tbuckley/cabot-search huggingface dataset:
A prospective, multi-center study of individualized, pharmacokinetically (PK)-guided dosing of 5-fluorouracil (5-FU) in metastatic colorectal cancer (mCRC) patients treated with weekly or biweekly 5-FU/oxaliplatin containing regimens.
Authors: Volker Kunzmann, Karin Link, Michael Craig Miller, Stefan Holdenrieder, Thomas Bertsch, Lothar Mueller, Yon-Dschun Ko, Oliver J. Stoetzer, Ingo Suttmann, Jan Braess, Ulrich Jaehde, Max Roessler, Berta Moritz, Stefanie Kraff, Achim Fritsch, Salvatore J. Salamone, Martin Wilhelm
Journal: Journal of Clinical Oncology (2015)

3542 Background: Numerousstudies have demonstrated that body surface area (BSA)-based dosing leads to under- and overexposure in a large number of patients. PK-guided dosing of 5-FU can optimize 5-FU exposure resulting in higher overall dose intensity with reduced toxicities and improved outcomes. This study was initiated to validate use of PK-guided 5-FU dosing for mCRC patients in clinical practice. Methods: 75 mCRC patients from 8 academic and/or community-based medical centers located throughout Germany received up to 6 cycles of infusional 5-FU according to either the AIO (n = 16), FOLFOX6 (n = 26) or FUFOX (n = 33) regimen. Initial dosing of infusional 5-FU for all patients was based on BSA and subsequent doses were adjusted according to the previous cycle 5-FU area under the concentration-time curve (AUC) to target an AUC of 20 to 30 mg•h/L. Primary objective was to confirm that PK-guided dosing of 5-FU leads to an increased proportion of patients in the target AUC range at cycle 4 versus cycle 1. Secondary objective was to determine whether PK-guided 5-FU dose adjustment reduced treatment-related toxicities compared to historical patient groups. Results: Average 5-FU AUC at cycle 1 was 20 ± 15 mg•h/L, with 62%, 32% and 6% of the patients below, within or above target AUC range, respectively. By cycle 4, average 5-FU AUC was 25 ± 7 mg•h/L (p = 0.007), and a significantly higher proportion of patients were within the target 5-FU AUC range (55%, p = 0.005). Fewer 5-FU-related grade 3-4 toxicities of diarrhea (5%), nausea (3%), fatigue (0%) and mucositis (0%) were observed compared to historical data (12%, 9%, 12%, 15%, respectively). Conclusion: PK-guided adjustment of 5-FU dosing in routine clinical practice resulted in significantly higher 5-FU exposure, more patients achieving target exposure, and less 5-FU-related toxicities. Clinical trial information: 2011-003553-26.
Unusual Aspects of Breast Cancer
Authors: Hamid Mansouri, Abdeloahed Jalil, Leila Choho, Abdelilah Souadka, Brahim El Gueddari
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.9.2570 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11331337 Unusual Aspects of Breast Cancer Case 1. Angiosarcoma of the Breast Hamid MansourixHamid MansouriSearch for articles by this author , Abdeloahed JalilxAbdeloahed JalilSearch for articles by this author , Leila ChohoxLeila ChohoSearch for articles by this author , Abdelilah SouadkaxAbdelilah SouadkaSearch for articles by this author , Brahim El GueddarixBrahim El GueddariSearch for articles by this author Show More Rabat University School of Medicine, Rabat, Morocco, Copyright © 2001 American Society of Clinical Oncology https://doi.org/10.1200/JCO.2001.19.9.2570 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
<i>IDH2</i> Mutation in a Patient with Metastatic Colon Cancer
Authors: Bing M Zhang, Alexin Aleshin, Chieh Y Lin, James Ford, James L Zehnder, Carlos J Suarez
Journal: New England Journal of Medicine (2017)

An IDH2 mutation that was not present in a patient’s tumor was detected in circulating DNA. However, the patient had clonal hematopoiesis with an IDH2 mutation that was responsible for the false positive result.
Targeting the gut-liver axis in liver disease
Authors: Reiner Wiest, Agustin Albillos, Michael Trauner, Jasmohan S. Bajaj, Rajiv Jalan
Journal: Journal of Hepatology (2017)

