tbuckley/cabot-search huggingface dataset:
Local Control in Pelvic Ewing Sarcoma: Analysis From INT-0091—A Report From the Children's Oncology Group
Authors: Torunn I. Yock, Mark Krailo, Christopher J. Fryer, Sarah S. Donaldson, James S. Miser, Zhengjia Chen, Mark Bernstein, Fran Laurie, Mark. C. Gebhardt, Holcombe E. Grier, Nancy J. Tarbell
Journal: Journal of Clinical Oncology (2006)

The impact of the modality used for local control of Ewing sarcoma is uncertain. We investigated the relationship between the type of local control modality, surgery, radiation (RT) or both (S + RT), and subsequent risk for local failure (LF) in patients with nonmetastatic pelvic Ewing sarcoma treated on INT-0091.Patients < or = 30 years with Ewing sarcoma, primitive neuroectodermal tumor or primitive sarcoma of bone were randomly assigned to receive chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin, (VACA) or with these four drugs alternating with ifosfamide and etoposide (VACA-IE). The local control modality, surgery, RT or both was chosen by the treating physicians. The effect of local control modality was assessed after adjusting for the size of tumor (< 8 cm, > or = 8 cm) and chemotherapy type.Seventy-five patients with pelvic tumors and a median follow-up of 4.4 years (0.6 to 11.4 years) comprised the study population. Twelve underwent surgery, 44 received RT, and 19 received both. The 5-year event-free survival (EFS) and cumulative incidence of LF was 49% and 21% (16%, LF only; 5%, LF and distant failure). There was no significant difference in EFS or LF by tumor size (< 8 cm, > or = 8 cm), local control (LC) modality, or chemotherapy. However, VACA-IE seems to confer an LC benefit (11% v 30%; P = .06).There was no significant effect of local control modality (surgery, RT or S + RT) selected by the treating physicians on rates of local failure or EFS. However, VACA-IE improves LC (11%) compared with previously published results for pelvic Ewing sarcoma.
Implicit analogy: New direct evidence and a challenge to the theory of memory
Authors: Anthony J. Greene
Journal: Behavioral and Brain Sciences (2008)

Abstract The authors propose that analogical reasoning may be achieved without conscious or explicit deliberation. The argument would be strengthened by more convincingly demonstrating instances of analogy that do not require explicit deliberation. Recent findings demonstrate that deliberative or explicit strategies are not necessary for flexible expression under novel circumstances (Greene et al. 2001) to include analogical transfer (Gross &amp; Greene 2007). This issue is particularly critical because the existence of relational priming poses a serious challenge to the widely held notion that flexible expression of learned relations requires deliberative processes.
<scp>γδ</scp>T Cells: First Line of Defense and Beyond
Authors: Yueh-hsiu Chien, Christina Meyer, Marc Bonneville
Journal: Annual Review of Immunology (2014)

γδ T cells, αβ T cells, and B cells are present together in all but the most primitive vertebrates, suggesting that each population contributes to host immune competence uniquely and that all three are necessary for maintaining immune competence. Functional and molecular analyses indicate that in infections, γδ T cells respond earlier than αβ T cells do and that they emerge late after pathogen numbers start to decline. Thus, these cells may be involved in both establishing and regulating the inflammatory response. Moreover, γδ T cells and αβ T cells are clearly distinct in their antigen recognition and activation requirements as well as in the development of their antigen-specific repertoire and effector function. These aspects allow γδ T cells to occupy unique temporal and functional niches in host immune defense. We review these and other advances in γδ T cell biology in the context of their being the major initial IL-17 producers in acute infection.
Childhood ALL Researchers Focus on High-Risk Patients
Authors: Mary Jane Friedrich
Journal: JNCI Journal of the National Cancer Institute (2009)

that fuses the BCR gene to the ABL1 gene. The alteration, commonly known as the Philadelphia chromosome, is associated primarily with chronic myelogenous leukemia but is also found in a few ALL cases. In a phase II dose escalation study conducted between 2002 and 2006, COG researchers combined an intensive chemotherapy regimen with the drug imatinib mesylate (Gleevec), which specifically targets the BCR – ABL1 gene product, an oncogenic kinase. Twentyfive children with Philadelphia chromosome – positive ALL received the combined therapy. Of these, 22, or 88%, had a 3-year event-free survival. Hunger noted that this finding compares favorably with the 35% event-free survival of children with this form of ALL who were treated in the era before imatinib. “While the numbers are small and longer follow-up is needed, we have not seen an increase in relapse after cessation of therapy,” he said.
The generation and regulation of lymphocyte populations: evidence from differentiative induction systems in vitro.
Authors: M P Scheid, G Goldstein, E A Boyse
Journal: The Journal of Experimental Medicine (1978)

