tbuckley/cabot-search huggingface dataset:
Authorship roles of oncology investigators with or without financial relationships to industry
Authors: S. L. Rose, J. S. Najita, M. K. Krzyzanowska, S. Joffe
Journal: Journal of Clinical Oncology (2008)

6564 Background: Financial ties between clinical investigators and industry are common. This proximity between investigators and industry has raised concerns about bias in study design, conduct and reporting. We hypothesized that authors with such ties are more likely than other authors to play key scientific roles in oncology trials, and therefore to be in positions of disproportionate influence. We also examined whether this association varies by funding source. Methods: Data were abstracted from all trials (n=219) of drugs or biologicals published in JCO between 1/1/06 and 6/30/07. Article-level data included funding source, age group (adult vs. pediatric), phase, single vs. multicenter, country (US vs. other), and number of authors. Author-level data (n=2,719) included financial ties (e.g., employment, consulting) and performance of key scientific roles (i.e., conception/design, analysis/interpretation, or manuscript writing). Associations between financial ties and performance of key roles, adjusting for article-level covariates, were tested using generalized linear mixed models to account for clustering of authors within articles. Results: 122 studies (56%) had industry funding. 782 authors (29%) reported at least one financial tie to industry, and 1,733 authors (64%) reported performing at least one key role. Authors with financial ties were more likely than other authors to report performing a key role (OR=4.2, 99% CI=3.0–6.0, p<0.0001; Table). This relationship was stronger in industry-sponsored trials (OR=5.0, CI=3.3–7.5, p<0.0001) than in non-industry trials (OR=2.3, CI=1.1–4.6, p=0.002). This difference was explained by the higher prevalence of authors with employment relationships, most of whom reported playing key scientific roles, among industry trials. Conclusion: Authors with financial ties to industry are more likely than authors without such ties to play key roles in conception and design, analysis and interpretation, and reporting of oncology clinical trials. Relationship between authors' financial ties to industry and performance of key scientific roles Financial Tie Key Scientific Role Total Yes No Yes 620 (79%) 162 (21%) 782 No 1,113 (57%) 824 (43%) 1,937 Total 1,733 986 2,719 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca, Roche
Effect of denosumab versus zoledronic acid (ZA) in preventing skeletal-related events (SREs) in patients with metastatic bone disease: Subgroup analyses by baseline characteristics.
Authors: Allan Lipton, Karim Fizazi, Alison Stopeck, David H. Henry, Matthew Raymond Smith, Neal D. Shore, Miguel Martin, Saroj Vadhan-Raj, Kefei Zhou, Arun Balakumaran, Ada H. Braun
Journal: Journal of Clinical Oncology (2014)

9501 Background: There is an interest in identifying patients at risk for SREs who may benefit most from treatment with bone-targeted agents (BTA). Previous results from a subgroup analysis of three phase 3 trials demonstrated denosumab was superior to ZA in preventing SREs (pathologic fracture, radiation or surgery to bone, or spinal cord compression) regardless of baseline clinical pain symptoms or prior SRE status. This analysis assesses if denosumab is superior to ZA in delaying patients’ time to SREs across relevant baseline characteristics. Methods: Patients with metastatic bone disease were randomized 1:1 to receive either SC denosumab 120 mg + IV placebo (n=2,862) or IV ZA 4 mg (adjusted for CrCl) + SC placebo Q4W (n=2,861) in double-blinded phase 3 studies. Time to first on study SRE and time to first and subsequent SRE were evaluated in patients by several baseline variables: location of skeletal metastases (mets) (axial vs appendicular), presence of visceral mets (yes/no), urinary N-telopeptide (uNTx) level (median; ≥43.5 vs <43.5 nmol/mmol), number of bone mets(<2 or ≥2), and ECOG performance status (0 or ≥1). Results: Denosumab significantly delayed time to first SRE compared to ZA regardless of patients’ baseline characteristics. Similar results were noted in preventing first and subsequent SREs in all subgroups. Conclusions: Denosumab significantly delayed patients’ time to SREs compared to ZA regardless of patient’s baseline status. Clinical trial information: NCT00321464, NCT00330759, NCT00321620.Benefit of denosumab vs ZA on time to first on-study SRE. Baseline characteristic HR (95% CI) P-value Axial bone mets only (n=1,422) 0.83 (0.70,1.00) 0.046 Appendicular bone mets only (n=753) 0.78 (0.61,0.99) 0.042 Both axial & appendicular bone mets (n=1,695) 0.83 (0.71, 0.97) 0.022 ≥2 bone mets (n=2,234) 0.81 (0.71,0.93) 0.003 <2 bone mets (n=3,489) 0.84 (0.74,0.94) 0.003 Visceral mets (n=2,341) 0.80 (0.69,0.93) 0.003 No visceral mets (n=3,382) 0.84 (0.75,0.94) 0.002 High uNTx (n=2,553) 0.86 (0.76,0.98) 0.028 Low uNTx (n=2,553) 0.75 (0.65, 0.86) <0.001 ECOG 0 (n=2,312) 0.82 (0.71,0.94) 0.006 ECOG ≥1 (n=3,398) 0.84 (0.75,0.94) 0.002
Chikungunya virus infections among travellers returning to Spain, 2008 to 2014
Authors: Maria Dolores Fernandez-Garcia, Mathieu Bangert, Fernando de Ory, Arantxa Potente, Lourdes Hernandez, Fatima Lasala, Laura Herrero, Francisca Molero, Anabel Negredo, Ana Vázquez, Teodora Minguito, Pilar Balfagón, Jesus de la Fuente, Sabino Puente, Eva Ramírez de Arellano, Mar Lago, Miguel Martinez, Joaquim Gascón, Francesca Norman, Rogelio Lopez-Velez, Elena Sulleiro, Diana Pou, Nuria Serre, Ricardo Fernández Roblas, Antonio Tenorio, Leticia Franco, Maria Paz Sanchez-Seco
Journal: Eurosurveillance (2016)

