tbuckley/cabot-search huggingface dataset:
Ceria Nanoparticles Fabricated with 6‐Aminohexanoic Acid that Overcome Systemic Inflammatory Response Syndrome
Authors: Han‐Gil Jeong, Bong Geun Cha, Dong‐Wan Kang, Do Yeon Kim, Wookjin Yang, Seul‐Ki Ki, Song I Kim, Juhee Han, Chi Kyung Kim, Jaeyun Kim, Seung‐Hoon Lee
Journal: Advanced Healthcare Materials (2019)

Abstract Systemic inflammatory response syndrome (SIRS) is self‐destructive and uncontrollable inflammatory response of the whole body triggered by infection, trauma, or a variety of severe injuries. Although reactive oxygen species play a pivotal role in the development of SIRS, the trials with conventional antioxidants have failed to improve patient outcome. Ceria nanoparticles (CeNPs) have potent, autocatalytic reactive oxygen species scavenging activities, which may have sufficient therapeutic effects for SIRS. Herein, 3 nm CeNPs are fabricated totally in aqueous phase by using 6‐aminohexanoic acid (6‐AHA) and their Ce 3+ to Ce 4+ ratio is increased to enhance antioxidative properties. The obtained 6‐AHA‐CeNPs demonstrate strong antioxidative and anti‐inflammatory effects in various biofluids and inflammatory cells. In SIRS animal models, 6‐AHA‐CeNPs are demonstrated to reduce multiple organ injuries and inflammation. Moreover, 6‐AHA‐CeNPs decrease mortality and improve clinical scores of SIRS models. These findings suggest that 6‐AHA‐CeNPs have potential as a therapeutic nanomedicine for SIRS.
Variations in treatment practices among pediatric solid tumor patients in Japan.
Authors: Momoko Iwamoto, Fumiaki Nakamura, Takahiro Higashi
Journal: Journal of Clinical Oncology (2015)

e17656 Background: Care of pediatric cancer patients is only mildly centralized in Japan, and it is not known whether this has led to variations in treatment practices for pediatric solid tumor patients. We aimed to investigate where practice variations exist among pediatric solid tumor patients, by evaluating the treatments patients received in eight pediatric solid tumors that have Japanese clinical guidelines. Methods: Using a database linking hospital-based cancer registry and administrative claims data obtained from 210 cancer treatment hospitals, we identified 20 hepatoblastoma (HB), 68 neuroblastoma (NB), 28 retinoblastoma (RB), 24 nephroblastoma (WT), 20 rhabdomyosarcoma (RMS), 14 Ewing’s sarcoma, 32 osteosarcoma, and 56 central nervous system germ cell tumor (CNSGCT) patients who were diagnosed from 69 hospitals in 2012. We reviewed each patient’s chemotherapy regimens, radiation therapy schedules, and surgical procedures using administrative claims data from September 2011 to December 2013. Results: Most pediatric solid tumor patients received treatment in concordance with clinical guidelines for their first course of treatment. For instance, first-line chemotherapy for HB were cisplatin (CDDP) + pirarubicin (66%) and CDDP + doxorubicin (DXR) ± carboplatin (33%). However, treatment practices varied greatly for both primary and recurrent CNSGCT patients, as well as patients receiving second and third-line chemotherapies. About a quarter of CNSGCT patients received resection or radiation alone as their first treatment, but a greater proportion of patients received surgery followed by various adjuvant chemotherapies or radiation therapy, and neoadjuvant chemotherapy followed by radiation. Regimens for recurrent tumors varied greatly, such that all recurrent RMS patients received different chemotherapy regimens. Conclusions: Despite lack of centralization of care among pediatric solid tumor patients, our study showed that the majority of patients were receiving treatments in concordance with clinical guidelines. However, practice variations existed in CNSGCTs and patients receiving second and third-line chemotherapies, which suggest that centralization of care may be necessary for these patients.
Strong increase of true and false positive mycobacterial cultures sent to the National Reference Centre in Belgium, 2007 to 2016
Authors: Karine Soetaert, Lorenzo Subissi, Pieter-Jan Ceyssens, Brigitte Vanfleteren, Marianne Chantrenne, Tommi Asikainen, Els Duysburgh, Vanessa Mathys
Journal: Eurosurveillance (2019)

