bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development assistance for global tobacco control
Authors: Ross Hana , Stoklosa Michal 
Published: June 2011

BackgroundBy 2030, the tobacco epidemic will be responsible for over eight million deaths worldwide per year, with 80% of those deaths occurring in low-resource countries. Despite the magnitude of the problem, little is known about the funding for global tobacco control.MethodsTo estimate the amount of tobacco control funding, we created an integrated database based on information provided by tobacco control donors. We focus on resources available to low-income and middle-income countries provided as Development Assistance to Control Tobacco (DACT).ResultsGlobal DACT grew from US$1.2 million in 2000 to US$44.2 million in 2009, primarily due to contributions from private philanthropies. Average annual 2000–2009 funding amounted to about US$0.003 per adult (US$0.0003 per adult in 2000 and US$0.011 per adult in 2009). DACT has been supplemented by domestic public funding that reached US$0.009 per adult in 2008. 28% of emerging and developing countries received zero DACT and 15% of those countries reported no funding at all. Out of US$21.8 billion disbursed in 2007 for health-related development assistance, DACT represented only US$0.02 billion, or 0.09%.ConclusionsSince the funding for both infectious and non-communicable diseases in low-resourced countries is inadequate, the solution for global tobacco control is not to shift resources from other public health priorities, but rather to generate additional tobacco control funding. Several mechanisms to achieve this goal are proposed.
A VENDOR MANAGED TWO-ECHELON INVENTORY SYSTEM FOR AN INTEGRATED PRODUCTION PROCUREMENT CASE
Authors: SINGH ABHIJEET , KOUL SAROJ , AGRAWAL ANIL K. 
Published: June 2011

Joint economic lot size models for purchasers and vendors are more economical than when considering their inventory problems independently. It requires vendors to have a complete knowledge of their purchaser's demands. In such a situation, the vendor shall manage the supply with comparatively more inventory at its end. The operational cost can further decrease provided supply is in sub-batches and logistics cost does not increase substantially. However, determining the right size for these sub-batches becomes an issue. Sub-batches of varying size may cause planning and control problems, but supply in sub-batches of uniform size will not. In this paper, joint economic lot size models are presented for the two supply situations, namely staggered supply and uniform supply. Cases are employed that describe the inventory situation of a single vendor supplying an item to a manufacturer that is further processed before it is supplied to the end-user. Using illustrative examples, the comparative advantages of the uniform sub-batch supply over the staggered alternative are investigated. From the analysis, uniform supply models are found to be comparatively more beneficial and robust than the staggered sub-batch supply.
Immunotherapy for Prostate Cancer: Recent Advances, Lessons Learned, and Areas for Further Research
Authors: Gulley James L. , Drake Charles G. 
Published: June 2011

Abstract
A surge of interest in therapeutic cancer vaccines has arisen in the wake of recent clinical trials suggesting that such vaccines can result in statistically significant and clinically meaningful improvements in overall survival—with substantially limited side effects compared with chemotherapy—in patients with metastatic castration-resistant prostate cancer. One of these trials led to the registration of sipuleucel-T, the first therapeutic vaccine to be approved for cancer patients. In this review we highlight emerging patterns from clinical trials that suggest a need for more-appropriate patient populations (i.e., with lower tumor volume and less-aggressive disease) and endpoints (i.e., overall survival) for studies of immunotherapy alone, as well as biologically plausible explanations for these findings. We also explore the rationale for ongoing and planned studies combining therapeutic vaccines with other modalities. Finally, we attempt to put these findings into a practical clinical context and suggest fertile areas for future study. Although our discussion focuses on prostate cancer, the concepts we address most likely have broad applicability to immunotherapy for other cancers as well. Clin Cancer Res; 17(12); 3884–91. ©2011 AACR.
Targeting Continued Androgen Receptor Signaling in Prostate Cancer
Authors: Massard Christophe , Fizazi Karim 
Published: June 2011

