tbuckley/cabot-search huggingface dataset:
Genomic profiling of lung adenocarcinoma patients reveals potential therapeutic targets when standard molecular testing is negative.
Authors: Seungtaek Lim, Sun Min Lim, HyeRyun Kim, Siraj Mahamed Ali, Hyo Sup Shim, Hyun Chang, Soonmyung Paik, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2016)

e20575 Background: Identification of oncogenic drivers is critical in selecting appropriate targeted therapy. Using next-generation sequencing (NGS), we performed comprehensive genomic profiling (CGP) of lung adenocarcinoma tumors. Methods: Formalin-fixed paraffin-embedded tumors from 51 lung adenocarcinoma patients whose tumors previously tested negative for EGFR/KRAS/ALK by conventional methods in an ongoing trial (NCT01964157) were collected, and CGP was performed via hybridization capture of 4,557 exons from 287 cancer-related genes and 47 introns from 19 genes frequently rearranged in cancer and next generation sequencing. Results: Genomic profiles of all 51 cases were obtained, with a median coverage of 564x and a total of 190 individual genomic alterations (GA). GA per specimen was a mean of 3.7 (range 0-10).Cancer genomes are characterized by 50% (80/190) non-synonymous base substitutions, 15% (29/190) insertions or deletion, and 3% (5/190) splice site mutation. TP53 was the most commonly mutated gene (30%, n = 24/80) among non-synonymous base substitutions, followed by KRAS (10%, n = 8/80) and EGFR (9%, 7/80). Insertions or deletions commonly occurred TP53 (17%, 5/29) and ERBB2 (14%, 4/29), and splice site mutations occurred in TP53, INPP4B, ATR, and MAP2K4. Gene amplification comprised 20% (39/190) of genomic alterations, and MDM2 amplification was the most frequent (13%, 5/39). Homozygous loss comprised 5% (10/190) of all GA which were CDKN2A/B. GA found with NCCN guidelines for NSCLC were identified in 16 patients (31%) (BRAF mutation [n = 1], EGFR mutation [n = 8], ERBB2 mutation [n = 4], MET amplification [n = 1], KIF5B-RET rearrangement [n = 2], CCDC6-RET rearrangement [n = 1], CD74-ROS1 rearrangement [n = 1], EZR-ROS1 rearrangement [n = 5], and SLC34A2-ROS1rearrangement [n = 1]). Other genes that conferred the possibility of benefit from targeted therapy were found in another 14 patients (27%). Conclusions: Fifty eight percent of patients wild type by standard testing for KRAS/EGFR/ALK have GA identifiable by CGP that suggest benefit from target therapy. CGP used when standard molecular testing for NSCLC is negative is able to reveal additional avenues of benefit from targeted therapy.
Lats1/2 Regulate Yap/Taz to Control Nephron Progenitor Epithelialization and Inhibit Myofibroblast Formation
Authors: Helen McNeill, Antoine Reginensi
Journal: Journal of the American Society of Nephrology (2016)

In the kidney, formation of the functional filtration units, the nephrons, is essential for postnatal life. During development, mesenchymal progenitors tightly regulate the balance between self-renewal and differentiation to give rise to all nephron epithelia. Here, we investigated the functions of the Hippo pathway serine/threonine-protein kinases Lats1 and Lats2, which phosphorylate and inhibit the transcriptional coactivators Yap and Taz, in nephron progenitor cells. Genetic deletion of Lats1 and Lats2 in nephron progenitors of mice led to disruption of nephrogenesis, with an accumulation of spindle-shaped cells in both cortical and medullary regions of the kidney. Lineage-tracing experiments revealed that the cells that accumulated in the interstitium derived from nephron progenitor cells and expressed E-cadherin as well as vimentin, a myofibroblastic marker not usually detected after mesenchymal-to-epithelial transition. The accumulation of these interstitial cells associated with collagen deposition and ectopic expression of the myofibroblastic markers vimentin and α -smooth-muscle actin in developing kidneys. Although these myofibroblastic cells had high Yap and Taz accumulation in the nucleus concomitant with a loss of phosphorylated Yap, reduction of Yap and/or Taz expression levels completely rescued the Lats1/2 phenotype. Taken together, our results demonstrate that Lats1/2 kinases restrict Yap/Taz activities to promote nephron progenitor cell differentiation in the mammalian kidney. Notably, our data also show that myofibroblastic cells can differentiate from nephron progenitors.
