tbuckley/cabot-search huggingface dataset:
Postoperative Chemotherapy Does Not Improve Survival in Gastric Cancer Patients
Authors: L. Savage
Journal: JNCI Journal of the National Cancer Institute (2008)

Postoperative Chemotherapy Does Not Improve Survival in Gastric Cancer PatientsThe use of combination chemotherapy following surgery did not improve survival in patients with gastric cancer, according to a randomized clinical trial published online March 11 in the Journal of the National Cancer Institute .The only potentially curative therapy currently available for non-metastatic gastric cancer is surgery.Recent studies have suggested that a combination of cisplatin, epirubicin, 5-fl uorouracil and leucovorin (PELF) improves outcome in patients with metastatic gastric cancer.To test the PELF combination in patients with localized disease, Francesco Di Costanzo, M.D., of the University Hospital Careggi in Florence, Italy, and colleagues in the Italian Oncology Group for Cancer Research conducted a randomized controlled trial in which 258 patients were treated with surgery or surgery followed by chemotherapy.With a median follow-up of 72.8 months, there was no signifi cant difference in disease-free survival or overall survival between the two trial arms.Specifi cally, 47.7 percent of the patients treated with chemotherapy had progressive disease compared with 51.6 percent of patients in the control arm.Overall survival was similar; at the end of the follow-up period, 47 percent of the patients in the chemotherapy were still alive compared with 45.3 percent in the surgery-only arm."Our study confi rms that a dose-intense regimen like PELF, which showed very promising results in advanced gastric cancer, is not effective in an adjuvant setting," the authors write.Considering the negative results in this trial and other recent adjuvant chemotherapy trials in gastric cancer, the authors write, "Adjuvant chemotherapy alone remains a controversial approach in operable gastric cancer."In an accompanying editorial, Aiwen Wu, M.D., and Jiafu Ji, M.D., of the Beijing Cancer Hospital and Institute in China discuss the confl icting results obtained from recent trials that tested the value of chemotherapy and radiation in localized gastric cancer.Despite the inconsistency of the overall data, the editorialists conclude that chemotherapy, radiation, or a combination of the two should be used in patients with gastric cancer."Surgery alone is no longer the standard treatment for patients with resectable gastric cancer, independent of the patient population or the practice location," they write.
In nonvalvular atrial fibrillation, effects of rivaroxaban compared with warfarin did not differ by patient age
Authors: Matthew Rondina
Journal: Annals of Internal Medicine (2014)

Source Citation Halperin JL, Hankey GJ, Wojdyla DM, et al; ROCKET AF Steering Committee and Investigators. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Circulation. 2014;130:138-46. 24895454
[18F]FLT–PET Imaging Does Not Always “Light Up” Proliferating Tumor Cells
Authors: Cathy C. Zhang, Zhengming Yan, Wenlin Li, Kyle Kuszpit, Cory L. Painter, Qin Zhang, Patrick B. Lappin, Tim Nichols, Maruja E. Lira, Timothy Affolter, Neeta R. Fahey, Carleen Cullinane, Mary Spilker, Kenneth Zasadny, Peter O'Brien, Dana Buckman, Anthony Wong, James G. Christensen
Journal: Clinical Cancer Research (2011)

