tbuckley/cabot-search huggingface dataset:
Safety of extending screening intervals beyond five years in cervical screening programmes with testing for high risk human papillomavirus: 14 year follow-up of population based randomised cohort in the Netherlands
Authors: Maaike G Dijkstra, Marjolein van Zummeren, Lawrence Rozendaal, Folkert J van Kemenade, Theo J M Helmerhorst, Peter J F Snijders, Chris J L M Meijer, Johannes Berkhof
Journal: BMJ (2016)

<b>Objectives</b>&nbsp;To provide an early risk assessment of extending screening intervals beyond five years for a human papillomavirus (HPV) based cervical screening programme in the Netherlands. <b>Design</b>&nbsp;14 year follow-up of a population based randomised cohort from the POBASCAM randomised trial. <b>Setting</b>&nbsp;Organised cervical screening in the Netherlands, based on a programme of three screening rounds (each round done every five years). <b>Participants</b>&nbsp;43 339 women aged 29-61 years with a negative HPV and/or negative cytology test participating in the POBASCAM trial. <b>Interventions</b>&nbsp;Women randomly assigned to HPV and cytology co-testing (intervention) or cytology testing only (control), and managed accordingly. <b>Main outcome measures</b>&nbsp;Cumulative incidence of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+). Associations with age were expressed as incidence rate ratios. In HPV positive women, reductions in CIN3+ incidence after negative cytology, HPV type 16/18 genotyping, and/or repeat cytology were estimated. <b>Results</b>&nbsp;The cumulative incidence of cervical cancer (0.09%) and CIN3+ (0.56%) among HPV negative women in the intervention group after three rounds of screening were similar to the cumulative among women with negative cytology in the control group after two rounds (0.09% and 0.69%, respectively). Cervical cancer and CIN3+ risk ratios were 0.97 (95% confidence interval 0.41 to 2.31, P=0.95) and 0.82 (0.62 to 1.09, P=0.17), respectively. CIN3+ incidence was 72.2% (95% confidence interval 61.6% to 79.9%, P&lt;0.001) lower among HPV negative women aged at least 40 years than among younger women. No significant association between cervical cancer incidence and age could be demonstrated. CIN3+ incidence among HPV positive women with negative cytology, HPV 16/18 genotyping, and/or repeat cytology was 10.4 (95% confidence interval 5.9 to 18.4) times higher than among HPV negative women. <b>Conclusions</b>&nbsp;Long term incidences of cervical cancer and CIN3+ were low among HPV negative women in this study cohort, and supports an extension of the cervical screening interval beyond five years for women aged 40 years and older. HPV positive women with subsequent negative cytology, HPV16/18 genotyping, and/or repeat cytology have at least a fivefold higher risk of CIN3+ than HPV negative women, indicating that HPV based programmes with long intervals (&gt;five years) should be implemented with risk stratification. <b>Trial registration</b>&nbsp;POBASCAM trial number ISRCTN20781131.
Rapid Functional and Sequence Differentiation of a Tandemly Repeated Species-Specific Multigene Family in<i>Drosophila</i>
Authors: Bryan D. Clifton, Pablo Librado, Shu-Dan Yeh, Edwin S. Solares, Daphne A. Real, Suvini U. Jayasekera, Wanting Zhang, Mijuan Shi, Ronni V. Park, Robert D. Magie, Hsiu-Ching Ma, Xiao-Qin Xia, Antonio Marco, Julio Rozas, José M. Ranz
Journal: Molecular Biology and Evolution (2016)