P0384 : Assessment of treatment response by sequential serum metabolomic profiling after percutaneous radiofrequency ablation of hepatocellular carcinoma
Authors: C. Goossens, P. Nahon, L. Le Moyec, M.N. Triba, N. Bouchemal, R. Amathieu, N. Ganne-Carrié, M. Ziol, J.-C. Trinchet, A. Diallo, O. Seror, P. Savarin
Journal: Journal of Hepatology (2015)
Liver Stiffness Measurement by Transient Elastography for the Prediction of Fibrosis in Patients with Primary Sclerosing Cholangitis in a Randomized Trial of Simtuzumab
Authors: C.L. Bowlus, A.J. Montano-Loza, P. Invernizzi, O. Chazouillères, G. Hirschfield, H.J. Metselaar, Z. Goodman, R.P. Myers, R. Aguilar, G. Mani Subramanian, J.G. McHutchison, R. Chapman, A.J. Muir, B. Eksteen, C. Levy
Journal: Journal of Hepatology (2016)
Liver Regeneration Capacity after Partial Hepatectomy in Rats with Non-Alcoholic Steatohepatitis
Authors: D. Haldrup, S. Heebøll, K.L. Thomsen, K.J. Andersen, M. Meier, F.V. Mortensen, J.R. Nyengaard, S.J.H. Dutoit, H. Grønbask
Journal: Journal of Hepatology (2016)
Treatment Discontinuation after HBsAg Loss is Safe in Chronic Hepatitis B Patients Treated with Nucleos/Tide Analogs: A Retrospective Multicenter Study (HEBESAS)
Authors: E. Suárez, M.A. Simón, M. Buti, M. Prieto, J.M. Pascasio, M. Rodríguez, T. Casanovas, J. Crespo, J. Arenas, R. Gómez, B. Figueruela, M. Diago, R.Ma. Morillas, J.M. Zozaya, J.L. Calleja, M. Casado, E. Molina, J. Fuentes
Journal: Journal of Hepatology (2016)
Long-Lasting Dysregulation of the Hematopoietic Stem Cell Compartment in Obesity
Authors: Jung-Mi Lee, Bryan Goddard, Ashwini S. Hinge, Bruce J. Aronow, Nathan Salomonis, Marie-Dominique Filippi, H. Leighton Grimes, Jose A Cancelas, Damien Reynaud
Journal: Blood (2015)
Corrigendum re: “Role of Magnetic Resonance Imaging in Prostate Cancer Screening: A Pilot Study Within the Göteborg Randomised Screening Trial” [Eur Urol 2016;70:566–73]
Authors: Anna Grenabo Bergdahl, Ulrica Wilderäng, Gunnar Aus, Sigrid Carlsson, Jan-Erik Damber, Maria Frånlund, Kjell Geterud, Ali Khatami, Andreas Socratous, Johan Stranne, Mikael Hellström, Jonas Hugosson
Journal: European Urology (2016)
Incidences of Acute Hepatitis D among 15 to 35 Years Old Mongolian Youths
Authors: D. Boldbaatar, O. Lkhagva-Ochir, M. Enkhbat, P. Bat-Ulzii, G. Jargalsaikhan, D. Zulkhuu, O. Nasan, N. Dashdorj
Journal: Journal of Hepatology (2016)
Local Mosquito-Borne Transmission of Zika Virus — Miami-Dade and Broward Counties, Florida, June–August 2016
Authors: Anna Likos, Isabel Griffin, Andrea M. Bingham, Danielle Stanek, Marc Fischer, Stephen White, Janet Hamilton, Leah Eisenstein, David Atrubin, Prakash Mulay, Blake Scott, Patrick Jenkins, Danielle Fernandez, Edhelene Rico, Leah Gillis, Reynald Jean, Marshall Cone, Carina Blackmore, Janet McAllister, Chalmers Vasquez, Lillian Rivera, Celeste Philip
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

