tbuckley/cabot-search huggingface dataset:
Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome
Authors: Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D. Allan Butterfield, Marzia Perluigi, Fabio Di Domenico
Journal: Translational Neurodegeneration (2018)

Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling in DS mice by a novel rapamycin intranasal administration protocol (InRapa) that maximizes brain delivery and reduce systemic side effects.Ts65Dn mice were administered with InRapa for 12 weeks, starting at 6 months of age demonstrating, at the end of the treatment by radial arms maze and novel object recognition testing, rescued cognition.The analysis of mTOR signalling, after InRapa, demonstrated in Ts65Dn mice hippocampus the inhibition of mTOR (reduced to physiological levels), which led, through the rescue of autophagy and insulin signalling, to reduced APP levels, APP processing and APP metabolites production, as well as, to reduced tau hyperphosphorylation. In addition, a reduction of oxidative stress markers was also observed.These findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis, thus ultimately resulting in improved cognition. Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals.
Real-world comparative effectiveness of nab-paclitaxel plus gemcitabine (nab-P/G) vs FOLFIRINOX (FFX) in patients (pts) with advanced pancreatic cancer (aPC)
Authors: E.G. Chiorean, W.Y. Cheung, G. Giordano, G. Kim, S.-E. Al-Batran
Journal: Annals of Oncology (2018)
P2.16-30 Surgical Strategy for Clinical Stage IA Non-Small Cell Lung Cancer Patients with Risk Factors of Pathological Invasion and/or Metastasis
Authors: T. Koike, M. Nakamura, Y. Shimizu, T. Goto, S. Sato, S. Toyabe, M. Tsuchida
Journal: Journal of Thoracic Oncology (2018)
PI3K/AKT pathway deleterious mutations in lethal prostate cancer
Authors: P. Rescigno, M. Rediti, D. Dolling, D.N. Rodrigues, D. Bianchini, R. Riisnaes, C. Messina, M. Barrero, A. Petremolo, A. Sharp, S. Sumanasuriya, G. Seed, I. Figueiredo, S. Miranda, J. Goodall, J. Mateo, R. Chandler, W. Yuan, S. Carreira, J.S. de Bono
Journal: Annals of Oncology (2018)
Pathogens and characteristics of candidemia in hospitals of Rostov-on-Don: Multicenter study in Russia
Authors: O.Y. Kutsevalova, O.I. Kit, N.I. Panova, I.B. Lysenko, V.V. Dmitrieva, D.A. Rozenko, E.A. Kalabanova, I.S. Mitashok, G. Klyasova, Y.V. Shatokhin, I.V. Snezhko, D.V. Martynov, V.N. Malygin, O.V. Korosteleva, A.A. Matsuga, K.S. Aslanyan, L.Y. Vladimirova
Journal: Annals of Oncology (2018)
OA13.05 Prophylactic Cranial Irradiation (PCI) for Limited-Stage Small-Cell Lung Cancer: Results from the Phase 3 CONVERT Trial
Authors: C. Le Pechoux, A. Levy, H. Mistry, I. Martel-Lafay, A. Bezjak, D. Lerouge, L. Padovani, P. Taylor, C. Faivre-Finn
Journal: Journal of Thoracic Oncology (2018)
P2.01-128 Low Positivity Rate in T790M Detection with ctDNA in NSCLC and Post EGFR-TKI Progression – Timing or Sensitivity?
