tbuckley/cabot-search huggingface dataset:
Mechanisms and consequences of bacterial resistance to antimicrobial peptides
Authors: D.I. Andersson, D. Hughes, J.Z. Kubicek-Sutherland
Journal: Drug Resistance Updates (2016)

Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings.
Is liver resection for colorectal liver metastases (CRLM) in the elderly (&gt;70 years of age) both safe and feasible?
Authors: G. J. Poston, N. D. Carino, B. van Leeuwen, R. Audisio
Journal: Journal of Clinical Oncology (2008)

4069 Background: 76% of newly diagnosed colorectal cancer patients are between 65-85 years old. A substantial proportion will develop CRLM, for which resection is the only potentially curative treatment. Although presently, such surgery is reported with ∼1% mortality, such surgery in the elderly is not without risk. We therefore investigated the feasibility, short and long terms outcomes of hepatectomy for CRLM in elderly (>70 yrs old) patients. Methods: We have retrospectively analysed a prospectively collected data base from 1990 to 2007 on patients >70 years old who underwent hepatectomy for CRLM in our single center. Results: 181 liver resections were performed in 178 consecutive patients >70 yrs of age. Median age: 74 years (range 70–86). 34 patients (18.8%) received neoadjuvant chemotherapy (all FOLFOX regimens) prior to liver surgery, and the majority (57.5%) of liver resections were major hepatectomies (involving >3/8 Couinaud's liver segments). Median hospital stay was 13 days. 70 (38.5%) patients had post-operative complications and overall in-hospital mortality was 4.9 % (9 patients). Median follow-up is 17.5 months (range 1–120). Overall and disease-free survival rates at 1, 3, and 5 years were 86.1%, 43.2%, and 31.5%, and 80.4%, 31.6%, and 17.4% respectively. Neoadjuvant chemotherapy and hepatic pedicle clamping did not significantly influence overall and disease free median survival (p>0.05). In multivariate analysis: T3 primary tumor; more than 3 liver lesions; major liver resections; and the occurrence of postoperative complications, were predictive of overall survival (p<0.05). Conclusions: This is the largest single center series of hepatectomy for CRLM reported to date. Liver resection for CRLM in elderly patients is safe, and may offer long time survival to a substantial percentage of these patients. We strongly recommend considering senior patients for surgical treatment whenever possible. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Serono, Pfizer, sanofi-aventis Novartis, sanofi-aventis
Abstract 689: Characterization of two novel oncogenic FGFR2 fusions sensitive to the FGFR-selective inhibitor Debio 1347 in cholangiocarcinoma
Authors: Anne Vaslin, Stefania Rigotti, Nathalie Lembrez, Grégoire Vuagniaux, Corinne Moulon, Hiroaki Tanaka
Journal: Cancer Research (2015)

Abstract Dysregulation of the fibroblast growth factor receptor (FGFR) signaling pathway due to receptor overexpression, gene amplification, point mutations or fusions/chromosomal translocations is associated with cancer development and progression. FGFR gene fusions have recently been discovered in several indications including bladder cancer, glioblastoma, lung squamous cell cancer and cholangiocarcinoma. Predominant gene fusions have been identified in some indications such as FGFR3-TACC3 (with different genomic variations in the two genes) for bladder cancer whereas for other indications the genomic-altered landscape is a lot more heterogeneous, as seen in cholangiocarcinoma where at least ten FGFR2 fusions each with a different fusion partner have been identified. We herein report for the first time the discovery of two novel FGFR fusions in intra hepatic cholangiocarcinoma patient samples. These new fusions contain an intact FGFR2 tyrosine kinase domain and fused partner harbor oligomerization domains that suggest similar mechanism of constitutive kinase activation. Both fusions display oncogenic activities when introduced into Rat 2 cells in in vitro colony formation assays as compared to parental cells. The two fusions are also tumorigenic in vivo when implanted subcutaneously in NMRI nude mice, whereas parental cell do not grow in vivo. FGFR inhibition by the FGFR selective inhibitor Debio 1347 (CH5183284) reduced cell proliferation in vitro. In vivo sensitivity to FGFR inhibition could also be demonstrated for the two fusions. Altogether, these results suggest that these two novel oncogenic fusions are actionable targets in cholangiocarcinoma and that patients harboring these fusions could benefit from targeted FGFR inhibition, such as Debio 1347, currently investigated in a Phase I trial in selected patients harboring FGFR genetic alterations (NCT01948297). Citation Format: Anne Vaslin, Stefania Rigotti, Nathalie Lembrez, Grégoire Vuagniaux, Corinne Moulon, Hiroaki Tanaka. Characterization of two novel oncogenic FGFR2 fusions sensitive to the FGFR-selective inhibitor Debio 1347 in cholangiocarcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 689. doi:10.1158/1538-7445.AM2015-689
TCTAP A-007 The Timing of Staged Percutaneous Coronary Intervention for a Non-Culprit Lesion in the Patients with Anterior Wall ST Segment Elevation Myocardial Infarction with Multiple Vessel Disease
Authors: Wei-Chieh Lee, Hsiu-Yu Fang, Chiung-Jen Wu
Journal: Journal of the American College of Cardiology (2016)
Zika virus detection in cerebrospinal fluid from two patients with encephalopathy, Martinique, February 2016
Authors: Benoît Rozé, Fatiha Najioullah, Aïssatou Signate, Kossivi Apetse, Yannick Brouste, Sarah Gourgoudou, Laurence Fagour, Sylvie Abel, Patrick Hochedez, Raymond Cesaire, André Cabié
Journal: Eurosurveillance (2016)

