tbuckley/cabot-search huggingface dataset:
Response to: ‘Mortality in ANCA-associated vasculitis: mission incomplete’ by Moiseev <i>et al</i>
Authors: Juan Antonio Avina-Zubieta, Natasha Dehghan, Ju Ann Tan
Journal: Annals of the Rheumatic Diseases (2017)

We thank Professor Moiseev and colleagues for their comments on our article.1 We acknowledge the limitations of including observational studies in our meta-analysis. We also agree that observational studies often suffer from confounding and selection biases, limiting the comparability between studies.2 This was also reflected by the …
Cancer screening among female nursing staff working in a government hospital.
Authors: S Mukesh, Sathya M
Journal: Journal of Clinical Oncology (2016)

e13062 Background: Cervical and breast cancer are the commonest malignancy among females in India. Though there are approved screening methods available to prevent and detect these cancers early, there is lack of knowledge about cancer screening among general public as well as the health care professionals. This study aims to identify the knowledge, attitude and practice (KAP) among the nursing staff regarding cancer screening in these two diseases. Methods: A cross-sectional interview based survey was conducted among 303 female nursing staff working in a government medical college hospital. Verbal informed consent was sought from the study subjects. A structured pretested questionnaire regarding KAP was used to collect the data. The questions were open-ended. The data was entered into MS Excel worksheet and analyzed using descriptive statistics. Results: Total of 303 nurses included in the study. The age ranged from 21 to 64 years. Median age is 38 years. Nurses who were aware of cancer screening were 24.4% (74/303). However many of them were aware of pap smear (55.1%, 167/303) and mammogram (66.3%, 201/303) as investigational tools in diagnosing cancer. The utilization of pap smear among nurses was 5.6% (17/303) with an average of 1.23% pap smear per individual. The utilization of mammogram among the eligible nurses was 13% (15/115) with an average of 1.2% mammogram per individual. The most common reason for not undergoing screening was that nurses did not feel the need to be screened unless they were symptomatic (55%). The other reasons given were they are young for screening (14.8%), shyness (11.1%), fear (11.1%) and lack of time (7.4%). However 90% of them were willing to undergo screening if conducted by the institute. Conclusions: This data suggest that levels of knowledge and practice of cancer screening are very poor among nursing staff working in government medical college hospital. Educating the nursing staff would definitely improve this. Cancer screening should also be incorporated for health care professionals in addition to general population.
Identification of Natural Regulatory T Cell Epitopes Reveals Convergence on a Dominant Autoantigen
Authors: John D. Leonard, Dana C. Gilmore, Thamotharampillai Dileepan, Wioletta I. Nawrocka, Jaime L. Chao, Mary H. Schoenbach, Marc K. Jenkins, Erin J. Adams, Peter A. Savage
Journal: Immunity (2017)
Safety and Efficacy of Bortezomib in Patients With Highly Relapsing Neuromyelitis Optica Spectrum Disorder
Authors: Chao Zhang, De-Cai Tian, Chun-Sheng Yang, Bin Han, Jing Wang, Li Yang, Fu-Dong Shi
Journal: JAMA Neurology (2017)

This study examines the safety and efficacy of bortezomib in patients with highly relapsing neuromyelitis optica spectrum disorder.
Erratum to: Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation, migration, invasion and epithelial mesenchymal transition by sponging miR-150-5p
Authors: Wei Lu, Honghe Zhang, Yuequn Niu, Yongfeng Wu, Wenjie Sun, Hongyi Li, Jianlu Kong, Kefeng Ding, Han-Ming Shen, Han Wu, Dajing Xia, Yihua Wu
Journal: Molecular Cancer (2017)

After the publication of this work [1] an error was noticed in Additional file 1: Table S1 regarding the siRNA sequences, in which two siRNAs (si-L4/L5) were omitted from the figure.The updated version (now correctly added) has the sequences of si-L1/L2/L3 and the other two, si-L4/L5.Since the last two siRNAs (si-L4/L5) served as further confirmation for the original data, this update does not affect the findings or conclusions of the article.Nevertheless, we apologize for the inconvenience.
SUNSHINE: Randomized double-blind phase II trial of vitamin D supplementation in patients with previously untreated metastatic colorectal cancer.
Authors: Kimmie Ng, Halla Sayed Nimeiri, Nadine Jackson McCleary, Thomas Adam Abrams, Matthew B. Yurgelun, James M. Cleary, Douglas Adam Rubinson, Deborah Schrag, Jill N. Allen, Dan Sayam Zuckerman, Rebecca A. Miksad, Emily Chan, Michael Constantine, Douglas Weckstein, Meredith Gail Faggen, Christian A. Thomas, Chryssanthi S. Kournioti, Christopher Mackintosh, Hui Zheng, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2017)