Authors: C.G. Ferreira, M. Zalis, M. Zukin, C. Mathias, C. Haddad, E. Mascarenhas, L.H. Araujo, T. Montella, M. Custodio, B. Silva, C. Bustamante, G. Montenegro, A. Muras, M. Reis
Journal: Journal of Thoracic Oncology (2018)
Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations
Authors: Kanika Bajaj Pahuja, Thong T. Nguyen, Bijay S. Jaiswal, Kumar Prabhash, Tarjani M. Thaker, Kate Senger, Subhra Chaudhuri, Noelyn M. Kljavin, Aju Antony, Sameer Phalke, Prasanna Kumar, Marco Mravic, Eric W. Stawiski, Derek Vargas, Steffen Durinck, Ravi Gupta, Arati Khanna-Gupta, Sally E. Trabucco, Ethan S. Sokol, Ryan J. Hartmaier, Ashish Singh, Anuradha Chougule, Vaishakhi Trivedi, Amit Dutt, Vijay Patil, Amit Joshi, Vanita Noronha, James Ziai, Sripad D. Banavali, Vedam Ramprasad, William F. DeGrado, Raphael Bueno, Natalia Jura, Somasekar Seshagiri
Journal: Cancer Cell (2018)
PL02.03 Brigatinib vs Crizotinib in Patients With ALK Inhibitor-Naive Advanced ALK+ NSCLC: First Report of a Phase 3 Trial (ALTA-1L)
Authors: R. Camidge, H.R. Kim, M. Ahn, J.C. Yang, J. Han, J. Lee, M. Hochmair, J.Y. Li, G. Chang, K. Lee, C. Gridelli, A. Delmonte, M.R. Garcia Campelo, D. Kim, A. Bearz, F. Griesinger, A. Morabito, E. Felip, R. Califano, S. Ghosh, A. Spira, S. Gettinger, M. Tiseo, J. Haney, D. Kerstein, S. Popat
Journal: Journal of Thoracic Oncology (2018)
IMpower132: Efficacy of atezolizumab (atezo) + carboplatin (carbo)/cisplatin (cis) + pemetrexed (pem) as 1L treatment in key subgroups with stage IV non-squamous non-small cell lung cancer (NSCLC)
Authors: F. Barlesi, M. Nishio, M. Cobo, N. Steele, V. Paramonov, B. Parente, R. Dear, H. Berard, N. Peled, L.C. Seneviratne, E. Baldini, S. Watanabe, K. Goto, D. Mendus, H. Patel, Y. Deng, M. Kowanetz, T. Hoang, W. Lin, V.A. Papadimitrakopoulou
Journal: Annals of Oncology (2018)
P2.17-03 A Propensity-Matched Analysis of Neoadjuvant Chemoradiotherapy and Adjuvant Chemoradiotherapy for IIIA(N2) Non-Small Cell Lung Cancer
Authors: Y. Zhu, C. Jiang, Y. Chen, J. Liu, Y. Xu, Q. Chen, W. Mao
Journal: Journal of Thoracic Oncology (2018)
Comparative effectiveness of nab-paclitaxel vs. paclitaxel monotherapy as first-line (1L) treatment of metastatic triple-negative breast cancer (mTNBC) in US clinical practice
Authors: T. Luhn, S. Chui, A. Hsieh, J. Yi, A. Mecke, P. Bajaj, W. Hasnain, A. Falgas, T.G.N. Ton, A. Kurian
Journal: Annals of Oncology (2018)
P1.01-26 Single-Centre Experience of Clinical Outcomes for Advanced Lung Cancer Patients in Phase I Clinical Trials
Authors: D. Graham, T. Jordan, N. Tinsley, S. Aruketty, A. Vickers, C. Kelly, R. Kurup, A. White, A. Smith, A. Walsh, C. Thomson, S. O'Reilly, M. Norfolk, D. Chang, F. Blackhall, Y. Summers, R. Califano, P. Taylor, F. Thistlethwaite, N. Cook, L. Carter, M. Krebs
Journal: Journal of Thoracic Oncology (2018)
Quality of life (QoL) in patients with metastatic pancreatic cancer receiving first-line Nab-paclitaxel/gemcitabine chemotherapy: Results of the large QoL study AIO-QoliXane/PARAGON
Authors: C. Schönherr, T.O. Götze, G. zur Hausen, A. Reichart, C. Pauligk, R. Schlag, G.M. Siegler, S. Dörfel, A. Aldaoud, L. Hahn, J. Schubert, M.-O. Zahn, H.-G. Höffkes, M. Reiser, M. Koenigsmann, W. Blau, O. Waidmann, N. Homann, J. Trojan, S.-E. Al-Batran
Journal: Annals of Oncology (2018)
IMvoke010: Randomized phase III study of atezolizumab (atezo) as adjuvant monotherapy after definitive therapy of squamous cell carcinoma of the head and neck (SCCHN)
Authors: R. Haddad, D.J. Wong, Y. Guo, J. Fayette, E.E.W. Cohen, M. Kowgier, A. Sandler, C. Matheny, F. Kabbinavar, D. Raben
Journal: Annals of Oncology (2018)
P2.01-124 SIB-IMRT in Symptomatic Brain Metastases for NSCLC: A Randomized Controlled Study of WBRT Comparing 25Gy and 30Gy
Authors: J. Zhu, Q. Dong, W. Wang, X. Tang, Y. Meng, F. Kong, H. Yang
Journal: Journal of Thoracic Oncology (2018)
In the pathway to response: Is aflibercept an optimal treatment for RASwt mCRC patients after progression to 1st line containing anti-EGFR?
