tbuckley/cabot-search huggingface dataset:
The burden and direct cost of cancer in Europe (EU-28).
Authors: Nils Erik Wilking, Thomas Hofmarcher, Peter Lindgren, Bengt Jönsson
Journal: Journal of Clinical Oncology (2016)

6618 Background: This study provides a cost estimate for 2014 and also estimates of the development of key components of the costs of cancer in the EU countries for the period 2005-2014. Studies on the development of costs over time provide important information about how changes in the burden of the disease and new treatment approaches are reflected in the costs of cancer. Methods: As with the method used in our previous comparator reports, we estimated the cost of cancer based on a country’s total health expenditure using data from the WHO and Eurostat. The cancer-specific expenditure as a share of total health expenditure was then determined for each country to infer the direct health cost of cancer (DHCC) for each country and the EU as a whole. Sales data on cancer drugs from IMS Health were used to calculate the share of those of the direct health costs. Results: In the EU in 2012 the estimated cancer incidence was 2.6 million cases (1.2 million women, 1.4 million men). The estimated cancer mortality was 1.3 million deaths (0.6 million women, 0.7 million men), accounting for 26% of all deaths. DHCC in the whole EU increased from €79 to €86 billion during 2005-2014 (in 2014 prices). The cost of cancer drugs as a share of direct health costs increased from 12 to 22% during the same period. Other direct costs remained stable or decreased since 2005 probably linked to a shift from in-patient to outpatient care. Conclusions: Cancer burden in EU is significant with 2.6 million new cancer cases and 1.3 million cancer deaths (2012). More than every fourth death is due to cancer. The direct health cost of cancer increased during 2005-2014 and the cost of cancer drugs as a share of direct health costs doubled. The direct health costs per capita vary with a factor 5-6 within the EU during 2005-2014. DHCC in each country in Euros (€) per capita adjusted for purchasing power parity (PPP) in 2014. < 100 €/ capita 100-200 €/ capita >200 €/ capita Bulgaria / 66 Cyprus / 105 Austria / 266 Croatia / 81 Denmark / 163 Belgium / 227 Czech Republic / 91 Finland / 125 France / 212 Estonia / 69 Greece / 127 Germany / 265 Latvia / 62 Hungary / 105 Luxembourg / 323 Lithuania / 79 Ireland / 164 Netherlands / 264 Poland / 81 Italy / 161 Sweden / 223 Portugal / 81 Malta / 134 Romania / 55 Slovakia / 107 Slovenia / 139 Spain / 129 United Kingdom / 136
Tau Protein Disrupts Nucleocytoplasmic Transport in Alzheimer’s Disease
Authors: Bahareh Eftekharzadeh, J. Gavin Daigle, Larisa E. Kapinos, Alyssa Coyne, Julia Schiantarelli, Yari Carlomagno, Casey Cook, Sean J. Miller, Simon Dujardin, Ana S. Amaral, Jonathan C. Grima, Rachel E. Bennett, Katharina Tepper, Michael DeTure, Charles R. Vanderburg, Bianca T. Corjuc, Sarah L. DeVos, Jose Antonio Gonzalez, Jeannie Chew, Svetlana Vidensky, Fred H. Gage, Jerome Mertens, Juan Troncoso, Eckhard Mandelkow, Xavier Salvatella, Roderick Y.H. Lim, Leonard Petrucelli, Susanne Wegmann, Jeffrey D. Rothstein, Bradley T. Hyman
Journal: Neuron (2018)
Abstract 12392: Optimal Balloon Size in Post-Stenting Angioplasty for Aortoiliac Occlusive Disease (AIOD) With Self-Expandable Nitinol Stent
Authors: Shota Tohoku, Yoshimitsu Soga, Yusuke Tomoi
Journal: Circulation (2014)

Introduction: Although the self-expandable nitinol stent is considered to be dilated by radial force in chronic phase after endovascular treatment (EVT), the optimal post-stenting angioplasty has r...
Stratifying Risk for Men With Low-Volume Intermediate-Risk Prostate Cancer—Reply
Authors: Hiten D. Patel, Jeffrey J. Tosoian, H. Ballentine Carter, Jonathan I. Epstein
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Metabolic recoding of epigenetics in cancer
Authors: Yi‐Ping Wang, Qun‐Ying Lei
Journal: Cancer Communications (2018)

