tbuckley/cabot-search huggingface dataset:
Abstract A60: Full-length transcripts identification from deep transcriptomic analysis of Bothrops jararaca venom gland
Authors: Elisa Alves Messias, Flavia Coltri Eguchi, Bruna Pereira Sorroche, Angela Das Neves Oliveira, Lidia Maria Rebolho Batista Arantes, Ana Carolina De Carvalho, Anita mitico tanaka Azevedo, Kathleen Fernandes Grego, Matias Eliseo Melendez, Andre Lopes Carvalho
Journal: Clinical Cancer Research (2018)

Abstract Introduction: Head and neck cancer is a collective term defined by topographic and anatomic features to describe malignant tumors of the upper aerodigestive tract. Despite the different strategies used in the treatment of head and neck squamous cell carcinoma (HNSCC), the overall survival rate is around 50% and the main reason for treatment failure is the frequent development of loco-regional recurrences, which affect around 30% of HNSCC patients. The increase in cancer diagnosis makes it necessary to search for alternative sources to inhibit tumor progression, as well as the development of more efficient drugs. Identification of natural resources as therapeutic potential may lead to the development of new antitumor treatments. Objectives: The aim was to identify transcripts expressed in venom glands of the Bothrops jararaca snake with therapeutic potential for head and neck squamous cell carcinoma (HNSCC) tumors. Materials and Methods: The mRNA library from B. jararaca was sequenced using Illumina NextSeq 500 platform (76 bp unpaired-end) and NextSeq 500/550 Mid Output v2 kit (150 cycles). Library was constructed using TruSeq Stranded mRNA LT Sample Prep Kit (Illumina). De novo assembly of the B. jararaca transcriptome was performed using Velvet software to assemble the transcriptome contigs. Results: The RNA-seq of B. jararaca venom gland generated 4,401,692 raw reads. The de novo Velvet assembly produced 3,498,133 contigs, which matched against NCBI-Blastn transcripts. From these contigs were identified 3,638 full-length transcripts, from which were selected two potential therapeutic genes, Fosfolipases A2 1 and Fosfolipases A2 2. Conclusions: In conclusion, this transcriptome sequencing identified two potential therapeutic transcripts, Fosfolipases A2 1 and Fosfolipases A2 2, which will be analyzed in HNSCC cell lines. Citation Format: Elisa Alves Messias, Flavia Coltri Eguchi, Bruna Pereira Sorroche, Angela Das Neves Oliveira, Lidia Maria Rebolho Batista Arantes, Ana Carolina De Carvalho, Anita mitico tanaka Azevedo, Kathleen Fernandes Grego, Matias Eliseo Melendez, Andre Lopes Carvalho. Full-length transcripts identification from deep transcriptomic analysis of Bothrops jararaca venom gland [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A60.
Patients with colorectal cancer have identical strains of <i>Fusobacterium nucleatum</i> in their colorectal cancer and oral cavity
Authors: Yasuhiko Komiya, Yumi Shimomura, Takuma Higurashi, Yutaka Sugi, Jun Arimoto, Shotaro Umezawa, Shiori Uchiyama, Mitsuharu Matsumoto, Atsushi Nakajima
Journal: Gut (2018)

Figure 1 Detection of Fusobacterium nucleatum subspecies in paired colorectal cancer and saliva samples.(A) Schematic of the experimental procedures.AP-PCR, arbitrarily primed PCR; CRC, colorectal cancer; Fn, Fusobacterium nucleatum.
Gastric cancer in Lynch Syndrome: Are precancerous conditions co- risk factors?
Authors: M. Fornasarig, R. Magris, S. Maiero, A. Viel, E. Canton, V. Canzonieri, R. Cannizzaro
Journal: Annals of Oncology (2018)