Authors: E. Mata Velasco, E. González-Flores, I. Juez Martel, V. Alonso, P. Iranzo Gomez, N. Martinez Lago, C. Lopez, J.M. Cabrera Romero, M.J. Safont Aguilera, A. Ruiz Casado, M. Salgado Fernandez, B. González Astorga, P. Escudero, F. Rivera Herrero, C. Pericay Pijaume, R. Vera
Journal: Annals of Oncology (2018)
Clinical impact of 18F-FDG-PET/CT (PET) in patients (P) with oligometastatic disease (OMD) at a skin and gastrointestinal tumour section
Authors: J.J. Garcia-Mosquera, L. Layos Romero, C. Buges, S. España Fernandez, S. Chen, J.M. Velarde, E. Felip, C. Erasun Lecuona, L. Angelats, M. Cucurull Salamero, J.L. Manzano
Journal: Annals of Oncology (2018)
P3.08-16 Prognostic Value of PDL-1 Expression and Correlation Between Primary Tissue and Brain Metastases in Oligometastatic NSCLC
Authors: V. Krishnan, K. Imane, L. Gaboury, R. Albadine, D. Tran-Thanh, C. Gauvin, N. Blais, B. Routy, M. Tehfe, M. Florescu
Journal: Journal of Thoracic Oncology (2018)
P1.01-20 Phase III Study Comparing Gefitinib (G) to Gefitinib Combined with Carboplatin and Pemetrexed (GCP) for NSCLC with EGFR Mutations (NEJ009)
Authors: T. Fukuhara, A. Inoue, S. Morita, S. Sugawara, Y. Hosomi, S. Ikeda, A. Gemma, K. Takahashi, Y. Fujita, T. Harada, K. Minato, K. Takamura, K. Kobayashi, T. Nukiwa
Journal: Journal of Thoracic Oncology (2018)
Phase I/IIa study of concomitant radiotherapy with olaparib and temozolomide in unresectable high-grade gliomas patients: OLA-TMZ-RTE-01
Authors: D. Stefan, P. Lesueur, J. Lequesne, E. Coquan, P.E. Brachet, L. Castera, N. Goardon, J. Lacroix, M. Lange, A. Capel, B. Andre, J.-M. Grellard, B. Clarisse
Journal: Annals of Oncology (2018)
Timing of palliative care referral before and after a cluster randomized controlled trial (RCT) of early palliative care
Authors: D. Hausner, C. Tricou, D. Wadhwa, A. Pope, M. Giruparajah, N. Swami, M. Krzyzanowska, K. Mah, C. Zimmermann
Journal: Annals of Oncology (2018)
P2.09-27 Prognostic Significance of Vascular Invasion in Pathological Stage IA Lung Adenocarcinoma According to the 8th Edition of the TNM Classification
Authors: J. Samejima, T. Yokose, H. Ito, H. Nakayama, T. Nagashima, J. Osawa, K. Inafuku, H. Yagasaki, M. Suzuki, K. Yamada, M. Masuda
Journal: Journal of Thoracic Oncology (2018)
Can Jiangsu province achieve the health-related Sustainable Development Goals and Healthy Jiangsu 2030 goals? A systematic analysis on the current situation and projected attainment
Authors: Shu Chen, Wenhui Mao, Weixi Jiang, Zhan Wang, Lei Guo, Xiyu Ding, Guanshen Dou, Shanquan Chen, Di Dong, John S Ji, Qian Long, Shenglan Tang
Journal: The Lancet (2018)
P1.01-28 Impact of Afatinib Dosing on Safety and Efficacy Real-World in Patients with EGFR Mutation-Positive Advanced NSCLC
Authors: B. Halmos, E. Tan, R. Soo, J. Cadranel, M.K. Lee, P. Foucher, T. Hsia, M. Hochmair, F. Griesinger, T. Hida, E. Kim, B. Melosky, A. Märten, E. Carcereny
