23% vs 18%), with a relative risk reduction of 20%. Participants in the intervention phase had 30% fewer total suicide attempts than participants in the TAU phase. Negative binomial regression analysis indicated that the participants in the intervention phase had significantly fewer total suicide attempts than participants in the TAU phase (incidence rate ratio, 0.72; 95% CI, 0.52-1.00; P = .05) but no differences between the TAU and screening phases (incidence rate ratio, 1.00; 95% CI, 0.71-1.41; P = .99). Among at-risk patients in the ED, a combination of brief interventions administered both during and after the ED visit decreased post-ED suicidal behavior.
P09.59 Phase 2 trial of palbociclib in adult patients with recurrent Rb positive glioblastoma
Authors: J. W. Taylor, A. M. Molinaro, J. J. Phillips, C. D. James, N. A. Butowski, J. L. Clarke, N. Oberheim Bush, S. M. Chang, M. S. Berger, M. Prados
Journal: Neuro-Oncology (2017)

Alterations in the CDK4/6 – RB signaling pathway are common causes of dysregulation of the cell cycle in many cancers, including glioblastoma. Palbociclib is an oral, highly selective, reversible inhibitor of CDK4/6, which leads to phosphorylation of RB and cell-cycle arrest. In a two-arm study, we evaluated the efficacy and safety of palbociclib in patients with recurrent glioblastoma. Notable eligibility criteria included confirmation of RB proficiency by IHC; ≤ 3 relapses; KPS ≥ 60; secondary glioblastomas were included; there were no limitation on prior treatments including bevacizumab. Patients were administered oral palbociclib 125 mg daily for 21 consecutive days followed by a 7 day break. Arm 1 planned for 15 patients to receive palbociclib for 7 days prior to indicated surgical resection for progression, followed by palbociclib. Arm 2 planned for 15 patients to receive palbociclib without additional resection. The primary objective was PFS-6, which was hypothesized to be 30% in this heavily pretreated population, and null hypothesis of 10%. Secondary objectives of toxicity, OS, and ORR. Exploratory results included biomarker assessment and pharmacodynamic effects for the surgical Arm 1 patients. A total of 22 patients were enrolled; 6 on Arm 1 and 16 on Arm 2. Median age for all arms was 47.5 years old (range 23 – 78 years old); 54% (12 patients) were male; and the median KPS was 90 (range 60 – 100). Palbociclib was started at first recurrence in 50% (11 patients – 3 in Arm 1 and 8 in Arm 2) of patients; at second recurrence in 36% (8 patients – 3 in Arm 1 and 5 in Arm 2); and at third recurrence in 14% (3 patients, all in Arm 2). Bevacizumab had previously been used in 77% (17 patients – 4 in Arm 1 and 13 in Arm 2) of cases. The trial was stopped early secondary to futility, with 95% (18 of 19) evaluable patients progressing within 6 months of intiating treatment. Four samples were available for immunohistochemistry for Rb and Ki67. There were no consistent changes in Rb expression or cell proliferation when compared to samples from diagnosis. Median progression free survival for all patients was 5.14 weeks (range 5 days – 142 weeks) and median overall survival was 15.4 weeks (range 2 – 274 weeks). Two patients (10%) had treatment related AEs that were grade ≥3. In this trial, palbociclib did not appear to have been an effective treatment for recurrent glioblastoma. However, this was a heavily pretreated patient population and targeting the CDK4/6 pathway may deserve further exploration.
SHOULDER FUNCTION AND SHOULDER COMPLAINTS IN DANISH ELITE BADMINTON PLAYERS
Authors: Connie Linnebjerg, Mette Zebis, Merete Møller, Niels Vollaard
Journal: British Journal of Sports Medicine (2017)

