tbuckley/cabot-search huggingface dataset:
Factors Predictive of Tumor-Positive Nonsentinel Lymph Nodes After Tumor-Positive Sentinel Lymph Node Dissection for Melanoma
Authors: Jonathan H. Lee, Richard Essner, Hitoe Torisu-Itakura, Leslie Wanek, Hejing Wang, Donald L. Morton
Journal: Journal of Clinical Oncology (2004)

Approximately 20% of sentinel node (SN) positive melanoma patients have additional non-SN (NSN) metastasis. The rationale for this study was to identify the factors associated with additional nodal disease, as a method to determine which patients may most benefit from completion lymph node dissection (CLND).During 1990 to 2002, 1,599 patients have undergone SN biopsy at our institute. 19.5% underwent CLND for tumor-positive SN. One hundred ninety-one of these patients had clinicopathologic information available for review. Univariate analyses used chi2 test, Wilcoxson rank sum test, and chi2 test for trend. Multivariate analyses used logistic regression and Wald test.Forty-six (24%) patients had tumor-positive NSN. Univariate analyses showed that primary thickness (Breslow and Clark), primary site, SN tumor size, and number of tumor-positive SNs were significantly associated with tumor-positive NSN. Multivariate analysis (167 patients), confirmed that Breslow and SN tumor size were independently predictive. Sex, histology, ulceration, mitotic index, and SN basin location were not predictive. Risk stratification by the number of prognostic factors present (Breslow > or = 3 mm and SN tumor size > or = 2 mm) showed that probability of finding tumor-positive NSN was 12.3% in the low-risk group (0 factors), 30.9% in the intermediate-risk group (1 factor), and 41.9% in the high-risk group (2 factors).Thicker primary and larger SN tumor size are factors that correlate best with tumor-positive NSN. Although none of these factors are absolutely predictive of residual nodal disease, these factors must be strongly considered if the SN contains metastasis, as they provide enhanced risk assessment for NSN tumor-positivity.
The Controversies in Obesity, Diabetes and Hypertension (CODHy) Meeting
Authors: Itamar Raz, Ram Weiss
Journal: Diabetes Care (2008)

The fields of obesity, diabetes, and hypertension are gaining major attention in the last 2 decades, since the obesity epidemic is driving a parallel increase in related morbidity. Recent progress in the research of these inter-related conditions is bringing a tremendous expansion of basic and clinical data alongside a wealth of novel technologies introduced for the investigation, monitoring, and treatment of these entities. The recent flux of novel insights, treatment modalities, and clinical observations, many of which have major implications that may change clinical practice, raises a significant number of questions by clinicians. The first Controversies in Obesity, Diabetes and Hypertension (COHDy) meeting, held in Berlin in October 2006, was designed as an exclusive forum where world experts and opinion leaders from the three disciplines met to discuss their current insights and experience in controversial issues relevant to these fields. The aims of the meeting were to provide clinicians with answers to unresolved questions of clinical relevance, provide a deeper understanding of and ability to integrate novel findings into clinical practice, and consolidate current knowledge by way of evidence-based research. Highlights from the …
Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma
Authors: Premal H Thaker, Liz Y Han, Aparna A Kamat, Jesusa M Arevalo, Rie Takahashi, Chunhua Lu, Nicholas B Jennings, Guillermo Armaiz-Pena, James A Bankson, Murali Ravoori, William M Merritt, Yvonne G Lin, Lingegowda S Mangala, Tae Jin Kim, Robert L Coleman, Charles N Landen, Yang Li, Edward Felix, Angela M Sanguino, Robert A Newman, Mary Lloyd, David M Gershenson, Vikas Kundra, Gabriel Lopez-Berestein, Susan K Lutgendorf, Steven W Cole, Anil K Sood
Journal: Nature Medicine (2006)
Acute Effects of Decaffeinated Coffee and the Major Coffee Components Chlorogenic Acid and Trigonelline on Glucose Tolerance
Authors: Aimée E. van Dijk, Margreet R. Olthof, Joke C. Meeuse, Elin Seebus, Rob J. Heine, Rob M. van Dam
Journal: Diabetes Care (2009)