Introduction: Gastric cancer (GC) risk in Lynch Syndrome (LS) is up to 13% instead of less than 1% in general population. LS is an autosomal dominant disorder caused by germ-line mutations in one of the mismatch repair (MMR) genes (MSH2, MLH1, MSH6, PMS2) or EpCAM gene determining mainly risk of colorectal and endometrial cancer and a lower risk of small bowel, urothelial and gastric cancer. GCs in this setting are usually intestinal type and show microsatellite instability (MSI-H) and loss of MMR protein expression. There are not clear guidelines for surveillance because the histopathologic transformation pathway is unknown. Since Helicobacter Pylori (HP) infection represents a clinical condition predisposing to gastric cancer its eradication is suggested. In our study we investigate clinical features of GC that develop in patients with this syndrome. Methods: 139 patients with LS were registered in hereditary tumor register settled in 1994 at our Institution. Thirty-three had mutation in MLH1, 10 in MSH6 and 96 in MSH2 (83 F,56 M; mean age 53).The average follow up time was 10,5 years (2-26 years). Patients were inserted in surveillance program consisting in: colonoscopy starting at 20 years every 2 years until 40 and then annually. Gynecological surveillance for women starting at 30 years, upper GI endoscopy staring at 35 years with an interval of 3 years and abdominal ultrasound and urinal cytology starting at 35 with an interval of 2 years. Results: Out of 139 Lynch patients 4 (2,8%) (2M; 2F) developed GCs. Three were symptomatic and one was diagnosed for surveillance. MSH2 was mutated in three of them and MLH1 in one. No family history of GC was reported. All GCs displayed MSI-H and loss of related miss match repair (MMR) protein at immunohistochemical analysis. MSH2 mutation patients were a man (62 years) and two women (73 and 50 years). Their GCs were intestinal type linked to HP infection at early stages (T2N0; T2N1; T1N0). MLH1 carrier was a man (53 years). His GC was a diffuse-type adenocarcinoma (T2N0) at fundus without HP infection. Four years before autoimmune gastritis was diagnosed with already atrophic gastritis and deficit of acid secretion and two pyloric gland adenomas were removed at corpus. Conclusion: Our data suggest that our GCs developed in association to MMR mutation and atrophic gastritis caused by HP infection or autoimmune gastritis. Actually pyloric gland adenomas have been reported as precancerous lesions in autoimmune gastritis. Guidelines suggest gastric surveillance only in selected cases with family history of gastric cancer and suggest testing and treatment of HP infection. Our cases did not display gastric cancer family history. Thus, HP and anti parietal cells antibodies tests should be taken in consideration to select LS patients for gastric surveillance instead of family history.
Gestational Diabetes Mellitus: Is It Time to Reconsider the Diagnostic Criteria?
Authors: N. Wah Cheung, Robert G. Moses
Journal: Diabetes Care (2018)

It has been 10 years since results from the landmark Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study were published (1) and 8 years since the recommendations of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) appeared in this journal (2). The HAPO study demonstrated a continuous relationship between glucose levels on a 75-g oral glucose tolerance test (GTT) and the risks for selected fetal outcomes. Potential diagnostic criteria for gestational diabetes mellitus (GDM) were considered by a Consensus Panel of the IADPSG, which, after a close vote, decided to select an odds ratio (OR) of 1.75, relative to the mean, for selected outcomes. This corresponded to glucose levels of ≥5.1 mmol/L at fasting, ≥10.0 mmol/L at 1 h, and ≥8.5 mmol/L at 2 h on a 75-g GTT. Although the prevalence of GDM varied markedly between the 15 study centers when applying these criteria, the relationship between glucose and outcomes was consistent, and therefore it was considered appropriate for these criteria to be applied globally (3).

The IADPSG recommendations were initially generally greeted with enthusiasm. Finally, diagnostic criteria based on fetal outcomes were available and would replace criteria in the U.S., for example, that were derived from the prediction of subsequent maternal diabetes. Furthermore, given the ethnic diversity of the HAPO participating centers, there was a realistic prospect that their universal adoption was both feasible and practical. However, in the same issue of Diabetes Care that the IADPSG recommendations appeared in there was also a commentary (4) that asked whether the new criteria represented a “problem solved or a …
Interleukin-10 treatment attenuates sinus node dysfunction caused by streptozotocin-induced hyperglycaemia in mice
Authors: Hidekazu Kondo, Shintaro Kira, Takahiro Oniki, Koro Gotoh, Akira Fukui, Ichitaro Abe, Yuki Ikebe, Kyoko Kawano, Shotaro Saito, Kohei Aoki, Norihiro Okada, Yasuko Nagano, Hidefumi Akioka, Tetsuji Shinohara, Kumiko Akiyoshi, Takayuki Masaki, Yasushi Teshima, Kunio Yufu, Mikiko Nakagawa, Naohiko Takahashi
Journal: Cardiovascular Research (2018)