Since the first documented autochthonous transmission of chikungunya virus in the Caribbean island of Saint Martin in 2013, the infection has been reported within the Caribbean region as well as North, Central and South America. The risk of autochthonous transmission of chikungunya virus becoming established in Spain may be elevated due to the large numbers of travellers returning to Spain from countries affected by the 2013 epidemic in the Caribbean and South America, as well as the existence of the Aedes albopictus vector in certain parts of Spain. We retrospectively analysed the laboratory diagnostic database of the National Centre for Microbiology, Institute of Health Carlos III (CNM-ISCIII) from 2008 to 2014. During the study period, 264 confirmed cases, of 1,371 suspected cases, were diagnosed at the CNM-ISCIII. In 2014 alone, there were 234 confirmed cases. The highest number of confirmed cases were reported from the Dominican Republic (n = 136), Venezuela (n = 30) and Haiti (n = 11). Six cases were viraemic in areas of Spain where the vector is present. This report highlights the need for integrated active case and vector surveillance in Spain and other parts of Europe where chikungunya virus may be introduced by returning travellers.
Homeostatic Plasticity of Subcellular Neuronal Structures: From Inputs to Outputs
Authors: Winnie Wefelmeyer, Christopher J. Puhl, Juan Burrone
Journal: Trends in Neurosciences (2016)

Neurons in the brain are highly plastic, allowing an organism to learn and adapt to its environment. However, this ongoing plasticity is also inherently unstable, potentially leading to aberrant levels of circuit activity. Homeostatic forms of plasticity are thought to provide a means of controlling neuronal activity by avoiding extremes and allowing network stability. Recent work has shown that many of these homeostatic modifications change the structure of subcellular neuronal compartments, ranging from changes to synaptic inputs at both excitatory and inhibitory compartments to modulation of neuronal output through changes at the axon initial segment (AIS) and presynaptic terminals. Here we review these different forms of structural plasticity in neurons and the effects they may have on network function.
Next Generation Sequencing Identifies DNA Methylation Patterns Indicative of Disease Progression in Ph+ CML
Authors: Gerwin Heller, Thais Topakian, Corinna Altenberger, Sabine Cerny-Reiterer, Barbara Ziegler, Paul Datlinger, Christoph Bock, Christine Mannhalter, Gregor Hörmann, Wolfgang R Sperr, Christoph C Zielinski, Peter Valent, Sabine Zöchbauer-Müller
Journal: Blood (2014)
Urinary Tract Tuberculosis
Authors: Hiromichi Masuda, Koji Kamada
Journal: New England Journal of Medicine (2016)