[(18)F]FLT (3'-Fluoro-3' deoxythymidine)-PET imaging was proposed as a tool for measuring in vivo tumor cell proliferation. The aim of this article was to validate the use of [(18)F]FLT-PET imaging for measuring xenograft proliferation and subsequent monitoring of targeted therapy.In exponentially growing xenografts, factors that could impact the outcome of [(18)F]FLT-PET imaging, such as nucleoside transporters, thymidine kinase 1, the relative contribution of DNA salvage pathway, and the ratio of FLT to thymidine, were evaluated. The [(18)F]FLT tracer avidity was compared with other proliferation markers.In a panel of proliferating xenografts, [(18)F]FLT or [(3)H]thymidine tracer avidity failed to reflect the tumor growth rate across different tumor types, despite the high expressions of Ki67 and TK1. When FLT was injected at the same dose level as used in the preclinical [(18)F]FLT-PET imaging, the plasma exposure ratio of FLT to thymidine was approximately 1:200. Thymidine levels in different tumor types seemed to be variable and exhibited an inverse relationship with the FLT tracer avidity. In contrast, high-dose administration of bromdeoxyuridine (BrdUrd; 50 mg/kg) yielded a plasma exposure of more than 4-fold higher than thymidine and leads to a strong correlation between the BrdUrd uptake and the tumor proliferation rate. In FLT tracer-avid models, [(18)F]FLT-PET imaging as a surrogate biomarker predicted the therapeutic response of CDK4/6 inhibitor PD-0332991.Tumor thymidine level is one of the factors that impact the correlation between [(18)F]FLT uptake and tumor cell proliferation. With careful validation, [(18)F]FLT-PET imaging can be used to monitor antiproliferative therapies in tracer-avid malignancies.
Hypoxemia in Inferior Pulmonary Veins in Supine Position Is Dependent on Obesity
Authors: Teiichi Yamane, Taro Date, Michifumi Tokuda, Yasuko Aramaki, Keiichi Inada, Seiichiro Matsuo, Kenri Shibayama, Satoru Miyanaga, Hidekazu Miyazaki, Ken-ichi Sugimoto, Michihiro Yoshimura
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Although arterial oxygen concentration decreases in obese subjects, the mechanism for this remains to be determined.The blood gas level in each pulmonary vein (PV) was measured in supine subjects with diverse body mass index (BMI) values, to determine whether there was a regional insufficiency in gas exchange depending on the subject's BMI.Forty subjects with normal cardiopulmonary function who underwent a catheter ablation for atrial fibrillation were included. Before delivering any radiofrequency energy application, blood samples were obtained from each of the four PVs during physiologic breathing in a supine position to measure the PO2 and PCO2 values. Spirometry and ventilation/perfusion lung scintigraphy were also performed.The PO2 value was significantly higher in superior veins than inferior veins (91.8 +/- 13.5, 70.8 +/- 16.3, 92.2 +/- 11.1, and 73.6 +/- 13.7 mm Hg, in the left superior, left inferior, right superior, and right inferior PV, respectively). There was a significant inverse relationship between the PO2 and PCO2 values. Neither the spirometry nor lung scintigraphy could detect any remarkable findings corresponding to the low PO2 values. Among the various clinical characteristics, only the BMI was significantly associated with the decreased PO2 value in the inferior veins.Hypoxia in obese subjects in a supine position is thus considered to be primarily caused by insufficient gas exchange in the regions of lung linked to the inferior PVs. The inverse relationship between the BMI and PO2 value in the inferior PVs suggests a possible subclinical manifestation of obesity-related respiratory insufficiency.
Unattended continuous positive airway pressure titration. Clinical relevance and cardiorespiratory hazards of the method.
Authors: J Juhász, J Schillen, A Urbigkeit, T Ploch, T Penzel, J H Peter
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The high cost of in-laboratory sleep studies and the insufficiency of available nights in most sleep laboratories has prompted clinical trials in an attempt to find an effective and safe method for continuous positive airway pressure (CPAP) titration in the unsupervised home environment. Earlier publications focused on the effectiveness of this new method but did not indicate the potential hazard and the selection criteria of patients. We accomplished a prospective study to evaluate a machine-controlled CPAP titration method in an unselected group of 21 patients with obstructive sleep apnea (OSA) requiring CPAP therapy. Unattended CPAP titrations were completed in the sleep laboratory, followed by conventional CPAP titration night. The CPAP levels assessed through automatic titrations showed strong agreement with those from the control nights. Fifteen patients had no pathologic cardiorespiratory events during machine-controlled titration. Undesirable cardiorespiratory complications developed in six patients with underlying cardiorespiratory disorder. Two patients had to stop the procedure. Two patients needed a reset of the actual pressure to baseline because of central apneas and one patient because of high-grade arrhythmia. The machine-controlled CPAP titration enabled reliable assessment of an effective pressure and appeared to be safe in selected patients with OSA. However, because the method caused significant adverse effects in some patients, we recommend that unattended CPAP titration not be attempted in patients with underlying cardiorespiratory disease.
Iniparib plus Chemotherapy in Metastatic Triple-Negative Breast Cancer
Authors: Joyce O'Shaughnessy, Cynthia Osborne, John E. Pippen, Mark Yoffe, Debra Patt, Christine Rocha, Ingrid Chou Koo, Barry M. Sherman, Charles Bradley
Journal: New England Journal of Medicine (2011)