Results with a dual assay, for the induction of Thy-1+ T cells and of CR+ B cells from marker-negative precursors, confirm that thymopoietin is at present the only known selective inducer of prothymocytes. In contrast, various inducers, including ubiquitin, are active in both assays. Pharmacological evidence indicates that there are different cellular receptors for ubiquitin and thymopoietin. Prothymocytes and pro-CR+ B cells compose two distinct populations in bone marrow and spleen; their distribution in density gradients is different, and elimination of either population enriches the other proportionately. There are no noteworthy differences between induction of these two populations in regard to (a) kinetics, (b) dependence on temperature and protein synthesis, (c) activation by cAMP, and (d) inhibition by cGMP. The opposite inductive effects of cAMP and cGMP were corroborated by the use of pharmacological agents that raise or lower the levels of intracellular cyclic nucleotides. In contrast, a third induction assay, which monitors acquisition of the PC+ surface phenotype, indicates that this differentiative step, the last known for B cells, is initiated by cGMP and inhibited by cAMP. Induction of PC is also inhibited by thymopoietin, signifying that the inductive selectivity of thymopoietin is not due to restriction of its receptors to the T lineage cells. Rather it seems that receptors for thymopoietin occur also on PC-inducible and other B cells, although in this case geared biochemically to inhibition rather than expression of the succeeding gene program. This suggests a role for thymopoietin in the coordinated interregulation of lymphocyte classes, in addition to its better-known function as the thymic inducer of prothymocytes. Present data conform to a general scheme in which the cyclic nucleotides cAMP and cGMP, and agents that affect intracellular levels of these mediators, influence reciprocally the early and late (functional) phases of lymphocyte differentiation as a whole, while thymopoietin influences reciprocally the differentiation of the B and T classes of lymphocyte.
Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects.
Authors: L J Goodyear, F Giorgino, L A Sherman, J Carey, R J Smith, G L Dohm
Journal: Journal of Clinical Investigation (1995)

To determine whether the impaired insulin-stimulated glucose uptake in obese individuals is associated with altered insulin receptor signaling, we measured both glucose uptake and early steps in the insulin action pathway in intact strips of human skeletal muscle. Biopsies of rectus abdominus muscle were taken from eight obese and eight control subjects undergoing elective surgery (body mass index 52.9 +/- 3.6 vs 25.7 +/- 0.9). Insulin-stimulated 2-deoxyglucose uptake was 53% lower in muscle strips from obese subjects. Additional muscle strips were incubated in the basal state or with 10(-7) M insulin for 2, 15, or 30 min. In the lean subjects, tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1), measured by immunoblotting with anti-phosphotyrosine antibodies, was significantly increased by insulin at all time points. In the skeletal muscle from the obese subjects, insulin was less effective in stimulating tyrosine phosphorylation (maximum receptor and IRS-1 phosphorylation decreased by 35 and 38%, respectively). Insulin stimulation of IRS-1 immunoprecipitable phosphatidylinositol 3-kinase (PI 3-kinase) activity also was markedly lower in obese subjects compared with controls (10- vs 35-fold above basal, respectively). In addition, the obese subjects had a lower abundance of the insulin receptor, IRS-1, and the p85 subunit of PI 3-kinase (55, 54, and 64% of nonobese, respectively). We conclude that impaired insulin-stimulated glucose uptake in skeletal muscle from severely obese subjects is accompanied by a deficiency in insulin receptor signaling, which may contribute to decreased insulin action.
Body fat distribution and male/female differences in lipids and lipoproteins.
Authors: D S Freedman, S J Jacobsen, J J Barboriak, K A Sobocinski, A J Anderson, A H Kissebah, E A Sasse, H W Gruchow
Journal: Circulation (1990)