3506 Background: In prospective observational studies of mCRC patients, higher plasma levels of 25-hydroxyvitamin D have been associated with improved progression-free (PFS) and overall survival (OS), but the role of vitamin D supplementation in the treatment of mCRC is unknown. Methods: SUNSHINE was a multi-center double-blind phase II randomized controlled trial in previously untreated mCRC patients. Patients were eligible if they had histologically confirmed mCRC, no prior therapy for metastatic disease, ECOG PS 0-1, and were not taking vitamin D &gt;2,000 IU/day x 1 year. All subjects received standard treatment with mFOLFOX6 + bevacizumab with 1:1 randomization to concurrent: HiVitD (vitamin D3 po 8,000 IU/d x 2 wks as loading dose followed by 4,000 IU/d) or LowVitD (standard vitamin D3 400 IU/d) until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was PFS, with the sample size designed to provide 80% power to detect a HR of 0.66 for PFS at a 1-sided alpha=0.2. Results: From April 2012 to November 2016, 139 patients were randomized. Median age was 54 yrs (range 24-82), 57% were male, 77% were white, and 7% had received prior adjuvant chemo. Baseline characteristics were balanced between arms except ECOG PS = 0 was 42% vs. 60% in HiVitD vs. LowVitD. Median follow-up was 16.1 mos (range 0-45.9) and median compliance with VitD capsules was 98%. Patients randomized to HiVitD experienced longer PFS than those receiving LowVitD (median PFS, 12.4 vs. 10.7 mos, respectively; log rank P=0.03). After multivariate adjustment for prognostic variables, HR was 0.66 (95% CI, 0.45-0.99, 2-sided P=0.04). Comparing HiVitD vs LowVitD, RR was 58% vs. 63% ( P=0.54) and disease control rate was 100% vs. 94% ( P=0.05). The most common grade 3-4 toxicities were as expected for FOLFOX-bevacizumab, and none were related to vitamin D. Currently, 14 patients are still actively receiving treatment, and OS data are not yet mature. Conclusion: SUNSHINE met its prespecified primary endpoint, with patients randomized to HiVitD experiencing longer PFS compared to those randomized to LowVitD. A larger confirmatory phase III randomized trial appears warranted. Clinical trial information: NCT01516216.
Base5, a versatile, highly integrated high-throughput methylation profiling platform for methylation specific PCR based marker identification applied to colorectal cancer
Authors: Josef Straub, Geert Trooskens, Luc Segers, James di Guiseppi, Katja Bierau, Joost Louwagie, Herman Spolders, John Beeler, Wim Van Criekinge
Journal: Clinical Cancer Research (2007)

A61   Testing the methylation status of one or more genomic loci is a new principle applicable to diagnosis and prognosis of disease, as well as prediction of therapeutic response. In an attempt to increase the success rate of marker discovery work in the field of methylation a new integrated system including bioinformatics, high throughput marker testing and data analysis has been created. The newly devised ‘Base5’ system is described and proof of principle data from studies in the field of colorectal cancer are presented.  Materials and Methods:  The Base5 methylation profiling platform (Base5) currently comprises several different modules:  The first module is a set of bioinformatics tools which allow the design of Methylation Specific PCR (MSP) assays in a highly efficient way, based on any annotated or known genomic DNA sequence. With this tool 224 different MSP assays in the promoter region of 145 different genes have been newly designed. In addition to these new candidates, several already known methylation markers for colorectal cancer were included in a “design list”. This list was used for manufacturing high throughput arrays capable of analyzing 12 different samples in parallel with all the assays of interest.  The second module of the Base5 system, a high throughput real time detection system was used to determine the methylation status of the genes processed in module 1. The equivalent of 200ng of genomic, bisulphite converted DNA from 90 samples (60 colorectal cancer samples and 30 normal colorectal tissue samples) was tested for the presence of methylated alleles.  The third module of the Base5 system was used to analyze and present the results in “methylation tables” which indicate the methylation status of each sample tested for each of the assays. Using the methylation tables, sensitivity and specificity for each gene was calculated and genes were ranked by specificity and sensitivity. In a final step, the performance of known colorectal cancer markers (CHFR, MGMT and others) included in the design was compared to the new candidate markers screened with the system.  Results:  Using the Base5 system it was possible to design 224 different MSP assays within two workdays. A total of 20160 MSP assays was performed by one technical staff within four workdays including genomic DNA isolation, bisulphite conversion, real-time detection and data interpretation.  Known methylation markers of colorectal cancer included in the list of designs were confirmed among the best performing assays. New markers, so far not associated with colorectal cancer, could be determined which perform as well or even better than the known markers, with a relatively small effort.
Evaluation of toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer (NSCLC).
Authors: Rathi Narayana Pillai, Madhusmita Behera, Taofeek Kunle Owonikoko, Alice O. Kamphorst, Suchita Pakkala, Chandra Prakash Belani, Fadlo Raja Khuri, Rafi Ahmed, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2016)