Triple-negative breast cancers have inherent defects in DNA repair, making this cancer a rational target for therapy based on poly(adenosine diphosphate–ribose) polymerase (PARP) inhibition.
Prospective Study of the Correlation Between Postoperative Computed Tomography Scan and Primary Surgeon Assessment in Patients With Advanced Ovarian, Tubal, and Peritoneal Carcinoma Reported to Have Undergone Primary Surgical Cytoreduction to Residual Disease 1 cm or Less
Authors: Dennis S. Chi, Pedro T. Ramirez, Jerrold B. Teitcher, Svetlana Mironov, Debra M. Sarasohn, Revathy B. Iyer, Eric L. Eisenhauer, Nadeem R. Abu-Rustum, Yukio Sonoda, Douglas A. Levine, Carol L. Brown, Carol Aghajanian, David M. Gershenson, William J. Hoskins, Hedvig Hricak, Richard R. Barakat
Journal: Journal of Clinical Oncology (2007)

Purpose To compare surgeons' operative assessments of residual disease (RD) to those identified on postoperative computed tomography (CT) scans in patients with advanced ovarian carcinoma reported to have undergone optimal primary cytoreduction. Patients and Methods All patients at one of two institutions, who were scheduled to have primary surgery for presumed advanced ovarian cancer, were asked to consent to a postoperative CT scan if cytoreduction to ≤ 1 cm RD was reported. CT scan findings were graded using a qualitative analysis scale from 1 (normal) to 5 (definitely malignant). Results From January 2001 to September 2006, 285 patients were enrolled. A total of 78 patients met eligibility criteria and had postoperative CT scans. In 41 cases (52%), postoperative scan findings correlated with the surgical report of no RD more than 1 cm, and in seven cases (9%), the CT findings were indeterminate. In 10 cases (13%), more than 1 cm RD was noted by the radiologist as probably malignant, and in 20 cases (26%), definitely malignant. In these 30 cases, the radiologically reported median largest residual mass was 1.9 cm (range, 1.1 to 5.1), with RD more than 1 cm reported most commonly in the right upper quadrant (15 patients [50%]) and central abdomen (nine patients [30%]). Conclusion There was only a 52% correlation between surgeons' assessments and postoperative CT scan evaluations of RD in patients reported to have undergone optimal cytoreduction. Further study is required to determine whether this lack of correlation is due to rapid interval tumor regrowth, RD underestimated by the surgeons, and/or overestimated by the radiologists; and to determine the clinical implications of these discrepancies.
Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis
Authors: A. C. Ford, N. C. Suares
Journal: Gut (2011)

There has been no definitive systematic review and meta-analysis to date examining the effect of laxatives and pharmacological therapies in chronic idiopathic constipation (CIC).To assess efficacy of these therapies systematically in CIC.Systematic review and meta-analysis of randomised controlled trials (RCTs).MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (up to September 2010).Placebo-controlled trials of laxatives or pharmacological therapies in adult CIC patients were eligible. Minimum duration of therapy was 1 week. Trials had to report either a dichotomous assessment of overall response to therapy at last point of follow-up in the trial, or mean number of stools per week during therapy.Symptom data were pooled using a random effects model. Effect of laxatives or pharmacological therapies compared to placebo was reported as RR of failure to respond to therapy, or a weighted mean difference (WMD) in mean number of stools per week, with 95% CIs.Twenty-one eligible RCTs were identified. Laxatives (seven RCTs, 1411 patients, RR=0.52; 95% CI 0.46 to 0.60), prucalopride (seven trials, 2639 patients, RR=0.82; 95% CI 0.76 to 0.88), lubiprostone (three RCTs, 610 patients, RR=0.67; 95% CI 0.56 to 0.80), and linaclotide (three trials, 1582 patients, RR=0.84; 95% CI 0.80 to 0.87) were all superior to placebo in terms of a reduction in risk of failure with therapy. Treatment effect remained similar when only RCTs at low risk of bias were included in the analysis. Diarrhoea was significantly more common with all therapies.Only two RCTs were conducted in primary care, and total adverse events data for laxatives and linaclotide were sparse.Laxatives, prucalopride, lubiprostone and linaclotide are all more effective than placebo for the treatment of CIC.
Decreased inward rectification of Kir2.1 channels is a novel mechanism underlying the short QT syndrome
Authors: S. Casini, A. V. Postma
Journal: Cardiovascular Research (2012)

