tbuckley/cabot-search huggingface dataset:
Pediatric trauma. The No. 1 killer of children
Authors: J. A. Haller
Journal: JAMA (1983)

WE HEAR so much about the tragic loss of children from congenital heart disease, lung abnormalities, and malignancy that we have overlooked the fact that more than half of the children who die in the United States die as a result of serious injuries. Almost half of the deaths in children last year resulted from trauma, as compared with approximately one death in 20 in the general population due to injuries. The death of a child is, in itself, a tragedy, but crippling injuries to a child and the resulting need for rehabilitation may have a far greater impact on society and our health care system than a child's death will. The expenditure of resources and personnel and the economic loss caused by termination of work potential when a child is seriously handicapped are relatively enormous when compared with similar losses following injuries in adults.  A child is usually affected
Potentiation of a Topoisomerase I Inhibitor, Karenitecin, by the Histone Deacetylase Inhibitor Valproic Acid in Melanoma: Translational and Phase I/II Clinical Trial
Authors: Adil I. Daud, Jana Dawson, Ronald C. DeConti, Elona Bicaku, Douglas Marchion, Sem Bastien, Frederick A. Hausheer, Richard Lush, Anthony Neuger, Daniel M. Sullivan, Pamela N. Munster
Journal: Clinical Cancer Research (2009)

The novel topoisomerase I inhibitor karenitecin (KTN) shows activity against melanoma. We examined whether histone deacetylase inhibition could potentiate the DNA strand cleavage, cytotoxicity as well as the clinical toxicity, and efficacy of KTN in melanoma.Apoptosis, COMET, and xenograft experiments were carried out as described previously. A phase I/II trial of valproic acid (VPA) and KTN was conducted in patients with stage IV melanoma, with any number of prior therapies, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function.VPA pretreatment potentiated KTN-induced apoptosis in multiple melanoma cell lines and in mouse A375 xenografts. VPA increased KTN-induced DNA strand breaks. In the phase I/II trial, 39 patients were entered, with 37 evaluable for toxicity and 33 evaluable for response. Somnolence was the dose-limiting toxicity. The maximum tolerated dose for VPA was 75 mg/kg/d; at maximum tolerated dose, serum VPA was approximately 200 microg/mL (1.28 mmol/L). At the dose expansion cohort, 47% (7 of 15) of patients had stable disease; median overall survival and time to progression were 32.8 and 10.2 weeks, respectively. Histone hyperacetylation was observed in peripheral blood mononuclear cells at maximum tolerated dose.VPA potentiates KTN-induced DNA strand breaks and cytotoxicity. VPA can be combined at 75 mg/kg/d for 5 days with full-dose KTN without overlapping toxicities. In metastatic poor prognosis melanoma, this combination is associated with disease stabilization in 47% of patients. Further testing of this combination appears warranted.
Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial
Authors: Gunter von Minckwitz, Fabio Puglisi, Javier Cortes, Eduard Vrdoljak, Norbert Marschner, Christoph Zielinski, Cristian Villanueva, Gilles Romieu, István Lang, Eva Ciruelos, Michele De Laurentiis, Corinne Veyret, Sabine de Ducla, Ulrich Freudensprung, Stefanie Srock, Joseph Gligorov
Journal: The Lancet Oncology (2014)
FOXP3 Defines Regulatory T Cells in Human Tumor and Autoimmune Disease
Authors: Ilona Kryczek, Rebecca Liu, Guobin Wang, Ke Wu, Xiaogong Shu, Wojciech Szeliga, Linhua Vatan, Emily Finlayson, Emina Huang, Diane Simeone, Bruce Redman, Theodore H. Welling, Alfred Chang, Weiping Zou
Journal: Cancer Research (2009)

Activated T cells may express FOXP3. It is thought that FOXP3 is not a specific marker to determine regulatory T cells (Treg) in humans. Here, we examined the functional phenotype and cytokine profile of the in vitro induced FOXP3(+) T cells, primary FOXP3(+) and FOXP3(-) T cells in patients with ulcerative colitis and tumors including colon carcinoma, melanoma, hepatic carcinoma, ovarian carcinoma, pancreatic cancer, and renal cell carcinoma. We observed similar levels of suppressive capacity of primary FOXP3(+) T cells in blood, tumors, and colitic tissues. Compared with primary FOXP3(-) T cells in the same microenvironment, these primary FOXP3(+) T cells expressed minimal levels of effector cytokines, negligible amount of cytotoxic molecule granzyme B, and levels of suppressive molecules interleukin-10 and PD-1. Although the in vitro activated T cells expressed FOXP3, these induced FOXP3(+) T cells expressed high levels of multiple effector cytokines and were not functionally suppressive. The data reinforce the fact that FOXP3 remains an accurate marker to define primary Tregs in patients with cancer and autoimmune disease. We suggest that the combination of FOXP3 and cytokine profile is useful for further functionally distinguishing primary Tregs from activated conventional T cells.
Regulation of Carbohydrate and Fat Metabolism During and After Exercise
Authors: John O. Holloszy, Wendy M. Kohrt
Journal: Annual Review of Nutrition (1996)

