tbuckley/cabot-search huggingface dataset:
MicroRNA (miR) expression signatures in molecular subsets of cytogenetically normal (CN) acute myeloid leukemia (AML): A Cancer and Leukemia Group B (CALGB) study
Authors: M. D. Radmacher, G. Marcucci, P. Paschka, T. Vukosavljevic, S. P. Whitman, A. S. Ruppert, K. Mrózek, J. E. Kolitz, R. A. Larson, C. D. Bloomfield
Journal: Journal of Clinical Oncology (2007)

7010 Background: Aberrantly expressed miRs contribute to malignant transformation by hybridizing to specific mRNA targets and suppressing their translation into proteins. In CN AML, the largest cytogenetic AML subset, several molecular markers are associated with favorable [e.g., NPM1 mutation (mutNPM1)] or unfavorable [e.g., FLT3 internal tandem duplication (ITD) or high ERG expression (↑ERG)] outcome. We explored if differentially expressed miRs are associated with the aforementioned markers. If so, this might indicate a role for miRs in leukemogenesis and prognosis in CN AML. Methods: Diagnostic samples from 100 adults &lt;60 years, treated on CALGB 19808 (Blood 2005; 106:122a), were analyzed on miR microarrays. Among 305 miR probes, we identified differentially expressed miRs (P&lt;0.005) when comparing patients (pts) with or without mutNPM1, FLT3 ITD or ↑ERG. Results: Nine miRs were differentially expressed in FLT3 ITD compared with FLT3 wild-type pts. miR 155, previously reported in aggressive cancers, was upregulated in FLT3 ITD pts. Strong signatures were associated with mutNPM1 (42 miR probes) and ↑ERG groups (54 miR probes). Consistent with their better prognosis, pts with mutNPM1 had upregulated miRs 10 and 196 targeting HOX genes, miRs 15 and 16 targeting BCL2 and let-7 targeting RAS. Consistent with a more aggressive phenotype, ↑ERG pts had downregulation of let-7 and miR 15 and 16 but also miRs 30, 103, and 24 which target, respectively, CDK6, FBXW11 and MAPK14, all involved in cell cycle regulation and proliferation. Four miRs were associated with event free survival (EFS); all were also associated with ↑ERG. High expression of miRs 124, 129, and 194 was significantly associated with worse EFS and ↑ERG. Low expression of miR 181 was associated with worse EFS and ↑ERG. Notably, downregulation of mir 181 has also been reported in pts with aggressive B-cell chronic lymphocytic leukemia. Conclusions: We report the first miR expression signatures within molecular subsets of CN AML. Further study is warranted to elucidate mechanisms by which miRs contribute to leukemogenesis and impact prognosis, and to determine whether miRs can be therapeutically targeted. No significant financial relationships to disclose.
HCV-associated cryoglobulinemia vasculitis: are its days numbered?
Authors: Sergey Moiseev, Pavel Novikov, Nikolay Mukhin
Journal: Annals of the Rheumatic Diseases (2016)

We read with great interest the article by Saadoun et al 1 who investigated the efficacy and safety of a 24-week treatment with sofosbuvir and ribavirin in a small, open-label and uncontrolled study of patients with hepatitis C virus (HCV)-associated cryoglobulinemia vasculitis. However, the limitations of the VASCUVALDIC study diminish the validity of the conclusions, although we agree with the authors that it would be unethical to delay effective antiviral therapy given the established role of HCV in the development of cryoglobulinemia vasculitis and its unfavourable prognosis.

As expected, the rate of sustained virological response (SVR) was higher (74%) than in previous trials of interferon-based antiviral treatment in patients with HCV-associated cryoglobulinemia vasculitis.2 ,3 However, this looks relatively moderate in light of the current efficacy of the interferon-free, all-oral antiviral regimens (up to 95%–100%). Nonetheless, the SVR rate was comparable with that identified in the previous phase III sofosbuvir plus ribavirin trial in patients with HCV infection.4 We can also assume that the proportion of virological responders among patients with HCV-associated cryoglobulinemia …
Indonesian doctors risk losing licence if they castrate paedophiles
Authors: Jane Parry
Journal: BMJ (2016)

Doctors in Indonesia who perform chemical castration on convicted paedophiles risk censure by their professional body, the Indonesian Medical Association, and put their licence to practise in jeopardy, an association spokesman told The BMJ .

