tbuckley/cabot-search huggingface dataset:
Overall survival (OS) results from OPTIMAL (CTONG0802), a phase III trial of erlotinib (E) versus carboplatin plus gemcitabine (GC) as first-line treatment for Chinese patients with <i>EGFR</i> mutation-positive advanced non-small cell lung cancer (NSCLC).
Authors: Caicun Zhou, Yi Long Wu, Xiaoqing Liu, Changli Wang, Gongyan Chen, Ji Feng Feng, Shucai Zhang, Jie Wang, Songwen Zhou, Shengxiang Ren, Shun Lu, Li Zhang, Cheng-ping Hu, Yi Luo, Lei Chen, Ming Ye, Jianan Huang, Xiuyi Zhi, Yiping Zhang, Qingyu Xiu
Journal: Journal of Clinical Oncology (2012)

7520 Background: The OPTIMAL study demonstrated significant superiority for E versus GC in terms of progression-free survival (PFS), objective response rate, tolerability and quality of life (QoL) in first-line advanced NSCLC patients with EGFR activating mutations (Act Mut+). Here we report OS data from OPTIMAL (ClinicalTrials.gov NCT00874419). Methods: Chemotherapy-naive Chinese patients with advanced NSCLC and EGFR Act Mut+, ECOG performance status (PS) 0–2 and measurable disease were randomized to E (150 mg/day), or GC, and stratified by histology, smoking status and mutation type. OS at final data cut-off (15 Nov 2011) was evaluated for the entire intent-to-treat (ITT) population. Subgroup analysis of OS by gender, histology, smoking status, PS, presence of skin rash and type of mutation was performed. Details of second- or later-line therapy were also documented for each patient. Results: A total of 165 patients were randomized to treatment and 154 patients received at least one dose of study drug (ITT population; E, n=82; GC, n=72). A total of 7 patients are still responding to erlotinib in the E arm. Post-study therapy included chemotherapy (doublet, n=38, or mono, n=8), or experimental drugs in clinical trials (n=10) in the E arm, and EGFR tyrosine kinase inhibitor (TKI) therapy (n=49) or chemotherapy (n=7) in the GC arm. Post-study treatment was not received by 26 and 16 patients in the E and GC arms, respectively. A total of 84 deaths were reported (E, n=47; GC, n=37). OS did not differ significantly between the two treatment arms (HR=1.065, p=0.6849), and no significant difference in OS was observed in the different subgroups. Conclusions: The lack of a statistically significant difference in OS in the OPTIMAL study was possibly due to a high level of cross-over to EGFR TKI therapy in the GC arm. However, the significant benefits reported with E in terms of PFS, QoL and tolerability in this study suggest that E should be considered as one of the standard first-line treatments for patients with advanced EGFR Act Mut+ NSCLC.
P68 PACIFIC: a phase III, randomised, multicentre, dose escalation, efficacy and safety study examining the effects of treatment with peginterferon alfa-2a in patients with Child's A or B cirrhosis in chronic hepatitis C virus infection
Authors: S Tanwar, M Wright, G Foster, S Ryder, P Mills, M Cramp, J Parkes, W Rosenberg
Journal: Gut (2010)

Introduction  Trials have found conflicting results about the efficacy of pegylated interferon α (PIFN), with or without pretreatment including ribavirin, as an antifibrotic agent in patients with established cirrhosis due to persistent HCV infection. We have investigated the use of an escalating dose of PIFN2a monotherapy for 48 weeks in the treatment of patients with established cirrhosis due to persistent HCV infection.  Method  A multicentre, randomised prospective controlled trial of escalating dose PIFN2a treatment of patients with HCV infection and Child9s A or B cirrhosis. 39 patients were enrolled at 5 UK centres and randomised to standard clinical care, or 48 weeks treatment with PIFN2a at 90 mcg p.w. escalating each month by 45 mcg to 180 mcg p.w. if tolerated and followed for 140 weeks. Primary outcomes were liver related death; “liver related morbidity” including variceal haemorrhage, ascites and SBP, hepatocellular cancer, transplantation and all cause mortality. Secondary outcomes were health related quality of life (HRLQ).  Results  There was no significant difference in the baseline characteristics between treatment and control groups (male 71:77%; mean age 55.2:52.1; Child9s score 5.35:5.32; MELD 8.23:7.95). Treatment was well tolerated. 15/17 (88%) completed 48 weeks treatment; 1 at 45 mcg; 1 at 90 mcg; 2 at 135 mcg; 11 at 180 mcg.  There were no differences between groups in HRQL except pain scores that were increased in the treatment group (Score=50.7:70.5, p=  Conclusion  Escalating PIFN2a monotherapy is associated with HCV clearance and a reduction in liver related mortality in this small RCT. The differences from HALT-C and EPIC, and similarity to COPILOT may relate to marked differences in methodology (specifically the omission of therapy in the control arm), cirrhosis stage or sample size. These findings warrant further investigation of PIFN2a for patients with advanced cirrhosis for whom there is no other treatment and where transplantation is associated with graft infection and rapid progression to cirrhosis.
Abstract 14811: Psychiatric Disorders, Drug Therapy and Risk of SCD in the Community
Authors: Audrey Uy-Evanado, Kyndaron Reinier, Carmen Teodorescu, Gregory A Nichols, Karen Gunson, Jonathan Jui, Sumeet S Chugh
Journal: Circulation (2012)