Diabetes, characterized by hyperglycaemia, causes sinus node dysfunction (SND) in several rodent models. Interleukin (IL)-10, which is a potent anti-inflammatory cytokine, has been reported to decrease in obese and diabetic patients. We tested the hypothesis that administration of IL-10 inhibits the development of SND caused by hyperglycaemia in streptozotocin (STZ)-induced diabetic mice. Six-week old CL57/B6 (WT) mice were divided into the following groups: control, STZ injection, and STZ injection with systemic administration of IL-10. IL-10 knockout mice were similarly treated. STZ-induced hyperglycaemia for 8 weeks significantly depressed serum levels of IL-10, but increased several proinflammatory cytokines in WT mice. STZ-induced hyperglycaemia-reduced resting heart rate (HR), and attenuated HR response to isoproterenol in WT mice. In isolated perfused heart experiments, corrected-sinus node recovery time was prolonged in WT mice with STZ injection. Sinus node tissue isolated from the WT-STZ group showed fibrosis, abundant infiltration of macrophages, increased production of reactive oxygen species (ROS), and depressed hyperpolarization activated cyclic nucleotide-gated potassium channel 4 (HCN4). However, the changes observed in the WT-STZ group were significantly attenuated by IL-10 administration and were further exaggerated in IL-10 knockout mice. In cultured cells, preincubation of IL-10 suppressed hyperglycaemia-induced apoptotic and profibrotic signals, and overproduction of ROS. IL-10 markedly inhibited the high glucose-induced p38 activation, and activated signal transducer and activator of transcription (STAT) 3 phosphorylation. Our results suggest that IL-10 attenuates ROS production, inflammation and fibrosis, and plays an important role in the inhibition of hyperglycaemia-induced SND by suppression of HCN4 downregulation. In addition, IL-10-mediated inhibition of p38 is dependent on STAT3 phosphorylation.
Plasma miRNAs signature validation for early detection of colorectal cancer
Authors: M. Herreros-Villanueva, S. Durán-Sanchón, A. Martín, R. Pérez-Palacios, E. Vila-Navarro, M. Marcuello, M. Díaz-Centeno, J. Cubiella, M. Diez, L. Bujanda, A. Lanas, R. Jover, V. Hernández, E. Quintero, J. Lozano, I. Martínez, A. Castells, M. Gironella, R. Arroyo
Journal: Annals of Oncology (2018)

Introduction: Specific miRNA signatures in biological fluids can facilitate earlier detection of the tumors being then minimally invasive diagnostic biomarkers. Circulating miRNAs have also emerged as promising diagnostic biomarkers for CRC screening. In this study we investigated the performance of a specific signature of miRNA in plasma samples in order to design a robust predictive model able to distinguish healthy individuals from those with Colorectal cancer and Advanced Adenomas. Methods: Case control study of 300 patients from eight Spanish hospitals including 100 healthy individuals, 101 diagnosed with advanced adenomas and 96 colorectal cancer cases. Real time quantitative reverse-transcriptase PCR was used to quantify a signature of miRNA (miR19a, miR19b, miR15b, miR29a, miR335, miR18a) in plasma samples. Binary classifiers (SVM linear, SVM radial, SVM polynomial) were built for the best predictive model. Results: A receiving operating characteristic curve (AUC ROC) of 0.9159 was obtained retrieving a model with a sensitivity of 0.9375 and specificity of 0.7403, positive predictive valued (PPV) of 0.8710 and negative predictive value (NPV) of 0.8836 when controls were compared to patients with advanced neoplasm (colon cancer and advanced adenomas). Conclusion: We identified and validated a signature of 6 miRNAs (miR19a, miR19b, miR15b, miR29a, miR335, miR18a) as predictors able to differentiate significantly patients with colon cancer and advanced adenomas from those who are healthy. This signature could be used for CRC screening purposes.
MBCL-22. RISK OF DEVELOPMENT OF SINUSOIDAL OBSTRUCTION SYNDROME ON HEAD START REGIMENS IN YOUNG CHILDREN WITH MEDULLOBLASTOMA
Authors: Ossama Maher, Jorge Galvez, Kamar Godder, Toba Niazi, Matthew Hall, Ziad Khatib
Journal: Neuro-Oncology (2018)