Journal: Journal of Thoracic Oncology (2018)
TRIBE2: A phase III, randomized strategy study by GONO in the 1st- and 2nd-line treatment of unresectable metastatic colorectal cancer (mCRC) patients (pts)
Authors: C. Cremolini, C. Antoniotti, S. Lonardi, D. Rossini, F. Pietrantonio, S.S. Cordio, S. Murgioni, F. Marmorino, E. Maiello, A. Passardi, G. Masi, E. Tamburini, D. Santini, R. Grande, A. Zaniboni, C. Granetto, F. Loupakis, L. Delliponti, L. Boni, A. Falcone
Journal: Annals of Oncology (2018)
Tegwondo-CCNU: A novel combination of protracted, near-continuous temozolomide and CCNU with activity in recurrent malignant gliomas.
Authors: Herwig Matthias Strik, Hans Rock, Kai Kallenberg
Journal: Journal of Clinical Oncology (2012)

2079 Background: Recent data have been raising doubt if dose-dense temozolomide is more efficient against malignant gliomas than with conventional dosing. We report here updated results of combined near-continuous temozolomide, aimed at depleting anti-alkylating MGMT, with once weekly application of low-dose lomustine (CCNU) at first or second relapse of malignant gliomas. Methods: 25 consecutive patients with recurrent malignant gliomas (12 anaplastic gliomas WHO III, 13 glioblastomas or gliosarkomas WHO IV) were treated: 15 males (60%), 10 females (40%); mean age at start of chemotherapy was 52 (20-78) years; Eight patients were treated at first, 15 at second and two at third recurrence. All patients were pretreated with temozolomide. Four patients received fractionated, stereotactically guided re-irradiation (FSRT). The treatment regimen consisted of near-continuous temozolomide 50mg/m 2 day 1‑5/7 and low-dose CCNU 40mg absolute dose day 6/7. In cases of bone-marrow depression, temozolomide was reduced in steps of 20mg total dose or – in more severe cases – chemotherapy was interrupted until normalization of blood counts. Results: In total, 89 cycles (months) of chemotherapy were applied. The combination was well tolerated in terms of nausea and fatigue. Blood counts usually decreased continuously, enabling a gradual dose adaptation. Hematological WHO grade 3+4 toxicity occurred in 5/25 patients (20%), two of them were symptomatic. Three patients had prolonged elevation of liver enzymes. Best responses after ≥ 3 months (23 patients) were: 2 complete and 1 partial remissions (13%, ), 13 stable diseases (57%), and 7 progressive diseases (30%). Progression-free survival at six months from start of chemotherapy of the 16 patients treated &gt; 6 months or deceased (PFS 6) was 37%, median overall survival 6.3 months. Conclusions: Although some hematotoxicity was observed, the regimen presented here is well tolerated and safe if carefully controlled. The objective responses and considerable rate of stable diseases indicate that this combination is active in malignant gliomas after pretreatment with temozolomide alone. The results have to be controlled in a prospective trial.