Abstract Dysregulation of metabolism allows tumor cells to generate needed building blocks as well as to modulate epigenetic marks to support cancer initiation and progression. Cancer‐induced metabolic changes alter the epigenetic landscape, especially modifications on histones and DNA, thereby promoting malignant transformation, adaptation to inadequate nutrition, and metastasis. Recent advances in cancer metabolism shed light on how aberrations in metabolites and metabolic enzymes modify epigenetic programs. The metabolism‐induced recoding of epigenetics in cancer depends strongly on nutrient availability for tumor cells. In this review, we focus on metabolic remodeling of epigenetics in cancer and examine potential mechanisms by which cancer cells integrate nutritional inputs into epigenetic modification.
Abstract 13948: High Intraprocedural Atrial Fibrillation Termination Rate by Large Area Rotor Ablation Combined With Pulmonary Vein Isolation
Authors: Zsuzsanna Kis, Rohit Bhagwandien, Dominic Theuns, Sip Wijchers, Tamas Szili-Torok
Journal: Circulation (2016)

Introduction: There remains contradictory data about the optimal ablation technique and the type of termination of atrial fibrillation (AF) ablation particularly in patient (pt) with persistent AF. The aim of this study was to determine the type of the termination of persistent AF during combined conventional and rotor ablation. Method: This is a single-center, prospective, observational study enrolled thirty-eight pts (24/63% male, mean age 63 years) with AF (mean left atrial size: 46,2 ± 7 mm), who underwent focal impulse and rotor modulation (FIRM) mapping and large area ablation around the core of the identified rotor(s), followed by conventional pulmonary vein isolation(PVI) using contact force catheter aiming 10-20 gr depending on the location. Two distinctive types of the AF termination were defined: sub-acute termination related to rotor elimination, furthermore acute termination due to PVI. Electric cardioversion (ECV) was executed only in the absence of spontaneous conversion to sinus rhythm (SR). Result: In 10(26%) pts acute AF termination after PVI was observed. In further 12 (31%) pts sub-acute termination of the AF could be observed after the identified rotor ablation. The combined technique of conventional and rotor ablation of pts with persistent AF resulted in 57,8% of termination rate. Spontaneous cardioversion could not be reached in 16 (42%) pts however 15 out of them were converted to SR by ECV. Procedural complication occurred in 3 pts presenting with groin hematoma, in one patient left atrial appendage (LAA) thrombus was revealed by transoesophageal echocardiography performed right after the ablation for guiding the planned LAA closure. Conclusion: Large area rotor ablation drag technique combined with contact force sensing technique results in a high termination rate of persistent AF. More studies are warranted to define the clinical significance and long term success rate of rotor ablation in pts with persistent atrial fibrillation.
Abstract #5526: MSH6 somatic mutations in mediating temozolomide resistance in recurrent glioblastomas
Authors: Jiangyong Miao, Stephen Yip, Daniel Cahill, A. John Iafrate, Ken Aldape, Catherine Nutt, David Louis
Journal: Cancer Research (2009)