Introduction In 2007, a new federal legislation in Belgium prohibited non-biosafety level 3 laboratories to process culture tubes suspected of containing mycobacteria. Aim To present mycobacterial surveillance/diagnosis data from the Belgian National Reference Centre for mycobacteria (NRC) from 2007 to 2016. Methods This retrospective observational study investigated the numbers of analyses at the NRC and false positive cultures (interpreted as containing mycobacteria at referring clinical laboratories, but with no mycobacterial DNA detected by PCR in the NRC). We reviewed mycobacterial species identified and assessed trends over time of proportions of nontuberculous mycobacteria (NTM) vs Mycobacterium tuberculosis complex (MTBc), and false positive cultures vs NTM. Results From 2007 to 2016, analyses requests to the NRC doubled from 12.6 to 25.3 per 100,000 inhabitants. A small but significant increase occurred in NTM vs MTBc proportions, from 57.9% (587/1,014) to 60.3% (867/1,437) (p &lt; 0.001). Although NTM infection notification is not mandatory in Belgium, we annually received up to 8.6 NTM per 100,000 inhabitants. M. avium predominated (ca 20% of NTM cultures), but M. intracellulare culture numbers rose significantly, from 13.0% (74/587) of NTM cultures in 2007 to 21.0% (178/867) in 2016 (RR: 1.05; 95% CI: 1.03–1.07). The number of false positive cultures also increased, reaching 43.3% (1,097/2,534) of all samples in 2016. Conclusion We recommend inclusion of NTM in sentinel programmes. The large increase of false positive cultures is hypothesised to result from processing issues prior to arrival at the NRC, highlighting the importance of sample decontamination/transport and equipment calibration in peripheral laboratories.
A randomized phase II study comparing cabazitaxel/prednisone to cabazitaxel alone in docetaxel-pretreated men with metastatic castration resistant prostate cancer (mCRPC): The CABACARE trial.
Authors: Carlo Buonerba, Francesco Grillone, Sabrina Rossetti, Lorenzo Livi, Mario Scartozzi, Pierosandro Tagliaferri, Dario Bruzzese, Luca Scafuri, Vittorio Riccio, Ferdinando Costabile, Davide Bosso, Simona Iaccarino, Gaetano Facchini, Simone Carrano, Michela Izzo, Michele Caraglia, Sabino De Placido, Giuseppe di Lorenzo
Journal: Journal of Clinical Oncology (2019)