Background Shoulder function and the prevalence of shoulder complaints in elite badminton are not well described. Objective The aims of this study were to compare players who reported previous or present shoulder complaints with those players who did not. Shoulder function and shoulder problems were quantified. And the players reported influence on performance because of shoulder complaints. Design A cross-sectional study. Setting The study was taken place in the Danish National Centre of badminton, a total of 30 active elite badminton players were asked to participate. Patients (or Participants) Sixteen elite badminton players volunteered to participate. All players were full time playing with a minimum of 12 hours of badminton training per week. Interventions Self-reported shoulder injury profile was quantified for each player by use of two questionnaires (modified Fahlstrom questionnaire and Western Ontario Shoulder Index (WOSI)). Internal rotation (IR) and external rotation (ER) shoulder strength and range of motion (ROM) were tested by use of Hand held dynamometer and Digital inclinometer. Main Outcome Measurements Based on the questionnaires, participants were divided into either complaints (COM) or non-complaints (NCOM). Results Nine players reported previous or present shoulder complaints (COM,) whereas seven players did not (NCOM,). All in the COM group reported changed training habits but only two players reported missed matches due to shoulder problems. No significant differences were observed in IR or ER shoulder strength between groups - i.e. IR: COM, 0.53±0.12 Nm vs. NCOM, 0.62±0.09 Nm and ER: COM, 0.48±0.12 Nm vs. NCOM, 0.57±0.09 Nm. No significant differences were observed in IR and ER ROM between groups; (58±8.4 vs. 60.0±9.3, and 101.8±15.7 vs. 96.4±18.3, respectively). Conclusions This study indicates that shoulder problems do exist in elite badminton. Future studies should aim to develop validated outcome measures that can identify players with shoulder problems in elite badminton.
Long-Term Effect of Endothelin Receptor Antagonism With Bosentan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure
Authors: Milton Packer, John J.V. McMurray, Henry Krum, Wolfgang Kiowski, Barry M. Massie, Avi Caspi, Craig M. Pratt, Mark C. Petrie, David DeMets, Isaac Kobrin, Sebastien Roux, Karl Swedberg, Milton Packer, Avi Caspi, Wolfgang Kiowski, Henry Krum, Craig Pratt, Karl Swedberg, Barry Massie, John McMurray, John McMurray, Eugene Connally, Mark Petrie, David DeMets, Susan Anderson, Jody Barnet, Robert Cody, Henry Dargie, Gary Francis, Barry Greenberg, Juerg Reichen, J. Karrasch, H. Krum, J. Horowitz, J. Amerena, A. Sindone, P. MacDonald, I. Jeffrey, I. Button, E. DeAngelis, R. Pacher, R. Davies, F. McAlister, P. Tanser, B. Sussex, G. Baumann, E. Fleck, H.-G. Olbrich, K. Werdan, H. Klein, F. Staffeld, A.M. Zeiher, C. Roediger, A. Caspi, A. Marmor, L. Reisin, Z. Vered, E. Klainman, N. Roguin, D. Tzivoni, D. David, B. Lewis, E. Abinader, M. Omary, Y. Rosenman, E. Kaluski, R.W. Breedveld, P.H. van der Burgh, P.H.J.M. Dunselman, H.J. Schaafsma, D.P. Hertzberger, N.J. Holwerda, J.A. Kragten, J. van Wijngaarden, J.L. Posma, S.A.M. Said, L.C. Slegers, R.M. Tjon Joe Gin, F.N. Wempe, J.C.L. Wesdorp, A.R. Willems, A.J.A.M. Withagen, J.M. Cornel, L.H.J. van Kempen, W. Kiowski, O. Bertel, T. Moccetti, J.J.V. McMurray, R.A. Greenbaum, P. Bennett, J. Swan, G. Davies, I. Findlay, B. Gould, S. Ball, P. Hubner, A. Lahiri, J. McLay, R. Northcote, S. Saltissi, I. Squire, J. Stephens, M. Stewart, G. Bridgen, J. Walsh, D.J. Webb, Z. Ansari, S. Baron, R. Bellinger, W. Bennet, D. Benvenuti, D. Dawley, L.C. Egbujiobi, I. Eisenstein, T. Little, A. Hertsberg, M. Greenspan, R.J. Grossman, P. Hanley, M. Jesrani, H. Kashou, R. Levites, R. Malik, B. Marmorstein, M. Schwartz, A. Nisar, R. Perelman, M.L. Schwarz, S. Sedlis, J. Srebro, M. Taveras, R. Weiss, P. Weitzman, G.K. Wetherley, M. El Shahawy, D. Kereiakes, L. Campos, G. Peterson, R.S. Small, W.R. Davis, M.-T. Olivari, W. Meengs, M. Koren, P. Slagona, S. Jennison, R. Hershberger, K.F. Browne, D.J. Farnham, S. Zelenkofske, C. Lawless, M. Nathan, T. Meyer, M. Kukin, H. Parekh, R. Berkowitz, J. Boehmer, S. Brozena, P. Dandona, G.W. Dec, V. DeQuattro, P. Fenster, M. Fowler, S. Ellaham, M. Geller, M. Gheorgiade, J. Ghali, S. Murali, S. Katz, C. Bott-Silverman, B. Singh, U. Thadani, G. Torre, J. Teerlink, T. Chandraratna, M. Kesselbrenner, A. Mukherjee, C. Che-Pin Tsai, K. Abbo, M. Goldberg, T. Smith, R.T. Martin
Journal: JACC Heart Failure (2017)
P12.09 Postoperatively delayed-onset seizure outcome in patients with primary supratentorial meningioma resection
Authors: K. Hwang, J. Joo, Y. Kim, C. Kim, J. Han
Journal: Neuro-Oncology (2017)

Introduction: Seizures are common among patients with meningiomas and are a significant cause of morbidity and poor quality of life. We identified factors associated with the onset of seizures as well as factors associated with postoperatively delayed-onset seizure control. Materials and Methods: Between July 2003 and December 2014, patients who underwent primary resection of a supratentorial meningioma at Seoul National University Bundang Hospital were retrospectively reviewed. Univariate analysis and multivariate logistic regression analysis were used to find associations with seizure occurrence and prolonged seizure outcome after surgery. Results: Of the 307 patients in this study, 49 (16%) presented with seizures. The factors independently associated with preoperative seizures were absence of preoperative neurologic deficit (p=0.004), parasagittal or parafalcine location (p=0.041), and vasogenic edema (p=0.002). Among patients with preoperative seizures, 32 (65.3%) were seizure free for the entire postoperative follow-up period (49.4 ± 31.5 months). Fourty-four of 307 patients (14.3%) had postoperatively delayed-onset seizures with mean interval of 16.4 ± 16.2 months after surgery, and associated risk factors included female gender (p=0.021), history of preoperative seizure (p<0.0001), tentorial location, and bigger tumor size (p=0.001). Eleven patients (25%) experienced poor seizure control, and the independently associated factors were parasagittal or parafalcine location (p=0.031) and high grade tumors (WHO Gr. II or III) (p=0.003). Although it was not statistically significant, the association between seizure control and tumor recurrence trended toward (p=0.055). Conclusions: The identification of factors associated with pre- and post-operative seizure occurrence may help guide treatment strategies aimed at improving the quality of life for patients with meningiomas.
ANGIOPOIETIN1 - a Novel Factor Implicated In MLL-Rearranged Acute Lymphoblastic Leukemia and Regulated In a Fusion Gene-Dependent Manner
Authors: Patricia Garrido Castro, Simon Bomken, Lidija Seslija, Ronald Stam, Elda S Latif, Michael A Batey, Hesta McNeill, Rob Pieters, Josef Vormoor, Johann Greil, Olaf Heidenreich
Journal: Blood (2010)