Background: Previous studies have reported associations between schizophrenia, psychotropic drugs, anti-depressants and the risk of sudden cardiac death (SCD) but risk conferred by the condition ha...
Correlation between vascular endothelial growth factor and c-met expressions in breast carcinoma
Authors: R. Matkowski, I. Gisterek, E. Suder, A. Lacko, J. Szelachowska, D. Ramsey, J. Kornafel
Journal: Journal of Clinical Oncology (2006)

10621 Background: Vascular endothelial growth factor (VEGF) is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis. This cytokine selectively induces cells proliferation and migration, increases permeability of microvessels and activates proteolitic enzymes involved in tumor invasiveness. C-met is tyrosine kinase receptor; its activation can increase tumorigenicity, induce cell motility and enhance invasiveness and metastasis. This protein can increase production of protease and urokinase which are associated with membrane degradation crucial for metastasis. The relationships between both cytokines are not clearly identified. In this study, we evaluated VEGF and c-met expression in homogenous group of 99 patients with stage II ductal breast carcinomas and analyzed correlations between both markers. Methods: Microscopic studies were performed on formalin-fixed, paraffin-embedded cancer tissues, obtained during surgery and stained routinely with haematoxylin and eosin. Expression of VEGF and c-met was evaluated using a standard immunoperoxidase technique and area with molecule expression, intensity of color reaction and product of both findings were counted. Association between markers expressions was tested by Spearman Correlation Coefficient. Results: Expression of c-met was found in 37 (37.37%) breast tumors, while expression of VEGF was observed in 67 (67.67%) cases. There were strong correlations between expressions of both cytokines. The relationships were found between area with molecules’ expression (p = 0.0438) and intensity of reaction (p = 0.0461), also in the product of both findings (p = 0.0229). Conclusions: The results of our study confirms hypothesis that c-met may act as an indirect angiogenic factor by inducing expression of VEGF. No significant financial relationships to disclose.
Genotypic diversity of Pseudomonas aeruginosa in cystic fibrosis patients with the CFTR I1234V mutation in a large kindred family
Authors: Atqah Abdul Wahab, Saad Taj-Aldeen, Ammar Saadoon, Sanjay Diophode, Corne Klaassen, Jacques Meis
Journal: European Respiratory Journal (2012)

Background:   Pseudomonas aeruginosa  is one of the primary pathogens within the cystic fibrosis (CF) lung and a cause of morbidity and mortality. Reports of cross infection and epidemics with this pathogen within and across CF centers raised the possibility of clonal spread among siblings with CF.   Aim:  To genotype  P. aeruginosa  by amplified fragment-length polymorphism (AFLP) analysis in CF patients with the CFTR I1234V mutation belonging to a large kindred tribe, and to determine whether the genotypes are identical among CF siblings and among different families with the same mutation.   Methods:  Sixty seven  P  aeruginosa  isolates from sputa of 27 CF patients were studied at Hamad General Hospital, Qatar. Genotypic relatedness was assessed using AFLP, and compared with 33  P. aeruginosa  isolates of a known genotype from the Netherlands.   Results:  Twenty seven CF patients were from 17 families, 16 males with a median age of 15 years (range 4 years-34 years). Twenty-two CF patients (12 families) with the CFTR I1234V mutation arising from a single large kindred tribe harboured chronic  P. aeruginosa  colonization. Twenty three unique genotype of  P. aeruginosa  were identified and different from  P. aeruginosa  strains isolated from Dutch CF patients. Ten families each had one unique genotype which were different from each other, four families harboured 2 different genotypes, one family 3 genotypes and two families had 4 genotypes. CF siblings within one family harboured the same genotypes of  P.aeruginosa .   Conclusions : This study demonstrated genotypic diversity of  P. aeruginosa, isolates between families and established cross-infection among CF siblings.
Drug-resistant pathogens prediction scores in CAP, HCAP and immunocompromised
Authors: Maria Carrabba, Alessandra Colombo, Marina Zarantonello, Anna Maraschini, Giovanna Fabio
Journal: European Respiratory Journal (2014)