<h2>Summary</h2> The gut-liver axis is widely implicated in the pathogenesis of liver diseases, where it is increasingly the focus of clinical research. Recent studies trialling an array of therapeutic and preventative strategies have yielded promising results. Considering these strategies, the armamentarium for targeting the gut-liver axis will continue to expand. Further clinical trials, translated from our current knowledge of the gut-liver axis, promise an exciting future in liver treatment.
Treatment Side Effects
Authors: S.P. Dourakis, V.A. Sevastianos, A. Alexopoulou, M. Deutsch, N. Stavrianeas
Journal: Journal of Clinical Oncology (2002)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.13.3030 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12089234 Treatment Side Effects Case 2. Toxic, Epidermal, Necrolysis-Like Reaction Associated With Docetaxel Chemotherapy S.P. DourakisxS.P. DourakisSearch for articles by this author , V.A. SevastianosxV.A. SevastianosSearch for articles by this author , A. AlexopoulouxA. AlexopoulouSearch for articles by this author , M. DeutschxM. DeutschSearch for articles by this author , N. StavrianeasxN. StavrianeasSearch for articles by this author Show More Hippokration General Hospital and Sigrou Hospital, Athens, Greece https://doi.org/10.1200/JCO.2002.20.13.3030 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Keynote Address: Blueprint of the Breast and Colorectal Cancer Genomes
Authors: Victor Velculescu
Journal: Clinical Cancer Research (2007)

KN-01  It is widely accepted that human cancer is a genetic disease caused by accumulation of mutations in oncogenes and tumor suppressor genes. These tumor-specific mutations provide clues to the cellular processes underlying tumorigenesis and have proven useful for diagnostic and therapeutic purposes. To date, however, only a small fraction of the genes has been analyzed and the number and type of alterations responsible for the development of common tumor types are unknown. The determination of the human genome sequence coupled with improvements in sequencing and bioinformatic approaches have now made it possible, in principle, to examine the cancer cell genome in a comprehensive and unbiased manner. We have begun a systematic study of the cancer genome through examination of gene families involved in signal transduction. These efforts have identified frequent activating mutations in a number of different kinases and phosphatases not previously linked to human cancer. For example, we have found genetic alterations in the PIK3CA gene encoding the p110 alpha phosphatidylinositol 3-kinase in ~30% of colon and breast cancers, providing a rational target for therapy in a large fraction of common malignancies. These studies have recently been extended to genome-wide analyses of the protein coding genes in breast and colorectal cancer. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.
Guideline recommendations on the use of allergen immunotherapy in house dust mite allergy: Time for a change?
Authors: Moisés A. Calderón, Jean Bousquet, G. Walter Canonica, Lars-Olaf Cardell, Dolores Hernandez Fernandez de Rojas, Jörg Kleine-Tebbe, Pascal Demoly
Journal: Journal of Allergy and Clinical Immunology (2017)
Precision Therapy: Materials, Devices and Systems of Soft Bioelectronics for Precision Therapy (Adv. Healthcare Mater. 10/2017)
Authors: Hao Wu, Wei Gao, Zhouping Yin
Journal: Advanced Healthcare Materials (2017)

Hao Wu and co-workers analyze recent key research achievements in soft bioelectronics enabled precision therapy, with emphasis on drug delivery, therapeutic and surgical mechanisms and tools enabled by integrated systems in article number 1700017. They also highlight the exciting prospects of this potentially new therapeutic modality and provide outlook on its opportunities and challenges in commercialization.
Concussion and mild traumatic brain injury (mtbi): towards a better integration of the two constructs
Authors: Pierre Frémont, Catherine Truchon
Journal: British Journal of Sports Medicine (2017)