A 76-year-old man with diabetes and mediastinal lymphadenopathy presented with fever and fatigue. Pyuria was seen on urinalysis. CT of the abdomen showed mild dilatation of the left renal pelvis and thickening of the ipsilateral ureteral wall.
Baseline Predictors of Mortality in Patients with Relapsed or Refractory Acute Myeloid Leukemia Treated with Vosaroxin Plus Cytarabine or Placebo Plus Cytarabine in the Phase 3 VALOR Study
Authors: Jeffrey E Lancet, Farhad Ravandi, Ellen K Ritchie, Hamid Sayar, Stephen A. Strickland, Gary J Schiller, Norbert Vey, Harry P Erba, Arnaud Pigneux, Heinz-August Horst, Christian Recher, Olatoyosi Odenike, Angelo-Michele Carella, Dominik Selleslag, Jonathan Kell, Utz Krug, Leigh Page, Art DeVault, Shuling Hwang, Adam R Craig, Robert K. Stuart
Journal: Blood (2015)
A5-04: The impact of EGFR mutation and smoking status on non-small-cell lung cancer patients treated with geftinib
Authors: Shinichi Toyooka, Toshimi Takano, Takayuki Kosaka, Shuji Ichihara, Yoshiro Fujiwara, Katsuyuki Hotta, Junichi Soh, Katsuyuki Kiura, Yasushi Yatabe, Yuichiro Ohe, Tetsuya Mitsudomi, Hiroshi Date
Journal: Journal of Thoracic Oncology (2007)
High Dose Intracoronary Adenosine for Myocardial Salvage in Patients with Acute ST-segment Elevation Myocardial Infarction
Authors: Walter Desmet, Jan Bogaert, Christophe Dubois, Tom Adriaenssens, Christos Pappas, Javier Ganame, Steven Dymarkowski, Ann Belmans, Frans Van de Werf
Journal: Circulation (2010)
Evaluating Elevated Hemoglobin—Reply
Authors: Robyn M. Scherber, Ruben A. Mesa
Journal: JAMA (2016)

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Physiologic Expression of Sf3b1 K700E Causes Impaired Erythropoiesis, Aberrant Splicing, and Sensitivity to Therapeutic Spliceosome Modulation
Authors: Esther A. Obeng, Ryan J. Chappell, Michael Seiler, Michelle C. Chen, Dean R. Campagna, Paul J. Schmidt, Rebekka K. Schneider, Allegra M. Lord, Lili Wang, Rutendo G. Gambe, Marie E. McConkey, Abdullah M. Ali, Azra Raza, Lihua Yu, Silvia Buonamici, Peter G. Smith, Ann Mullally, Catherine J. Wu, Mark D. Fleming, Benjamin L. Ebert
Journal: Cancer Cell (2016)
Oral contraceptives and thromboembolic disease
Authors: Philip E. Sartwell
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Dr. Drill's paper on oral contraceptives and thromboembolic disease (<b>219</b>:583, 1972) makes some erroneous statements about a study by my colleagues and myself<sup>1</sup>which should be corrected. He states that an increased hospital admission risk was found for certain cities but not for others, and for certain diagnoses but not for others. In all five cities in our study, the use of oral contraceptives was associated with thromboembolism. In the two areas with the smallest numbers of cases the association was not statistically significant. Using R. A. Fisher's method for the combination of probabilities from tests of signigicance, it can be shown that the overall association is highly significant (<i>P</i>&lt;.001). Likewise, for each of the five thromboembolic conditions encountered often enough to permit a significance test to be conducted, there was association with the use of oral contraceptives, which reached a level of significance for
Epigenetic Silencing of Mir-218 Regulates CDK6 Expression In Pre-B Acute Lymphoblastic Leukemia Cells
Authors: Xiaoqing Li, Jun Liu, Rui Zhou, Jine Zheng, Junxia Yao, Yanli He, Xiangjun Chen, Jie Ding, Shiang Huang, Xian-Ming Chen
Journal: Blood (2010)
Generalizability of the Prostate Cancer Intervention Versus Observation Trial (PIVOT) Results to Contemporary North American Men with Prostate Cancer
Authors: Deepansh Dalela, Patrick Karabon, Jesse Sammon, Akshay Sood, Björn Löppenberg, Quoc-Dien Trinh, Mani Menon, Firas Abdollah
Journal: European Urology (2016)
PTEN and MDM2 inhibitors: Toward a novel pro-senescence therapy approach for patients with cancer.
Authors: A. Alimonti, C. Nardella, I. Pavese, J. G. Clohessy, A. Carracedo, L. C. Trotman, R. Woscholski, F. Cognetti, H. I. Scher, P. Pandolfi
Journal: Journal of Clinical Oncology (2010)