The role of body fat distribution, as assessed by the ratio of waist-to-hip circumferences (WHR), in statistically explaining differences in levels of lipoproteins between men and women was studied using data collected in 1985-1986 from employed adults (mean age, 40 years). As compared with the 415 women, the 709 men had higher mean levels of triglycerides (+38 mg/dl) and apolipoprotein B (+11 mg/dl) as well as lower mean levels of high density lipoprotein (HDL) cholesterol (-15 mg/dl) and apolipoprotein A-I (-19 mg/dl). Additionally, men were more overweight, consumed more alcohol, and exercised more frequently than women but were less likely to smoke cigarettes. Controlling for these characteristics, however, did not alter the differences in lipoprotein levels between men and women. In contrast, adjustment for WHR (which was greater among men) reduced the sex differences in levels of apolipoprotein B (by 98%), triglycerides (by 94%), HDL cholesterol (by 33%), and apolipoprotein A-I (by 21%). Similar results were obtained using analysis of covariance, stratification, or matching; at comparable levels of WHR, differences in lipid and lipoprotein levels between men and women were greatly reduced. Although these results are based on cross-sectional analyses of employed adults and need to be replicated in other populations, the findings emphasize the relative importance of body fat distribution. Whereas generalized obesity and body fat distribution are associated with lipid levels, fat distribution (or a characteristic influencing fat patterning) can be an important determinant of sex differences in levels of triglycerides, HDL cholesterol, and apolipoproteins B and A-I.
Self-deception, lying, and the ability to deceive
Authors: Aldert Vrij
Journal: Behavioral and Brain Sciences (2011)

Abstract Von Hippel &amp; Trivers (VH&amp;T) argue that people become effective liars through self-deception. It can be said, however, that people who believe their own stories are not lying. VH&amp;T also argue that people are quite good lie detectors, but they provide no evidence for this, and the available literature contradicts their claim. Their reasons to negate this evidence are unconvincing.
The long term clinical course of acute deep vein thrombosis of the arm: prospective cohort study
Authors: Paolo Prandoni, Enrico Bernardi, Antonio Marchiori, Anthonie W A Lensing, Martin H Prins, Sabina Villalta, Paola Bagatella, Donatella Sartor, Andrea Piccioli, Paolo Simioni, Antonio Pagnan, Antonio Girolami
Journal: BMJ (2004)

The diagnosis and treatment of deep vein thrombosis of the arm are documented extensively.1 2 The long term clinical course of the condition is, however, poorly defined.

Fifty three consecutive patients with a first, symptomatic deep vein thrombosis of the arm, confirmed by ultrasonography or venography—including six cases related to catheter insertion—were treated with high dose heparin, followed by at least three months of warfarin (targeted international normalised ratio 2.0-3.0) (table).

View this table:

Characteristics of the study patients (n=53). Values are numbers (percentages) of patients unless otherwise indicated



Follow up visits were scheduled after three and six months, and then every six months up to five years. At each visit, patients underwent a clinical evaluation, for which we used a standardised scale previously validated in patients with venous thrombosis in the leg,3 4 and an ultrasound assessment of the affected venous segments. Each of five symptoms (heaviness, pain, itching, physical …
Screening for Colorectal Cancer With Fecal Occult Blood Testing and Sigmoidoscopy
Authors: S. J. Winawer, B. J. Flehinger, D. Schottenfeld, D. G. Miller
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : The high incidence of and mortality from colorectal cancer (160000 new cases and 60000 deaths in the United States each year) are compelling public health concerns. Following the evolution of effective surgery for this disease since the 1960s, the focus has been on improving methods of detection and integrating them into effective screening programs. Purpose : This was the first study to evaluate the effectiveness, in a setting of comprehensive medical examinations, of using the fecal occult blood test in conjunction with sigmoidoscopy, rather than sigmoidoscopy alone, to screen for colorectal cancer. Our end points were extent of compliance with fecal occult blood test and sigmoidoscopy, numbers of cancers detected, and mortality rate. Methods : From 1975 through 1979, a total of 21756 patients (aged 40 and older) who presented at the Preventive Medicine Institute—Strang Clinic for routine medical examinations were enrolled by calendar period into study and control groups. Study patients were offered annually both rigid sigmoidoscopy examinations and fecal occult blood tests requiring two stool specimens per day for 3 days, while control patients were offered only annual sigmoidoscopy. The majority of fecal occult blood tests cards were not rehydrated before assay. Patients with positive tests were referred for double-contrast barium enema and colonoscopy. Two distinct trials were carried out. Trial I was primarily a demonstration of feasibility of using the fecal occult blood test as a supplemental screening method. Of the 9277 participants, 7168 (77%) were assigned to the study group and offered the fecal occult blood test. In trial II, approximately half of the 12479 patients were assigned to each group. Patients in both trials had followup through 1984. Results : Compliance with the fecal occult blood test was initially high in both trials, but diminished such that only 56% of study patients in trial I and 20% of those in trial II returned for second tests. On the initial (prevalence) screen, a substantial number of early-stage cancers were detected by the fecal occult blood test, primarily in trial II. In trial II, survival probability was significantly greater ( P <.001) in the study group than in the controls (70% versus 48%), and colorectal cancer mortality was lower (0.36 versus 0.63) with borderline significance ( P = .053, one-sided). Conclusions and Implications : The screening of averagerisk individuals (aged 50 and older) for colorectal cancer through use of the fecal occult blood test in conjunction with sigmoidoscopy can increase the likelihood of early detection of this disease. This practice, coupled with prompt diagnostic work-up following positive tests, will result in treatment of earlier stage cancers and increased survival after treatment. [J Natl Cancer Inst 85:1311–1318, 1993]
Cost-effectiveness of Screening Strategies for Identifying Pediatric Diabetes Mellitus and Dysglycemia
Authors: En-Ling Wu, Nayla G. Kazzi, Joyce M. Lee
Journal: JAMA Pediatrics (2012)