In the wake of a series of high profile cases involving rape of children, earlier this month the Indonesian government amended the Protection of Children law to impose forced chemical castration as an additional punishment for “anyone who commits violence or threatens violence to force a child—person below 18 years—to have intercourse with him or with another person” …
A Pooled Analysis of Four Pivotal Studies of Rivaroxaban for the Prevention of Venous Thromboembolism after Orthopaedic Surgery: Effects of Specified Co-Medications.
Authors: Bengt Eriksson, Alexander GG Turpie, Michael Rud Lassen, Ajay K Kakkar, Frank Misselwitz, Tiemo Joerg Bandel, Martin Homering, Torsten Westermeier, Michael Gent
Journal: Blood (2008)
A Study of <i>TP53</i> RNA Splicing Illustrates Pitfalls of RNA-seq Methodology
Authors: Sunali Mehta, Peter Tsai, Annette Lasham, Hamish Campbell, Roger Reddel, Antony Braithwaite, Cristin Print
Journal: Cancer Research (2016)

TP53 undergoes multiple RNA-splicing events, resulting in at least nine mRNA transcripts encoding at least 12 functionally different protein isoforms. Antibodies specific to p53 protein isoforms have proven difficult to develop, thus researchers must rely on the transcript information to infer isoform abundance. In this study, we used deep RNA-seq, droplet digital PCR (ddPCR), and real-time quantitative reverse transcriptase PCR (RT-qPCR) from nine human cell lines and RNA-seq data available for tumors in The Cancer Genome Atlas to analyze TP53 splice variant expression. All three methods detected expression of the FL/40TP53α_T1 variant in most human tumors and cell lines. However, other less abundant variants were only detected with PCR-based methods. Using RNA-seq simulation analysis, we determined why RNA-seq is unable to detect less abundant TP53 transcripts and discuss the implications of these findings for the general interpretation of RNA-seq data. Cancer Res; 76(24); 7151-9. ©2016 AACR.
Immunohistochemical analysis of tumor regression grade for rectal cancer after neoadjuvant chemoradiotherapy
Authors: V. Moreno Garcia, P. Cejas, J. Feliu, J. De Castro, C. Belda-Iniesta, J. Barriuso, J. Larrauri, M. Gonzalez Baron, E. Casado
Journal: Journal of Clinical Oncology (2009)

e22089 Background: Tumor regression grade (TRG) as defined by Rodel et al. has been suggested as an independent prognostic factor for rectal carcinoma patients treated by preoperative chemoradiotherapy (CRT). However TRG 2 and 3 determination, semiquantitatively defined as more/less than 50% tumor regression, respectively, do not clearly correlate with prognosis. TRG 2 vs 3 discrimination is largely subjective hurdling prognostic analysis. The purpose of our study was to find an immunohistochemical pattern to better stratify these patients according to prognosis in term of disease free survival (DFS) and overall survival (OS). Methods: Immunohistochemistry of EGFR, VEGF, CD133, p53 and Ki67 was evaluated by tissue microarrays on surgical specimens from 88 patients. Preoperative chemotherapy was UFT-LV (30%) or oxaliplatin-based (70%) plus pelvic radiotherapy (50 Gy) followed by mesorectal excision. TRG was determined by the amount of viable tumor versus fibrosis, ranging from TRG 4 when no viable tumor cells were detected, to TRG 1 when regression was less than 25%. TRG 2 and 3 were defined as described above. Univariate analyses were performed according to the Kaplan-Meier method. Comparisons between curves were evaluated by the log-rank test. Cox regression was used for the multivariate analysis. Results: At a median follow-up of 39 months, the TRG was an independent predictor of DFS (p=0.05) and OS (p=0.001) but no differences were found between TRG 2 and 3 in terms of DFS (p=0.74) or OS (p=0.41). Our results show an immunohistochemical bad prognostic profile for tumors TRG 2 and 3 configured by double negativity of EGFR and CD133 expression (less than 5% of tumor cells membrane immunoreactivity for both antibodies). 3-year DFS and OS for these patients (vs. TRG 2 and 3 not-double negative) were 33 vs 65% (p=0.05) [HR=2.4 (95%CI, 0.9–6.1) p=0.06] and 77 vs 95% (p=0.06) [HR=4.1 (95%CI, 0.7–21.5) p=0.09]. Conclusions: The EGFR/CD133 double negative rectal tumors with TRG 2 or 3 after chemoradiotherapy show a higher risk of relapse or death. These results can help clinicians to determine better individual prognosis and are worth to confirm prospectively. No significant financial relationships to disclose.
Relationship of PTEN expression with trastuzumab resistance.
Authors: M. Cano, J. De la Haba, I. Porras, C. Morales, G. Pulido, J. Jimenez, E. Aranda
Journal: Journal of Clinical Oncology (2010)