TPS345 Background: In the TROPIC trial, cabazitaxel (CAB) plus daily prednisone (PDN) was associated with a significant advantage in OS and PFS in docetaxel (DOC)-pretreated patients (Pts). Whether daily PDN may significantly contribute to CAB efficacy or improve its safety profile is unknown. In the CHARTEED trial, DOC was administered without daily PDN with no concerns about the lack of efficacy or greater toxicity. Safety data about CAB without PDN are scarce. Corticosteroids present multiple biological effects, which may potentially be either positive, such as those mediated by adrenal androgen and cytokine suppression, or detrimental, such as those associated with the activation of the glucocorticoid receptor (GR) and of the androgen receptor (AR). Furthermore, PDN is a CYP3A4 inducer and can potentially negatively affect CAB clearance. Finally, AR-V7 positivity in circulating tumor cells and retinoblastoma (RB) loss/inactivation have been identified as potential mechanisms of resistance to hormonal and chemotherapy treatments in prostate cancer. For this reason, we also aim to evaluate if CAB activity is related to such biomarkers. Methods: CABACARE (EudraCT 2016-005251-25) is a randomized, phase II, open label, multi-center study comparing CAB at 25 mg/m2 q21 plus daily PDN (10 mg) vs CAB at 25 mg/m2 q21 alone in mCRPC pts progressed during or after DOC treatment. The study is designed to test non inferiority in terms of PFS, according PCWG-2, of CAB alone vs CAB plus PDN assuming that the two arms are equally effective (non-inferiority HR = 1.4). Main secondary objectives are: safety, QoL, pain assessment, overall response rate (ORR), PSA response, time to PSA progression, Time to radiological progression; OS; time to skeletal related events . The influence of AR-V7 and RB status measured in circulating epithelial cells at baseline on CAB activity will also be evaluated. A total of 35 Italian centers have started / will start recruiting pts in the CABACARE trial. Of the 220 pts required by the trial design, 43 pts have been enrolled since 30 th Nov , 2017 until 2 nd Oct, 2018 in 10 different Italian Institutions. Clinical trial information: 2016-005251-25.
Translating genomic medicine to the clinic: challenges and opportunities
Authors: Huan Zhang, Lars Klareskog, Andreas Matussek, Stefan M. Pfister, Mikael Benson
Journal: Genome Medicine (2019)

Genomic medicine has considerable potential to provide novel diagnostic and therapeutic solutions for patients who have molecularly complex diseases and who are not responding to existing therapies. To bridge the gap between genomic medicine and clinical practice, integration of various data types, resources, and joint international initiatives will be required.
NCIC CTG IND.206: A phase II umbrella trial of sunitinib (S) or temsirolimus (T) in advanced rare cancers.
Authors: Janet Dancey, Monika K. Krzyzanowska, Diane M. Provencher, Winson Y. Cheung, Robyn Jane Macfarlane, Thierry Alcindor, Prafull Ghatage, Abha A. Gupta, Scott Andrew Laurie, Michael B. Sawyer, Stephen Welch, Muhammad Salim, Susan Ellard, Donna Ann Wall, Ming Sound Tsao, Joana Sederias, Hao Xu, Torsten O. Nielsen, Sylvia L. Asa, Hal W. Hirte
Journal: Journal of Clinical Oncology (2015)

2594 Background: Patients (Pts) with rare cancers have few treatment options due to the challenges of conducting clinical trials when projected accrual is low. However, rare cancers may have driver mutations that can be targeted with potentially dramatic therapeutic effects. Methods: IND.206 is a multi-center, non-randomized phase II study of S or T in 11 rare tumor cohorts ( < 100 eligible patients/year in Canada). Cohorts: 8 histologic, 2 genetic, 1 exploratory unspecified. Pts received S (50 mg PO daily x 28 days, q 6 weeks) or T (25 mg IV weekly, q 6 weeks). Each cohort and drug was evaluated separately using a 2 stage design targeting 5 versus 25% RECIST response rate. Blood and tumor were collected for genomic analyses. For trial efficiency, 1) pts could be re-entered to the alternate drug at progression; 2) data collection and SAE reporting were streamlined; 3) cohorts could be stopped early for activity, inactivity or failure to accrue. Central pathology review was performed. Results: The trial was activated in 7/2011. To date, 134 patients were enrolled, 156 registered (22 pts crossed over). 132 are evaluable for response, 134 are evaluable for toxicity. 4 cohorts failed meet the minimum accrual. Only the medullary thyroid cohort treated with S met the protocol defined activity level. Responses were seen in the following: medullary thyroid carcinoma (7/16 on S), clear cell carcinomas of ovary/endometrium (3/22 S; 3/22 T), pheochromocytomas and paragangliomas (1/4 S), 1 extraskeletal myxoid chondrosarcoma (ESMCS) on S, 1 perivascular epithelioid cell tumor on T. Responses were not seen in vascular sarcomas (n = 16 10 S, 6 T) Ewing’s sarcoma family tumours (n = 10, T), adrenocortical (n = 12 S, 10 T) or thymic carcinomas (n = 5 S, 2 T) despite case reports in the literature. Toxicity was consistent with previously studies although quantity of grade 1-2 and expedited reports were reduced as per protocol. Genomic studies are underway. Conclusions: S and T induce responses in clear cell carcinomas of ovary and endometrium, medullary carcinoma of thyroid, paraganglioma and ESMCS. Case reports in the literature may overestimate activity. Our umbrella design is efficient for evaluating drug activity in rare cancers. Clinical trial information: NCT01396408.
Immunological features of esophageal tumors.
Authors: Oleg Ivanovich Kit, Vladimir Sez Trifanov, Elena Yurievna Zlatnik, Inna Arnoldovna Novikova, Evgenia Markovna Nepomnashaya, Evgeniy N. Kolesnikov, Stanislav Stanislavovich Mezentsev, Adlan Lechaevich Bazaev
Journal: Journal of Clinical Oncology (2015)