e13572 Background: Cellular senescence, an irreversible cell growth arrest, is an intrinsic tumor suppressive mechanism, which restricts progression of early cancerous lesions in humans. We have demonstrated in a murine model for prostate cancer that complete inactivation of the tumor suppressor Pten elicits a senescence response, which significantly opposes tumorigenesis (Chen ZB, Nature 2005). Here we characterize Pten loss induced cellular senescence (PICS) as a novel type of senescence. Additionally, we show that compounds which target PTEN and MDM-2 can be used alone or in combination to potentiate the senescence pathway in tumors of genetically engineered mouse (GEM) and human xenografts models. Methods: Cell growth inhibition, western blot analysis and senescence assay (SA) were performed on LnCAP, MDA-PCa2b and PC3 cancer cell lines. Immunohistochemestry analysis and SA were performed in murine tumors. Cells were incubated with the PTEN inhibitor VO-OHpic (V) and the MDM-2 inhibitor, Nutlin-3 (N) at doses including the IC50 for each drug and cell type. In vivo evaluation of V and N were done both in Pten null prostate conditional mice (Ptenpc−/−) and human xenograft models. Results: PICS, represents a distinct type of senescence response that can be targeted for cancer therapy. PICS occurs at early time points after Pten inactivation and in the absence of cellular proliferation and DNA damage. Importantly, we have identified and developed for cancer therapy a novel PTEN inhibitor. Pharmacological inhibition of PTEN drives senescence in vitro and inhibits tumourigenesis in vivo in a human xenograft model. We also find that PICS is associated with enhanced mTOR-dependent p53 translation. In agreement with these mechanistic findings, N dramatically potentiate senescence and strongly inhibits tumorigenesis in Ptenpc−/− mice. Combination of V and N acts synergistically in inducing senescence in vitro and reducing cell growth. Conclusions: Taken together, our data identify a type of cellular senescence that can be triggered in non-proliferating cells in the absence of DNA damage . On the basis of this concept, we define a molecular framework for “pro-senescence” therapy against cancer. No significant financial relationships to disclose.
Excellent Results in Children and Adolescents with Isolated Mature B-Acute Lymphoblastic Leukemia (B-ALL) (Burkitt): Report from the French-American-British (FAB) International LMB Study FAB/LMB96.
Authors: Stan Goldman, Mary Gerrard, Richard Sposto, Ginny Davenport, Anne Auperin, Ross Pinkerton, Jean Michon, Claire Weston, Sherrie L. Perkins, Martine Raphael, Keith McCarthy, Catherine Patte, Mitchell S. Cairo
Journal: Blood (2005)
Effect of Hepatitis B virus replication on oxidative stress, gene expression and induction of genetic changes in an inducible cell culture model of HepAD38 cells
Authors: Tamara Severi, Chunxiao Ying, Joris Vermeesch, Marcel Zeegers, Alfons Van Lommel, Roger Servaes, Johan Neyts, Johan Fevery, Jos van Pelt
Journal: Journal of Hepatology (2005)
The Projected Epidemic of Chronic Obstructive Pulmonary Disease Hospitalizations over the Next 15 Years. A Population-based Perspective
Authors: Amir Khakban, Don D. Sin, J. Mark FitzGerald, Bruce M. McManus, Raymond Ng, Zsuzsanna Hollander, Mohsen Sadatsafavi
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

COPD is currently one of the leading causes of hospitalizations in industrialized countries. The future burden of COPD is uncertain as the trends in the prevalence of the main risk factors for COPD, namely cigarette smoking and population aging, are moving in opposite directions in many jurisdictions. Here, we used data from British Columbia (BC), a Canadian Province of 4.7 million people, as an exemplary jurisdiction to illustrate the projected growth of COPD hospitalizations over the next 15 years in developed countries. We combined forecasts of population growth and aging with an Autoregressive Integrated Moving Average (ARIMA) model applied to BC’s population-based administrative health databases (2001 to 2010) to project the trends in the incidence, prevalence, deaths, and total length of inpatient stays to 2030. Based on this model, we predict that the absolute number of COPD cases will increase by more than 150% from 2010 to 2030 with the greatest growth in the older age group (75 years of age and ...
Cetuximab monotherapy is active in patients (pts) with platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN): Results of a phase II study
Authors: J. Trigo, R. Hitt, P. Koralewski, E. Diaz-Rubio, F. Rolland, R. Knecht, N. Amellal, E. H. Bessa, J. Baselga, J. B. Vermorken
Journal: Journal of Clinical Oncology (2004)