During vigorous exercise, carbohydrate, in the form of muscle glycogen and blood glucose, is the primary energy source, whereas fatty acids play a secondary, carbohydrate-sparing role. In the postabsorptive state, nearly all of the carbohydrate used during exercise comes from muscle and liver glycogen. The size of these glycogen stores plays a major role in determining how long vigorous endurance exercise can be performed if other causes of fatigue, such as dehydration or heat exhaustion, are avoided. In a “fight or flight” situation, individuals whose muscles are glycogen depleted are helpless, as they are unable to either run or fight. The same is true of someone who has become markedly hypoglycemic as a result of liver glycogen depletion.
Gemcitabine, dexamethasone and cisplatin is an active andnon-toxic chemotherapy regimen in relapsed or refractory Hodgkin’s disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group
Authors: T. Baetz, A. Belch, S. Couban, K. Imrie, J. Yau, R. Myers, K. Ding, N. Paul, L. Shepherd, J. Iglesias, R. Meyer, M. Crump
Journal: Annals of Oncology (2003)
Pivotal Role of mTORC2 and Involvement of Ribosomal Protein S6 in Cardioprotective Signaling
Authors: Toshiyuki Yano, Marcella Ferlito, Angel Aponte, Atsushi Kuno, Tetsuji Miura, Elizabeth Murphy, Charles Steenbergen
Journal: Circulation Research (2014)

There is tight coupling between Akt activation and suppression of cell death. Full Akt activation requires mammalian target of rapamycin complex 2 (mTORC2), but the regulation of mTORC2 is unclear.To gain new insights into mechanisms of mTORC2/Akt signaling.The role of mTORC2 in cardioprotection was examined. In perfused mouse hearts, ischemic preconditioning increased mTORC2 activity, leading to phosphorylation of Akt on Ser473. The protective effect of ischemic preconditioning was lost by pretreatment with dual mTORC inhibitors but not with rapamycin, an mTORC1 inhibitor, which indicates the fundamental role of mTORC2 activation in cardioprotection. Next, the regulation and downstream targets of mTORC2/Akt signaling were explored. We have found that ischemic preconditioning and other Akt activators (insulin and opioids) result in phosphorylation of ribosomal protein S6 (Rps6) at Ser235/236 in mouse hearts and neonatal rat ventricular myocytes. Rps6 interacts with components of mTORC2, and siRNA-mediated knockdown of Rps6 attenuates insulin-induced mTORC2 activation and Akt-Ser473 phosphorylation. On the other hand, Rps6 overexpression enhanced Akt-Ser473 phosphorylation, indicating that Rps6 activation amplifies mTORC2/Akt signaling. Disruption of the Rps6/mTORC2 pathway by knockdown of Rps6 or rictor abrogated insulin-induced cytoprotection against oxidative stress. Although rapamycin blocks Rps6-dependent mTORC2 activation, mTORC2 is still activated by an alternative signaling pathway, demonstrating the redundancy in cardioprotective signaling.Activation of mTORC2 plays a pivotal role in cardioprotection, and Rps6 is a convergence point of cardioprotective signaling, providing positive feedback regulation of mTORC2/Akt signaling.
14-3-3σ Methylation in Pretreatment Serum Circulating DNA of Cisplatin-Plus-Gemcitabine-Treated Advanced Non–Small-Cell Lung Cancer Patients Predicts Survival: The Spanish Lung Cancer Group
Authors: José Luis Ramirez, Rafael Rosell, Miquel Taron, Maria Sanchez-Ronco, Vicente Alberola, Ramon de las Peñas, José Miguel Sanchez, Teresa Moran, Carlos Camps, Bartomeu Massuti, José Javier Sanchez, Fernanda Salazar, Silvia Catot
Journal: Journal of Clinical Oncology (2005)