Coffee consumption has been associated with lower risk of type 2 diabetes. We evaluated the acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance.We conducted a randomized crossover trial of the effects of 12 g decaffeinated coffee, 1 g chlorogenic acid, 500 mg trigonelline, and placebo (1 g mannitol) on glucose and insulin concentrations during a 2-h oral glucose tolerance test (OGTT) in 15 overweight men.Chlorogenic acid and trigonelline ingestion significantly reduced glucose (-0.7 mmol/l, P = 0.007, and -0.5 mmol/l, P = 0.024, respectively) and insulin (-73 pmol/l, P = 0.038, and -117 pmol/l, P = 0.007) concentrations 15 min following an OGTT compared with placebo. None of the treatments affected insulin or glucose area under the curve values during the OGTT compared with placebo.Chlorogenic acid and trigonelline reduced early glucose and insulin responses during an OGTT.
The Wnt inhibitory factor 1 (WIF1) is targeted in glioblastoma and has a tumor suppressing function potentially by induction of senescence
Authors: Wanyu L. Lambiv, Irene Vassallo, Mauro Delorenzi, Tal Shay, Annie-Claire Diserens, Anjan Misra, Burt Feuerstein, Anastasia Murat, Eugenia Migliavacca, Marie-France Hamou, Davide Sciuscio, Raphael Burger, Eytan Domany, Roger Stupp, Monika E. Hegi
Journal: Neuro-Oncology (2011)

Gene expression—based prediction of genomic copy number aberrations in the chromosomal region 12q13 to 12q15 that is flanked by MDM2 and CDK4 identified Wnt inhibitory factor 1 (WIF1) as a candidate tumor suppressor gene in glioblastoma. WIF1 encodes a secreted Wnt antagonist and was strongly downregulated in most glioblastomas as compared with normal brain, implying deregulation of Wnt signaling, which is associated with cancer. WIF1 silencing was mediated by deletion (7/69, 10%) or epigenetic silencing by promoter hypermethylation (29/110, 26%). Co-amplification of MDM2 and CDK4 that is present in 10% of glioblastomas was associated in most cases with deletion of the whole genomic region enclosed, including the WIF1 locus. This interesting pathogenetic constellation targets the RB and p53 tumor suppressor pathways in tandem, while simultaneously activating oncogenic Wnt signaling. Ectopic expression of WIF1 in glioblastoma cell lines revealed a dose-dependent decrease of Wnt pathway activity. Furthermore, WIF1 expression inhibited cell proliferation in vitro, reduced anchorage-independent growth in soft agar, and completely abolished tumorigenicity in vivo. Interestingly, WIF1 overexpression in glioblastoma cells induced a senescence-like phenotype that was dose dependent. These results provide evidence that WIF1 has tumor suppressing properties. Downregulation of WIF1 in 75% of glioblastomas indicates frequent involvement of aberrant Wnt signaling and, hence, may render glioblastomas sensitive to inhibitors of Wnt signaling, potentially by diverting the tumor cells into a senescence-like state.
Epstein-Barr virus-infected T lymphocytes in Epstein-Barr virus-associated hemophagocytic syndrome.
Authors: H Kawaguchi, T Miyashita, H Herbst, G Niedobitek, M Asada, M Tsuchida, R Hanada, A Kinoshita, M Sakurai, N Kobayashi
Journal: Journal of Clinical Investigation (1993)

The clonal composition of EBV-infected cells was examined in three cases of EBV-associated hemophagocytic syndrome by analysis of the heterogeneity of terminal repetitive sequences in the EBV genome, indicating monoclonal expansion of EBV-infected cells in all cases. Involvement of T lymphoid cells was determined by in situ hybridization using 35S-labeled RNA probes specific for the small EBV-encoded nuclear RNAs, EBER1 and EBER2, in combination with immunostaining for the TCR-beta chain, CD45RO, CD20, CD30 and CD68 antigens in these three cases. The majority of lymphoid cells showing EBER transcripts were stained by antibodies against CD45RO and T cell receptor-beta. In contrast, EBER-specific signals were not detectable on B cells or hemophagocytic cells. These data support the concept that EBV-associated T cell proliferation is a primary feature of EBV-AHS.
The Serotonin Transporter Genotype and Social Support and Moderation of Posttraumatic Stress Disorder and Depression in Hurricane-Exposed Adults
Authors: Dean G. Kilpatrick, Karestan C. Koenen, Kenneth J. Ruggiero, Ron Acierno, Sandro Galea, Heidi S. Resnick, John Roitzsch, John Boyle, Joel Gelernter
Journal: American Journal of Psychiatry (2007)