During the first 6 months of 2016, large outbreaks of Zika virus disease caused by local mosquito-borne transmission occurred in Puerto Rico and other U.S. territories, but local mosquito-borne transmission was not identified in the continental United States (1,2). As of July 22, 2016, the Florida Department of Health had identified 321 Zika virus disease cases among Florida residents and visitors, all occurring in either travelers from other countries or territories with ongoing Zika virus transmission or sexual contacts of recent travelers.* During standard case investigation of persons with compatible illness and laboratory evidence of recent Zika virus infection (i.e., a specimen positive by real-time reverse transcription-polymerase chain reaction [rRT-PCR], or positive Zika immunoglobulin M [IgM] with supporting dengue serology [negative for dengue IgM antibodies and positive for dengue IgG antibodies], or confirmation of Zika virus neutralizing antibodies by plaque reduction neutralization testing [PRNT]) (3), four persons were identified in Broward and Miami-Dade counties whose infections were attributed to likely local mosquito-borne transmission. Two of these persons worked within 120 meters (131 yards) of each other but had no other epidemiologic connections, suggesting the possibility of a local community-based outbreak. Further epidemiologic and laboratory investigations of the worksites and surrounding neighborhood identified a total of 29 persons with laboratory evidence of recent Zika virus infection and likely exposure during late June to early August, most within an approximate 6-block area. In response to limited impact on the population of Aedes aegypti mosquito vectors from initial ground-based mosquito control efforts, aerial ultralow volume spraying with the organophosphate insecticide naled was applied over a 10 square-mile area beginning in early August and alternated with aerial larviciding with Bacillus thuringiensis subspecies israelensis (Bti), a group biologic control agent, in a central 2 square-mile area. No additional cases were identified after implementation of this mosquito control strategy. No increases in emergency department (ED) patient visits associated with aerial spraying were reported, including visits for asthma, reactive airway disease, wheezing, shortness of breath, nausea, vomiting, or diarrhea. Local and state health departments serving communities where Ae. aegypti, the primary vector of Zika virus, is found should continue to actively monitor for local transmission of the virus.(†).
CCGs to get £6 a patient to extend general practice opening hours
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Every clinical commissioning group (CCG) in England will be given recurrent funding of at least £6 (€7; $7.8) per head of population to allow GP surgeries to extend their opening hours, NHS leaders have announced.

CCGs will be required to commission at least an extra 1.5 hours of evening appointments after 6 30 pm on weekdays, but will have the flexibility to offer Saturday and Sunday appointments according to local need.

The BMA said that it was pleased that NHS England had accepted its argument that it was “a nonsense” to force GPs to open from 8 am to 8 pm on Saturdays and Sundays.