We report two cases of encephalopathy (one with seizures, one with electroencephalogram changes) in patients with Zika virus infection. The cases occurred on Martinique in February 2016, during the Zika virus outbreak. Awareness of the various neurological complications of Zika virus infection is needed for patients living in areas affected by Zika virus infections or for travellers to these areas.
Visual Acuity after Retinal Gene Therapy for Choroideremia
Authors: Thomas L Edwards, Jasleen K Jolly, Markus Groppe, Alun R Barnard, Charles L Cottriall, Tanya Tolmachova, Graeme C Black, Andrew R Webster, Andrew J Lotery, Graham E Holder, Kanmin Xue, Susan M Downes, Matthew P Simunovic, Miguel C Seabra, Robert E MacLaren
Journal: New England Journal of Medicine (2016)

In this study, the subfoveal injection of a gene-therapy vector carrying nonmutated CHM, the gene that, when mutated, causes a form of blindness called choroideremia, was followed by an improvement in visual acuity in two of six patients at 3.5 years after injection.
TCTAP A-061 The Importance of Patency Rate in Both Posterior Descending Artery and Posterolateral Branch After Successful Percutaneous Coronary Intervention of Right Coronary Artery Chronic Total Occlusion
Authors: Hsiu-Yu Fang, Wei-Chieh Lee, Chih-Yuan Fang, Chiung-Jen Wu
Journal: Journal of the American College of Cardiology (2016)
Procedural Volumes, Outcomes, and Quality in Hypertrophic Cardiomyopathy
Authors: Robert O. Bonow, Clyde W. Yancy
Journal: JAMA Cardiology (2016)

Luke K. Kim, MD; Rajesh V. Swaminathan, MD; Patrick Looser, MD; Robert M. Minutello, MD; S. Chiu Wong, MD; Geoffrey Bergman, MD; Srihari S. Naidu, MD; Christopher L. F. Gade, MD; Konstantinos Charitakis, MD; Harsimran S. Singh, MD; Dmitriy N. Feldman, MD
SIRT2-Mediated Deacetylation and Tetramerization of Pyruvate Kinase Directs Glycolysis and Tumor Growth
Authors: Seong-Hoon Park, Ozkan Ozden, Guoxiang Liu, Ha Yong Song, Yueming Zhu, Yufan Yan, Xianghui Zou, Hong-Jun Kang, Haiyan Jiang, Daniel R. Principe, Yong-Il Cha, Meejeon Roh, Athanassios Vassilopoulos, David Gius
Journal: Cancer Research (2016)