e15096 Background: The surgical method is the leading radical treatment of esophageal cancer. However, choosing the type of surgery for each patient needs to be clarified. The role of combined clinical histopathologic and immunological approach in the diagnosis and subclassification of primary esophageal tumors was evaluated. Methods: From 1987 to 2013 in Rostov Research Institute of Oncology 542 patients underwent radical resections for esophageal cancer. 410 were men and 132 women (ratio 3.1 to 1), the age of patients ranged from 32 to 84 years, most in the range from 50 to 70 years, mean age 62. Histologically, in the upper and middle third of the esophagus in most cases (over 95%) a squamous cell carcinoma was determined, varying degrees of differentiation, adenocarcinoma was in 3% of all cases, 2% were undifferentiated cancer and GIST-tumors. In the lower-thoracic and abdominal part of esophagus squamous cell carcinoma was in 74%, adenocarcinoma in 23% of cases. Among them we retrospectively identified 21 patients from which clinico-pathologic and immunohistological data were analyzed. Lymphocytes content was measured by flow cytometry in homogenates of tumor tissue, perifocal area and resection line. Results: Over the past 5 years we performed 214 radical operations for esophageal cancer. 6 (2.8%) patients died after surgery. In stage T1-3 N0 3 year overall survival (OS) was 68%, 5 year OS was 52%. In stage III the 3 year OS was 38%, 5 year OS was 18%. Immunohistochemistry was useful in supporting the diagnosis of esophageal tumors. Esophagus tumor tissue was characterized by a higher content of T-lymphocytes with helper inducer phenotype (CD3+CD4+), and also by a higher content of proinflammatory cytokines in comparison with surrounding tissues. Significant difference between peritumoral zone and resection line was not detected. Conclusions: We suppose that CD3+CD4+ cells migrate from blood through tumor vessels with higher permeability and adhesive features of endothelium. There may be high content of T cells among them, which will be the subject for the separate research in future. The high content of proinflammatory cytokines may be the factor, supporting the growth and spreading of tumor.
Gossypium barbadense and Gossypium hirsutum genomes provide insights into the origin and evolution of allotetraploid cotton
Authors: Yan Hu, Jiedan Chen, Lei Fang, Zhiyuan Zhang, Wei Ma, Yongchao Niu, Longzhen Ju, Jieqiong Deng, Ting Zhao, Jinmin Lian, Kobi Baruch, David Fang, Xia Liu, Yong-ling Ruan, Mehboob-ur Rahman, Jinlei Han, Kai Wang, Qiong Wang, Huaitong Wu, Gaofu Mei, Yihao Zang, Zegang Han, Chenyu Xu, Weijuan Shen, Duofeng Yang, Zhanfeng Si, Fan Dai, Liangfeng Zou, Fei Huang, Yulin Bai, Yugao Zhang, Avital Brodt, Hilla Ben-Hamo, Xiefei Zhu, Baoliang Zhou, Xueying Guan, Shuijin Zhu, Xiaoya Chen, Tianzhen Zhang
Journal: Nature Genetics (2019)