The funding will initially be released during 2016-17 in areas of England that have been piloting extended hours through …
Trustworthiness of Patient-Reported Outcomes in Unblinded Cancer Clinical Trials
Authors: Thomas M. Atkinson, Jan-Samuel Wagner, Ethan Basch
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
A New Method including the Quantification of Circulating Mirnas Allows the Efficient Identification of Nash Patients at Risk who should be Treated
Authors: A. Sanyal, G. Cordonnier, J. Brozek, A. Roudot, S. Deledicque, M. Barbazanges, E. Praca, F.B. Sudrik, S. Megnien, R. Hanf, B. Staels, P. Bedossa, V. Ratziu, D. Hum, R. Darteil
Journal: Journal of Hepatology (2016)
P0882 : Pilot study of ezetimibe for chronic hepatitis C infection: Effect of treatment in plasma, bile and stool viral load in humans
Authors: H. Monrroy, J. Angulo, K. Pino, J.F. Miquel, C. Benitez, M. Arrese, F. Barrera, B. Norero, R. Wolff, P. Labbe, M. Lopez-Lastra, A. Soza
Journal: Journal of Hepatology (2015)
Bosutinib therapy resulting in severe deterioration of pre-existing pulmonary arterial hypertension
Authors: Peter M. Hickey, Alfred A.R. Thompson, Athanasios Charalampopoulos, Charles A. Elliot, Neil Hamilton, David G. Kiely, Allan Lawrie, Ian Sabroe, Robin Condliffe
Journal: European Respiratory Journal (2016)

We read with interest the recent correspondence from Quilot et al. [1] describing a likely case of ponatinib-associated pulmonary arterial hypertension (PAH). The authors hypothesised that the mechanism by which tyrosine kinase inhibitors (TKIs) such as dasatinib and ponatinib, used for the treatment of chronic myeloid leukaemia (CML), induce PAH may involve their common inhibition of the non-receptor tyrosine kinase, Src [1]. Here, we present a patient who developed marked worsening of pre-existing TKI-associated PAH following commencement of bosutinib, a third-generation TKI also known to inhibit Src [2]. After marked improvement on withdrawal of bosutinib, the patient experienced further significant worsening of PAH after commencing ponatinib. We believe this is the first reported case linking bosutinib with PAH. It also supports the association between ponatinib and PAH and represents the first time that the development or worsening of PAH associated with multiple TKIs in the same patient has been reported. A patient with severe worsening of pre-existing PAH following treatment with bosutinib improved on cessation <http://ow.ly/gJy7302uXL7>
The Real World Experience of Daclatasvir and Asunaprevir Combination Therapy for More Elderly Patients thanthe Clinical Trial Subjects with Genotype 1b Chronic Hepatitis C
Authors: S. Hige, Y. Karino, I. Ozeki, M. Yamaguchi, M. Kimura, T. Arakawa, T. Nakajima, Y. Kuwata, T. Sato, T. Ohmura, J. Toyota
Journal: Journal of Hepatology (2016)
Impact of Longitudinal Lesion Geometry on Location of Plaque Rupture and Clinical Presentations
Authors: Joo Myung Lee, Gilwoo Choi, Doyeon Hwang, Jonghanne Park, Hyun Jin Kim, Joon-Hyung Doh, Chang-Wook Nam, Sang-Hoon Na, Eun-Seok Shin, Charles A. Taylor, Bon-Kwon Koo
Journal: JACC. Cardiovascular imaging (2016)
Development of Somatic NRAS Mutation Associated with Rapid Transition from Germline GATA2 Mutation Associated Myelodysplastic Syndrome to Acute Myeloid Leukemia
Authors: Yanqin Yang, Yubo Zhang, Jun Zhu, Catherine E. Lai, Jingrong Tang, Lisa J. McReynolds, Amy P Hsu, Dennis D. Hickstein, Danielle M. Townsley, Steven M. Holland, Katherine R. Calvo, Christopher S. Hourigan
Journal: Blood (2015)
Correlation Between serum ferritin Level at diagnosis and Survival In Lower Risk, Non-Transfusion Dependent, MDS Patients.A Report by the Groupe Francophone Des Myelodysplasies (GFM)
Authors: Sophie Park, Rosa Sapena, Dominique Vassilieff, Charikleia Kelaidi, Dominique Bordessoule, Aspasia Stamatoullas, Stéphane Cheze, Odile Beyne-Rauzy, Norbert Vey, Christian Rose, Agnès Guerci, Shanti Ame, Gerard Tertian, Borhane Slama, Pierre Fenaux, Francois Dreyfus
Journal: Blood (2010)