Sinusoidal obstruction syndrome (SOS) in the pediatric population is not limited to a well-defined group of patients who undergo autologous stem cell transplantation. We describe the clinical characteristics of five patients with history of medulloblastoma who developed SOS during treatment as per Head Start (HS) regimens. A chart review of 31 patients from 2006 to 2017 revealed that five patients (16.1%) developed SOS during the course of their therapy (2 patients were enrolled on HS IV). The median age at diagnosis was 2.5 years (range 2-5 years). All three patients diagnosed in the era of HSII/III developed SOS in transplant setting. The other 2 patients on HS IV developed SOS during the induction chemotherapy cycles. In the follow-up period, one patient developed metastatic disease 2 years after completion of therapy. Another patient died from pulmonary fibrosis 4 years post-transplant. Two patients developed fibronodular hyperplasia of the liver on further imaging. The dose of carboplatin for the 3 patients treated as per HSII/III was dosed by the AUC using the Calvert method. The remaining 2 patients had received the induction chemotherapy cycles (second and third) based on the square meter dose on the HS IV guidelines; one of them continued on the same regimen after the dose was adjusted to weight based in the subsequent cycles. Dose calculation based on the weight and age of young patients, particularity those who are under five should be taken into consideration in future studies. Long term consequences of severe SOS should be monitored.
Secukinumab in pregnancy: outcomes in psoriasis, psoriatic arthritis and ankylosing spondylitis from the global safety database
Authors: R.B. Warren, K. Reich, R.G. Langley, B. Strober, D. Gladman, A. Deodhar, T. Bachhuber, W. Bao, E. Altemeyer, S. Hussain, J. Safi
Journal: British Journal of Dermatology (2018)

missing outcome data and the relatively short exposure to secukinumab.The majority of patients discontinued in the first trimester, whereas secukinumab would be expected to be transferred across the placenta in the third trimester.There are no human data on the effects of secukinumab on the immune system of neonates born after in utero exposure.Although there may be a bias towards reporting of detrimental events, there was no evidence for increased rates of adverse pregnancy outcomes with secukinumab in this review of the safety database.However, given the limited exposure reported to date, the continuous use of secukinumab throughout pregnancy requires further research.
Treatment based on tumor sidedness in mCRC: Effect of online education on clinician knowledge, competence and confidence
Authors: G. Fisher, W. Guerra, C. Day, M. Ducreux
Journal: Annals of Oncology (2018)

Introduction: Emergent data on the impact of tumour sidedness on the treatment of metastatic colorectal cancer (mCRC) has important implications to clinical practice. This study determined whether online continuing medical education (CME) could improve oncologists' knowledge of the most current data supporting the use of available therapeutic options in left- vs right-sided tumors, and improve clinician competence in evidence-based selection and optimal use of EGFR antibodies in clinical practice. Methods: A 30-minute online video roundtable discussion between 3 experts was launched for countries outside the United States in March 2017, with data collected until June 2017. Educational effect was assessed with a repeated-pairs pre-/post-assessment study design, where individual participants served as his/her own control. 3 multiple-choice, knowledge questions and 1 self-efficacy, 5-point Likert scale (confidence) question were analyzed. Chi-squared test assessed pre- to post-assessment change (5% significance level, P<.05). Magnitude of change in total number of correct responses overall, and for each question, were determined with Cramer's V (effect size: <0.05 none/minimal; 0.06-0.15 small, 0.16-0.30 medium, >0.30 large). Results: 142 oncologists completed both pre- and post-assessments. Although these specialists demonstrated a good baseline knowledge for all three questions (70-80% with the correct answer), a significant improvement and small/medium education effect was observed regarding: identification of EGFR antibody as the correct treatment preference for a patient with a left sided tumour (21% improvement, P =.005; V = 0.169) and recognising that this is based on the superior OS and PFS observed for EGFR antibodies in this patient group compared with those with right-sided tumours (21% improvement, P .001; V = 0.222). Interestingly, when asked to identify the correct management approach for a patient presenting with a Grade 2 EGFR-related rash, there was a 15% decrease in the number of participants identifying the correct answer post-assessment (from 80 to 68%). This suggests a lack of certainty on the right approach and a potential need for further education. Approximately 30% of participants reported increased confidence in selecting treatment based on tumour sidedness as a result of participation in this activity. Conclusion: This on-demand, online video roundtable discussion resulted in a positive education effect. Encouragingly, the participants had a good baseline understanding of the importance of tumour sidedness in informing treatment selection. However, further education appears to be required in the area of management of EGFR-related side effects. Online medical education is valuable in supporting the interpretation and application of new data, as well as identifying areas of continued educational need.
NFM-14. IDENTIFICATION OF A THERAPEUTIC TIME WINDOW THAT IMPROVES VISION IN AN NF1-DEFICIENT OPTIC PATHWAY GLIOMA MOUSE MODEL
Authors: Miriam Bornhorst, Emma Jecrois, Daphine Kwesiga Mugayo, Wang Zheng, Steven Stasheff, Patrick Mateas, Austin Friend, Yuan Zhu
Journal: Neuro-Oncology (2018)