e13152 Background: Suppressor gene PTEN with phosphatase activity that is mutated in different tumors is located on chromosome 10q23.3. PTEN antagonizes phosphatidyl-inositol 3-kinase (PI3K) function and negatively regulates Akt activity. PTEN expression is reduced by 38% of invasive tumors and 11% of tumors in situ. Recent studies have demonstrated that resistance to trastuzumab treatment depends on the level of PTEN present and demonstrated that decreased expression of PTEN confers trastuzumab resistance in HER2 /neu-overexpressing breast cancer cells. Methods: From registration of the Medical Oncology Department in Hospital Universitario Reina Sofia has been determined by immunohistochemistry (Anti-Human PTEN Clone 6H2.1 DAKO) the PTEN expression in 12 patients with Erb B2 overexpressing and locally advanced breast cancer treated with the same schedule of chemotherapy with anthracyclines, taxanes and trastuzumab. Inmunohistochemical criteria of absence of expression of PTEN was the complete negative for PTEN expression in tumoral tissue and positive in vascular tumoral tissue. Results: The pathological complete response (pCR) rate in our series was 77.8% (7 patients). PTEN expression was observed in 75% (9 patients) and no expression in 25% (3 patients). Any patient with loss of PTEN expression has been pCR (3 patients) p <0.045. Conclusions: The absence of PTEN expression is a predictive biomarker of resistance to treatment with trastuzumab. The study is ongoing. No significant financial relationships to disclose.
EAR-2: Identification of a Gene Involved in Maintenance of Clonogenicity in Haematopoiesis.
Authors: Christine V. Ichim, Mahadeo A. Sukhai, J. Brandwein, Mark D. Minden, Aaron D. Schimmer, Andre C. Schuh, Suzanne Kamel-Reid, Norman N. Iscove, Richard A. Wells
Journal: Blood (2004)
Bortezomib and dexamethasone from cycle 1 as treatment and maintenance for multiple myeloma relapse (The BoMeR trial): Impact on response and time to progression.
Authors: S. J. Harrison, H. Quach, J. Dean, A. Milner, M. C. Copeman, H. M. Prince
Journal: Journal of Clinical Oncology (2010)