Prevention and prophylaxis of thrombosis in cancer patients
Authors: N.G. Tsoukalas, P. Papakotoulas, A.N. Christopoulou, A. Ardavanis, G. Koumakis, C. Papandreou, G. Papatsimpas, P. Papakostas, C. Andreadis, G. Aravantinos, N. Ziras, H. Kalofonos, E. Samantas, M. Sougleri, P. Makrantonakis, G. Pentheroudakis, A. Athanasiadis, E. Bournakis, I.I. Varthalitis, I. Boukovinas
Journal: Annals of Oncology (2018)
P1.16-25 A Propensity Score Model for Appropriate Treatment Selection (Sublobar Resection vs. SBRT) In Patients With cStage I NSCLC
Authors: Y. Matsuo, T. Chen-Yoshikawa, M. Hamaji, T. Mitsuyoshi, T. Shintani, Y. Iizuka, M. Sonobe, H. Date, T. Mizowaki
Journal: Journal of Thoracic Oncology (2018)
Real world cfDNA collection in EGFR-mutant NSCLC
Authors: N. Marcoux, L.V. Sequist, A. Hata, M. Banwait, I. Dagogo-Jack, R. Nagy, R.B. Lanman, A. Muzikansky, S.R. Digumarthy, Z. Piotrowska
Journal: Annals of Oncology (2018)
MA06.09 XRCC6BP1: A DNA Repair Gene in Cisplatin Resistant Lung Cancer Stem Cells That May Predict Survival Outcomes in Patients
Authors: M. Barr, R. Farrell, S. Singh, E. Foley, Y. He, L. Brady, V. Young, R. Ryan, S. Nicholson, N. Leonard, S. Cuffe, S. Finn
Journal: Journal of Thoracic Oncology (2018)
From basic science to diagnostics ‐ History of a patent on a honeybee venom allergen
Authors: Simon Blank
Journal: Allergy (2018)

Dr. Blank reports non-financial support from ALK-Abelló, grants, personal fees and non-financial support from Bencard Allergie GmbH, personal fees from Teomed AG, personal fees from Thermo Fisher Scientific, grants from Allergy Therapeutics, outside the submitted work. In addition, Dr. Blank has a patent “Cloning of honey bee allergen C” licensed to Thermo Fisher Scientific.
Prevalence of clinically actionable germline pathogenic variants (PVs) in advanced prostate cancer (aPC)
Authors: A.W. Hahn, A.L. Kapron, J. Boyle, W. Kohlmann, A. Poole, D.M. Gill, S. Greenberg, P. Hale, C. Teerlink, B.L. Maughan, L. Cannon-Albright, N. Agarwal, K.A. Cooney
Journal: Annals of Oncology (2018)
HLA-DrbB1 heterozygosis and early auto-antibody rise predict prolonged survival in metastatic NSCLC patients undergoing PD-1 blockade
Authors: P. Correale, R. Giannicola, C. Botta, P.S. Tagliaferri, P. Pastina, M. Monoriti, R. Saladino, A. Falzea, V. Barbieri, G. D'Arrigo, G. Tripepi, P. Tassone, L. Pirtoli
Journal: Annals of Oncology (2018)
Prediction of overall survival with 2nd-line (L2OS) chemotherapy (CT) in patients with advanced biliary tract cancer (aBTC): AGEO CT2BIL cohort update and international multicenter external validations
Authors: C. Neuzillet, A. Casadei Gardini, B. Brieau, C. Vivaldi, C. Smolenschi, G. Brandi, D. Tougeron, R. Filippi, A. Vienot, N. Silvestris, A.-L. Pointet, S. Murgioni, B.J.-C. Rousseau, M. Scartozzi, L. Dahan, T. Boussaha, S. Crusz, A. Meurisse, A. Lievre, D. Vernerey
Journal: Annals of Oncology (2018)
Abstract 001: Effects of Intensive Blood Pressure Control in Adults With and Without Albuminuria: Results From the SPRINT Trial
Authors: Alex Chang
Journal: Circulation (2018)

