tbuckley/cabot-search huggingface dataset:
Etoposide and cisplatin (EP) chemotherapy for good risk germ cell tumors (GCT): The Memorial Sloan-Kettering Cancer Center (MSKCC) experience
Authors: G. V. Kondagunta, J. Bacik, D. Bajorin, M. Mazumdar, D. Dobrzynski, J. Sheinfeld, R. J. Motzer, G. J. Bosl
Journal: Journal of Clinical Oncology (2004)

4533 Background: Phase 3 trials at MSKCC showed 4 cycles of EP to be effective and tolerable treatment for good risk advanced GCTs (JCO 1997;15:2553). Additional patients (pts) have been treated and follow-up (f/u) updated to detect late relapses. Methods: 379 pts with good risk GCT received EP from 11/82–12/02 on 4 protocols. MSKCC criteria (Cancer 1991;67:28) were used to assign risk status prospectively until 8/1994. Thereafter, the International Germ Cell Consensus Classification Group (IGCCCG) criteria were used. All pts were retrospectively classified according to IGCCCG criteria. EP consisted of 4 cycles of etoposide 100 mg/m2 and cisplatin 20 mg/m2 days 1–5 every 21 days. Results: 295/379 (78%) had nonseminoma; 84 (22%) had seminoma. Primary site was testis-365 (96%), retroperitoneum-8 (2%), mediastinum-6 (2%). By IGCCCG criteria, 291 (77%) were good risk, 75 (20%) intermediate risk and 13 (3%) poor risk. Of 291 IGCCCG good risk pts, 284 achieved a CR [98%; 273 to chemotherapy (c) and 11 to chemo+surgery (c+s)], 18 (6%) relapsed, and 9 (3%) died of disease (DOD). Among 75 IGCCCG intermediate risk pts originally classified as MSKCC good risk, 67 achieved a CR (89%; 64 CR-c and 3 CR-c+s), 8 (11%) relapsed, and 11 (15%) DOD. Of 13 IGCCCG poor risk pts originally classified as MSKCC good risk, 8 achieved a CR-c, 2 relapsed, and 7 DOD. 27/379 (7%) pts died of disease. 7 died of other causes (3-heme malignancy, 2-infection, 1-myocardial infarction, 1-accident). Four pts NED at last f/u died of unknown cause (death confirmed by Social Security index; 3 good risk, 1 intermediate risk). Overall, 275/291 (95%) good risk pts were alive at median f/u of 7.5 years and 16 (5%) were dead (9 DOD, 7 dead of unknown/other cause). Of 144 good risk pts treated from 11/82–12/90 (reported in JCO 1997;15:2553), at a median f/u of 12.9 years, no relapses occurred after f/u of 3 years. Conclusions: 4 cycles of EP is a highly effective therapy (with surgery as necessary) for pts with good risk GCT with a high cure rate and no evidence of increased rate of early or late relapses. No significant financial relationships to disclose.
Predictors of mortality in rheumatoid arthritis-associated interstitial lung disease
Authors: Joshua J. Solomon, Jonathan H. Chung, Gregory P. Cosgrove, M. Kristen Demoruelle, Evans R. Fernandez-Perez, Aryeh Fischer, Stephen K. Frankel, Stephen B. Hobbs, Tristan J. Huie, Jill Ketzer, Amar Mannina, Amy L. Olson, Gloria Russell, Yutaka Tsuchiya, Zulma X. Yunt, Pearlanne T. Zelarney, Kevin K. Brown, Jeffrey J. Swigris
Journal: European Respiratory Journal (2015)

Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis. There is lack of clarity around predictors of mortality and disease behaviour over time in these patients.We identified rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients evaluated at National Jewish Health (Denver, CO, USA) from 1995 to 2013 whose baseline high-resolution computed tomography (HRCT) scans showed either a nonspecific interstitial pneumonia (NSIP) or a "definite" or "possible" usual interstitial pneumonia (UIP) pattern. We used univariate, multivariate and longitudinal analytical methods to identify clinical predictors of mortality and to model disease behaviour over time.The cohort included 137 subjects; 108 had UIP on HRCT (RA-UIP) and 29 had NSIP on HRCT (RA-NSIP). Those with RA-UIP had a shorter survival time than those with RA-NSIP (log rank p=0.02). In a model controlling for age, sex, smoking and HRCT pattern, a lower baseline % predicted forced vital capacity (FVC % pred) (HR 1.46; p<0.0001) and a 10% decline in FVC % pred from baseline to any time during follow up (HR 2.57; p<0.0001) were independently associated with an increased risk of death.Data from this study suggest that in RA-ILD, disease progression and survival differ between subgroups defined by HRCT pattern; however, when controlling for potentially influential variables, pulmonary physiology, but not HRCT pattern, independently predicts mortality.
MAGRIT phase III trial: MAGE-A3 antigen-specific cancer immunotherapy (ASCI) as adjuvant therapy in patients with completely resected stage IB-IIIA NSCLC.
Authors: P. Therasse, J. F. Vansteenkiste, M. Zielinski, T. M. De Pas, D. Atanackovic, L. V. Sequist, E. Vallieres, S. Swisher, S. Adams, B. Passlick, W. E. E. Eberhardt, D. Grunenwald, T. Mok, M. Boyer, A. Katz, J. Douillard, M. Debois, V. G. Brichard, N. K. Altorki
Journal: Journal of Clinical Oncology (2011)

TPS210 Background: Active immunization with MAGE-A3 Antigen-Specific Cancer Immunotherapeutic (ASCI) showed clinical activity in a randomized Phase II study (NCT00290355) in patients with completely resected non-small cell lung cancer (NSCLC) and in a randomized Phase II study (NCT00086866) in metastatic melanoma. Methods: MAGRIT (NCT00480025) is a double-blind, placebo-controlled, randomized (2:1; MAGE-A3 ASCI vs. Placebo) Phase III trial in patients with pathological stage IB-IIIA NSCLC (AJCC TNM v6). Tumors of eligible patients have been resected by complete anatomic lobectomy/pneumonectomy and must be MAGE-A3+. Patients are allowed to receive up to 4 cycles of adjuvant platinum-based chemotherapy (CT), when clinically indicated, post-operatively and before study treatment. Adjuvant radiotherapy is not permitted. MAGE-A3 ASCI (recombinant MAGE-A3 protein and immunostimulant AS15) or placebo is administered intramuscularly for a total of 13 doses: 5 doses every 3 weeks followed by 8 doses every 12 weeks. Randomization of patients is performed using a central web-based system, stratified for chemotherapy (CT vs. no-CT) and accounting for the following minimization factors: number of CT cycles (1-4), pathological stage (IB vs. II vs. IIIA), type of lymph node sampling (minimal vs. systematic radical resection), ECOG performance status (0, 1 and 2), and smoking status (never-, ex-, or current smoker). Co-primary endpoints are disease-free survival (DFS) in the overall population and DFS in the population that has not received adjuvant CT prior to study treatment. Secondary endpoints include additional clinical efficacy indicators such as overall survival; safety health-related quality of life (EQ-5D), and validation of a predictive gene signature (GS) associated with clinical benefit of the MAGE-A3 ASCI. As of 21 Jan 2011, 9898 patients were screened, 1579 randomized (2270 targeted). 9057 valid tumor samples have been tested for MAGE-A3 expression, 33% were positive. At their last meeting (Sep 2010), The Independent Data Monitoring Committee suggested no safety issue and allowing the trial to continue as planned.
Genome editing: the end of the beginning
Authors: Jennifer A. Doudna, Charles A. Gersbach
Journal: Genome biology (2015)

Editorial It has recently become commonplace to editorialize on the extent to which genome editing has transformed modern biological research and perhaps, in the future, biomedicine. Nonetheless, each time the scope of scientific progress and the state of the field is appraised, it is followed in rapid succession by another wave of seemingly momentous developments. Each of these rounds of advances pushes at the boundaries of what can be done to the DNA within cells and organisms, expands the number of systems that can be used to engineer genomes, and increases the resolution of our understanding of how these systems work. This is also true for the articles included in this special issue of Genome Biology that is focused on genome editing, which provide important new insights in each of these areas. The clear takeaway from this collection is that the recent flurry of progress and excitement around genome editing marks only the beginning. Even greater challenges lie ahead for refining and applying these new technologies, interpreting their results, and deciding in what capacity they should be used. The most sophisticated biotechnologies continue to emerge from the seemingly most simplistic organisms. Similar to the repurposing of green fluorescent protein from jellyfish for imaging studies or small interfering RNAs from worms for gene knockdown applications, the adoption of the CRISPR/Cas9 system from prokaryotes has enabled genome editing for the broad scientific community [1]. Despite the massive impact that the Streptococcus pyogenes CRISPR/Cas9 system has had directly on genome editing, it has also shone a light into the depths of alternative prokaryotic gene editing systems that can be mined for unique and orthogonal properties [2]. Consequently, several alternative Cas9 systems from other species have been described [3–5], and now other types of CRISPR systems that are
Reply: <i>FAIM3</i>:<i>PLAC8</i> Ratio Compared with Existing Biomarkers for Diagnosis of Severe Community-acquired Pneumonia: Comparing Apples to Oranges?
Authors: Brendon P. Scicluna, Lonneke A. van Vught, Tom van der Poll, Peter M. C. Klein Klouwenberg, Olaf L. Cremer
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