Over the past few years, the alkylating agent temozolomide (TMZ) has become the standard-of-care therapy for patients with glioblastoma, the most common primary brain tumor. Recent large-scale cancer genome sequencing efforts have identified a hypermutation phenotype and inactivating  MSH6  mismatch repair gene mutations in recurrent, post-TMZ glioblastomas, particularly those growing more rapidly during TMZ treatment.  MSH6  sequence and microsatellite instability (MSI) status were determined in matched pre- and post-chemotherapy glioblastomas identified by The Cancer Genome Atlas (TCGA) as having  post-treatment  MSH6  mutations. These were confirmed in post-treatment TCGA glioblastomas but absent in matched pre-treatment tumors. The post-treatment hypermutation phenotype was biased toward CpC transitions and was not associated with MSI. This is consistent with development of  MSH6  mutations as an escape mechanism during alkylator therapy  in vivo . Next, we sought to explore the role of  MSH6  mutations in mediating TMZ cytotoxicity  in vitro . We derived TMZ-resistant clones  in vitro  via selective growth under TMZ exposure and the  MSH6  gene was sequenced in resistant clones. One clone (A172TR3) showed an  MSH6  mutation (T1219I) that was not present in the parental line but that had been noted in two treated TCGA glioblastomas. The role of MSH6 inactivation in mediating resistance to TMZ exposure was further explored using lentiviral shRNA knockdown of MSH6 in the human glioblastoma line U251. Clones with suppressed MSH6 expression demonstrated increased resistance to TMZ cytotoxicity. Previously, we have shown that  MSH6  mutations are selected for in glioblastomas during TMZ therapy  in vivo . Recently, additional cases are reported by TCGA in large-scale profiling of glioblastomas. In this study, we showed that somatic  MSH6  mutations in TCGA post-treatment tumors with hypermutation are not present in matched pre-treatment tumors. Additionally, both  in vitro  genetic approaches -sequencing of TMZ- resistant clones and lentiviral knockdown of  MSH6  in glioblastoma cells- have further confirmed the importance of  MSH6  in mediating TMZ resistance. In summary, our  in vitro  data support the  in vivo  observation of  MSH6  in TMZ treatment failure in recurrent glioblastomas.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5526.
Optimization of taste-masking on ibuprofen microspheres with selected structure features
Authors: Wei Qin, Yuanzhi He, Zhen Guo, Liu Zhang, Li Wu, Xianzhen Yin, Shailendra Shakya, Abi Maharjan, Yan Tang, Weifeng Zhu, Jiwen Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The microsphere was a primary particulate system for taste-masking with unique structural features defined by production process. In this article, ibuprofen lipid microspheres of octadecanol and glycerin monostearate were prepared to mask the undesirable taste of ibuprofen via three kinds of spray congealing processes, namely, air-cooling, water-cooling and citric acid solution-cooling. The stereoscopic and internal structures of ibuprofen microspheres were quantitatively analyzed by synchrotron radiation X-ray micro-computed tomography (SR-µCT) to establish the relationship between the preparation process and microsphere architectures. It was found that the microstructure and morphology of the microspheres were significantly influenced by preparation processes as the primary factors to determine the release profiles and taste-masking effects. The sphericity of ibuprofen microspheres congealed in citric acid solution was higher than that of other two and its morphology was more regular than that being congealed in air or distilled water, and the contact angles between congealing media and melted ibuprofen in octadecanol and glycerin monostearate well demonstrated the structure differences among microspheres of three processes which controlled the release characteristics of the microspheres. The structure parameters like porosity, sphericity, and radius ratio from quantitative analysis were correlated well with drug release behaviors. The results demonstrated that the exterior morphology and internal structure of microspheres had considerable influences on the drug release behaviors as well as taste-masking effects.
Will women with breast cancer (BC) be willing to take an adjuvant CDK4/6 inhibitor in addition to endocrine therapy (ET)?
Authors: Jessica Jesin, Danielle Desautels, Alex Kiss, Ellen Warner, Katarzyna Joanna Jerzak
Journal: Journal of Clinical Oncology (2018)