Gene clusters of recently duplicated genes are hotbeds for evolutionary change. However, our understanding of how mutational mechanisms and evolutionary forces shape the structural and functional evolution of these clusters is hindered by the high sequence identity among the copies, which typically results in their inaccurate representation in genome assemblies. The presumed testis-specific, chimeric gene Sdic originated, and tandemly expanded in Drosophila melanogaster, contributing to increased male-male competition. Using various types of massively parallel sequencing data, we studied the organization, sequence evolution, and functional attributes of the different Sdic copies. By leveraging long-read sequencing data, we uncovered both copy number and order differences from the currently accepted annotation for the Sdic region. Despite evidence for pervasive gene conversion affecting the Sdic copies, we also detected signatures of two episodes of diversifying selection, which have contributed to the evolution of a variety of C-termini and miRNA binding site compositions. Expression analyses involving RNA-seq datasets from 59 different biological conditions revealed distinctive expression breadths among the copies, with three copies being transcribed in females, opening the possibility to a sexually antagonistic effect. Phenotypic assays using Sdic knock-out strains indicated that should this antagonistic effect exist, it does not compromise female fertility. Our results strongly suggest that the genome consolidation of the Sdic gene cluster is more the result of a quick exploration of different paths of molecular tinkering by different copies than a mere dosage increase, which could be a recurrent evolutionary outcome in the presence of persistent sexual selection.
Absence of an IgD−/CD27+ Switched Memory B Cell Population with Persistent Hypogammaglobulinemia after Rituximab Administration as an Adjuvant Therapy after Autologous Stem Cell Transplantation for Non-Hodgkin Lymphoma.
Authors: Mitsufumi Nishio, Katsuya Fujimoto, Satoshi Yamamoto, Toshiya Sakai, Masato Obara, Koki Kumano, Koichiro Minauchi, Masayuki Yamakura, Norihiro Sato, Takao Koike
Journal: Blood (2005)
Prediction of gestational age based on genome-wide differentially methylated regions
Authors: J. Bohlin, S. E. Håberg, P. Magnus, S. E. Reese, H. K. Gjessing, M. C. Magnus, C. L. Parr, C. M. Page, S. J. London, W. Nystad
Journal: Genome biology (2016)

We explored the association between gestational age and cord blood DNA methylation at birth and whether DNA methylation could be effective in predicting gestational age due to limitations with the presently used methods. We used data from the Norwegian Mother and Child Birth Cohort study (MoBa) with Illumina HumanMethylation450 data measured for 1753 newborns in two batches: MoBa 1, n = 1068; and MoBa 2, n = 685. Gestational age was computed using both ultrasound and the last menstrual period. We evaluated associations between DNA methylation and gestational age and developed a statistical model for predicting gestational age using MoBa 1 for training and MoBa 2 for predictions. The prediction model was additionally used to compare ultrasound and last menstrual period-based gestational age predictions. Furthermore, both CpGs and associated genes detected in the training models were compared to those detected in a published prediction model for chronological age. There were 5474 CpGs associated with ultrasound gestational age after adjustment for a set of covariates, including estimated cell type proportions, and Bonferroni-correction for multiple testing. Our model predicted ultrasound gestational age more accurately than it predicted last menstrual period gestational age. DNA methylation at birth appears to be a good predictor of gestational age. Ultrasound gestational age is more strongly associated with methylation than last menstrual period gestational age. The CpGs linked with our gestational age prediction model, and their associated genes, differed substantially from the corresponding CpGs and genes associated with a chronological age prediction model.
The efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: A phase III randomized, double blind, placebo-controlled NCCTG trial, N01C3
Authors: S. I. Renno, R. D. Rao, J. Sloan, G. Wong, D. Johnson, G. M. Howard, P. Novotny, F. J. Patrick, C. L. Loprinzi
Journal: Journal of Clinical Oncology (2006)

8530 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose limiting complication of chemotherapy. Lamotrigine (an anti-convulsant drug) appears to have some benefit when used to treat pain from neuropathy due to various etiologies. Based on these data, we conducted a phase III randomized placebo controlled study to determine the efficacy of lamotrigine in treating symptoms from CIPN. Methods: Patients with CIPN for 1 month or more were randomly assigned to lamotrigine (target dose 300 mg/day, increased by 50 mg/2 weeks) or placebo for 10 weeks. The co-primary endpoints were differences in average CIPN symptoms assessed by pro-rated area under the curve (AUC) of a numerical pain rating scale (NRS) and the Eastern Cooperative Oncology Group sensory neuropathy (ESN) scale. Accrual of 60 patients per group provided t-tests with 80% power to detect a difference of 0.57 standard deviation for each co-primary endpoint (moderate effect size) with a type I error of 0.025. Results: 131patients were enrolled, with complete data available for analysis in 93 (72%). Analyses were limited to this cohort but will be updated. Chemotherapy drugs considered to be causative of the CIPN were vinca alkaloids (30%), taxanes (25%), platinum-agents (7%), combinations (34%), and others (3%). Patients were equally matched with regards to baseline characteristics. Patients who enrolled had severe symptoms, with a baseline median ESN at enrollment of 3 (out of 3) in both groups. Toxicities were similar in both groups, however, more patients discontinued lamotrigine due to toxicities/refusals than those on placebo (32% vs 13% resp; p=0.04) and were therefore less likely to complete the 10 weeks therapy (60% vs. 78% resp, p=0.08). Average AUC of NRS score for patients on lamotrigine and placebo was 30.5 and 33.7 resp (p=0.48). The corresponding average AUC of the ESN scores were 12.4 and 14.5 (p=0.23). The proportions of patients with a 10 point (of 100) improvement in worst pain score (39% vs 36%) and a 1 point change in ESN (25% vs 27%) were similar between the lamotrigine and placebo arms, resp. Conclusions: These results suggest that lamotrigine is not effective for managing pain and symptoms due to CIPN. No significant financial relationships to disclose.
Prognostic impact of tumor MET expression among patients with stage IV gastric cancer: A Danish cohort study.
Authors: Rune Erichsen, Kelly S. Oliner, Michael A. Kelsh, Karsten B. Nielsen, Trine Frøslev, Anne-Vibeke Lænkholm, Mogens Vyberg, John F. Acquavella, Henrik Toft Sørensen
Journal: Journal of Clinical Oncology (2014)