Purpose Survival in patients with advanced non–small-cell lung cancer (NSCLC) who are treated with platinum-based chemotherapy is rather variable. Methylation-dependent transcriptional silencing of 14-3-3σ, a major G 2 -M checkpoint control gene, could be a predictor of longer survival. Patients and Methods A sensitive methylation-specific polymerase chain reaction assay was used to evaluate 14-3-3σ methylation status in pretreatment serum DNA obtained from 115 cisplatin-plus-gemcitabine–treated advanced NSCLC patients. Results 14-3-3σ methylation was observed in all histologic types of 39 patients (34%). After a median follow-up of 9.8 months, median survival was significantly longer in the methylation-positive group (15.1 v 9.8 months; P = .004). Median time to progression was 8 months in the methylation-positive group and 6.3 months in the methylation-negative group (log-rank test, P = .027). A multivariate Cox regression model identified only 14-3-3σ methylation status and Eastern Cooperative Oncology Group performance status as independent prognostic factors for survival. In an exploratory analysis, median survival for 22 methylation-positive responders has not been reached, whereas survival was 11.3 months for 29 methylation-negative responders (P = .001). Conclusion Methylation of 14-3-3σ is a new independent prognostic factor for survival in NSCLC patients receiving platinum-based chemotherapy. It can be reliably and conveniently detected in the serum, thus obviating the need for tumor tissue analysis.
ROENTGEN RAY INTOXICATION
Authors: S. L. Warren, G. H. Whipple
Journal: The Journal of Experimental Medicine (1923)

X-rays which injure intestinal epithelium (and presumably other body or tumor cells) travel in straight lines from the target through the living tissues, forming a cone or beam of rays as controlled by impervious screens. It is probable that secondary radiation is formed, especially deep in the body tissues, but such radiation does no injury to intestinal epithelium outside of the cone or path of radiation. Lesions in the stomach and intestine may be confidently predicted from a knowledge of the size and form of the cone or beam of x-rays given over the abdomen. These lesions even more than skin burns do not heal and may in fact go on after many weeks to perforation. Even in the depths of the abdomen the duodenal lesions are as clean-cut as a peptic ulcer, indicating the lack of dispersion or scattering of the primary or secondary rays in passage through the living tissues. Transition from normal to necrotic mucosa rarely occupies more than 2 to 3 mm. and often can be observed in a single low power microscopic field.
Clinical Use of Respiratory Changes in Arterial Pulse Pressure to Monitor the Hemodynamic Effects of PEEP
Authors: FRÉDÉRIC MICHARD, DENIS CHEMLA, CHRISTIAN RICHARD, MARC WYSOCKI, MICHAEL R. PINSKY, YVES LECARPENTIER, JEAN-LOUIS TEBOUL
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

In ventilated patients with acute lung injury (ALI) we investigated whether respiratory changes in arterial pulse pressure ( Δ PP) could be related to the effects of PEEP and fluid loading (FL) on cardiac index (CI). Measurements were performed before and after application of a PEEP (10 cm H2O) in 14 patients. When the PEEP-induced decrease in CI was > 10% (six patients), measurements were also performed after FL. Maximal (PPmax) and minimal (PPmin) values of pulse pressure were determined over one respiratory cycle and Δ PP was calculated: Δ PP (%) = 100 × {(PPmax − PPmin)/ ([PPmax + PPmin]/2)}. PEEP decreased CI from 4.2 ± 1.1 to 3.8 ± 1.3 L/min/m2 (p < 0.01) and increased Δ PP from 9 ± 7 to 16 ± 13% (p < 0.01). The PEEP-induced changes in CI correlated with Δ PP on ZEEP (r = − 0.91, p < 0.001) and with the PEEP-induced increase in Δ PP (r = − 0.79, p < 0.001). FL increased CI from 3.5 ± 1.1 to 4.2 ± 0.9 L/min/m2 (p < 0.05) and decreased Δ PP from 27 ± 13 to 14 ± 9% (p < 0.05). The FL-induced changes in CI correlated with Δ PP before FL (r = 0.97, p < 0.01) and with the FL-induced decrease in Δ PP (r = − 0.85, p < 0.05). In ventilated patients with ALI, Δ PP may be useful in predicting and assessing the hemodynamic effects of PEEP and FL.
Nuclear–Mitochondrial Sequences as Witnesses of Past Interbreeding and Population Diversity in the Jumping Bristletail Mesomachilis
Authors: Laura Baldo, Alan de Queiroz, Marshal Hedin, Cheryl Y. Hayashi, John Gatesy
Journal: Molecular Biology and Evolution (2010)