Abstract
Prostate cancer is the most common cancer and the second leading cause of death from cancer in males in most Western countries. Prostate cancer has an exquisite sensitivity to androgen deprivation therapy and is the most endocrine-sensitive solid neoplasm, although advanced disease eventually progresses to castration-resistant prostate cancer (CRPC). Recent evidence has shown that cancer progression at the CRPC stage is often mediated by androgen receptor signaling, so that subsequent androgen receptor targeting may further contribute to disease control and, eventually, survival improvement. Abiraterone acetate, an androgen biosynthesis inhibitor, was tested in patients with CRPC pretreated with docetaxel in a phase III trial with demonstration of an overall survival benefit, confirming that CRPC remains hormone driven, even in advanced stages of the disease. Several novel agents also targeting androgen receptor signaling are currently being evaluated, including MDV3100 and orteronel (TAK-700). With the availability of newer endocrine treatments and also nonendocrine treatments (e.g., chemotherapy, immunotherapy, and bone-targeting agents), data supporting a more rational use of therapeutic agents are urgently required in patients with CRPC. It is likely that molecular characterization of prostate cancer will lead to the identification of different subsets of prostate cancer disease with a different natural history, sensitivity, and resistance to treatment; efforts to develop, validate, and implement predictive biomarkers in clinical trials and eventually in routine care should now be strongly supported. Clin Cancer Res; 17(12); 3876–83. ©2011 AACR.
Statin Use and Colorectal Cancer Risk According to Molecular Subtypes in Two Large Prospective Cohort Studies
Authors: Lee Jung Eun , Baba Yoshifumi , Ng Kimmie , Giovannucci Edward , Fuchs Charles S. , Ogino Shuji , Chan Andrew T. 
Published: June 2011

Abstract
Use of statins is hypothesized to reduce colorectal cancer risk but the evidence remains inconsistent. This may be partly explained by differential associations according to tumor location or molecular subtypes of colorectal cancer. We examined the association between statin use and colorectal cancer risk according to tumor location, KRAS mutation status, microsatellite instability (MSI) status, PTGS2 (COX-2) expression, or CpG island methylator phenotype (CIMP) status in two large prospective cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study. We applied Cox regression to a competing risks analysis. We identified 1,818 colorectal cancers during 1990 to 2006. Compared with nonusers, current statin use was not associated with colorectal cancer [relative risk (RR) = 0.99, 95% CI = 0.86–1.14] or colon cancer (RR = 1.10, 95% CI = 0.94–1.29) but was inversely associated with rectal cancer (RR = 0.59, 95% CI = 0.41–0.84, Pheterogeneity &lt; 0.001). When we examined the association within strata of KRAS mutation status, we found no association with KRAS-mutated cancers (RR = 1.20, 95% CI = 0.87–1.67) but did observe a possible inverse association among KRAS wild-type cancers (RR = 0.80, 95% CI = 0.60–1.06, Pheterogeneity = 0.06). The association did not substantially differ by PTGS2 expression, MSI status, or CIMP status. Current statin use was not associated with risk of overall colorectal cancer. The possibility that statin use may be associated with lower risk of rectal cancer or KRAS wild-type colorectal cancer requires further confirmation. Cancer Prev Res; 4(11); 1808–15. ©2011 AACR.
Cafestol, the Cholesterol-Raising Factor in Boiled Coffee, Suppresses Bile Acid Synthesis by Downregulation of Cholesterol 7α-Hydroxylase and Sterol 27-Hydroxylase in Rat Hepatocytes
Authors: Post Sabine M. , de Wit Elly C. M. , Princen. Hans M. G. 
Published: June 2011

Abstract
Consumption of boiled coffee raises serum cholesterol levels in humans. The diterpenes cafestol and kahweol in boiled coffee have been found to be responsible for the increase. To investigate the biochemical background of this effect, we studied the effects of cafestol and a mixture of cafestol/kahweol/isokahweol (48:47:5 w/w) on bile acid synthesis and cholesterol 7α-hydroxylase and sterol 27-hydroxylase in cultured rat hepatocytes.