<h3>Objective</h3> To analyse the potential ways to reunite the mTBI and concussion constructs in order to harmonise screening, diagnosis and management. <h3>Design</h3> Narrative review. <h3>Setting</h3> In Quebec, the initial management of concussions sustained in a sport or school-based setting falls under the authority of the Ministry of education and sports whereas the Ministry of health governs the clinical management of mTBI. The recent work of a task force on concussions in Quebec has emphasised the need to achieve a unified understanding and operationalization of the two constructs so that persons affected receive consistent information and care. <h3>Main results</h3> Sport and school-based concussion management is generally based on the Concussion In Sport Group definition whereas the Quebec health care system relies on the 5 diagnostic criteria proposed by the WHO task force in 2004. Although the 5 classification criteria of mTBI include normal values, the actual definition requires the presence of one or more abnormal criteria. In a public health care system, such a definition structures access to limited public resources. However unfavourable evolution can occur in the absence of phenomena such as LOC or PTA. Yet these cases represent a potentially serious health condition if proper identification and management is not initiated. <h3>Conclusion</h3> So far, sport, education and health care stakeholders in Quebec have agreed that the constructs of concussion and TBI must be revisited and better integrated. This process raises challenges and opportunities in terms of operationalization and management. Studies on prognostic indicators should guide this analysis. <h3>Conclusion</h3> Competing interests Pierre Frémont is chair of the Canadian Concussion Collaborative. None.
Linking Amyloid-β and Tau Deposition in Alzheimer Disease
Authors: Prashanthi Vemuri, Michael Schöll
Journal: JAMA Neurology (2017)

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 Neurology 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 Neurology journal
A Non-photosynthetic Diatom Reveals Early Steps of Reductive Evolution in Plastids
Authors: Ryoma Kamikawa, Daniel Moog, Stefan Zauner, Goro Tanifuji, Ken-Ichiro Ishida, Hideaki Miyashita, Shigeki Mayama, Tetsuo Hashimoto, Uwe G. Maier, John M. Archibald, Yuji Inagaki
Journal: Molecular Biology and Evolution (2017)

Nonphotosynthetic plastids retain important biological functions and are indispensable for cell viability. However, the detailed processes underlying the loss of plastidal functions other than photosynthesis remain to be fully understood. In this study, we used transcriptomics, subcellular localization, and phylogenetic analyses to characterize the biochemical complexity of the nonphotosynthetic plastids of the apochlorotic diatom Nitzschia sp. NIES-3581. We found that these plastids have lost isopentenyl pyrophosphate biosynthesis and ribulose-1,5-bisphosphate carboxylase/oxygenase-based carbon fixation but have retained various proteins for other metabolic pathways, including amino acid biosynthesis, and a portion of the Calvin–Benson cycle comprised only of glycolysis/gluconeogenesis and the reductive pentose phosphate pathway (rPPP). While most genes for plastid proteins involved in these reactions appear to be phylogenetically related to plastid-targeted proteins found in photosynthetic relatives, we also identified a gene that most likely originated from a cytosolic protein gene. Based on organellar metabolic reconstructions of Nitzschia sp. NIES-3581 and the presence/absence of plastid sugar phosphate transporters, we propose that plastid proteins for glycolysis, gluconeogenesis, and rPPP are retained even after the loss of photosynthesis because they feed indispensable substrates to the amino acid biosynthesis pathways of the plastid. Given the correlated retention of the enzymes for plastid glycolysis, gluconeogenesis, and rPPP and those for plastid amino acid biosynthesis pathways in distantly related nonphotosynthetic plastids and cyanobacteria, we suggest that this substrate-level link with plastid amino acid biosynthesis is a key constraint against loss of the plastid glycolysis/gluconeogenesis and rPPP proteins in multiple independent lineages of nonphotosynthetic algae/plants.
The use of CTCAE v3.0 in cancer clinical trial publications.
Authors: Sheng Zhang, Xi-Chun Hu
Journal: Journal of Clinical Oncology (2015)

e20662 Background: Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) was released in 2003 and has been widely used as the predominant criteria for toxicity in cancer clinical trials and oncology scientific meetings. The degree to which the elements of CTCAE v3.0 are followed in oncology publications has not been comprehensively evaluated. Methods: Phase III randomized clinical trials (RCTs) evaluating systemic cancer therapy published between Jan 1, 2012, and December 31,2013, were reviewed to identify eligible studies that explicitly stated CTCAE v3.0 as the toxicity criteria. The 10-point score based on CTCAE v3.0 was used to assess the studies. Multivariable linear regression was used to identify features associated with improved adherence. Results: A total of 104 publications reporting data on 86,957 patients were included in this analysis. The mean total score for all 4 elements of CTCAE v3.0 was 4.03 on a 10-point scale (range, 1 to 9), with 16 publications (15%) having a total score ≤ 2. Highly heterogeneous and unstandardized AE lexicons were frequently used. In addition, the correct use of Supra-ordinate terms and the Terms using 'Other, specify' was suboptimal. the Grades were often misjudged. The multivariable regression model subsequently revealed that the absence of placebo (P= .003) and no. of total AE terms in the table (P< .001) were independent predictors of a lower total score. Conclusions: Given the importance of toxicity in evaluating new treatments, improvement in adherence to CTCAE v3.0 should be encouraged to ensure consistency and comparison for toxicity across different studies.
Concussion incidence and mechanism among youth volleyball players
Authors: Derek W Meeuwisse, Kerry MacDonald, Willem H Meeuwisse, Kathryn Schneider
Journal: British Journal of Sports Medicine (2017)