Sirtuins participate in sensing nutrient availability and directing metabolic activity to match energy needs with energy production and consumption. However, the pivotal targets for sirtuins in cancer are mainly unknown. In this study, we identify the M2 isoform of pyruvate kinase (PKM2) as a critical target of the sirtuin SIRT2 implicated in cancer. PKM2 directs the synthesis of pyruvate and acetyl-CoA, the latter of which is transported to mitochondria for use in the Krebs cycle to generate ATP. Enabled by a shotgun mass spectrometry analysis founded on tissue culture models, we identified a candidate SIRT2 deacetylation target at PKM2 lysine 305 (K305). Biochemical experiments including site-directed mutants that mimicked constitutive acetylation suggested that acetylation reduced PKM2 activity by preventing tetramerization to the active enzymatic form. Notably, ectopic overexpression of a deacetylated PKM2 mutant in Sirt2-deficient mammary tumor cells altered glucose metabolism and inhibited malignant growth. Taken together, our results argued that loss of SIRT2 function in cancer cells reprograms their glycolytic metabolism via PKM2 regulation, partially explaining the tumor-permissive phenotype of mice lacking Sirt2 Cancer Res; 76(13); 3802-12. ©2016 AACR.
Role of MRD in Ph+ Pediatric Acute Lymphoblastic Leukemia Patients Treated with and without Tirosine Kinase Inhibitor in the Esphall Study
Authors: Giovanni Cazzaniga, Martin Schrappe, Paola de Lorenzo, Anders Castor, Giovanna Lucchini, Virginie Gandemer, Rob Pieters, Jan Stary, Gabriele Escherich, Jeremy Hancock, Maurizio Arico', Silja Röttgers, Vaskar Saha, Andrea Biondi, Maria Grazia Valsecchi
Journal: Blood (2012)
TCTAP A-116 The Impact of Coronary Artery Disease and Left Ventricular Ejection Fraction on the Prognosis of Patients with Peripheral Artery Disease
Authors: Takuya Tsujimura, Osamu Iida, Shin Okamoto, Takayuki Ishihara, Kiyonori Nanto, Tatsuya Shiraki, Shota Okuno, Koji Yanaka, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2016)
TCTAP A-134 Clinical Efficacy of Contrast Medium Induced Fractional Flow Reserve to Assess Functional Lesion Severity in Left Anterior Descending Artery
Authors: Akihiro Suzuki, Hiroaki Takashima, Katsuhisa Waseda, Akiyoshi Kurita, Hirohiko Ando, Kazuyuki Maeda, Shinichiro Sakurai, Yuki Saka, Tetsuya Amano
Journal: Journal of the American College of Cardiology (2016)
Case 35-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Robert S. Schwartz, Austin L. Vickery
Journal: New England Journal of Medicine (1970)

Presentation of CaseA 58-year-old woman was admitted to the hospital because of fever and cutaneous lesions.She had been well until two weeks previously, when anorexia, fatigue and night sweats developed. Four days before entry she noticed a tender, red area on the dorsum of the left wrist; during the day a vesicle appeared in the center of the lesion and became ulcerated. Chills and fever occurred. On the following day a physician prescribed orally administered penicillin, which caused no improvement. During the next two days the lesion on the wrist increased in size, and the temperature rose to . . .
High disease activity according to the Ankylosing Spondylitis Disease Activity Score is associated with accelerated radiographic spinal progression in patients with early axial spondyloarthritis: results from the GErman SPondyloarthritis Inception Cohort
Authors: Denis Poddubnyy, Mikhail Protopopov, Hildrun Haibel, Jürgen Braun, Martin Rudwaleit, Joachim Sieper
Journal: Annals of the Rheumatic Diseases (2016)

The aim of this work was to investigate the association between disease activity measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) and radiographic spinal progression in patients with early axial spondyloarthritis (axSpA).Altogether, 178 patients with definite axSpA (100 with ankylosing spondylitis and 78 with non-radiographic axSpA) were included. Spinal radiographs (baseline and year 2) were assessed according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and for the presence of syndesmophytes. Clinical and lab data were collected at baseline and every 6 months thereafter. Time-averaged (over 2 years) values of the C-reactive protein based ASDAS were calculated.There was a clear positive association between disease activity according to ASDAS and radiographic spinal progression. In the logistic regression analysis, mSASSS progression by ≥2 points over 2 years was significantly associated with the time-averaged ASDAS: unadjusted OR=1.64 (95% CI 1.03 to 2.62), adjusted (for presence of syndesmophytes at baseline, smoking status and intake of non-steroidal anti-inflammatory drugs) OR=1.80 (95% CI 1.04 to 3.13). Syndesmophyte formation/progression demonstrated an even stronger association with the time-averaged ASDAS: unadjusted OR=2.62 (95% CI 1.46 to 4.68), adjusted OR=2.45 (95% CI 1.26 to 4.77).Persisting high disease activity according to the ASDAS is associated with accelerated radiographic spinal progression in early axSpA.
Interaction of Quinidine with Anticonvulsant Drugs
Authors: Joann L. Data, Grant R. Wilkinson, Alan S. Nies
Journal: New England Journal of Medicine (1976)