43 Background: Recent clinical trial data indicate poor prognosis for patients with late-stage gastric cancer and positive tumor mesenchymal epithelial transition factor (MET) protein expression. However, there is limited information about the real-world prevalence of MET-positive (-pos) cancers and the associated prognosis. Methods: Using medical registries, we identified a cohort of patients with stage IV gastric cancer in a single institution in Northern Denmark from 2003-2010. From these patients, we collected archived (paraffin-embedded) cancer specimens and analyzed MET protein expression by immunohistochemistry (MET-pos if ≥25% of tumor cells showed membrane staining). We calculated the prevalence of patients with MET-pos tumors. We estimated survival using the Kaplan-Meier method and computed mortality rate ratios comparing MET-pos to MET-negative (-neg) patients using Cox proportional hazards models adjusted for age, gender, and Charlson’s Comorbidity Index (score of 0, 1-2, and 3+). Results: 101 patients with stage IV gastric cancer were included in the study of which 55% had MET-pos tumors. The group of patients with MET-pos tumors were younger at diagnosis than patients with MET-neg tumors (median age 65 vs 68 years), included more men, showed higher comorbidity levels, included more poorly differentiated cancers, and were less likely to undergo surgery or chemotherapy. In patients with MET-pos tumors, one-year survival was 18% compared to 39% in patients with MET-neg tumors (mortality rate ratio=2.3, 95% CI: 1.4-3.9). Conclusions: A large proportion of patients with stage IV gastric cancer had tumors demonstrating MET protein expression, and these patients had poor survival compared with patients without tumor MET expression. [Table: see text]
Improving quality of care and health outcomes for cancer survivors: Insights from the Patient-Centered Outcomes Research Institute’s (PCORI) cancer portfolio.
Authors: Neeraj K. Arora, Christopher Gayer, William Lawrence, Vadim Gershteyn, Carly Parry, Kelly Dunham, Steven Clauser
Journal: Journal of Clinical Oncology (2016)

10 Background: PCORI funds comparative effectiveness research (CER) which aims to produce evidence-based information to help people make informed health care decisions and improve outcomes that matter to patients. Cancer studies form one of the largest disease-specific PCORI-funded portfolios. Methods: We conducted a systematic analysis of PCORI’s cancer portfolio overall and of the subset of studies that focus on post-treatment survivorship. Results: As of June 2015, PCORI has funded 47 cancer projects totaling $125 million. Cancer studies account for 17% of PCORI’s dollar investment in CER research. These studies have focused on breast, lung, prostate, colorectal, cervical, ovarian, and pancreatic cancers as well as leukemia. A majority of PCORI-funded cancer studies are randomized trials (60% of studies, 72% of dollar investment). One-in-four studies address post-treatment survivorship (n = 12, $23 million). The 12 CER studies on post-treatment survivorship address a range of patient-centered issues. Four studies are evaluating different post-treatment surveillance approaches for breast (2 studies), colorectal, and lung cancer survivors respectively. Three studies are focusing on optimizing the care planning process for cancer survivors while another is evaluating the impact of an oncology medical home model on patient-centered outcomes. Four studies are addressing quality of life (QOL) issues, one is evaluating approaches for incorporating patient reported outcomes data in the clinical encounter, a second is evaluating a multi-component intervention to improve the QOL of cancer survivors, a third study is evaluating the comparative effectiveness of complementary therapies to treat symptoms, and another is addressing distress among caregivers of stem cell transplant survivors. Conclusions: PCORI-funded CER studies are rigorously evaluating the real world impact of a range of interventions aimed at optimizing the quality of care delivered to and outcomes experienced by cancer survivors. Our analysis of the cancer portfolio will inform future funding priorities aimed at improving patient-centered outcomes for cancer survivors.
Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients
Authors: M. A. Portelli, C. Moseley, C. E. Stewart, D. S. Postma, P. Howarth, J. A. Warner, J. W. Holloway, G. H. Koppelman, C. Brightling, I. Sayers
Journal: Allergy (2016)

Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (uPAR/PLAUR) have been associated with lung function decline and uPAR blood levels in asthma subjects. Preliminary studies have identified uPAR elevation in asthma; however, a definitive study regarding which clinical features of asthma uPAR may be driving is currently lacking.We aimed to comprehensively determine the uPAR expression profile in asthma and control subjects utilizing bronchial biopsies and serum, and to relate uPAR expression to asthma clinical features.uPAR levels were determined in control (n = 9) and asthmatic (n = 27) bronchial biopsies using immunohistochemistry, with a semi-quantitative score defining intensity in multiple cell types. Soluble-cleaved (sc) uPAR levels were determined in serum through ELISA in UK (cases n = 129; controls n = 39) and Dutch (cases n = 514; controls n = 96) cohorts.In bronchial tissue, uPAR was elevated in inflammatory cells in the lamina propria (P = 0.0019), bronchial epithelial (P = 0.0002) and airway smooth muscle cells (P = 0.0352) of patients with asthma, with uPAR levels correlated between the cell types. No correlation with disease severity or asthma clinical features was identified. scuPAR serum levels were elevated in patients with asthma (1.5-fold; P = 0.0008), and we identified an association between high uPAR serum levels and severe, nonatopic disease.This study provides novel data that elevated airway and blood uPAR is a feature of asthma and that blood uPAR is particularly related to severe, nonatopic asthma. The findings warrant further investigation and may provide a therapeutic opportunity for this refractory population.
Progress in Myeloma — A Monoclonal Breakthrough
Authors: S. Vincent Rajkumar, Robert A. Kyle
Journal: New England Journal of Medicine (2016)

In the past decade, we have witnessed more progress in the treatment of multiple myeloma than any other cancer. An improved understanding of disease pathogenesis coupled with biomarker discovery has led to a new disease definition.1 The pronounced depth of response that is possible with new treatments has prompted the development of the assessment of minimal residual disease.2 More importantly, overall survival among patients with myeloma has more than doubled, which is attributable in large part to the effective incorporation of lenalidomide (an immunomodulatory, cereblon-binding drug) and bortezomib (a first-in-class proteasome inhibitor) into the modern therapy for the disease.In . . .
Zika Virus—A Public Health Emergency of International Concern
Authors: Raymond P. Roos
Journal: JAMA Neurology (2016)

Adriana Suely de Oliveira Melo, MD, PhD; Renato Santana Aguiar, PhD; Melania Maria Ramos Amorim, MD, PhD; Monica B. Arruda, PhD; Fabiana de Oliveira Melo, MD; Suelem Taís Clementino Ribeiro, MD; Alba Gean Medeiros Batista, MD; Thales Ferreira, MD; Mayra Pereira dos Santos, MD; Virgínia Vilar Sampaio, MD; Sarah Rogéria Martins Moura, MD; Luciana Portela Rabello, MD; Clarissa Emanuelle Gonzaga, MD; Gustavo Malinger, MD; Renato Ximenes, MD; Patricia Soares de Oliveira-Szejnfeld, MD; Fernanda Tovar-Moll, MD, PhD; Leila Chimelli, MD, PhD; Paola Paz Silveira, MSc; Rodrigo Delvechio, MSc; Luiza Higa, PhD; Loraine Campanati, PhD; Rita M. R. Nogueira, PhD; Ana Maria Bispo Filippis, PhD; Jacob Szejnfeld, MD, PhD; Carolina Moreira Voloch, PhD; Orlando C. Ferreira Jr, MD, PhD; Rodrigo M. Brindeiro, PhD; Amilcar Tanuri, MD, PhD
Randomized phase II study of cabazitaxel versus methotrexate in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) previously treated with platinum-based therapy.
Authors: Sylvie Rottey, Aline Van Maanen, Jean-Marie Vandenbulcke, Bertrand Filleul, Emmanuel Seront, Stefanie Henry, Lionel A. D'Hondt, Christophe Lonchay, Stephane Holbrechts, Petra Boegner, Dany J. Brohee, Didier Dequanter, Ingrid Louviaux, Brieuc Sautois, Nicolas Whenham, Guy J. Berchem, Brigitte Vanderschueren, Christel Fontaine, Sandra Schmitz, Jean-Pascal H. Machiels
Journal: Journal of Clinical Oncology (2015)