5502 Background: Pts with refractory SCCHN have a poor prognosis with few therapeutic options. Cetuximab (Erbitux), an IgG1 monoclonal antibody that binds selectively to EGFR, has shown activity in combination with cisplatin or carboplatin in pts with recurrent/metastatic SCCHN progressing on the same platinum-based regimen (Baselga #900, Kies #925; ASCO 2002). Methods: This multicenter phase II study was designed to investigate the efficacy of cetuximab as monotherapy in pts with platinum-refractory SCCHN. Main inclusion criteria were: stage III/IV recurrent and/or metastatic SCCHN not suitable for local therapy, with documented progression on or within 30 days after 2 to 6 cycles of a platinum-based CT. Cetuximab was given at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression, with the option to switch to the combination of cetuximab with the same platinum that the pts had previously progressed on, after failure to cetuximab monotherapy. Results: 103 pts (84 M, 19 F) were enrolled. Median age was 57 years (23–77), median baseline KPS was 80 (60–100) and median time from diagnosis to study entry was 20 months (3–283). Drug-related adverse events occurring in >10% of pts included: skin rash/acne 80% (1% grade 3), fatigue 24% (4% grade 3), fever/chills 19% (2% grade 3), nail changes 15% (all grade 1–2) and nausea 13% (1% grade 3). There was one treatment-related death due to hypersensitivity reaction in a patient not suitable to receive mechanical ventilation. Preliminary efficacy data (based on investigator assessment) were as follows: 5 CR, 12 PR, 38 SD, 47 PD, 1 not assessable, for an overall objective response rate of 16.5% (95% CI: 9.9%–25.1%). Disease control rate was 53.4% (95% CI: 43.3%–63.3%). Median TTP and median survival were 85 and 175 days, respectively. An independent review of all pre-treatment and on-study imaging assessments is ongoing and will be available at the meeting. Conclusions: Cetuximab as single agent can produce major objective responses in pts with platinum-refractory recurrent/metastatic SCCHN, with acceptable toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck
Unsupervised High-Dimensional Analysis Aligns Dendritic Cells across Tissues and Species
Authors: Martin Guilliams, Charles-Antoine Dutertre, Charlotte L. Scott, Naomi McGovern, Dorine Sichien, Svetoslav Chakarov, Sofie Van Gassen, Jinmiao Chen, Michael Poidinger, Sofie De Prijck, Simon J. Tavernier, Ivy Low, Sergio Erdal Irac, Citra Nurfarah Mattar, Hermi Rizal Sumatoh, Gillian Hui Ling Low, Tam John Kit Chung, Dedrick Kok Hong Chan, Ker Kan Tan, Tony Lim Kiat Hon, Even Fossum, Bjarne Bogen, Mahesh Choolani, Jerry Kok Yen Chan, Anis Larbi, Hervé Luche, Sandrine Henri, Yvan Saeys, Evan William Newell, Bart N. Lambrecht, Bernard Malissen, Florent Ginhoux
Journal: Immunity (2016)

Dendritic cells (DCs) are professional antigen-presenting cells that hold great therapeutic potential. Multiple DC subsets have been described, and it remains challenging to align them across tissues and species to analyze their function in the absence of macrophage contamination. Here, we provide and validate a universal toolbox for the automated identification of DCs through unsupervised analysis of conventional flow cytometry and mass cytometry data obtained from multiple mouse, macaque, and human tissues. The use of a minimal set of lineage-imprinted markers was sufficient to subdivide DCs into conventional type 1 (cDC1s), conventional type 2 (cDC2s), and plasmacytoid DCs (pDCs) across tissues and species. This way, a large number of additional markers can still be used to further characterize the heterogeneity of DCs across tissues and during inflammation. This framework represents the way forward to a universal, high-throughput, and standardized analysis of DC populations from mutant mice and human patients.
Specific Inhibition of DNMT3A/ISGF3γ Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth
Authors: Mathilde Cheray, Romain Pacaud, Arulraj Nadaradjane, Lisa Oliver, François M Vallette, Pierre-François Cartron
Journal: Theranostics (2016)

DNA methylation is a fundamental feature of genomes and is a candidate for pharmacological manipulation that might have important therapeutic advantage. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug intervention. By focusing on interactions existing between DNMT3A and DNMT3A-binding protein (D3A-BP), our work identifies the DNMT3A/ISGF3γ interaction such as a biomarker whose the presence level is associated with a poor survival prognosis and with a poor prognosis of response to the conventional chemotherapeutic treatment of glioblastoma multiforme (radiation plus temozolomide). Our data also demonstrates that the disruption of DNMT3A/ISGF3γ interactions increases the efficiency of chemotherapeutic treatment on established tumors in mice. Thus, our data opens a promising and innovative alternative to the development of specific DNMT inhibitors.