To conduct a cost-effectiveness analysis of screening strategies for identifying children with type 2 diabetes mellitus and dysglycemia (prediabetes/diabetes).Cost simulation study.A one-time US screening program.A total of 2.5 million children aged 10 to 17 years.Screening strategies for identifying diabetes and dysglycemia.Effectiveness (proportion of cases identified), total costs (direct and indirect), and efficiency (cost per case identified) of each screening strategy based on test performance data from a pediatric cohort and cost data from Medicare and the US Bureau of Labor Statistics.In the base-case model, 500 and 400 000 US adolescents had diabetes and dysglycemia, respectively. For diabetes, the cost per case was extremely high ($312 000-$831 000 per case identified) because of the low prevalence of disease. For dysglycemia, the cost per case was in a more reasonable range. For dysglycemia, preferred strategies were the 2-hour oral glucose tolerance test (100% effectiveness; $390 per case), 1-hour glucose challenge test (63% effectiveness; $571), random glucose test (55% effectiveness; $498), or a hemoglobin A1c threshold of 5.5% (45% effectiveness; $763). Hemoglobin A1c thresholds of 5.7% and 6.5% were the least effective and least efficient (ranges, 7%-32% and $938-$3370) of all strategies evaluated. Sensitivity analyses for diabetes revealed that disease prevalence was a major driver of cost-effectiveness. Sensitivity analyses for dysglycemia did not lead to appreciable changes in overall rankings among tests.For diabetes, the cost per case is extremely high because of the low prevalence of the disease in the pediatric population. Screening for diabetes could become more cost-effective if dysglycemia is explicitly considered as a screening outcome.
Acylglycerol kinase augments JAK2/STAT3 signaling in esophageal squamous cells
Authors: Xiuting Chen, Zhe Ying, Xi Lin, Huanxin Lin, Jueheng Wu, Mengfeng Li, Libing Song
Journal: Journal of Clinical Investigation (2013)

JAK2 activity is tightly controlled through a self-inhibitory effect via its JAK homology domain 2 (JH2), which restricts the strength and duration of JAK2/STAT3 signaling under physiological conditions. Although multiple mutations within JAK2, which abrogate the function of JH2 and sustain JAK2 activation, are widely observed in hematological malignancies, comparable mutations have not been detected in solid tumors. How solid tumor cells override the autoinhibitory effect of the JH2 domain to maintain constitutive activation of JAK2/STAT3 signaling remains puzzling. Herein, we demonstrate that AGK directly interacted with the JH2 domain to relieve inhibition of JAK2 and activate JAK2/STAT3 signaling. Overexpression of AGK sustained constitutive JAK2/STAT3 activation, consequently promoting the cancer stem cell population and augmenting the tumorigenicity of esophageal squamous cell carcinoma (ESCC) cells both in vivo and in vitro. Furthermore, AGK levels significantly correlated with increased STAT3 phosphorylation, poorer disease-free survival, and shorter overall survival in primary ESCC. More importantly, AGK expression was significantly correlated with JAK2/STAT3 hyperactivation in ESCC, as well as in lung and breast cancer. These findings uncover a mechanism for constitutive activation of JAK2/STAT3 signaling in solid tumors and may represent a prognostic biomarker and therapeutic target.
A critical role for monocytes and CD14 in endotoxin-induced endothelial cell activation.
Authors: J Pugin, R J Ulevitch, P S Tobias
Journal: The Journal of Experimental Medicine (1993)