Nuclear–mitochondrial sequences (NUMTs) can be especially powerful tools for evolutionary studies by providing a window into the nature of ancestral mitochondrial (mt) lineages. Here, we illustrate this property of NUMTs through a survey of such sequences in two species of the jumping bristletail genus Mesomachilis. An ∼1,800 basepair fragment encompassing three mt genes—COI, tRNA-Leu, and COII—was cloned twice for a sample of specimens, and colonies were screened. NUMTs in this genus are abundant and genetically diverse (up to 23% different from the associated mt sequence). Numerous independent nuclear integration events are scattered at different time depths, suggesting a continuous process of NUMT generation. By combining phylogenetic reconstruction with analyses of the pattern of nucleotide substitution on mt and NUMT branches, we inferred the dynamics of NUMT origin and evolution. The majority of NUMTs in the data set have apparently evolved from source mt lineages that were substantially different from the currently associated mt sequence, indicating NUMT transfer via matings among divergent lineages. The original source mt lineages either were unsampled or are extinct. Translocations of NUMTs to new nuclear genomes can preserve NUMTs following extinction of their ancestral mt lineages and can be used to detect mixing between divergent mt lineages and past levels of mt diversity.
562 TUMOR NECROSIS FACTOR-ALPHA PROMOTER GENE POLYMORPHISMS AFFECT THE OCCURRENCE OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH CHRONIC HEPATITIS B
Authors: Danbi Lee, Y.-H. Chung, J.A. Kim, S.E. Kim, J.-K. Choi, D.-J. Yoo, Y.-J. Jin, J.H. Shim, Y.-S. Lee, Don Lee, N.H. Park
Journal: Journal of Hepatology (2010)
Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin Plus Etoposide for Patients With Relapsed Primary Mediastinal Nonseminomatous Germ Cell Tumors: Benefit From Chemotherapy, Surgery, or Both?
Authors: Lawrence H. Einhorn, Rafat Abonour, Kenneth A. Kesler
Journal: Journal of Clinical Oncology (2010)
Apolipoprotein E and protection against hepatitis E viral infection in American non‐Hispanic blacks
Authors: Lyna Zhang, Ajay Yesupriya, Man‐Huei Chang, Eyasu Teshale, Chong‐Gee Teo
Journal: Hepatology (2015)

Hepatitis E viral (HEV) infection imposes a heavy health burden worldwide and is common in the United States. Previous investigations of risks addressed environmental and host behavioral/lifestyle factors, but host genetic factors have not been examined. We assessed strength of associations between antibody to HEV (anti-HEV) immunoglobulin G seropositivity indicating past or recent HEV infection and human genetic variants among three major racial/ethnic populations in the United States, involving 2434 non-Hispanic whites, 1919 non-Hispanic blacks, and 1919 Mexican Americans from the Third National Health and Nutrition Examination Survey, 1991-1994. We studied 497 single-nucleotide polymorphisms across 190 genes (particularly those associated with lipid metabolism). The genomic control method was used to adjust for potential population stratification. Non-Hispanic blacks had the lowest seroprevalence of anti-HEV immunoglobulin G (15.3%, 95% confidence interval [CI] 12.3%-19.0%) compared with non-Hispanic whites (22.3%, 95% CI 19.1%-25.7%) and Mexican Americans (21.8%, 95% CI 19.0%-25.3%; P<0.01). Non-Hispanic blacks were the only population that showed association between anti-HEV seropositivity and functional ε3 and ε4 alleles of the apolipoprotein E (APOE) gene, encoding the apolipoprotein E protein that mediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying APOE ε4 (odds ratio=0.5, 95% CI 0.4-0.7; P=0.00004) and ε3 (odds ratio=0.6, 95% CI 0.4-0.8; P=0.001) compared to those carrying APOE ε2. No significant associations were observed between other single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic blacks or between any single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic whites or Mexican Americans.Both APOE ε3 and ε4 are significantly associated with protection against HEV infection in non-Hispanic blacks; additional studies are needed to understand the basis of protection so that preventive services can be targeted to at-risk persons.
Metal sensitivities and orthopaedic implants revisited: the potential for metal allergy with the new metal-on-metal joint prostheses
Authors: D.J. Gawkrodger
Journal: British Journal of Dermatology (2003)