e12566 Background: The steady decline in BC mortality has come at the cost of increasingly long, complex, toxic (and expensive) adjuvant therapies. Trials evaluating the addition of CDK4/6 inhibitors to adjuvant ET are ongoing but patients’ willingness to take them is unknown. Methods: We surveyed 100 consecutive, consenting post-menopausal women with non-metastatic ER+ BC who had initiated adjuvant ET within the past 2 years. Participants were asked about perceived recurrence risk, BC worry and overall health. They were then asked about their willingness to accept 2 years of treatment with an additional adjuvant oral drug for a range of baseline recurrence risks in 2 hypothetical scenarios (both requiring monthly bloodwork) assuming that the drug caused i) no side effects or ii) mild fatigue only. In a 3rd scenario patients were asked for what absolute risk reduction they would take the drug if it caused fatigue and rarely infection or bleeding. For each scenario, the drug was presented as providing a constant 40% relative risk reduction. Results: Mean age of the 100 participants (of 162 eligible) was 62; 79% had lymph node negative disease. Their likelihood of taking the drug with varying hypothetical recurrence risks and side effects is outlined in Table 1. There was no significant correlation between age, self-perceived risk of BC recurrence or self-perceived overall health with patient responses. However, women who worried about BC recurrence were more likely to accept additional adjuvant therapy that caused mild fatigue. For the scenario including rare infection or bleeding the mean absolute risk reduction women would need to take the drug was 34%. Conclusions: Assuming positive results of ongoing trials, the willingness of ER+ BC patients to take an adjuvant CDK4/6 inhibitor will be highly dependent on the expected benefit and toxicities described to them. Table 1. Percentage of women likely or very likely to take the oral drug Drug does not cause side effects Drug causes mild fatigue Baseline risk of 50% reduced to 30% Baseline risk of 20% reduced to 12% Baseline risk of 10% reduced to 6% Baseline risk of 5% reduced to 3% Baseline risk of 50% reduced to 30% Baseline risk of 5% reduced to 3% 84% 70% 59% 49% 65% 39%
T Cell–Dependent Affinity Maturation and Innate Immune Pathways Differentially Drive Autoreactive B Cell Responses in Rheumatoid Arthritis
Authors: Daniel R. Lu, Andrew N. McDavid, Sarah Kongpachith, Nithya Lingampalli, Jacob Glanville, Chia‐Hsin Ju, Raphael Gottardo, William H. Robinson
Journal: Arthritis & Rheumatology (2018)

Rheumatoid arthritis (RA) is characterized by the activation of B cells that produce anti-citrullinated protein antibodies (ACPAs) and rheumatoid factors (RFs), but the mechanisms by which tolerance is broken in these B cells remain incompletely understood. We undertook this study to investigate whether ACPA+ and RF+ B cells break tolerance through distinct molecular mechanisms.We developed antigen-tetramers to isolate ACPA+ and RF+ B cells and performed single-cell RNA sequencing on 2,349 B cells from 6 RA patients and 1 healthy donor to analyze their immunoglobulin repertoires and transcriptional programs. Prominent immunoglobulins were expressed as monoclonal antibodies and tested for autoantigen reactivity.ACPA+ and RF+ B cells were enriched in the peripheral blood of RA patients relative to healthy controls. Characterization of patient-derived monoclonal antibodies confirmed ACPA and RF targeting of tetramer-specific B cells at both antigen-inexperienced and affinity-matured B cell stages. ACPA+ B cells used more class-switched isotypes and exhibited more somatic hypermutations relative to RF+ B cells, and these differences were accompanied by down-regulation of CD72 and up-regulation of genes that promote class-switching and T cell-dependent responses. In contrast, RF+ B cells expressed transcriptional programs that stimulate rapid memory reactivation through multiple innate immune pathways. Coexpression analysis revealed that ACPA+ and RF+ B cell-enriched genes belong to distinct transcriptional regulatory networks.Our findings suggest that ACPA+ and RF+ B cells are imprinted with distinct transcriptional programs, which suggests that these autoantibodies associated with increased inflammation in RA arise from 2 different molecular mechanisms.
Is the Cognitive Cardiologist Obsolete?
Authors: John E. Brush
Journal: JAMA Cardiology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Impact of next-generation sequencing (NGS) on treatment selection in acute myeloid leukemia (AML).
Authors: Rita Elias Assi, Ana Alfonso Pierola, Devendra KC, Yasmin Mohammed Abaza, Abdallah Abou Zahr, Kamal Chamoun, Guillermo Montalban-Bravo, Koichi Takahashi, Elias Jabbour, Tapan M. Kadia, Farhad Ravandi, Jorge E. Cortes, Courtney Denton Dinardo, Naval Guastad Daver, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Andrew Futreal, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Journal of Clinical Oncology (2018)