Disasters are associated with increased risk of posttraumatic stress disorder (PTSD) and major depression, but no study, to the authors' knowledge, has determined whether genotype interacts with disaster exposure and social support to moderate risk of these phenotypes. The authors tested the hypothesis that a polymorphism in the serotonin transporter gene (locus, SLC6A4; variant, serotonin 5-HTTLPR) moderates risk of posthurricane PTSD and major depression given high hurricane exposure and low social support.The authors interviewed a household probability sample of adults 6-9 months after the 2004 hurricanes about hurricane exposure, social support, and posthurricane PTSD and major depression. DNA was collected from a subset of participants. Participants were 589 adults ages 18 and older from 38 Florida counties who provided valid DNA samples. Outcome measures were DSM-IV diagnoses of posthurricane PTSD and major depression derived from structured interviews.The low-expression variant of the 5-HTTLPR polymorphism increased risk of posthurricane PTSD and major depression but only under the conditions of high hurricane exposure and low social support after adjustment for sex, ancestry (as determined by Bayesian clustering of genotypes), and age. Similar effects were found for major depression. High-risk individuals (high hurricane exposure, the low-expression 5-HTTLPR variant, low social support) were at 4.5 times the risk of developing PTSD and major depression of low-risk individuals.The low-expression variant of the 5-HTTLPR polymorphism modifies risk of postdisaster PTSD and major depression under conditions of high hurricane exposure and low social support, confirming and extending previous research.
CHANGING CONCEPTS IN MELANOMA MANAGEMENT
Authors: F. Rampen
Journal: British Journal of Dermatology (1981)

Journal Article CHANGING CONCEPTS IN MELANOMA MANAGEMENT Get access F. Rampen F. Rampen Department of Dermatology, University of Amsterdam, Binnengasthuis, 1012 GA Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 104, Issue 3, 1 March 1981, Pages 341–348, https://doi.org/10.1111/j.1365-2133.1981.tb00960.x Published: 01 March 1981
Selectionism: Complex outcomes from simple processes
Authors: John W. Donahoe, José E. Burgos
Journal: Behavioral and Brain Sciences (2005)

both the target article and the precommentary demonstrate that relatively simple biobehavioral processes have the cumulative effect of fostering behavioral outcomes characteristic of attention-deficit/hyperactivity disorder (adhd). as such, the articles illustrate a central theme of darwinian thinking – basic processes acting over time can produce complex and diverse outcomes. in this commentary, we indicate that tracing the action of processes over time can be facilitated by quantitative methods such as artificial neural networks.
Intravenous immunoglobulin therapy in severe lupus myocarditis: good outcome in three patients
Authors: D Micheloud, M Calderon, M Caparrros, D P D'Cruz
Journal: Annals of the Rheumatic Diseases (2007)

Myocarditis occurs in 8–78% of necropsy studies of patients with systemic lupus erythematosus (SLE)1,2 but is rare in clinical practice. We describe three patients with severe lupus myocarditis, who improved dramatically after intravenous immunoglobulin (IVIg) therapy.

Table 1 gives details of the cases studied. 

View this table:

 Table 1  
 Characteristics of the patients studied



A 37-year-old woman (patient 3) was diagnosed with lupus, confirmed by strongly positive anti-DNA, low complement, and positive anti-RNP and anti-Sm antibodies. She developed breathlessness and a restrictive lung function pattern and received mycophenolate. She was admitted with a respiratory tract infection, neutropenia (1.6×10 …
Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus
Authors: Robert Silbergleit, Valerie Durkalski, Daniel Lowenstein, Robin Conwit, Arthur Pancioli, Yuko Palesch, William Barsan
Journal: New England Journal of Medicine (2012)

Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.This double-blind, randomized, noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics. Subjects whose convulsions had persisted for more than 5 minutes and who were still convulsing after paramedics arrived were given the study medication by either intramuscular autoinjector or intravenous infusion. The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy. Secondary outcomes included endotracheal intubation, recurrent seizures, and timing of treatment relative to the cessation of convulsive seizures. This trial tested the hypothesis that intramuscular midazolam was noninferior to intravenous lorazepam by a margin of 10 percentage points.At the time of arrival in the emergency department, seizures were absent without rescue therapy in 329 of 448 subjects (73.4%) in the intramuscular-midazolam group and in 282 of 445 (63.4%) in the intravenous-lorazepam group (absolute difference, 10 percentage points; 95% confidence interval, 4.0 to 16.1; P<0.001 for both noninferiority and superiority). The two treatment groups were similar with respect to need for endotracheal intubation (14.1% of subjects with intramuscular midazolam and 14.4% with intravenous lorazepam) and recurrence of seizures (11.4% and 10.6%, respectively). Among subjects whose seizures ceased before arrival in the emergency department, the median times to active treatment were 1.2 minutes in the intramuscular-midazolam group and 4.8 minutes in the intravenous-lorazepam group, with corresponding median times from active treatment to cessation of convulsions of 3.3 minutes and 1.6 minutes. Adverse-event rates were similar in the two groups.For subjects in status epilepticus, intramuscular midazolam is at least as safe and effective as intravenous lorazepam for prehospital seizure cessation. (Funded by the National Institute of Neurological Disorders and Stroke and others; ClinicalTrials.gov number, ClinicalTrials.gov NCT00809146.).
AN ELECTROENCEPHALOGRAPHIC STUDY OF CASES WITH SYNCOPE AND RELATED DISORDERS
Authors: SIDNEY LEVIN, JEROME KATZ, MILTON GREENBLATT
Journal: American Journal of Psychiatry (1945)

In a study of the EEGs (between attacks) of a selected group of 229 patients subject to "fainting spells" and "dizzy spells" the following observations were made: 1. In patients subject to typical "fainting spells," the incidence of EEG. abnormality (11 percent) was as low as one finds in normal controls. Patients subject to "dizzy spells" had an even lower incidence of EEG. abnormality (4 percent). Patients subject to "fainting spells accompanied by rigidity" had a considerably higher incidence of EEG. abnormality (45 percent), suggesting that of the three groups this was the only one in which a significant number of the group might belong to the epileptic category. 2. There was no correlation between EEG. abnormality and frequency, duration and number of spells. It appears that repeated syncopal attacks do not produce EEG. abnormality. 3. Within the total group of 229 cases there were only two patients whose EEGs showed typical 3 per second spike and wave discharges (petit mal waves).
Does the parenchyma mediate the ability of one airway to modulate the contraction of another
Authors: Baoshun Ma, Jason Bates
Journal: European Respiratory Journal (2013)

If two airways are sufficiently close, the parenchymal distortion forces between them may interfere with their abilities to narrow. This mechanism may act to homogenize airway narrowing throughout the lung. We investigated this in a 2-dimensional computational model of a pair of airways embedded in parenchyma represented as a linear elastic continuum (Fig. 1a).  Airway contraction was achieved by imposing an inward radial force on the hole boundaries and calculated using the finite element method. We determined how airway lumen area was affected as a function of the separation distance between their centers when only one airway contracted versus when both airways contracted equally. We found that airway contraction was identical under both conditions until the two airways came within about 2 uncontracted diameters of each other (Fig. 1b) at which point a contracting airway narrowed less if its companion airway also narrowed. We also found that when airways were close they narrowed more than when they were far apart, no doubt due to the reduced parenchymal interdependence forces caused by the hole representing a nearby companion. These model results suggest that airway-parenchymal interdependence will only significantly affect the heterogeneity of airway narrowing if the airways are, on average, within about 2 diameters of each other, provided that the parenchyma behaves like an elastic continuum.
Relative Effect of Chronic Ischemia and a Myocardial Revascularization Procedure on the Ventricular Fibrillation Threshold
Authors: LLOYD D. MACLEAN, CLIFFORD M. PHIBBS
Journal: Circulation Research (1960)