Background: Albuminuria is strongly associated with elevated risk of cardiovascular disease (CVD). While the Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive blood pressure (BP) lowering reduces CVD in high-risk non-diabetic adults, it is unclear whether this effect varies by albuminuria status. Methods: SPRINT randomized non-diabetic adults with elevated blood pressure and increased CVD risk to a systolic BP (SBP) goal of &lt;120 or &lt;140 mmHg. Albuminuria (&gt;=30 mg/g) was measured by albumin/creatinine ratio (ACR) at baseline. Outcomes examined included the primary composite CVD outcome (myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from CVD) and all-cause death. Results: A total of 8913/9361 (95.2%) participants had baseline ACR data; 51.9%, 28.7%, and 19.4% had baseline ACR &lt; 10, 10-29.9, and &gt;=30 mg/g, respectively. The primary composite outcome occurred in 4.0%, 6.7%, and 11.2% of individuals with baseline ACR &lt;10, 10-29.9, and &gt;=30 mg/g, respectively. The effect of intensive BP lowering on the primary outcome was similar in patients with albuminuria (HR 0.74, 95% CI: 0.55-0.99) and without albuminuria (HR 0.73, 95% CI: 0.59-0.91; p for interaction = 0.77). Intensive BP lowering reduced risk of stroke in patients with albuminuria (HR 0.45, 95% CI: 0.24-0.85) but not patients without albuminuria (1.13, 95% CI: 0.73-1.74; p for interaction = 0.03). Absolute risk reduction was particularly high in those with albuminuria, with a number needed to treat (NNT) of 32 to prevent 1 primary outcome and a NNT of 37 to prevent 1 death from any cause at 3 years of follow-up. By comparison, the NNT to prevent 1 primary outcome was 72 for ACR &lt; 30 mg/g at 3 years of follow-up. Conclusions: The effect of Intensive BP lowering reduces CVD risk similarly in non-diabetic adults with and without albuminuria. Given the high CVD risk in patients with albuminuria, this high-risk population may particularly benefit from efforts to intensify BP control.
Cell free DNA and hepatic arterial infusion of oxaliplatin plus systemic capecitabine for patients with colorectal cancer liver metastases
Authors: A.K. Boysen, J.V. Schou, B.V. Jensen, D.L. Nielsen, B.S. Sørensen, J.S. Johansen, K.-L.G. Spindler
Journal: Annals of Oncology (2018)
A phase II trial of gemcitabine, S-1 and LV combination therapy in patients with advanced pancreatic cancer
Authors: K.O. Saito, Y. Nakai, H. Isayama, K. Ishigaki, T. Saito, N. Takahara, S. Mizuno, H. Kogure, K. Koike
Journal: Annals of Oncology (2018)
Analysis of resistance mechanisms to osimertinib in patients with EGFR T790M advanced NSCLC from the AURA3 study
Authors: V.A. Papadimitrakopoulou, Y.-L. Wu, J.-Y. Han, M.-J. Ahn, S.S. Ramalingam, T. John, I. Okamoto, J.C.-H. Yang, K.C. Bulusu, G. Laus, B. Collins, J.C. Barrett, J. Chmielecki, T.S.K. Mok
Journal: Annals of Oncology (2018)
P1.13-12 EGFR Therapy in ASCL1 Positive Lung Adenocarcinoma
Authors: F. Kosari, K. Bhinge, T. Peikert, A. Mansfield, M. Aubry, L. Yang, P. Muppa, I. Kovtun, G. Vasmatzis, S. Murphy
Journal: Journal of Thoracic Oncology (2018)
KRAS-dependent and independent mechanisms of progressive disease (PD) in colorectal cancer (CRC) patients (pts) with liver metastases (LM) while monitoring on circulating cell free DNA (cfDNA)
Authors: A. Kirov, Z. Mihaylova, V. Petrova, T. Todorov, D. Petkova, A. Garev, A. Todorova-Georgieva
Journal: Annals of Oncology (2018)
P3.01-52 The Role of Serum Carcinoembryonic Antigen to Predict the Response of Treatment in Non-Small Cell Lung Cancer Patients
Authors: N. Akdeniz, M.A. Kaplan, M. Kucukoner, Z. Urakci, O. Karhan, A. Isikdogan
Journal: Journal of Thoracic Oncology (2018)
Classic dermatological tools: Foreign body removal with punch biopsy
Authors: Jesus Alberto Cardenas-de la Garza, Adrian Cuellar-Barboza, Jesus Ancer-Arellano, Cesar Jair Ramos-Cavazos, Osvaldo Tomas Vazquez-Martinez, Jorge Ocampo-Candiani
Journal: Journal of the American Academy of Dermatology (2018)