9035 Background: Monoclonal antibodies against Programmed Cell Death 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) have therapeutic efficacy in NSCLC. We conducted a systematic review of trials to evaluate differences in toxicity patterns of PD-1 and PD-L1 inhibitors. Methods: An electronic literature search was performed of public databases (MEDLINE, EMBASE) and conference proceedings for trials utilizing PD-1 inhibitors (nivolumab, pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, avelumab) in NSCLC patients. Studies that did not report toxicities were excluded. A formal meta-analysis was conducted with Comprehensive Meta-Analysis software (Version 2.2). Clinical and demographic characteristics, response, and toxicity data were compared between the two groups. Results: Sixteen studies reported between 2013-2015 were eligible for this analysis, with a total number of 2,845 patients in the PD-1 group and 1,595 patients in the PD-L1 group evaluated for toxicities. Patient characteristics % (PD-1/PD-L1): median age 64.5/64 years, male 58/56, smokers 82/83, squamous histology 26/32, performance status 0-1 98/100. The response rate was similar in both groups: 17% in PD-1 versus 18% in PD-L1, p = 0.9. There was a trend towards higher rates of adverse events (AEs) in the PD-L1 group (All AEs: 72% versus 82% p = 0.13 and grade 3-4 AEs 15% versus 25.5%, p = 0.06, PD-1 and PD-L1 respectively). There was no difference in rates of immune related AEs, 11% in PD-1 versus 7% in PD-L1 (p = 0.3). The incidence of pneumonitis was similar in both groups: 3.6% in PD-1 versus 2.2 in PD-L1 (p = 0.15). Conclusions: In this large meta-analysis involving 4440 patients, there are no significant differences in the toxicity profiles of PD-1 and PD-L1 inhibitors in NSCLC patients.
Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial
Authors: Franco Locatelli, Maria Ester Bernardo, Alice Bertaina, Carla Rognoni, Patrizia Comoli, Attilio Rovelli, Andrea Pession, Franca Fagioli, Claudio Favre, Edoardo Lanino, Giovanna Giorgiani, Pietro Merli, Daria Pagliara, Arcangelo Prete, Marco Zecca
Journal: The Lancet Oncology (2017)
The impact of body mass index on survival in stage 3 and 4 lung cancer.
Authors: Kit Man Wong, Sinead Cuffe, Linda E. Coate, Osvaldo Espin-Garcia, Kevin Boyd, Ronald Feld, Natasha B. Leighl, Frances A. Shepherd, Wei Xu, Geoffrey Liu
Journal: Journal of Clinical Oncology (2013)