Vascular endothelium activated by endotoxin (lipopolysaccharide [LPS]) and cytokines plays an important role in organ inflammation and blood leukocyte recruitment observed during sepsis. Endothelial cells can be activated by LPS directly, after its interaction with LPS-binding protein and soluble CD14 in plasma. LPS-LPS-binding protein complexes in blood also interact with monocytes and neutrophils bearing glycosyl-phosphatidylinositol (GPI) anchored membrane CD14 (mCD14), promoting the release of cytokines such as tumor necrosis factor and interleukin 1 (IL-1). These molecules, in turn, have the capacity to activate endothelial cells providing an indirect pathway for LPS-dependent endothelial cell activation. In this work, we address the relative importance of the direct and the indirect pathway of in vitro LPS-induced human umbilical vein endothelial cell (HUVEC) activation. Substituting whole blood for plasma resulted in a 1,000-fold enhancement of HUVEC sensitivity to LPS. Both blood- and plasma-dependent enhanced activation of HUVEC were blocked with an anti-CD14 monoclonal antibody. Blood from patients with paroxysmal nocturnal hemoglobinuria, whose cells lack mCD14 and other GPI anchored proteins, was unable to enhance LPS activation of HUVEC above the level observed with plasma alone. IL-10, an inhibitor of monocyte release of cytokines, decreased the blood-dependent enhancement of HUVEC activation by LPS. Blood adapted to small doses of LPS was also less efficient than nonadapted blood in producing this enhancement. Addition of purified mononuclear cells to HUVEC or the transfer of plasma from whole blood incubated with LPS to HUVEC, duplicated the enhancement effect observed when whole blood was incubated with HUVEC. Taken together, these data suggest that the indirect pathway of LPS activation of endothelial cell is mediated by monocytes and mCD14 through the secretion of a soluble mediator(s). The indirect pathway is far more efficient than the direct, plasma-dependent pathway.
Comparision of catheter-directed therapy with the systemic thrombolysis for the treatment of acute pulmonary embolism with right ventricular dysfunction
Authors: Asli Gorek Dilektasli, Ezgi Demirdogen Cetinoglu, Nilufer Aylin Acet, Cuneyt Erdogan, Ahmet Ursavas, Funda Coskun, Ercument Ege
Journal: European Respiratory Journal (2014)

BACKGROUND :Cathater-directed therapy(CDT)has been considered as an alternative to systemic thrombolysis(ST) in acute pulmonary embolism(PE) in the presence of contraindications for ST.We aimed to evaluate the efficacy and safety of CDT compared to SIT in acute PE management with right ventricular dysfunction(RVD).   MATERIAL-METHODS: Acute PE patients with RVD diagnosed between 2007-2013 treated by CDT were included.Afterwards PE patients treated by CDT were matched by age,sex,mean pulmonary artery pressure,and shock index at admission with a PE patient whom recieved ST.The primary,secondary and tertiary outcomes were mortality,complications and the change in haemodynamic parameters in thefirst 24 hours.   RESULTS: Thirty-two acute PE patients(58.5±15.3 years old)were included.Seventeen(53%)and fifteen(47%)of the study group were diagnosed as massive and submassive PE, respectively. CDT was performed in six(40%)patients with massive PE and nine(60%)with submassive PE. All-cause mortality,major and minor bleeding complications did not differ among CDT and ST groups(p>0,05). Haemodynamic parameters were stabilized in 93% of CDT group and76.5% of the ST group in thefirst 24 hours(p>0,05).24 th  hour systolic blood pressure(116±13mmHg vs.110±23 mmHg,p=0.078)and diastolic blood pressure(72±4mmHg vs.67±9 mmHg,p=0.017)were found to be higher while heart rate(88±16mmHg vs.90±10 mmHg,p=0.068)were found to be lower in the CDT group.   CONCLUSION: CDT is a safe and effective treatment option for acute PE with RVD.It should be considered as a first-line treatment for patients having contraindications for ST with acute PE and RVD in experienced centers.