than procalcitonin and had a better specificity than procalcitonin in differentiating "CAP" from "no-CAP."However, the threshold value of procalcitonin (0.159 ng/ml) used by the authors in their study is different and lower than the previously reported values (2), which would increase the falsepositive rates and hence reduce the specificity of a test (3).Further, in routine clinical practice, a clinician's dilemma for correctly diagnosing CAP arises only in the presence of an abnormal chest radiograph, along with incongruous clinical features of CAP; a normal chest radiograph makes the diagnosis of CAP unlikely (4, 5).Also, in severe CAP requiring admission to the intensive care unit, the likelihood of a normal chest radiograph is even bleaker.Thus, we believe that the true predictive power of this novel genomic marker to correctly identify severe CAP would have been more apt if the no-CAP group had included patients with abnormal chest radiograph resulting from other conditions such as pulmonary edema, atelectasis, lung contusions, diffuse alveolar hemorrhage, and others.Despite performing better than protein biomarkers, the negative and positive predictive values of the FAIM3:PLAC8 ratio were 80 and 77.2%, respectively, making it neither a good rule-in nor rule-out test in the diagnosis of severe CAP in the intensive care unit.
Understanding Age-Related Changes in Skeletal Muscle Metabolism: Differences Between Females and Males
Authors: Brandon J.F. Gheller, Emily S. Riddle, Melinda R. Lem, Anna E. Thalacker-Mercer
Journal: Annual Review of Nutrition (2016)

Skeletal muscle is the largest metabolic organ system in the human body. As such, metabolic dysfunction occurring in skeletal muscle impacts whole-body nutrient homeostasis. Macronutrient metabolism changes within the skeletal muscle with aging, and these changes are associated in part with age-related skeletal muscle remodeling. Moreover, age-related changes in skeletal muscle metabolism are affected differentially between males and females and are likely driven by changes in sex hormones. Intrinsic and extrinsic factors impact observed age-related changes and sex-related differences in skeletal muscle metabolism. Despite some support for sex-specific differences in skeletal muscle metabolism with aging, more research is necessary to identify underlying differences in mechanisms. Understanding sex-specific aging skeletal muscle will assist with the development of therapies to attenuate adverse metabolic and functional outcomes.
Frontal Glutamate and γ-Aminobutyric Acid Levels and Their Associations With Mismatch Negativity and Digit Sequencing Task Performance in Schizophrenia
Authors: Laura M. Rowland, Ann Summerfelt, S. Andrea Wijtenburg, Xiaoming Du, Joshua J. Chiappelli, Nithin Krishna, Jeffrey West, Florian Muellerklein, Peter Kochunov, L. Elliot Hong
Journal: JAMA Psychiatry (2015)