Objective To assess the incidence of concussions among adolescent volleyball players in Canada. Design Cross sectional survey. Setting Online survey. Participants In total, 663 registered Volleyball Canada members completed a national survey, with a response rate of 13.0%; web-based survey response rates rarely exceed 5%. The 452 (68.2%) female and 211 (31.8%) male responders had a mean age of 16.2 (95% CI: 16.1to 16.4) years with a range from 14 to 19 years. Assessment of risk factors The type of environment: controlled non-competitive environment (practice or warm-up) versus competitive game play environment. Outcome measures Whether the athletes sustained a concussion as defined by the 2012 Zurich Consensus. Main results A total of 86 concussions were reported, of which 52 were in the previous 12 months, yielding a one-year cumulative incidence per 100 athletes of 7.1 (95% CI: 4.3 to 11.4) and 7.5 (95% CI: 5.4 to 10.3) for males and females, respectively. In total, 57.1% (95% CI: 46.2 to 67.5) of all concussions involved ball-to-head contact. Player-to-player contact and head-to-floor contact were less prevalent at 20.2% (95% CI: 12.8 to 30.4) and 15.5% (95% CI: 9.1 to 25.1) respectively. Practice environment accounted for 46.5% of all concussions while 38.4% occurred in game play. The remaining 15.1% occurred in warm-up. In total, 61.6% (95% CI: 50.2 to 71.7) of concussions occurred outside of free-flow competitive game play, in a more structured environment. Conclusions There is a significant margin for injury prevention as a substantial proportion (61.6%) of concussions happening in a noncompetitive, controlled environment that may be amenable to change that would reduce the potential for such injury. Competing interests The authors have no competing interest to state.
Do measures of cervical, vestibulo-ocular function, balance and divided attention change over a year in youth ice hockey players?
Authors: Kathryn J Schneider, Luz Palacios-Derflingher, Qian Shi, Willem H Meeuwisse, Carolyn A Emery
Journal: British Journal of Sports Medicine (2017)

Objective To determine if preseason measures of cervical, vestibulo-ocular function, balance and divided attention change over one year in 10-12 year old ice hockey players. Design Prospective cohort study Setting Sport Injury Prevention Research Centre, Alberta, Canada Participants Youth Ice Hockey players (10-12 years old) who completed cervical, vestibular and divided attention tasks at a preseason assessment during two seasons of play. Outcome measures Numeric pain rating scores (neck pain, headache, dizziness), cervical flexor endurance test (CFE), cervical flexion rotation test (CFRT), anterolateral cervical spine strength, head perturbation test, functional gait assessment (FGA), walking while talking test, head thrust test and dynamic visual acuity (DVA). Main results A total of 193 uninjured youth ice hockey players [95% males; median age 11 (range 10-12) in the first season] completed preseason testing measures in two consecutive seasons (2013-2015). After Bonferroni corrections (α=0.0042), using Wilcoxon Signed-Rank Test, anterolateral neck strength increased (right: z=−5.96, p&lt;0.0001; left: z=−6.52, p&lt;0.0001), head perturbation test improved (z=4.40, p&lt;0.0001), walking while dividing attention improved (z=6.41, p&lt;0.0001) and there were more positive head thrust tests (chi 2 =13.64, p=0.0034) in the second year. There was no evidence of a difference in symptom reports, CFE, CFRT, DVA and FGA between the two testing sessions. Conclusions Symptom reports did not differ between two years of play. However, tests of clinical function were different between two seasons of play in youth ice hockey players. These data suggest that developmental and/or maturational changes should be taking into consideration when interpreting these tests in youth. Competing interests None.
BIOL-05. SHORT TERM MEK-INHIBITOR TREATMENT IMPROVES OPTIC NERVE GLIA PATHOLOGY IN AN NF1-DEFICIENT MOUSE MODEL
Authors: Miriam Bornhorst, Daphine Mugayo, Emmanuelle Jecrois, Yuan Zhu
Journal: Neuro-Oncology (2017)