103 Background: Until recently, therapy options for AML patients (pts) were limited. The advent of NGS and novel targeted agents raise the question of how broader use of testing will impact treatment and outcomes. Methods: From October 2012 to June 2016, we included 1470 AML pts with available NGS-based detection of somatic mutations. 17 genes (ALK, CSF1R, FGFR1/2/3, FLT3, IDH1/2, JAK2, KDR, KRAS/NRAS, NPM1, PDGFRA, PTPN11, RET and TP53) were considered potentially actionable due to the possibility to be directly or indirectly targeted with standard or investigational agents. Results: of the 1271 treated pts, 982 (77%) had a median of 2 actionable mutations (AMs) (1-5): TP53 (n = 241; 16%), IDH2 (n = 240; 16%), IDH1 (n = 238; 16%), FLT3 (200; 14%), NPM1 (n = 195; 13%), NRAS (n = 175; 12%), JAK2 (103; 7%), KRAS (n = 82; 6%). 41% (271/518) of pts started new therapy after NGS results availability. NGS guided targeted therapy in 36% of pts: 53% of these enrolled on clinical trials (CT) and 6% received off-label agents. Considering AMs only, relapsed/refractory (R/R) pts were more likely to receive targeted therapy than newly diagnosed (51% vs 23%, p < 0.0001). At different timepoints, the probability of receiving targeted agent for pts with AMs was 9% (13/140) for the period 2012-Sept 2013, 21% (143/685) for Oct 2013-2014 and 23% (147/645) in 2015-June 2016 (p = 0.001). Pts who received targeted therapy had higher response rate compared to those who did not whether newly diagnosed (72% vs 60%;p = 0.04) or R/R (31% vs 21%; p = 0.001). Conclusions: NGS can impact therapy decision in more than 30% of AML pts when performed in a timely manner. R/R pts were more likely to receive targeted agents than newly diagnosed. Possible reasons are delays in NGS results, urgency to start therapy and presumption that standard therapy may be better than investigational targeted agents. The results of current CT may change the way we treat AML pts. Treated pts 1271/1470 (86%) Median age 63 yrs (17-92) Male 782 (62%) Median time to inform results 9 days (3-90) Newly diagnosed (N = 519) R/R (N = 463) Actionable mutation(s) 390 (75%) 338 (73%) Subsequent targeted therapy p < 0.0001 91/390 (23%) 173/338 (51%) On CT 75 (19%) 149 (44%) Off-label 16 (4%) 24 (7%) Alive at last follow-up 55% 76%
InFlo: A systems biology framework to discover molecular mechanisms underlying response to therapy.
Authors: Salendra Singh, Lyndsay Harris, Hannah L. Gilmore, Yee Him Cheung, Nevenka Dimitrova, Vinay Varadan
Journal: Journal of Clinical Oncology (2018)

e12635 Background: There is a dearth of reliable analytic solutions that enable integration of tumor and immune profiles to determine mechanisms of response to targeted therapies. We developed a systems biology framework, InFlo, to enable robust discovery of predictive biomarkers and delineation of therapeutic response mechanisms (Oncogene, 2017). We highlight InFlo’s capabilities by discovering immune-related signaling networks associated with response to preoperative anti-HER2 therapy in early-stage breast cancer. Methods: InFlo has been implemented as a flexible and extensible interactive analytics engine to enable clinicians and translational researchers to perform complex analyses of multi-omics tumor profiles derived from clinical tumor samples. The web-application additionally enables validation of the InFlo-based discoveries through comparative analysis of multi-omics data obtained from publicly-available resources such as the Genomics Data Commons. We employed InFlo to integrate gene expression and copy-number data derived from HER2+ early breast cancer (EBC) patients enrolled in two independent multi-center clinical trials, DFCI 03-311 (N= 80) and BrUOG 211B (N= 60). Results: Unsupervised clustering analyses using InFlo-based signaling network activity estimates revealed signaling networks associated with PAM50 subtypes as well as immune infiltration. Furthermore, InFlo-based analysis of signaling network activities in patient tumors after a single dose of trastuzumab revealed significantly higher activity (P= 0.008) of signaling networks associated with CD4+ T-cells in responders (pCR & RCB I) versus non-responders (RCB II & III). Finally, InFlo also revealed potential resistance mechanisms, specifically, higher activity of mTOR pathway (P= 0.0014) in non-responders after one dose of trastuzumab. Conclusions: InFlo-based analysis enabled by the interactive web-application resulted in the discovery and validation of signaling networks associated with modulation of the tumor immune microenvironment by trastuzumab in clinical trial datasets. InFlo is a transformative functional genomics software platform with widespread applications in translational oncology.