IMPORTANCE Auditory mismatch negativity (MMN) is a biomarker for schizophrenia thought to reflect glutamatergic N-methyl-D-aspartate receptor function and excitatory-inhibitory neurotransmission balance.However, the association of glutamate level with MMN has not been directly examined in patients with schizophrenia, to our knowledge.OBJECTIVE To investigate the contributions of glutamate and γ-aminobutyric acid (GABA) to MMN and digit sequencing task (DST) performance, an assessment of verbal working memory, in schizophrenia.DESIGN, SETTING, AND PARTICIPANTS Fifty-three control participants from the community and 45 persons with schizophrenia from outpatient clinics completed an electroencephalographic session for MMN, magnetic resonance spectroscopy for glutamate and GABA, and a DST.The study dates were July 2011 to May 2014, and the dates of our analysis were May 2014 to August 2015.MAIN OUTCOMES AND MEASURES Glutamate, GABA, the ratio of glutamine to glutamate, MMN amplitude, and DST.Structural equation modeling was used to test the effects of neurochemistry and MMN amplitude on DST performance. RESULTSThe 45 persons with schizophrenia were a mean (SD) of 37.7 (12.8) years and the control participants were 37.1 (13.1) years.The schizophrenia group had a mean (SD) of 14.7 (12.1) years of illness.Mismatch negativity amplitude (F = 4.39, P = .04)and glutamate (F = 9.69, P = .002)were reduced in the schizophrenia group.Smaller MMN amplitude was significantly associated with lower GABA level (P = .008),lower glutamate level (P = .05),and higher ratio of glutamine to glutamate (P = .003).Reduced MMN amplitude was linked to poor verbal working memory in schizophrenia (P = .002).Modeling revealed that a proxy of glutamatergic function, indexed by the ratio of glutamine to glutamate, influenced a path from the ratio of glutamine to glutamate to MMN to verbal working memory (P = .38[root-mean-square error of approximation, P < .001]by χ 2 test), supporting the contention that MMN serves as an intermediate biomarker linking glutamatergic function to DST performance in schizophrenia. CONCLUSIONS AND RELEVANCEThe role of glutamate and GABA in MMN and verbal working memory deficits in schizophrenia has been frequently debated.These data provide in vivo evidence that support glutamatergic and GABAergic regulation of MMN and verbal working memory function in schizophrenia.
Liberal or Restrictive Transfusion after Cardiac Surgery
Authors: Marc-Olivier Fischer, Emmanuel Lorne, Benoît Vallet
Journal: New England Journal of Medicine (2015)

To the Editor: In their article on red-cell transfusion, Murphy et al. (March 12 issue) 1 report substantial nonadherence to treatment in both study groups -one of which had a restrictive threshold for hemoglobin level in red-cell transfusions and one of which had a liberal threshold.Although nonadherence (defined as either the to transfuse red cells within 24 hours after a patient's hemoglobin fell below an assigned threshold or the administration of a transfusion when the hemoglobin level was above the assigned threshold) increases the likelihood of a null result for the primary outcome, it might confound the finding of increased 90-day mortality in the restrictive-threshold group, since patients in that group who received transfusions above the restrictive threshold were assumed to be sicker, whereas patients in the group with a liberal threshold were assumed to be healthier (and hence not receiving transfusions below the liberal threshold).Did the authors observe an increase in mortality in association with nonadherence to treatment in the restrictive-threshold group?
A systematic review comparing the functional changes and complications of DIEP and TRAM flaps in patients receiving breast reconstruction
Authors: E.D. Mills, K. Dynes, N.N.Y. Boon, Q. Liao, W.H. Chan
Journal: International Journal of Surgery (2015)

Each eyelid was cut into sagittal slices and stained with Miller's solution to specifically illustrate the distribution of elastin fibres.Representative sliced specimens were then photographically assessed to quantify the colour density using ImageJ analysis software.All quantitative values were standardised relative to the elastin-rich aorta.Euclidean geometrical modelling principles were applied to calculate the total elastic fibre distribution in the meibomian gland acini.Results: The morphological analysis of the meibomian glands indicated the average acini diameter to be 152.40 m.The elastic fibres were found to be concentrated around the meibomian gland acini with a relative elastic concentration of 53.64%.There was no statistical significant difference noted in elastic fibre concentrations with respect to side and gender. Conclusion:This study introduces a novel approach to calculating the elastic fibre concentrations within structures of the upper eyelid.The presence of a high concentration of elastic fibres around the meibomian gland acini indicates its importance in the secretory process.
Alternating Electric Fields for the Treatment of Glioblastoma
Authors: John H. Sampson
Journal: JAMA (2015)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
How to get a better picture of the ACL injury problem? A call to systematically include conservatively managed patients in ACL registries
Authors: Romain Seil, Caroline Mouton, Daniel Theisen
Journal: British Journal of Sports Medicine (2015)

ACL injury registries have provided substantial new knowledge to sports medicine/sports physio. Registries aggregate a large amount of individual data,1 sometimes via collaboration among different institutions.2 Nevertheless, a systematic recording of ACL-injured patients is non-existent or at its very beginnings in many countries.