1579 Background: Obesity is an adverse prognostic factor in several cancers, including colorectal, breast, endometrial and prostate. Studies on body mass index (BMI) and lung cancer outcomes are lacking. Understanding the clinical impact of body weight is important given the high prevalence of obesity globally. We retrospectively evaluated the BMI at diagnosis and its effects on survival in stage 3/4 lung cancer patients. Methods: 1,121 patients with stage 3/4 lung cancer were analyzed. Clinicopathologic data were collected retrospectively. Adjusted hazard ratios (aHR) for overall survival (OS) were generated by Cox regression for each BMI (kg/m2) category (underweight: &lt;18.5, normal: 18.5-24.9, overweight: 25.0-29.9, obese: ≥30), after adjusting for age, gender, Charlson Comorbidity Index, performance status (PS), clinical stage and treatment regimen. Results: In this cohort (n=1,121), the frequencies of stage 3A, 3B and 4 lung cancers were 35%, 32% and 33%, respectively. There were 633 (57%) adenocarcinomas, 238 (21%) squamous cell carcinomas, 38 (3%) small cell lung cancers, and 210 (19%) other histologies. Patients had variable BMI: 82 (7%) underweight, 550 (49%) normal weight, 333 (30%) overweight, 156 (14%) obese. Being overweight/obese was associated with older age (p=0.002) and stage 3A disease (p=0.001); underweight patients were more likely current smokers (p&lt;0.001). OS was significantly decreased with age ≥65, males, PS 2-3, stage 4, and lack of systemic therapy (p&lt;0.001). Median OS in underweight, normal weight, overweight and obese patients were 14, 23, 24 and 26 months, respectively. Compared with BMI≥18.5, being underweight was associated with poorer OS (aHR 1.33, 95% CI 1.01-1.77, p=0.045), but not progression-free survival (aHR 1.12, 95% CI 0.86-1.46, p=0.414). The magnitude of this association was greatest in those aged &lt;65 (aHR 1.57, 95% CI 1.11-2.22, p=0.011). Conclusions: Underweight patients with stage 3/4 lung cancer, especially if aged &lt;65, have significantly poorer OS. Lower BMI was mostly observed in current smokers, while above normal BMI was seen in stage 3A. Unlike other cancers, obesity does not increase mortality in this population. The inverse BMI-survival relationship in lung cancer requires further study.
Navigating the highlights of phase III trials: a watchful eye on evidence-based radiotherapy
Authors: J.C. Trone, S. Espenel, A. Rehailia-Blanchard, E. Guillaume, N. Vial, C. Rancoule, C. Rodriguez-Lafrasse, M. Ben Mrad, A. El Meddeb Hamrouni, E. Ollier, C. Chargari, E. Deutsch, A. Vallard, N. Magné
Journal: Annals of Oncology (2017)

BackgroundPhase III randomized controlled trials (RCTs) are the cornerstone of evidence-based oncology. However, there is no exhaustive review describing the radiotherapy RTCs characteristics. The objective of the present study was to describe features of all phase III RCTs including at least a radiation therapy.Methods and materialsRequests were performed in the Medline database (via PubMed). The latest update was performed in April 2016, using the following MESH terms: 'clinical trials: phase III as topic', 'radiotherapy', 'brachytherapy', as keywords.ResultsA total of 454 phase III RCTs were identified. Studies were mainly based on open (92.1%) multicenter (77.5%) designs, analyzed in intend to treat (67.6%), aiming at proving superiority (91.6%) through overall survival assessment (46.5%). Most frequently studied malignancies were head and neck (21.8%), lung (14.3%) and prostate cancers (9.9%). Patients were mainly recruited with a locally advanced disease (73.7%). Median age was 59 years old. Out of 977 treatment arms, 889 arms experienced radiotherapy, mainly using 3D-conformal radiotherapy (288 arms, 32.4%). Intensity-modulated techniques were tested in 12 arms (1.3%). The intervention was a non-cytotoxic agent addition in 89 studies (19.6%), a radiation dose/fractionation modification in 74 studies (16.3%), a modification of chemotherapy regimen in 63 studies (13.9%), a chemotherapy addition in 63 studies (13.9%) and a radiotherapy addition in 53 trials (11.7%). With a median follow-up of 50 months, acute all-grade and grade 3–5 toxicities were reported in 49.6% and 69.4% of studies, respectively. Radiotherapy technique, follow-up and late toxicities were reported in 60.1%, 74%, and 31.1% of studies, respectively.ConclusionPhase III randomized controlled trials featured severe limitations, since a third did not report radiotherapy technique, follow-up or late toxicities. The fast-paced technological evolution creates a discrepancy between literature and radiotherapy techniques performed in daily-routine, suggesting that phase III methodology needs to be reinvented.
Response to Dr. Bain's comment on our review article: Pure Erythroid Leukemia
Authors: Wei Wang, Sa A. Wang, L. Jeffrey Medeiros, Joseph D. Khoury
Journal: American Journal of Hematology (2017)