This editorial refers to ‘A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents’ by T. Hattori et al ., pp. 666–673, this issue. 

The short QT syndrome (SQTS) is a recently recognized cardiac channelopathy characterized by a shortened QT interval in the electrocardiogram (ECG). It is associated with a high incidence of atrial fibrillation (AF), syncope, and sudden death in the absence of structural cardiac abnormalities. Gussak et al. first described the syndrome in 2000 within the context of an isolated case of sudden cardiac death in a young female and the presence of early-onset AF in a separate family.1 Cardiac workup demonstrated a structurally normal heart in affected individuals, but a remarkable short QTc interval on the ECG ranging between 248 and 300 ms. These first studies led to the emerging recognition of SQTS as a distinct clinical entity and were followed by reports on similar cases (reviewed in Gollob et al. 2). The diagnosis of SQTS is somewhat complicated as QT intervals overlap between affected cases and apparently healthy subjects. The presence of a short QT interval by itself is not always predictive of an increased arrhythmic risk and therefore should not invariably lead to a diagnosis of SQTS.3 To address this, Gollob et al. 2 recently proposed a set of formal diagnostic criteria …
STUDIES ON BARTONELLA MURIS ANEMIA
Authors: Marta Sandberg, David Perla, J. Marmorston-Gottesman
Journal: The Journal of Experimental Medicine (1933)

1. The blood chemistry of normal adult rats and of splenectomized adult rats suffering with Bartonella muris anemia has been studied. 2. Non-protein nitrogen rises with the increase in severity of the anemia. Total serum proteins, serum albumin and serum globulin decrease slightly. Uric acid remains unchanged. 3. Serum chloride concentration remains unchanged, but the concentration of chlorides in the blood increases. 4. An acidosis as estimated by the carbon dioxide-combining capacity of the blood is observed at the height of the infection. 5. The blood sugar decreases and the liver glycogen is depleted in rats with a hemoglobin content of the blood of 10 per cent. 6. Total fats and fatty acids are increased at the height of the anemia. Total cholesterol, the lipoid phosphorus and lecithin are diminished in amount. 7. These changes result from the infection or the anemia. Splenectomy itself plays no part in the changes observed in the chemical constituents of the blood in Bartonella muris anemia of adult albino rats.
Efficacy and Safety of Low-Carbohydrate Diets
Authors: Dena M. Bravata, Lisa Sanders, Jane Huang, Harlan M. Krumholz, Christopher D. Gardner, Dawn M. Bravata
Journal: JAMA (2003)

ion Methods One author reviewed the 2609 titles and abstracts identified by the combined Table 1. Results of Literature Search Description No. of Articles MEDLINE key word searches Search 1, diet* 192 654 Search 2, low carbohydrate* 567 Search 3, high fat* 5782 Search 4, high protein* 3473 Search 5, ketogenic 706 Search 6, isocaloric 2808 Search 7, hypocaloric 706 Search 8, protein sparing 2014 Search 9, carbohydrate restricted 6362 Combine searches: 1 AND (2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9) LIMIT by (participant types: adults and humans) then discard duplicates 2609 Exclusion criteria Articles included only pediatric participants (no adults) 21 Diet duration 4 d 95 Did not report sufficient data to be able to calculate grams per day of carbohydrates per diet 72 Did not report sufficient data to be able to calculate calories per day per diet 97 Participants hospitalized or confined to a research center 146 Diets that provided 500 kcal/d 26
MicroRNA-sensitive Oncolytic Measles Viruses for Cancer-specific Vector Tropism
Authors: Mathias F Leber, Sascha Bossow, Vincent HJ Leonard, Karim Zaoui, Christian Grossardt, Marie Frenzke, Tanner Miest, Stefanie Sawall, Roberto Cattaneo, Christof von Kalle, Guy Ungerechts
Journal: Molecular Therapy (2011)