8151 Background: In relapsed multiple myeloma (MM), bortezomib (Btz) is often combined with dexamethasone (Dex), as adding Dex to Btz later in patients only achieving SD or PD improved overall response (OR) by 18% in the SUMMIT trial (Richardson, 2003). Yet, no large trial of Btz/Dex from Cycle 1 in relapsed MM has been published. Although maintenance Btz/Dex might further extend time to progression (TTP) Btz/Dex are usually ceased after 11 cycles. We conducted a large phase II trial in relapsed MM patients (pts) of standard Btz/Dex for Cycles 1-11, then q14d to progression, prospectively comparing OR and TTP to the APEX trial Btz-only arm (Richardson, 2005). Methods: 20 Australian and New Zealand sites enrolled 100 MM pts requiring 2nd line therapy (or 3rd line if prior thalidomide (Thal) and or Dex), with Karnofsky score ≥60, platelets ≥50×109/L and eGFR ≥20 mL/min. Treatment was Btz (1.3mg/m2; D1, 4, 8 and 11) plus Dex (20mg; D1, 2, 4, 5, 8, 9, 11 and 12) for <11 (8 × 21day and 3 × 35day) cycles. Pts with >stable disease received Btz (1.3mg/m2; D1) and Dex (20mg; D1,2) q14d until progression. OR was 1o endpoint; 2o endpoints included complete response (CR) rate and TTP. Results: BoMeR pts were similar to APEX trial pts: Median age 61 years (62 APEX); 56% male (59%); median initial beta-2 microglobulin 3.15 (3.70); median years from diagnosis 2.56 (3.50); prior Thal in 61% (48%) and 2+ prior therapies in 45% (60%). OR was 51% [95% CI: 41-61%] (38% APEX) with CR 14% (6% APEX) by EBMT criteria. Toxicity was similar in Cycles 1-11: 70% of pts (75% APEX) had a Grade 3+ adverse event (55% non-hematological and 36% hematological), with 35% Gr 2+ neuropathy (27% APEX) and 30% Gr 3+ thrombocytopenia (30% APEX). 35 pts completed at least 1 cycle of maintenance Bz/Dex. In 81/100 evaluable pts, with 6 months median follow-up (range 1-27) at October 08, median TTP was >12 months (6 months APEX). Conclusions: Combining Btz/Dex from Cycle 1 in relapsed MM significantly improves response (51% vs. 38%) without higher toxicity and should now be regarded as a standard of care. Our initial analysis of TTP (>12 vs. 6 months) suggests that Btz/Dex q14d maintenance may delay relapse in this setting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Janssen-Cilag Janssen-Cilag Janssen-Cilag
Outcome of Patients with Chronic Myeloid Leukemia After Allogeneic Stem Cell Transplantation in Europe; Data From the EUTOS for CML Registry
Authors: Susanne Saussele, Verena Hoffmann, Doris Lindörfer, Andreas Hochhaus, Francisco Cervantes, Gert Ossenkoppele, Henrik Hjorth-Hansen, Steve O'Brien, Jiri Mayer, Karel Indrak, Andrzej Hellmann, Adriana Colita, Anna Turkina, Andrey Zaritskey, Juan Luis Steegmann, David Marin, Markus Pfirrmann, Michele Baccarani, Joelle Guilhot, Joerg Hasford, Carmen Piccolo, Bengt Simonsson, Rüdiger Hehlmann, Gianantonio Rosti
Journal: Blood (2011)
Impact of Nucleated Cell Dose On Engraftment and Survival After Unrelated Cord Blood Transplantation for Severe Aplastic Anemia: A Retrospective Study On Behalf of Eurocord and the EBMT SAA WP.
Authors: Regis Peffault de Latour, Duncan Purtill, Annalisa Ruggeri, Guillermo Sanz, Gerard Michel, Virginie Gandemer, Sebastien Maury, Joanne Kurtzberg, Carmem Bonfim, Mahmoud Aljurf, Eliane Gluckman, Gerard Socie, Jakob R. Passweg, Vanderson Rocha
Journal: Blood (2009)
Is Now-or-Never language processing good enough?
Authors: Fernanda Ferreira, Kiel Christianson
Journal: Behavioral and Brain Sciences (2016)