Allotetraploid cotton is an economically important natural-fiber-producing crop worldwide. After polyploidization, Gossypium hirsutum L. evolved to produce a higher fiber yield and to better survive harsh environments than Gossypium barbadense, which produces superior-quality fibers. The global genetic and molecular bases for these interspecies divergences were unknown. Here we report high-quality de novo–assembled genomes for these two cultivated allotetraploid species with pronounced improvement in repetitive-DNA-enriched centromeric regions. Whole-genome comparative analyses revealed that species-specific alterations in gene expression, structural variations and expanded gene families were responsible for speciation and the evolutionary history of these species. These findings help to elucidate the evolution of cotton genomes and their domestication history. The information generated not only should enable breeders to improve fiber quality and resilience to ever-changing environmental conditions but also can be translated to other crops for better understanding of their domestication history and use in improvement. High-quality de novo–assembled genomes of two cultivated allotetraploid cotton species and whole-genome comparative analyses provide insights into the evolution of cotton genomes and improvement of fiber quality and resilience to stress.
2018 ATS BEAR Cage Winning Proposal: Cell-Free DNA to Improve Lung Transplant Outcomes
Authors: Sean Agbor-Enoh
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

The first lung transplantation in 1963 brought hope to patients with endstage lung disease.In the two decades that followed, short-term survival remained dismal, primarily because of early surgical complications such as anastomosis dehiscence and early post-transplant allograft rejection.With advances in surgical techniques and new immunosuppression regimens, 1-year survival improved to greater than 90%.Unfortunately, long-term survival still remains low, with only 50% of patients surviving 5-6 years after transplant.Chronic lung allograft dysfunction (CLAD), an umbrella term used to describe recognized phenotypes of chronic lung rejection (1), is a leading contributor to poor long-term survival.With no available therapies for CLAD, current management strategies are focused on early detection and treatment of CLAD risk factors, which include primary graft dysfunction, acute cellular rejection (ACR), antibody-mediated rejection (AMR), and community-acquired respiratory viral infections (1-4).The introduction of genomic, proteomic, and other "omic" approaches have reenergized a new wave of innovative research that promises to improve long-term outcomes via early detection of CLAD and its risk factors.One such innovative project focused on assessing the benefit of early detection and treatment of AMR by means of a noninvasive genomic technology-donorderived cell-free DNA (%ddcfDNA; Figure 1)-and received the
Left Atrial Dynamics During Exercise in Mitral Regurgitation of Primary and Secondary Origin
Authors: Tadafumi Sugimoto, Francesco Bandera, Greta Generati, Eleonora Alfonzetti, Marta Barletta, Maurizio Losito, Valentina Labate, Marina Rovida, Michela Caracciolo, Carlo Pappone, Giuseppe Ciconte, Marco Guazzi
Journal: JACC. Cardiovascular imaging (2019)
Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis
Authors: Otavio Berwanger, Renato D. Lopes, Diogo D.F. Moia, Francisco A. Fonseca, Lixin Jiang, Shaun G. Goodman, Stephen J. Nicholls, Alexander Parkhomenko, Oleg Averkov, Carlos Tajer, Germán Malaga, Jose F.K. Saraiva, Helio P. Guimaraes, Pedro G.M. de Barros e Silva, Lucas P. Damiani, Renato H.N. Santos, Denise M. Paisani, Tamiris A. Miranda, Nanci Valeis, Leopoldo S. Piegas, Christopher B. Granger, Harvey D. White, Jose C. Nicolau
Journal: Journal of the American College of Cardiology (2019)
Late events in an audit of sequential studies of seminoma receiving single agent carboplatin.
Authors: R. Oliver
Journal: Journal of Clinical Oncology (2015)