To the Editor: We appreciate Dr. Bain's comments on our recent review article on PEL.1 With regards to the point that PEL cases evolving from MDS should be classified as “acute myeloid leukemia with myelodysplasia-related changes (AML-MRC),” it should be noted that a prerequisite criterion for AML-MRC in the WHO classification is the presence of 20% or more blasts in peripheral blood or bone marrow. By definition, PEL has >80% immature erythroid precursors, typically with only a minor component of myeloblast that is often well below the required cutoff for AML-MRC. The latter feature was incorporated in the 2016 revision of the WHO classification.2 Some may argue that proerythroblasts may be counted as blasts; however, if that were the case then all PEL, with or without antecedent MDS, would have to be called AML-MRC since the WHO classification calls for including under AML-MRC all AML with a complex karyotype, a salient feature seen in nearly all PEL.3 Calling all PEL cases as AML-MRC will eliminate PEL as a distinct category and mitigates increased knowledge of this rare subtype. Indeed, PEL highlights some of the inherent limitations of the AML-MRC category, which is based to a large extent on “consensus” criteria that are mostly not evidence-based (e.g., number of lineages with dysplasic changes, proportion of cells with dysplastic changes in a given lineage, blast percentage cutoff, cytogenetic abnormalities regarded as “sufficient” for calling AML-MRC). With regards to the TP53 mutation data reported in our article, 6 patients presented with de novo disease, 3 had antecedent MDS, and 1 had therapy-related disease. We would underscore that PEL presenting de novo, following MDS or cytotoxic therapy, has the same distinctive morphologic, cytogenetic, and molecular features and is equally associated with a dismal outcome. In summary, the authors contend that WHO classification criteria for AML-MRC are not applicable to PEL and, as such, the diagnosis of PEL should be applied regardless of whether or not a history of antecedent hematologic malignancy or exposure to cytotoxic therapy exists.
Abstract 088: JNK2 Impairs Atrial Conduction And Enhances Arrhythmogenicity In Mouse Atria
Authors: Jiajie Yan, Weiwei Zhao, Qiang Zhang, Vladimir G Fast, Sumanth D Prabhu, Xun Ai
Journal: Circulation Research (2013)

The c-Jun N-terminal kinase (JNK) is a stress-activated kinase that is important in the development of cardiovascular diseases. We have previously shown that enhanced JNK activation was associated with suppressed gap junction Cx43, slow conduction, and increased atrial fibrillation (AF) in aged rabbit left atrium (LA). In an atrial cellular model (HL-1), we further demonstrated that JNK activation downregulated Cx43 and enhanced arrhythmogenicity. However, direct evidence for JNK inducing atrial arrhythmia in vivo is lacking. In the present study, we found that JNK activator anisomycin (aniso) treatment in wild-type (WT) mouse in vivo resulted in a 30% decrease in Cx43 protein in LA vs that of vehicle-treated WT LA (p&lt;0.001; n=4, 6; each sample contained mixed LAs from 5 mice). From optical mapping recordings in the intact LA, conduction velocity (CV) in aniso-treated WT mice slowed by 36% (30±2 vs. 47±1 cm/sec in vehicle-treated WT, pacing cycle length (CL) = 100ms, p&lt;0.01; n=4, 3). Additional in vivo treatment with SP600125 (a specific JNK inhibitor) reversed aniso-induced Cx43 suppression (n=3) and CV slowing (50±2 cm/sec; n=6) as compared with WT LA treated with aniso alone (p&lt;0.001). Moreover, we assessed atrial arrhythmia susceptibility in vivo using burst pacing delivered via an octapolar cardiac catheter. JNK activated hearts exhibited an increased incidence of pacing-induced AF (13%; n=7), while no AF was induced in WT-vehicle mice (n=4). To further confirm the specific role of JNK activation in atrial arrhythmogenicity, JNK2 (one of the cardiac JNK isoforms) knockout mice (JNK2KO) were treated with aniso in vivo. Similar to the effect of JNK inhibition by SP600125, JNK2 knockout prevented aniso-induced Cx43 suppression (n=3) and slowing of CV (47±1cm/sec, CL=100ms; n=4) compared with aniso-treated WT (p&lt;0.05 &amp; p&lt;0.001, respectively). Furthermore, a dramatically decreased susceptibility to pacing-induced AF (1.7%; n=6) was found in aniso-treated JNK2KO vs aniso-treated WT mice. In conclusion, our results strongly suggest that JNK, especially JNK2, activation contributes to impaired cell-cell communication that in turn promotes AF development. Modulation of JNK2 could be a novel therapeutic approach to prevent and treat AF in the elderly.