Sofosbuvir/Velpatasvir in Combination with Ribavirin for 24 Weeks is Effective Retreatment for Patients who failed Prior NS5A Containing DAA Regimens: Results of the GS-US-342-1553 Study
Authors: E.J. Gane, M.L. Shiffman, K. Etzkorn, G. Morelli, C. Stedman, M.N. Davis, F. Hinestrosa, H. Dvory-Sobol, K.C. Huang, A. Osinusi, J. McNally, D. Brainard, J. McHutchison, A. Thompson, M. Sulkowski
Journal: Journal of Hepatology (2016)
Efficacy and Safety of Direct Acting Antiviral Therapy for HCV Genotype 4 in Egypt; Multicenter Real Life Experience
Authors: M. Serafy, M. Said, G. Esmat, A. Yosry, I. Waked, W. Alakel, M.H. Elsayed, K. Kabil, M. Hassany, M. Elraziky, N. Alkeliny, M. Anis, W. Doss
Journal: Journal of Hepatology (2016)
Endurance-3: A Phase 3, Randomized, Open-Label, Active-Controlled Study to Compare Efficacy and Safety of ABT-493/ABT-530 to Sofosbuvir Co-Administered with Daclatasvir in Adults with HCV Genotype 3 Infection
Authors: G. Foster, E. Gane, A. Asatryan, S. Pol, F. Poordad, J. Vierling, J. Kort, C.-W. Lin, S.S. Lovell, T.I. Ng, F. Mensa
Journal: Journal of Hepatology (2016)
Feasibility study of concurrent etoposide and cisplatin plus accelerated hyperfractionated thoracic radiotherapy followed by amrubicin and cisplatin for limited-disease small cell lung cancer.
Authors: M. Satouchi, I. Sekine, M. Nishio, T. Kozuka, S. Niho, K. Nihei, N. Yamamoto, H. Harada, S. Ishikura, T. Tamura
Journal: Journal of Clinical Oncology (2010)

e18057 Background: Amrubicin (AMR), a novel 9-aminoanthracycline, displays activity on small cell lung cancer (SCLC) with a response rate of 88% and median survival time (MST) of 13.8 months when combined with cisplatin (CDDP) for extensive disease (ED)-SCLC. Etoposide (ETP) and cisplatin (EP) used with concurrent accelerated hyperfractionated (AHF) thoracic radiotherapy (TRT) is the current standard treatment for limited disease (LD)-SCLC. The purpose of this study was to evaluate the feasibility of concurrent EP-TRT followed by AMR combined with CDDP (AP). Methods: Patients (pts) with chemo naïve LD-SCLC, an ECOG-PS of 0 or 1, age of 20-70, and normal kidney, liver, and bone marrow functions were assigned to a regimen of EP-TRT followed by AP; ETP (100 mg/m2 on days 1.2.3) and CDDP (80 mg/m2 on day 1), with concurrent TRT (45 Gy, 1.5 Gy twice daily, 5 days per week, 3 weeks) followed by 3 courses of AMR (40 mg/m2 on days 1, 2, 3, every 3 weeks)/CDDP (60 mg/m2 on day 1, every 3 weeks). The primary endpoint was treatment completion rate (TCR), and the secondary endpoints were toxicity, response, progression free survival (PFS), and overall survival (OS). Results: A total of 21 pts were entered. All patients completed EP and TRT. Of the 21pts, 18 (85.7%) received 3 cycles of AP. Though the dose was not reduced for 14 (66.7%) pts, 16 (76.2%) did require G-CSF support. Hematological toxicities were common and relatively severe. Grade 3/4 leukopenia and neutropenia occurred in all pts. Febrile neutropenia (FN) was observed in 9 pts (duration of FN was 1 day in 5 pts). The incidence of Grade 3/4 thrombocytopenia was 42.9% and anemia, 23.8%. Grade 3 infection occurred in 2 pts, and Grade 3 anorexia, 3 pts. The objective response rate (ORR) was 95.2%. (complete response [CR] 9.5%, partial response [PR] 85.7%, not evaluable 4.8%). Median PFS has yet to be reached. Conclusions: EP-TRT followed by AP was well tolerated, though ultimately required G-CSF support. The regimen showed encouraging activities, so we are planning a phase II trial for chemo naïve LD- SCLC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Dainippon Sumitomo Pharma, Nippon Kayaku
Prevalence and Predictors of the Metabolic Syndrome Post Liver Transplantation
Authors: L. De Luca, M. Kalafateli, S. Bianchi, N. Alasaker, E. Buzzetti, D. Thorburn, D. Patch, J. O’Beirne, R. Westbrook, E. Tsochatzis
Journal: Journal of Hepatology (2016)
A Randomized Trial of Valacyclovir Versus Valganciclovir To Prevent CMV Reactivation in Patients with CLL Receiving Alemtuzumab.