Abstract Christiansen &amp; Chater's (C&amp;C's) Now-or-Never bottleneck framework is similar to the Good-Enough Language Processing model (Ferreira et al. 2002), particularly in its emphasis on sparse representations. We discuss areas of overlap and review experimental findings that reinforce some of C&amp;C's arguments, including evidence for underspecification and for parsing in “chunks.” In contrast to Good-Enough, however, Now-or-Never does not appear to capture misinterpretations or task effects, both of which are important aspects of comprehension performance.
Effectiveness of HypoAware, a Brief Partly Web-Based Psychoeducational Intervention for Adults With Type 1 and Insulin-Treated Type 2 Diabetes and Problematic Hypoglycemia: A Cluster Randomized Controlled Trial
Authors: Stefanie M.P.A. Rondags, Maartje de Wit, Jos W. Twisk, Frank J. Snoek
Journal: Diabetes Care (2016)

OBJECTIVE To establish the effectiveness of a brief, partly web-based group intervention, HypoAware, in patients with problematic hypoglycemia, in terms of the reduction of severe hypoglycemic episodes, impaired hypoglycemia awareness, and worries. RESEARCH DESIGN AND METHODS A two-arm, cluster randomized controlled trial was conducted in insulin-treated patients with problematic hypoglycemia in eight Dutch clinics comparing HypoAware with care as usual. Primary outcomes included self-reported severe hypoglycemia, impaired hypoglycemia awareness (Gold score), and worries and distress about hypoglycemia (Hypoglycemia Fear Survey-II/Problem Areas In Diabetes scale hypo-item), assessed at baseline, and at 2, 4, and 6 months of follow-up. We used t tests, nonparametric tests, and intention-to-treat generalized estimation equation (GEE) analyses with linear, logistic, and Poisson or negative binomial models. RESULTS We enrolled 137 participants. Adjusted GEE analyses over four time points showed a nonsignificant 33% fewer episodes of severe hypoglycemia in the HypoAware group compared with the control group (relative risk [RR] 0.67 [95% CI 0.39–1.16], P = 0.150); a significant reduced odds of impaired awareness (odds ratio 0.38 [95% CI 0.15–0.95], P = 0.038), a trend toward 20% fewer worries about hypoglycemia (RR 0.80 [95% CI 0.64–1.01], P = 0.059), and a significant 30% less hypo-distress (RR 0.70 [95% CI 0.56–0.88], P = 0.002). Over the 6-month study duration, participants experienced a median of 2.5 events of severe hypoglycemia (interquartile range [IQR] 1–10) in the control condition versus 1 event (IQR 0–6.5) in the HypoAware group (P = 0.030). There was no significant change in HbA1c level within and between both groups. CONCLUSIONS HypoAware resulted in fewer severe hypoglycemic episodes, significantly improved hypoglycemia awareness, and less hypo-distress in comparison with usual care, and deserves further dissemination.
Allogeneic Stem Cell Transplantation with Intermediate Conditioning Is Effective in High Risk Relapse and Progressive Disease of Aggressive Non-Hodgkin-Lymphoma.
Authors: Bertram Glass, Justin Hasenkamp, Anke Goerlitz, Peter Dreger, Joerg Schubert, Gerald Wulf, Maike Nickelsen, Lorenz H. Truemper, Norbert Schmitz
Journal: Blood (2009)
GW26-e0805 Intracoronary and Retrograde Coronary Venous Myocardial Delivery of Adipose-Derived Stem Cells in Swine Infarction Lead to Transient Myocardial Trapping With Predominant Pulmonary Redistribution
Authors: Jie Qin, Xiuzhen Chen, Yuefei Guo, Xuelian Liu
Journal: Journal of the American College of Cardiology (2015)
Euthanasia and Physician-Assisted Suicide
Authors: Kenneth R. Stevens, William L. Toffler
Journal: JAMA (2016)