Optic pathway gliomas (OPGs) are glial tumors that arise early during development in 15-20% of patients with Neurofibromatosis Type I (NF1). While chemotherapy is often used for patients who have growing tumors and/or vision loss associated with the tumor, a minority of patients have improvement in their vision following treatment. Thus, a new approach to treatment is needed to improve the visual outcomes in this patient population. In our laboratory, we have a Nf1-deficient conditional knockout mouse model that develops optic pathway gliomas around 60 days of age (P60). These mice have associated axon degeneration, loss of retinal ganglion cells, and evidence of vision loss on behavioral testing, thus making this a good model to use in order to identify the optimal therapeutic time window that improves or prevents vision loss. In this study, we treated NF1-deficient mice with a Mek-inhibitor during different developmental time windows and measured response to treatment in terms of nerve cellularity, axon integrity, and retinal ganglion cell loss. We found that response to treatment is highly dependent on when the therapy is initiated during OPG development, and the best response occurred when therapy was initiated early during this process. This study suggests that the timing of therapy initiation is critical for optimal outcomes in NF1-associated OPGs.
NSRG-25. THE MOST INFLUENTIAL PAPERS IN THE NEUROSURGICAL MANAGEMENT OF PAEDIATRIC CENTRAL NERVOUS SYSTEM TUMOURS
Authors: Charlotte Burford, Yasmine Cherfi, Cristina Bleil, Bassel Zebian
Journal: Neuro-Oncology (2018)

Citation number can be considered a measure of a publication’s academic influence. Previous studies have suggested a citation number greater than 50 and a citation rate higher than 5 per year constitute a high impact in neurosurgery. We set out to determine and categorise the most highly influential papers related to the neurosurgical management of paediatric central nervous system (CNS) tumours between 2005-2010. Child’s Nervous System, Journal of Neurosurgery: Pediatrics and Pediatric Neurosurgery were previously identified as publishing the most influential papers in paediatric neurosurgery. All papers published by these journals between 2005-2010 were collected from Web of Science. Papers describing surgical management of paediatric CNS neoplasms were identified and the 50 most cited were determined. Of the most highly cited papers, 54% were published in Child’s Nervous System, 26% in Journal of Neurosurgery: Pediatrics and 20% in Pediatric Neurosurgery. The citation number ranged from 27-93 (mean = 43) and citations rate (per year) ranged from 2.31-8.25. Of the top 50 papers, 24% had more than 50 citations and 8 of these had a citation rate greater than 5 per year. 72% of papers were experiential studies and 24% were review articles. 42% described surgical management of craniopharyngiomas and 10% related to management of posterior fossa tumours. There were no randomised controlled trials. Between 2005-2010, 8 papers related to surgical management of paediatric CNS tumours can be considered as having high impact in the literature. The majority of papers focused on surgical management of craniopharyngiomas.