Drug-disposition studies of orally administered quinidine in four normal healthy volunteers indicated that phenobarbital and phenytoin reduced the half-life of quinidine by approximately 50 per cent (control, 3.0 to 6.1 hours, and with anticonvulsants, 1.6 to 2.6 hours). Alterations of similar magnitude in the apparent plasma clearance of quinidine after oral administration (control 20.0 to 32.0 liters per hour; with anticonvulsant 44.0 to 94.0 liters per hour) suggest that this effect is probably due to an increase in the rate of metabolism of quinidine, although decreased absorption cannot be entirely ruled out. In two index patients the concomitant use of anticonvulsant drugs resulted in inadequate blood levels of quinidine with standard dosages of that drug.
TCTAP C-169 Percutaneous Coronary Intervention of Diffuse Ostio Proximal Left Anterior Descending Coronary Artery Lesion Following Implantation of Bare Metal Stent (Late Instent Restenosis)
Authors: Zillur Rahman, Afzalur Rahman, Farhana Ahmed, Mohammad Arifur Rahman
Journal: Journal of the American College of Cardiology (2016)
Survival Analysis of Papillary Thyroid Carcinoma in Relation to Stage and Recurrence Risk
Authors: Aamna Hassan, Mairah Razi, Saima Riaz, Madeeha Khalid, M. Khalid Nawaz, Aamir Ali Syed, Humayun Bashir
Journal: Clinical Nuclear Medicine (2016)

The aim of this study was to evaluate the overall and progression-free survival of papillary thyroid carcinoma (PTC), comparing the American Thyroid Association (ATA) guideline for risk of recurrence with the TNM staging system with dynamic assessment at 2 years.This study is a retrospective analysis of 689 PTC patients over a 20-year period at a single center. Disease-free survival based on the TNM staging and ATA recurrence risk was calculated using Kaplan-Meier curves. Dynamic response assessment during the first 2 years was compared for both systems. Survival was calculated based on age, baseline resectability, and postthyroidectomy serum tumor marker levels.Six hundred eighty-nine (72.2%) of the total thyroid cancer patients had PTC. Four hundred sixty-nine patients were females, and 220 patients were males. The age range was 6 to 87 years. Five hundred thirty-five patients were resectable, and 56 patients were unresectable. One hundred fifty-one patients were excluded due to insufficient information on recurrence risk. By ATA categorization, 39% had low risk, no disease-related mortality; 44% had intermediate risk, 3 died; and 17% had high risk, 32 died. The 5-year disease-free survival was 54%, 26%, and 5% in low-, intermediate-, and high-risk groups, respectively. The log-rank test showed a significant difference in the percent survival (P < 0.01). TNM stage wise, in terms of survival, 1.3% in stage I, 2.2% in stage II, 0% in stage III, and 37.5% in stage IV died. The 20-year disease-free survival showed the following: stage I, 43%; stage II, 28%; stage III, 18%; and stage IV, 2%. There is significant difference in survival rate (P < 0.01). Both ATA risk classification and TNM staging were significant predictors of disease-free survival. On bivariate analysis, ATA classification (hazards ratio, 2.1; 95% confidence interval, 1.64-2.67; P = 0.001) was better predictive of overall survival versus TNM classification (hazards ratio, 1.3; 95% confidence interval, 1.11-1.43; P = 0.063).The ATA risk stratification and continuous reassessment during the first 2 years predicts disease-free survival better than the TNM staging. Age older than 45 years, unresectable disease, and elevated postthyroidectomy thyroglobulin levels dictate a poorer prognosis.
Epidemiology, Natural History, and Practice Patterns of Patients with Myelodysplastic Syndromes in 2010
Authors: Mikkael A Sekeres
Journal: Journal of the National Comprehensive Cancer Network (2011)

The incidence rate of the myelodysplastic syndromes (MDS) in the United States is approximately 3.4 per 100,000 people, accounting for more than 10,000 new diagnoses annually and an estimated 60,000 people living with the disease. Common risk factors for developing MDS include advanced age, male gender, and antecedent exposure to chemotherapy or radiation as treatment for other cancers, which alone accounts for 10% of MDS cases. Patients with MDS typically are diagnosed when they are in their 70s, have significant cytopenias, and have substantive transfusion needs. Erythropoiesis stimulating agents are used by more than 50% of patients, although the use of disease-modifying agents is increasing, and may ultimately have an impact on the number of patients living with MDS.
Case 23-1981
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, M. A. Samuels, A. L. Schiller, E. P. Richardson
Journal: New England Journal of Medicine (1981)