Summary The potential of metal-containing orthopaedic prostheses to induce problems through metal allergy taxes dermatologists and orthopaedic surgeons alike. Metal-on-plastic joint replacements are not thought to induce metal allergy but wear products, principally polypropylene particles, produce a foreign body reaction in bone and may lead to aseptic loosening of the joint. Orthopaedic surgeons are increasingly using metal-on-metal joint replacements, particularly for younger patients, as some evidence suggests that there is less wear debris and hence less aseptic loosening. The original metal-on-metal hip joints of the 1960s were associated with sensitivities to cobalt, nickel and chromate when loosening occurred. The potential for modern metal-on-metal joint prostheses, with their lower production of wear debris, to sensitize the recipient to metals or to induce a problem in subjects already allergic to metals, is unclear. One uncontrolled series suggested an association between nickel allergy and prosthesis loosening in some subjects, but the question has yet to be addressed in a prospective study and to date there is no other observation in the orthopaedic literature to suggest a problem.
Reduced Inflammation in the Tumor Microenvironment Delays the Accumulation of Myeloid-Derived Suppressor Cells and Limits Tumor Progression
Authors: Stephanie K. Bunt, Linglin Yang, Pratima Sinha, Virginia K. Clements, Jeff Leips, Suzanne Ostrand-Rosenberg
Journal: Cancer Research (2007)

Abstract Chronic inflammation is frequently associated with malignant growth and is thought to promote and enhance tumor progression, although the mechanisms which regulate this relationship remain elusive. We reported previously that interleukin (IL)-1β promoted tumor progression by enhancing the accumulation of myeloid-derived suppressor cells (MDSC), and hypothesized that inflammation leads to cancer through the production of MDSC which inhibit tumor immunity. If inflammation-induced MDSC promote tumor progression by blocking antitumor immunity, then a reduction in inflammation should reduce MDSC levels and delay tumor progression, whereas an increase in inflammation should increase MDSC levels and hasten tumor progression. We have tested this hypothesis using the 4T1 mammary carcinoma and IL-1 receptor (IL-1R)–deficient mice which have a reduced potential for inflammation, and IL-1R antagonist–deficient mice, which have an increased potential for inflammation. Consistent with our hypothesis, IL-1R–deficient mice have a delayed accumulation of MDSC and reduced primary and metastatic tumor progression. Accumulation of MDSC and tumor progression are partially restored by IL-6, indicating that IL-6 is a downstream mediator of the IL-1β–induced expansion of MDSC. In contrast, excessive inflammation in IL-1R antagonist–deficient mice promotes the accumulation of MDSC and produces MDSC with enhanced suppressive activity. These results show that immune suppression by MDSC and tumor growth are regulated by the inflammatory milieu and support the hypothesis that the induction of suppressor cells which down-regulate tumor immunity is one of the mechanisms linking inflammation and cancer. [Cancer Res 2007;67(20):10019–26]
Sudden Death in Hospital after Discharge from Coronary Care Unit
Authors: P. Thompson, G. Sloman
Journal: BMJ (1971)

In a group of 339 patients with acute myocardial infarction treated in a coronary care unit, 273 left the unit while improving and were expected to leave hospital alive; 23 had a cardiac arrest or died suddenly while still in hospital-17 died immediately or after temporary resuscitation and six were resuscitated to leave hospital alive. Ventricular fibrillation was found in 13 of the 20 patients attended by the cardiac arrest team. The incidents were scattered from the 4th to the 24th day after the onset of infarction. Risk factors in these "late sudden death" patients were compared with the 250 patients who left the unit while improving and did not die or suffer cardiac arrest. The patients susceptible to late sudden death were characterized early in their hospital course by the findings of severe, predominantly anterior infarction, left ventricular failure, persistent sinus tachycardia, and frequent ventricular arrhythmias. It is suggested that such patients be chosen for prolonged observation in a second-stage coronary care unit.
A Hydrostatic Pressure Stocking for the Treatment of Ulcers due to Chronic Venous Insufficiency
Authors: J. EDWIN WOOD
Journal: Circulation (1959)

Chronic venous insufficiency may be complicated by ulceration of the skin of the involved extremity. The ulcers appear to be caused by the prolonged elevation of venous pressure in the leg and the resultant edema. A device is described that counterbalances exactly the elevated pressure in the veins of the leg, regardless of the position of the patient. This hydrostatic pressure stocking prevents formation of edema without interfering with the flow of blood through the tissues. The use of this device in the treatment of ulcers due to chronic venous insufficiency is also described.