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Precision Medicine: What Challenges Are We Facing?
Authors: Yu Xue, Eric-Wubbo Lameijer, Kai Ye, Kunlin Zhang, Suhua Chang, Xiaoyue Wang, Jianmin Wu, Ge Gao, Fangqing Zhao, Jian Li, Chunsheng Han, Shuhua Xu, Jingfa Xiao, Xuerui Yang, Xiaomin Ying, Xuegong Zhang, Wei-Hua Chen, Yun Liu, Zhang Zhang, Kun Huang, Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2016)
Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma
Authors: Jia-Jie Hao, De-Chen Lin, Huy Q Dinh, Anand Mayakonda, Yan-Yi Jiang, Chen Chang, Ye Jiang, Chen-Chen Lu, Zhi-Zhou Shi, Xin Xu, Yu Zhang, Yan Cai, Jin-Wu Wang, Qi-Min Zhan, Wen-Qiang Wei, Benjamin P Berman, Ming-Rong Wang, H Phillip Koeffler
Journal: Nature Genetics (2016)
Gene Expression Profiling Can Predict Responsiveness to Chemotherapy in Patients with Transformation of Follicular Lymphoma.
Authors: Marie Jose Kersten, Annuska M. Glas, Leonie J. Delahaye, Robby E. Kibbelaar, Han H. van Krieken, Philip M. Kluin, Laura van ‘t Veer, Daphne de Jong
Journal: Blood (2006)
Study of V617F JAK2-Positive and JAK2-Negative Patients within 18 Families with Myeloproliferative Disorders (MPD): Disease Characteristics and Evolution, EPOR and MPL Analysis.
Authors: Christine Bellanne-Chantelot, Myriam Labopin, Florence Bellanger, Isabelle Chaumarel, Françoise Isnard, Nicole Casadevall, William Vainchenker, Gilles Thomas, Albert Najman
Journal: Blood (2006)
Phase I study of PTK787/ZK222584 (PTK/ZK) and RAD001 for patients with advanced solid tumors and dose expansion in renal cell carcinoma patients
Authors: J. C. Speca, A. L. Mears, P. A. Creel, S. E. Yenser, J. C. Bendell, M. A. Morse, H. I. Hurwitz, A. J. Armstrong, D. J. George
Journal: Journal of Clinical Oncology (2007)

5039 Background: PTK/ZK is an orally active tyrosine kinase inhibitor that blocks all known VEGF receptors. RAD001 is an orally active macrolide which selectively inhibits mTOR. Combination therapy with VEGFR and mTOR inhibition may have additive efficacy in several tumor types, particularly renal cell carcinoma (RCC). Materials and Methods: A phase I/II study of PTK/ZK and RAD001 was performed in patients with advanced solid tumors to determine the maximum tolerated dose (MTD), safety and tolerability. Patients were given escalating daily doses of PTK/ZK in combination with RAD001 (see table ) in 28-day cycles. Patients were assessed for adverse events every 2 weeks and tumor response every 2 cycles. A dose expansion cohort of 20 patients with metastatic RCC is ongoing to further evaluate safety and preliminary efficacy. Results: To date, 27 patients have received a total of 136 cycles. The dose escalation phase included 14 patients and 3 dose levels; dose-limiting toxicities included grade 3 diarrhea and hypertriglyceridemia (14%); asthenia, fatigue and mucositis (7%). Pharmacokinetic studies are pending. A MTD of PTK/ZK 1,000 mg and RAD001 5 mg daily was determined and studied in an expanded cohort of RCC patients. Prior therapy with a VEGF inhibitor was allowed. To date, 13 evaluable RCC patients demonstrate 2 (15%) partial responses and 8 (62%) with stable disease &gt; 3 months; median TTP is 6 months. Conclusions: PTK/ZK and RAD001 combination is well-tolerated and demonstrates clinical activity in patients with RCC despite prior exposure to VEGF inhibition. An MTD of 1,000 mg daily of PTK/ZK and 5 mg daily of RAD001 is the recommended dose for Phase II/III testing. [Table: see text] No significant financial relationships to disclose.
GW26-e3964 Remnant cholesterol predicts periprocedural myocardial injury following percutaneous coronary intervention in poorly-controlled type 2 diabetes
Authors: Rui-xiang Zeng, Cheng-Gang Zhu, Min-Zhou Zhang, Xiao-Lin Li, Yuan-Lin Guo, Li-Heng Guo, Sha Li, Yan Zhang, Jian-Jun Li
Journal: Journal of the American College of Cardiology (2015)