Background.  Multi-drug resistant pathogens (MDR-P) causing pneumonia in the community have made challenging identification and treatment. The predictive value of health care-associated pneumonia (HCAP) developed in 2005 ATS/IDSA guidelines, is debated. Administration of broad-spectrum antibiotics is overloaded in HCAP patients because of wide regional variation of MDR-P in HCAP. Investigators recently proposed scoring systems to predict MDR pneumonia arising in communities.   Aim.  To compare the performance of HCAP criteria, the Aliberti and Shorr scores in predicting pneumonia caused by MDR-P.   Methods.  A prospective observational study was conducted between 2008 and 2013. 454 consecutive patients admitted for pneumonia to a tertiary care university hospital in Milan, Italy, were enrolled. The accuracy of the three scores was explored for correctly indicating the MDR pneumonia via a receiver-operating characteristic (ROC) curve.   Results.  Patients with at least one risk factor for MDR-P (2005 ATS/IDSA guidelines) were 280 (61.7%), HCAP were 224 and immunocompromised patients were 163. PSI severity score IV and V classes accounted for 87.5% of patients with MDR-P risk and 76.4% of patients without (p=0.002). There was no difference between the two groups for the % of patients with Barthel score more than 50. Among 375 cultures obtained at admission, positive identification rate was 34.7%. The most frequent pathogens were: Staphylococcus aureus (19.2%), Enterobacteriacee (16.9%), Streptococcus pneumoniae (16.2%), Pseudomonas aeruginosa (7.7%), Acinetobacter baumanii (2.3%). According to ROC analysis, Shorr score performed better than Aliberti in prediction of MDR pneumonia. HCAP score had the lowest accuracy.
Experimental Carcinoma of Liver in Macaque Monkeys Exposed to Diethylnitrosamine and Hepatitis B Virus2
Authors: F. Gyorkey, J. L. Melnick, R. Mirkovic, G. A. Cabral, P. Gyorkey, F. B. Hollinger
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Experimental Carcinoma of Liver in Macaque Monkeys Exposed to Diethylnitrosamine and Hepatitis B Virus Get access F. Gyorkey, M.D., F. Gyorkey, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. L. Melnick, Ph.D., J. L. Melnick, Ph.D. 5 5Address reprint requests to Dr. Melnick. Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Mirkovic, M.D., R. Mirkovic, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar G. A. Cabral, Ph.D., G. A. Cabral, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar P. Gyorkey, M.A., P. Gyorkey, M.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar F. B. Hollinger, M.D. F. B. Hollinger, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 5, November 1977, Pages 1451–1467, https://doi.org/10.1093/jnci/59.5.1451 Published: 01 November 1977 Article history Received: 20 December 1976 Accepted: 23 May 1977 Published: 01 November 1977
Detection of ALL-1/AF4 fusion transcript by reverse transcription- polymerase chain reaction for diagnosis and monitoring of acute leukemias with the t(4;11) translocation
Authors: A Biondi, A Rambaldi, V Rossi, L Elia, C Caslini, G Basso, R Battista, T Barbui, F Mandelli, G Masera
Journal: Blood (1993)
춘계학술대회 발표 : 구연 ; Cyclosporine을 사용한 간이식 환자에서 장기생존 후 Tregulatory 세포의 비율이 높다
Authors: 유찬란, 최종영, 박호성, 윤승규, 조세현, 한남익, 최상욱, 한준열, 이창돈, 조재영, 김동구, 오은지
Journal: Clinical and Molecular Hepatology (2006)
Prebiotic‐supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high‐risk infants: a randomized controlled trial
Authors: R. J. Boyle, M. L.‐K. Tang, W. C. Chiang, M. C. Chua, I. Ismail, A. Nauta, J. O'B. Hourihane, P. Smith, M. Gold, J. Ziegler, J. Peake, P. Quinn, R. Rao, N. Brown, A. Rijnierse, J. Garssen, J. O. Warner, Christine Axelrad, Suzan Jeffries, Yvette Donald, Heather Barham, Jenny Brown, Rita Wickenden, Teresa Barnes, Simone Taylor, Susan Smith, Natalie Thomas, Anne Goh, Wong Anng Anng, Christy Cao Yu Hua, Deirdre Daly, Sinead Lafford, Claire Cullinane, Jacques Bindels, Liandre Merwe, Dineke Klaassen, Sophie Swinkels, Karen Knipping
Journal: Allergy (2016)

Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months, but evidence is mixed. Adding specific oligosaccharides may improve outcomes.To evaluate whether partially hydrolysed whey formula containing oligosaccharides (0.8 g/100 ml) (pHF-OS) can prevent eczema in high-risk infants [ISRCTN65195597].We conducted a parallel-group, multicentre, randomized double-blind controlled trial of pHF-OS vs standard cow's milk formula. Infants with a family history of allergic disease were randomized (stratified by centre/maternal allergy) to active (n = 432) or control (n = 431) formula until 6 months of age if formula was introduced before 18 weeks. Primary outcome was cumulative incidence of eczema by 12 months in infants randomized at 0-4 weeks (375 pHF-OS, 383 control). Secondary outcomes were cumulative incidence of eczema by 12 or 18 months in all infants randomized, immune markers at 6 months and adverse events.Eczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF-OS at 0-4 weeks of age, vs 93/324 (28.7%) control (OR 0.98 95% CI 0.68, 1.40; P = 0.90), and 107/347 (30.8%) pHF-OS vs 112/370 (30.3%) control in all infants randomized (OR 0.99 95% CI 0.71, 1.37; P = 0.94). pHF-OS did not change most immune markers including total/specific IgE; however, pHF-OS reduced cow's milk-specific IgG1 (P < 0.0001) and increased regulatory T-cell and plasmacytoid dendritic cell percentages. There was no group difference in adverse events.pHF-OS does not prevent eczema in the first year in high-risk infants. The immunological changes found require confirmation in a separate cohort.
Children Exposed to Abuse in Youth-Serving Organizations
Authors: Anne Shattuck, David Finkelhor, Heather Turner, Sherry Hamby
Journal: JAMA Pediatrics (2016)

Protecting children in youth-serving organizations is a national concern.To provide clinicians, policymakers, and parents with estimates of children's exposure to abuse in youth-serving organizations.Telephone survey data from the 3 National Surveys of Children's Exposure to Violence (2008, 2011, and 2014) were combined to create a sample of 13,052 children and youths aged 0 to 17 years. The survey participants included youths aged 10 to 17 years and caregivers of children aged 0 to 9 years.Items from the Juvenile Victimization Questionnaire.In the combined sample of 13 052 children and youths aged 0 to 17 years, the rate of abuse by persons in youth-serving organizations was 0.4% (95% CI, 0.2-0.7) for the past year and 0.8% (95% CI, 0.5-1.1) over the lifetime. Most of the maltreatment (63.2%) was verbal abuse and only 6.4% was any form of sexual violence or assault.Abuse in youth-serving organizations was a relatively rare form of abuse, dwarfed by abuse by family members and other adults.
Directly converted patient-specific induced neurons mirror the neuropathology of FUS with disrupted nuclear localization in amyotrophic lateral sclerosis
Authors: Su Min Lim, Won Jun Choi, Ki-Wook Oh, Yuanchao Xue, Ji Young Choi, Sung Hoon Kim, Minyeop Nahm, Young-Eun Kim, Jinhyuk Lee, Min-Young Noh, Seungbok Lee, Sejin Hwang, Chang-Seok Ki, Xiang-Dong Fu, Seung Hyun Kim
Journal: Molecular Neurodegeneration (2016)