Authors: Susan O’Brien, Farhad Ravandi-Kashani, William G. Wierda, Francis Giles, Deborah Thomas, Xuelin Huang, Todd D. Riehl, Jeffrey J. Tarrand, O’Neal Brandi, Hagop M. Kantarjian, Michael J. Keating
Journal: Blood (2005)
The Safety and Efficacy of Direct-Acting Antiviral Treatment for Patients with Genotype 1 Chronic Hepatitis C and Renal Impairment
Authors: N. Furusyo, E. Ogawa, N. Yamashita, A. Kawano, K. Takahashi, K. Dohmen, M. Nakamuta, T. Satoh, H. Nomura, K. Azuma, T. Koyanagi, K. Kotoh, S. Shimoda, E. Kajiwara, J. Hayashi
Journal: Journal of Hepatology (2016)
P1117 : Histologic findings in liver biopsy of alcoholic cirrhosis patients after hematopoietic stem cell transplantation
Authors: G.R. Burganova, S.R. Abdulkhakov, A.A. Gumerova, I.M. Gazizov, M.A. Titova, A.P. Kiyasov
Journal: Journal of Hepatology (2015)
Abstract 11683: Recurrence of Atrial Arrhythmias Following Ablation in Adults With Congenital Heart Disease: New Substrate Formation or Late Procedural Failure?
Authors: Jacqueline Shuplock, Gregory Barker, Andrew Radbill, Prince Kannankeril, Frank A Fish
Journal: Circulation (2014)

Introduction: Using current mapping and ablation tools, high acute success rates can be achieved in repaired adult congenital heart disease (CHD) patients with atrial arrhythmias, but recurrences are common. We examined the nature of recurrence in a cohort of repaired adult CHD patients. Hypothesis: We tested the hypothesis that recurrences after ablation in repaired CHD patients represent the development of new substrates. Methods: A retrospective chart review was performed on all repaired adult CHD patients undergoing ablation for atrial arrhythmias, excluding atrial fibrillation (AF), at our institution from Jan. 2003-Nov. 2013. CHD lesions were grouped as tetralogy-type, atrial switch, single ventricle, and other. Latest follow-up data were obtained on all patients. Acute procedural success was defined as ablation of all targeted circuits. All recurrences warranting clinical intervention were noted. Results: A total of 118 patients underwent 157 ablation procedures, and 253 tachycardias were targeted. Of these, 99 utilized the cavo-tricuspid isthmus (CTI), 88 were non-isthmus-dependent scar-related macro-reentry, 55 were focal tachycardias, and 13 were atrioventricular reciprocating tachycardias. Acute procedural success was obtained in 147/157 (94%) procedures and 237/253 (94%) targeted arrhythmias. Recurrence was observed after 78 (50%) procedures after a median time of 6 months. Of those undergoing repeat ablations, new substrates were found to be the cause of recurrence in 18 (23%), while recurrence of the original substrate was documented in 20 (26%). AF accounted for 9 (12%) of the recurrences. By lesion type, recurrence was most common among single ventricle patients (81% vs. all others 42%, p &lt;0.001).By substrate, recurrence was lowest with CTI-dependent circuits (35% vs. all others 56%, p=0.016). Conclusions: Despite high acute procedural success rates, patients with repaired CHD had frequent recurrence of atrial arrhythmias. These represented both new substrates, including the development of AF, and recurrence of previously-ablated substrates with a similar frequency. Repeat ablation may be warranted in those with recurrences as a new target for ablation may be identified.