BACKGROUND: Up to 20% of patients with Neurofibromatosis 1 (NF1) are diagnosed with optic pathway gliomas (OPGs) before 7 years of age, suggesting these tumors are formed during development. Yet, the early events that occur in the optic nerve (ON), resulting in OPG formation, have not been described. The aims of this project were to determine 1) how early, following loss of Nf1, glial abnormalities occur in the developing ON and 2) whether targeted treatment with a Mek-inhibitor during this timeframe can improve the abnormalities seen. METHOD: We used a well-established Nf1-deficient (Nf1-/-) conditional knockout mouse model that develops visible OPGs by postnatal day 60 (P60) to characterize the glial cell populations (Olig2+ oligodendrocytes and GFAP+ astrocytes) and proliferation rate (Ki67) in E17.5, P0.5, P2, and P5 nerves. We then treated mice from P0.5-P5 with PD0325901, using a Meki-in-milk protocol, and analyzed the nerves at P5 to look for response. RESULTS: Nf1-/- mice had an increase in both the Olig2+ and GFAP+ cell populations starting as early as P0.5. Consistent with a previously described migration pattern for oligodendrocytes, Olig2+ cells did not appear in the proximal nerve (near the retina) until between P2-P5. In contrast, Olig2+ cells in the mutant mice were present in the proximal nerve as early as P0.5, reaching their maximum number by P2 in this region. Interestingly, proliferation was only increased at P0.5, returning to control level at other time points. Following treatment with PD0325901, the mutant nerve glial phenotype was rescued to the control level at P5. CONCLUSION: These results provide support that the events preceding OPG formation begin early during ON development, and treatment with a Mek-inhibitor during this critical time window may prevent tumors from forming all together. Future studies will focus on whether this treatment strategy can prevent glial abnormalities long term.
Stratification of recovery from concussion using an objective multi-factorial approach to neurocognitive and motor performance assessment
Authors: Susan M Linder, Andrew Russman, Rick Figler, Jason Cruickshank, Bob Grey, Maureen Lally, Tanujit Dey, Jay L Alberts
Journal: British Journal of Sports Medicine (2017)

Objective To characterise neurologic impairment and recovery associated with concussion in youths and young adults using the Cleveland Clinic Concussion application (C3 app). Design Retrospective observational study Setting Concussion clinic at an academic medical centre Participants 181 student-athletes aged 14–20 diagnosed with concussion by a Cleveland Clinic physician were included. Intervention C3 data were collected pre-season and at least once post-injury. At least one clinical examination by a physician was obtained to characterise clinical impairments. Individuals were stratified into two groups based on recovery time: typical &lt;21 days (n=97) or protracted 21+ days (n=84). Outcome measures The following modules of the C3 app were administered across groups: 1) Graded symptom checklist (GSC); 2) Standardised Assessment of Concussion (SAC); 3) Trail Making Test; 4) Simple and Choice Reaction Time; 5) Processing Speed Test; 6) Biomechanical quantification of balance during the BESS. Main results At baseline, both groups performed similarly on all modules. However, significant differences were evident at 21 days post-injury in the protracted recovery group with worse performance in: simple and choice reaction time (p&lt;0.001), Trail Making Test B (p=0.01), Biomechanical quantification of BESS (p&lt;0.05), and GSC (p=0.0001). No difference between the groups at 21 days was found in BESS error scores, SAC or processing speed. Conclusions An approach that utilises objective and quantitative measures to characterise multiple aspects of neurocognitive and motor function are more sensitive than traditional measures of concussion assessment. These new outcomes provide value in the stratification of patients and their potential time to recovery. Competing interests JLA and SML have authored intellectual property associated with the mobile application presented in this study. The remaining authors declare no competing interest. None.