Mutations in the fused in sarcoma (FUS) gene have been linked to amyotrophic lateral sclerosis (ALS). ALS patients with FUS mutations exhibit neuronal cytoplasmic mislocalization of the mutant FUS protein. ALS patients’ fibroblasts or induced pluripotent stem cell (iPSC)-derived neurons have been developed as models for understanding ALS-associated FUS (ALS-FUS) pathology; however, pathological neuronal signatures are not sufficiently present in the fibroblasts of patients, whereas the generation of iPSC-derived neurons from ALS patients requires relatively intricate procedures. Here, we report the generation of disease-specific induced neurons (iNeurons) from the fibroblasts of patients who carry three different FUS mutations that were recently identified by direct sequencing and multi-gene panel analysis. The mutations are located at the C-terminal nuclear localization signal (NLS) region of the protein (p.G504Wfs*12, p.R495*, p.Q519E): two de novo mutations in sporadic ALS and one in familial ALS case. Aberrant cytoplasmic mislocalization with nuclear clearance was detected in all patient-derived iNeurons, and oxidative stress further induced the accumulation of cytoplasmic FUS in cytoplasmic granules, thereby recapitulating neuronal pathological features identified in mutant FUS (p.G504Wfs*12)-autopsied ALS patient. Importantly, such FUS pathological hallmarks of the patient with the p.Q519E mutation were only detected in patient-derived iNeurons, which contrasts to predominant FUS (p.Q519E) in the nucleus of both the transfected cells and patient-derived fibroblasts. Thus, iNeurons may provide a more reliable model for investigating FUS mutations with disrupted NLS for understanding FUS-associated proteinopathies in ALS.
P0168 : The impact on hospital resource utilisation of Rifaximin-alpha for hepatic encephalopathy in routine clinical practice: Real world data from seven UK liver centres
Authors: J.G. Orr, A. Goel, K. Moriarty, A. Sinha, F.H. Gordon, A. Dethier, J. Dillon, V. Patel, D.L Shawcross, K. Clark, P. Richardson, H. Preedy, R. Aspinall, C.J. Currie, M. Hudson
Journal: Journal of Hepatology (2015)
Quality of life in patients with pure and mixed anaplastic oligodendroglioma treated with dose-intense temozolomide: A phase II multicenter study.
Authors: N. Hashemi Sadraei, M. S. Ahluwalia, C. Brewer, D. Schiff, P. G. Fisher, M. C. Chamberlain, S. Panullo, H. B. Newton, P. Elson, D. Peereboom
Journal: Journal of Clinical Oncology (2010)

2080 Background: Treatment options for patients with newly diagnosed pure and mixed anaplastic oligodendrogliomas (AO and MAO, respectively) include chemotherapy (CXT), radiation therapy (RT), or combined CXT and RT. Due to concerns about radiation-induced toxicities, we conducted a multicenter phase II trial using dose-intense temozolomide (TMZ) with delayed RT in AO/MAO. Outcomes of this trial have been reported previously. This trial achieves results similar to sequential TMZ followed by immediate RT. To further delineate potential benefits of this approach, quality of life (QOL) was evaluated as a secondary endpoint. Methods: Eligible patients had newly diagnosed AO/MAO with no prior chemotherapy or RT. Patients received TMZ, 150 mg/m2/d on days 1-7 and 15-21 of a 28 day cycle. QOL questionnaires (EORTC QOL-C30 and the accompanying Brain Module) were completed pretreatment and after cycles 2, 4, 6, and 8 (every 8 weeks). Results: Sixty five patients were enrolled from 7 centers and QOL related data are available on 62 patients. Median age: 43 years (range 18- 83) and median KPS: 90% (range 70-100). Forty two patients had AO; 20 had MAO. Forty four patients completed at least one posttreatment evaluation; 20 patients had complete data on all QOL questionnaires through the first 6 cycles The following domains were significantly improved compared to baseline: future uncertainty after cycle 4 (p < 0.001, n = 30), pain after cycle 4 (p = 0.01, n = 30), and role functioning after cycle 6 (p = 0.02, n = 25). Several domains, including physical functioning, social functioning, motor dysfunction, visual disorder, and insomnia revealed an improvement in mean scores over time but did not reach statistical significance. Patients reported worsening of TMZ-related toxicity including anorexia, nausea, vomiting, and diarrhea. Conclusions: Despite toxicities related to TMZ, several QOL domains improved over time in patients with AO/MAO treated with dose-intense temozolomide. This trial supports the use of CXT alone as initial therapy for patients with CXT-responsive gliomas. Additional analysis of completed questionnaires and longer-term posttreatment follow-up is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough Schering-Plough Schering-Plough