Oncolytic measles viruses (MV) derived from the live attenuated vaccine strain have been engineered for increased tumor-cell specificity, and are currently under investigation in clinical trials including a phase I study for glioblastoma multiforme (GBM). Recent preclinical studies have shown that the cellular tropism of several viruses can be controlled by inserting microRNA-target sequences into their genomes, thereby inhibiting spread in tissues expressing cognate microRNAs. Since neuron-specific microRNA-7 is downregulated in gliomas but highly expressed in normal brain tissue, we engineered a microRNA-sensitive virus containing target sites for microRNA-7 in the 3'-untranslated region of the viral fusion gene. In presence of microRNA-7 this modification inhibits translation of envelope proteins, restricts viral spread, and progeny production. Even though highly attenuated in presence of microRNA-7, this virus retained full efficacy against glioblastoma xenografts. Furthermore, microRNA-mediated inhibition protected genetically modified mice susceptible to MV infection from a potentially lethal intracerebral challenge. Importantly, endogenous microRNA-7 expression in primary human brain resections tightly restricted replication and spread of microRNA-sensitive virus. This is proof-of-concept that tropism restriction by tissue-specific microRNAs can be adapted to oncolytic MV to regulate viral replication and gene expression to maximize tumor specificity without compromising oncolytic efficacy.
High-Resolution Imaging of Intravascular Atherogenic Inflammation in Live Mice
Authors: Raphael Chèvre, Jose María González-Granado, Remco T.A. Megens, Vinatha Sreeramkumar, Carlos Silvestre-Roig, Pedro Molina-Sánchez, Christian Weber, Oliver Soehnlein, Andrés Hidalgo, Vicente Andrés
Journal: Circulation Research (2013)

The inflammatory processes that initiate and propagate atherosclerosis remain poorly understood, largely because defining the intravascular behavior of immune cells has been technically challenging. Respiratory and pulsatile movements have hampered in vivo visualization of leukocyte accumulation in athero-prone arteries at resolutions achieved in other tissues. To establish and to validate a method that allows high-resolution imaging of inflammatory leukocytes and platelets within the carotid artery of atherosusceptible mice in vivo. We have devised a procedure to stabilize the mouse carotid artery mechanically without altering blood dynamics, which dramatically enhances temporal and spatial resolutions using high-speed intravital microscopy in multiple channels of fluorescence. By applying this methodology at different stages of disease progression in atherosusceptible mice, we first validated our approach by assessing the recruitment kinetics of various leukocyte subsets and platelets in athero-prone segments of the carotid artery. The high temporal and spatial resolution allowed the dissection of both the dynamic polarization of and the formation of subcellular domains within adhered leukocytes. We further demonstrate that the secondary capture of activated platelets on the plaque is predominantly mediated by neutrophils. Finally, we couple this procedure with triggered 2-photon microscopy to visualize the 3-dimensional movement of leukocytes in intimate contact with the arterial lumen. The improved imaging of diseased arteries at subcellular resolution presented here should help resolve many outstanding questions in atherosclerosis and other arterial disorders.
Wheat retrotransposon families identified by reverse transcriptase domain analysis
Authors: Y. Matsuoka, K. Tsunewaki
Journal: Molecular Biology and Evolution (1996)

Variations in the reverse transcriptase domain were analyzed to clarify the family structure of retrotransposons in the wheat genome. Seven families were identified on the basis of the nucleotide sequence similarities of the domain. These families are common to the genomes of ancestral diploid species of wheat, evidence that they were established prior to diploid speciation, and their presence in barley and rice was suggested. Recent activity of some of the families was inferred in wheat on the basis of data that included synonymous and nonsynonymous nucleotide substitution rates in the reverse transcriptase domain.