CRISPR-Cas9 off-targeting assessment with nucleic acid duplex energy parameters
Authors: Ferhat Alkan, Anne Wenzel, Christian Anthon, Jakob Hull Havgaard, Jan Gorodkin
Journal: Genome biology (2018)

Recent experimental efforts of CRISPR-Cas9 systems have shown that off-target binding and cleavage are a concern for the system and that this is highly dependent on the selected guide RNA (gRNA) design. Computational predictions of off-targets have been proposed as an attractive and more feasible alternative to tedious experimental efforts. However, accurate scoring of the high number of putative off-targets plays a key role for the success of computational off-targeting assessment. We present an approximate binding energy model for the Cas9–gRNA–DNA complex, which systematically combines the energy parameters obtained for RNA–RNA, DNA–DNA, and RNA–DNA duplexes. Based on this model, two novel off-target assessment methods for gRNA selection in CRISPR-Cas9 applications are introduced: CRISPRoff to assign confidence scores to predicted off-targets and CRISPRspec to measure the specificity of the gRNA. We benchmark the methods against current state-of-the-art methods and show that both are in better agreement with experimental results. Furthermore, we show significant evidence supporting the inverse relationship between the on-target cleavage efficiency and specificity of the system, in which introduced binding energies are key components. The impact of the binding energies provides a direction for further studies of off-targeting mechanisms. The performance of CRISPRoff and CRISPRspec enables more accurate off-target evaluation for gRNA selections, prior to any CRISPR-Cas9 genome-editing application. For given gRNA sequences or all potential gRNAs in a given target region, CRISPRoff-based off-target predictions and CRISPRspec-based specificity evaluations can be carried out through our webserver at https://rth.dk/resources/crispr/ .
P1.03-23 The Molecular Landscape and Outcome of Chinese Patients with Non-Small Cell Lung Cancer Harboring NTRK1 Point Mutations: A Retrospective Study
Authors: X. Chen, C. Xu, W. Wang, Q. Zhang, W. Zhuang, Y. Zhu, Y. Chen, M. Fang, G. Chen, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2018)
Abstract 19514: Effect of Reductive Tricuspid Annuloplasty on Subvalvular and Ventricular Geometry
Authors: Marcin Malinowski, Tomasz Jazwiec, Jeremy Wodarek, Nathan Quay, Matthew Goehler, Tomasz A Timek
Journal: Circulation (2017)

Introduction: Surgical repair of tricuspid regurgitation is focused on prosthetic reduction of the tricuspid annulus (TA), but the effect of reductive annuloplasty on subvalvular and right ventricular (RV) geometry is unknown. Hypothesis: Reductive tricuspid prosthetic annuloplasty alters subvalvular and RV geometry. Methods: Twenty-one healthy sheep had 6 sonomicrometry crystals implanted around TA, one on each papillary muscle (PM) tip, 4 on RV wall, and 1 at the apex. Pressure transducers were placed in the LV, RV, and right atrium. Ten animals underwent implantation of the Medtronic TriAd incomplete annuloplasty ring (28±1mm) and 11 served as control. Sonomicrometric data were collected after weaning off cardiopulmonary bypass and hemodynamic stabilization. TA area, RV volume, and cross sectional area were calculated from 3D crystal coordinates. Subvalvular geometry was expressed as the distance from each PM tip to TA plane. Results: Hemodynamic parameters are presented in the Table. Ring implantation...