Presentation of Case First admission. A 68-year-old man was admitted to the hospital because of inability to walk.There was a long history of Paget's disease of bone. Four years before admission urinary retention developed and led to the findings of a urethral stricture and benign prostatic hypertrophy. A urethrotomy was performed. An x-ray film of the chest showed a smooth, elongated paravertebral density parallel to the right cardiac border, interpreted as extraosseous Paget's disease. Two years before entry the patient returned to the hospital because of cellulitis of the left leg. Examination disclosed that the liver descended 4 . . .
144O Comparison of efficacy and safety of paclitaxel and capecitabine followed by capecitabine as maintenance therapy versus cisplatin and capecitabine therapy for advanced gastric cancer: a multicentre, randomised, active-controlled phase III study
Authors: X. Zhang, L. Shen, Z. Lu, W. Liu, T. Liu, B. Hu, W. Li, Q. Fan, J. Xu, N. Xu, Y. Bai, Y. Pan, Q. Xu, W. Bai, L. Xia, Y. Gao, W. Wang, Y. Shu, G. Dai, J. Feng
Journal: Annals of Oncology (2015)
Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale
Authors: N C P Cross, H E White, T Ernst, L Welden, C Dietz, G Saglio, F-X Mahon, C C Wong, D Zheng, S Wong, S-S Wang, S Akiki, F Albano, H Andrikovics, J Anwar, G Balatzenko, I Bendit, J Beveridge, N Boeckx, N Cerveira, S-M Cheng, D Colomer, S Czurda, F Daraio, S Dulucq, L Eggen, H El Housni, G Gerrard, M Gniot, B Izzo, D Jacquin, J J W M Janssen, S Jeromin, T Jurcek, D-W Kim, K Machova-Polakova, J Martinez-Lopez, M McBean, S Mesanovic, G Mitterbauer-Hohendanner, H Mobtaker, M-J Mozziconacci, T Pajič, N Pallisgaard, P Panagiotidis, R D Press, Y-Z Qin, J Radich, T Sacha, T Touloumenidou, P Waits, E Wilkinson, R Zadro, M C Müller, A Hochhaus, S Branford
Journal: Leukemia (2016)

Molecular monitoring of chronic myeloid leukemia patients using robust BCR-ABL1 tests standardized to the International Scale (IS) is key to proper disease management, especially when treatment cessation is considered. Most laboratories currently use a time-consuming sample exchange process with reference laboratories for IS calibration. A World Health Organization (WHO) BCR-ABL1 reference panel was developed (MR(1)-MR(4)), but access to the material is limited. In this study, we describe the development of the first cell-based secondary reference panel that is traceable to and faithfully replicates the WHO panel, with an additional MR(4.5) level. The secondary panel was calibrated to IS using digital PCR with ABL1, BCR and GUSB as reference genes and evaluated by 44 laboratories worldwide. Interestingly, we found that >40% of BCR-ABL1 assays showed signs of inadequate optimization such as poor linearity and suboptimal PCR efficiency. Nonetheless, when optimized sample inputs were used, >60% demonstrated satisfactory IS accuracy, precision and/or MR(4.5) sensitivity, and 58% obtained IS conversion factors from the secondary reference concordant with their current values. Correlation analysis indicated no significant alterations in %BCR-ABL1 results caused by different assay configurations. More assays achieved good precision and/or sensitivity than IS accuracy, indicating the need for better IS calibration mechanisms.
Lesson of the Week: Importance of accurate assessment of fetomaternal haemorrhage after late abortions
Authors: I. Bromilow, J K M Duguid, S Walkinshaw
Journal: BMJ (1996)

As we have noted before, many statistical methods of analysis assume that the data have a normal distribution.'When the data do not they can often be transformed to make them more normal.2Readers of published papers may wish to be reassured that the authors have carried otit an appropriate analysis.When authors present data in the form of a histogram or scat- ter diagram then readers can see at a glance whether the distributional assumption is met.If, however, only sum- mary statistics are presented-as is often the case-this is much more difficult.If the summary statistics include the range of the data then some idea of the distribution may be gained.For example, a range from 7 to 41 around a mean of 15 suggests that the data have positive skewness.However, as the range is based on the two most extreme (and hence atypical) values this inference is not reliable.Similar asymmetry affecting the lower and upper quartiles' would be much more convincing