6051 Background: Cabazitaxel (caba) is a second-generation taxane that improves overall survival (OS) of patients with metastatic castrate resistant prostate cancer who progress on/after docetaxel. Caba has activity in SCCHN cell lines as well as in taxanes-resistant cell lines. We investigated cabazitaxel in recurrent SCCHN patients. Methods: Patients with non-curable SCCHN with an ECOG 0-2 and progressive disease within 1 year after platinum-based therapy were randomized between caba every 3 weeks (1st cycle : 20 mg/m2, increased to 25mg/m2 for the subsequent cycles, if no adverse event (AE) > grade 3 during the 1st cycle) and methotrexate (MTX) (40 mg/m2/week). Stratification parameters were ECOG PS (0-1vs 2) and prior chemotherapy given for palliation versus the curative treatment. The primary endpoint was the progression free survival rate (PFSR) at 18 weeks (central review). This trial was a randomized phase II trial (P0 = 0.15, P1 = 0.3, a = 0.1, b = 0.1; Fleming one stage). Results: 101 patients (53 in caba and 48 in MTX) were randomized. The median age was 58 years (range 46-80), 63% had received prior platinum for recurrent disease and 37% as part of the multimodal therapy. 17% were ECOG PS 2. 37% had been previously treated with taxanes. PFSR at 18 weeks was 13.2 % (95% IC : 5-25%) for caba and 8.5% (95% IC : 2-20%) for MTX. Median PFS was 1.9 months in both arms. Median OS was 5 and 3.6 months for caba and MTX, respectively. No objective responses were recorded in both arms. More patients experienced Serious AE in caba than in MTX (54 vs 34%). The most common grade ¾ AE in the caba arm was febrile neutropenia (17.3%). Otherwise, the toxicity profile was as expected in both arms. Conclusions: This study did not meet the primary endpoint. Caba has low activity in recurrent SCCHN. Clinical trial information: NCT01528163.
Access to Accredited Cancer Hospitals Within Federal Exchange Plans Under the Affordable Care Act
Authors: Kenneth L. Kehl, Kai-Ping Liao, Trudy M. Krause, Sharon H. Giordano
Journal: Journal of Clinical Oncology (2017)

Purpose The Affordable Care Act expanded access to health insurance in the United States, but concerns have arisen about access to specialized cancer care within narrow provider networks. To characterize the scope and potential impact of this problem, we assessed rates of inclusion of Commission on Cancer (CoC) -accredited hospitals and National Cancer Institute (NCI) -designated cancer centers within federal exchange networks. Methods We downloaded publicly available machine-readable network data and public use files for individual federal exchange plans from the Centers for Medicare and Medicaid Services for the 2016 enrollment year. We linked this information to National Provider Identifier data, identified a set of distinct provider networks, and assessed the rates of inclusion of CoC-accredited hospitals and NCI-designated centers. We measured variation in these rates according to geography, plan type, and metal level. Results Of 4,058 unique individual plans, network data were available for 3,637 (90%); hospital information was available for 3,531 (87%). Provider lists for these plans reduced into 295 unique networks for analysis. Ninety-five percent of networks included at least one CoC-accredited hospital, but just 41% of networks included NCI-designated centers. States and counties each varied substantially in the proportion of networks listed that included NCI-designated centers (range, 0% to 100%). The proportion of networks that included NCI-designated centers also varied by plan type (range, 31% for health maintenance organizations to 49% for preferred provider organizations; P = .04) but not by metal level. Conclusion A large majority of federal exchange networks contain CoC-accredited hospitals, but most do not contain NCI-designated cancer centers. These results will inform policy regarding access to cancer care, and they reinforce the importance of promoting access to clinical trials and specialized care through community sites.