e15568 Background: Seminoma is the least malignant subtype of testicular germ cell cancer and has the least risk of metastasis at presentation. Less established compared with its radio-sensitivity, is the fact that it is more chemo-sensitive than non-seminoma. Despite reporting single agent Platinum data in 1982 which supported this concept most standards of care do not treat seminoma differently from non-seminoma. This abstract reviews personal series some with more than 25 years follow up to support this concept and suggests future International Collaborative studies worth pursuing Methods: A total of 97 metastatic seminoma (20 cisplatin, 77 Carboplatin) treated 1980-2006, 167 Stage 1 cases receiving either 1 or two courses of adjuvant therapy treated 1985-2006 and 54 cases receiving chemotherapy as part of testis conservation (12 single agent Platinum and 42 BEP therapy) treated between 1978 and 2006. Prior to 1996 participation was through verbal informed consent and since this time ethical committee approval has been obtained for the ongoing studies Results: A total of 11 relapses have occurred in patients in 5 studies of carboplatin monotherapy in 264 patients with various stages of seminoma. All have been salvaged by BEP as have 16 relapses after I course carboplatin in the MRC TE19 randomised trial No relapses have occurred after 24 months despite median of 96 months follow-up, 51(19%) >20 years. Though late malignant and non-malignant events have occurred, the frequency in the cohort followed between 10 and 15 years (n=93) is not in excess of age matched controls Conclusions: While in primum non noce does not trump the Sword of Damocles, these results provide justification for further prospective evaluation of the less toxic option in patient preference studies. A further 5 years follow up will be available by the time of presentation. Given the reduced costs and toxicity, web-based patient preference studies should be pursued to establish the place of this therapy compared to BEP in routine care
Comparing radical cystectomy with trimodal therapy for patients diagnosed with bladder cancer: Critical assessment of statistical methodology and interpretation of observational data.
Authors: Mohamed Danny Ray-Zack, Yong Shan, Preston Kerr, Christopher David Kosarek, Hogan K Hudgins, Usama Jazzar, Sapna Kaul, Ashish M. Kamat, Douglas S. Tyler, Todd A. Swanson, Hemalkumar B Mehta, Stephen Bentley Williams
Journal: Journal of Clinical Oncology (2019)

373 Background: Treatment guidelines for muscle-invasive bladder cancer recommend radical cystectomy. However, use of trimodal therapy has increased in recent years with conflicting survival outcomes. The aim of this study was to compare radical cystectomy and trimodal therapy in terms of survival outcomes and cost of treatment according to varying statistical methodology in order to interpret findings using observational data. Methods: Patients aged 66 years or older diagnosed with clinical stage T2-4a bladder cancer from January 1, 2002-December 31, 2011 were included from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Outcomes included cancer-specific survival, overall survival, and 6-month costs. Cox proportional hazards regression, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to control for baseline differences between patients undergoing radical cystectomy vs. trimodal therapy, and to determine predictors for overall and cancer-specific survival. Results: A total of 2,963 patients were included: 728 (24.6%) who underwent trimodal therapy were compared to 2,235 (75.4%) who underwent radical cystectomy. In all adjusted analyses, patients who underwent trimodal therapy had significantly decreased cancer-specific survival (Cox regression: Hazard Ratio (HR) 1.51, 95% Confidence Interval (CI) 1.40-1.63; PSM: HR 1.55, 95% CI 1.32-1.83; IPTW: HR 1.51, 95% CI 1.40-1.63) and overall survival (Cox regression: HR 1.54, 95% CI 1.39-1.71; PSM: HR 1.49, 95% CI 1.31-1.69; IPTW: HR 1.54, 95% CI 1.39-1.71). However, median total costs over six months were significantly higher with trimodal therapy than radical cystectomy ($171,401 vs. $99,890, p&lt;0.001). Conclusions: Trimodal therapy was associated with decreased cancer-specific and overall survival at increased costs compared to radical cystectomy. In the absence of data from randomized controlled trials, this observational study provides further evidence to suggest the superiority of radical cystectomy over trimodal therapy in patients with muscle-invasive bladder cancer.