Owing to the variety and available resources of different healthcare systems, organising registries on a national level is difficult. In Europe, the pioneering Scandinavian countries were followed by a private initiative from the UK, which started in 2014.3 Currently, efforts to set up data collection are also being made in the German-speaking countries. Registry data are helpful in at least three ways: (1) in improving treatment outcomes through feedback to the treating physicians and institutions, (2) in detecting unreliable procedures and devices and (3) in identifying outcome-associated prognostic factors.4 Despite this focused …
Use of α-2a-Interferon to Treat Cytogenetic Relapse of Chronic Myeloid Leukemia After Marrow Transplantation
Authors: Celestia S. Higano, Deborah Chielens, Wendy Raskind, Eileen Bryant, Mary E.D. Flowers, Jerald Radich, Reginald Clift, Frederick Appelbaum
Journal: Blood (1997)
Positivity for Zinc Transporter 8 Autoantibodies at Diagnosis Is Subsequently Associated With Reduced β-Cell Function and Higher Exogenous Insulin Requirement in Children and Adolescents With Type 1 Diabetes
Authors: Matilda Juusola, Anna Parkkola, Taina Härkönen, Heli Siljander, Jorma Ilonen, Hans K. Åkerblom, Mikael Knip
Journal: Diabetes Care (2015)

This study assessed the relationship between autoantibodies against zinc transporter 8 (ZnT8A) and disease characteristics at diagnosis of type 1 diabetes and during the first 2 years.Children, younger than 15 years of age (n = 723) who were newly diagnosed with diabetes, were analyzed for ZnT8A, other diabetes-associated autoantibodies, HLA DR-DQ alleles, and metabolic status, which was monitored by pH, plasma glucose, and occurrence of ketoacidosis at diagnosis and through follow-up of C-peptide concentrations, exogenous insulin dose, and glycosylated hemoglobin for 2 years after the diagnosis.ZnT8A positivity was detected in 530 children (73%). Positivity for ZnT8A was associated with older age (median 8.9 vs. 8.2 years, P = 0.002) and more frequent ketoacidosis (24% vs. 15%, P = 0.013). Children carrying the HLA DR3 allele were less often ZnT8A positive (66% vs. 77%, P = 0.002) than others. ZnT8A-positive children had lower serum C-peptide concentrations (P = 0.008) and higher insulin doses (P = 0.012) over time than their ZnT8A-negative peers.Positivity for ZnT8A at diagnosis seems to reflect a more aggressive disease process before and after diagnosis.
Gene expression profiles defining molecular subtypes, coupled with signatures of tumor biology and chemotherapy sensitivity provide a novel therapuetic approach to multiple myeloma
Authors: A. Anguiano, S. A. Tuchman, B. Perez, K. H. Salter, R. C. Redman, F. Zhan, B. Barlogie, A. Potti, J. D. Shaughnessy
Journal: Journal of Clinical Oncology (2008)

8501 Gene expression profiles reflecting hyperploidy (HY) or specific genetic lesions leading to translocations, (including C-MAF, MAFB, CCND1, CCND3 and MMSET (MS)), have been used to define distinct phenotypes of multiple myeloma. That several of these subtypes are at higher risk of progression and death emphasizes the need for novel therapeutic strategies. Employing gene expression analysis in a cohort of 560 newly diagnosed multiple myeloma patients (training-352, validation-208) we applied expression signatures reflecting the deregulation of oncogenic signaling pathways (Myc, Ras, Src, B-catenin, E2F1 and PI3K), profiles representing an altered tumor microenvironment (chromosomal instability, angiogenesis, hypoxia and TNF-a) and signatures of chemotherapy sensitivity (melphalan, vincristine, adriamycin, cyclophosphamide, cisplatin and etoposide) to a training cohort patients previously enrolled in Total Therapy 2 (TT2). Distinct patterns of altered tumor biology and chemosensitivity between the molecular subtypes (CD1, CD2, LB, HY, MF, MS and PR) was observed. In particular, the low risk HY group (EFS 68% and OS 79% with 3 years median follow-up) demonstrated increased activation of Myc (p<0.0001) and PI3K (p=0.03) pathways when compared to the high risk MS group (EFS 31% and OS 51%). Alternatively, the MS group demonstrated increased evidence of chromosomal instability (p=0.0002). The HY group demonstrated increased sensitivity to vincristine (p=0.04) and adriamycin (p=0.003), while the MS group demonstrated increased sensitivity to cyclophosphamide (p<0.0001) and to cisplatin (p=0.02). Importantly, similar analysis in an independent validation set of 208 patients enrolled in the Total Therapy 3 (TT3) demonstrated the reproducibility of the patterns. This analysis has demonstrated distinct patterns of altered tumor biology and chemotherapy sensitivity amongst the clinically relevant subtypes of multiple myeloma. Additional results dissecting the molecular phenotypes of multiple myeloma will be presented. Genomic evidence of chemotherapy sensitivity and oncogenic pathway activation may provide an opportunity for selection of therapeutic modalities. No significant financial relationships to disclose.