Since ventricular fibrillation is the predominate cause of death following experimental coronary occlusion, measurement of the ventricular fibrillation threshold is recommended to assess the value of cardiac revascularization procedures. This determination is quantitative, precise and permits measurement under controlled circumstances. It was dissatisfaction with measurement of mortality rate following coronary occlusion in control and experimental animals (bioassay technic) that led to the adoption of the present more exact method. Acute ligation of the anterior descending branch of the left coronary artery causes an immediate drop in the fibrillation threshold to one-fifth of normal. This is not changed if one releases the artery and retests the animal with occlusion 5 to 6 months later. Implantation of the internal mammary artery into the myocardium of the left ventricle creates a greater resistance to ventricular fibrillation after coronary occlusion. In animals in which the internal mammary artery remained patent, the fibrillation threshold remained after coronary occlusion at 85 per cent (mean) of control without coronary occlusion. This was highly significant. If the internal mammary artery was thrombosed, as demonstrated by vinyl plastic injection technics, the fibrillation threshold dropped markedly after coronary occlusion and did not vary significantly from the controls. When the anterior descending branch of the left coronary artery was permanently ligated in 1 group of dogs, the expected decline of fibrillation threshold occurred. When the survivals from this group were retested 5 to 6 months later, the fibrillation threshold had increased slightly (not statistically significant) but remained below 50 per cent of control without coronary occlusion and significantly different from the threshold of animals with patent internal mammary artery implants. The results of this investigation suggest that a greater resistance to ventricular fibrillation associated with coronary occlusion can be achieved by operative means than by either mild or severe ischemia alone.
Genetic Testing in the Long QT Syndrome
Authors: Carlo Napolitano, Silvia G. Priori, Peter J. Schwartz, Raffaella Bloise, Elena Ronchetti, Janni Nastoli, Georgia Bottelli, Marina Cerrone, Sergio Leonardi
Journal: JAMA (2005)

In long QT syndrome (LQTS), disease severity and response to therapy vary according to the genetic loci. There exists a critical need to devise strategies to expedite genetic analysis.To perform genetic screening in patients with LQTS to determine the yield of genetic testing, as well as the type and the prevalence of mutations.We investigated whether the detection of a set of frequently mutated codons in the KCNQ1, KCNH2, and SCN5A genes may translate in a novel strategy for rapid efficient genetic testing of 430 consecutive patients referred to our center between June 1996 and June 2004. The entire coding regions of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 were screened by denaturing high-performance liquid chromatography and DNA sequencing. The frequency and the type of mutations were defined to identify a set of recurring mutations. A separate cohort of 75 consecutive probands was used as a validation group to quantify prospectively the prevalence of the recurring mutations identified in the primary LQTS population.Development of a novel approach to LQTS genotyping.We identified 235 different mutations, 138 of which were novel, in 310 (72%) of 430 probands (49% KCNQ1, 39% KCNH2, 10% SCN5A, 1.7% KCNE1, and 0.7% KCNE2). Fifty-eight percent of probands carried nonprivate mutations in 64 codons of KCNQ1, KCNH2, and SCN5A genes. A similar occurrence of mutations at these codons (52%) was confirmed in the prospective cohort of 75 probands and in previously published LQTS cohorts.We have developed an approach to improve the efficiency of genetic screening for LQTS. This novel method may facilitate wider access to genotyping resulting in better risk stratification and treatment of LQTS patients.
Preliminary Data Release for Randomized Clinical Trials of Noninferiority: A New Proposal
Authors: Edward L. Korn, Sally Hunsberger, Boris Freidlin, Malcolm A. Smith, Jeffrey S. Abrams
Journal: Journal of Clinical Oncology (2005)

Noninferiority trials often require a long follow-up period for the data to reach the maturity needed for definitive analysis. A proposal is presented that allows for early release of outcome data from a carefully specified subset of noninferiority trials. This subset is defined so that the early release of the data will be potentially useful to patients who face a treatment decision but will not compromise the integrity of the trial or interfere with the completion of the trial to its definitive analysis. In particular, the release of the data will only occur after the last participant has been randomly assigned and is off treatment-arm–specific therapy and only if it is unlikely that subsequent treatment and/or follow-up practices will change based on the knowledge of released data. In contrast to standard interim monitoring, (1) the release of the data would be automatic and independent of the observed data, and (2) the trial would continue on to its planned final analysis and not be stopped. Examples are given demonstrating how the proposal would work, along with a discussion of possible objections to the proposal.