Dose-dependent decreases of bile acid mass production and cholesterol 7α-hydroxylase and sterol 27-hydroxylase activity were found, showing a maximal reduction of −91%, −79%, and −49% respectively, at a concentration of 20 μg/mL cafestol. The decrease in 7α-hydroxylase and 27-hydroxylase activity paralleled well the suppression of the respective mRNAs, being −79% and −77%, and −49% and −46%, respectively, at 20 μg/mL cafestol. Run-on data showed a reduction in 7α-hydroxylase and 27-hydroxylase gene transcriptional activity after incubation with cafestol. The mixture of cafestol/kahweol/isokahweol was less potent in suppression of bile acid synthesis and cholesterol 7α-hydroxylase. Cafestol (20 μg/mL) had no effect on lithocholic acid 6β-hydroxylase mRNA, another enzyme involved in bile acid synthesis. LDL-receptor, HMG-CoA reductase, and HMG-CoA synthase mRNAs were significantly decreased by cafestol (−18%, −20%, and −43%, respectively).
We conclude that cafestol suppresses bile acid synthesis by downregulation of cholesterol 7α-hydroxylase and of, to a lesser extent, sterol 27-hydroxylase in cultured rat hepatocytes, whereas kahweol and isokahweol are less active. We suggest that suppression of bile acid synthesis may provide an explanation for the cholesterol-raising effect of cafestol in humans.
Prostaglandin F2-Like Compounds, F2-Isoprostanes, Are Present in Increased Amounts in Human Atherosclerotic Lesions
Authors: Gniwotta Christina , Morrow Jason D. , Roberts L. Jackson , Kühn Hartmut 
Published: June 2011

AbstractOxidative modification of LDL is believed to play a major role in atherogenesis. As major lipid peroxidation products oxygenated linoleic acid derivatives and oxysterols have been described in human atherosclerotic lesions. Here we report that human lesions contain isoprostanes as peroxidation products of arachidonic acid at a level of 27.1±21.2 pg/mg wet weight (n=10), which corresponds to 75.9±59.3 pg/mg dry weight. n contrast, human umbilical veins (n=10), which were used as nonatherosclerotic control vessels, contain much smaller amounts of isoprostanes (1.4±0.7 pg/mg wet weight, which corresponds to 11.7±6.2 pg/mg dry weight), and there are significant differences between the two types of vessels. As major products of linoleic acid oxidation, racemic hydroxy linoleate isomers were detected in the lesional ester lipids. In human lesions, the hydroxy linoleic acid/linoleic acid ratio was about 0.5%, a result indicating that 5 out of 1000 linoleate residues are present as hydroxylated derivatives. In umbilical veins, no hydroxy linoleic acid could be detected.These data show that human atherosclerotic lesions contain increased amounts of hydroxy linoleic acid isomers and isoprostanes when compared with nonatherosclerotic vessel wall and suggest a link between local lipid peroxidation and progression of atherosclerosis. For evaluation of the degree of lipid peroxidation, the determination of the hydroxy linoleic acid/linoleic acid ratio appears to be more suitable than the isoprostane content.
Transorbital Approach to the Middle Cerebral Artery of the Squirrel Monkey: A Technique for Experimental Cerebral Infarction Applicable to Ultrastructural Studies
Authors: HUDGINS W. R. , GARCIA JULIO H. 
Published: June 2011

An appropriate surgical technique for the production of cerebral infarction must fulfill, among others, the following criteria in order to be suitable for electron microscopy (EM) studies: (1) the method of arterial occlusion should yield a high percentage of infarcts with predictable average size; (2) there must be avoidance of surgical manipulation (i.e., retraction) of the cerebral tissues or exposure of the same to the atmosphere; and (3) the method for occluding the artery must be one that permits fixation by perfusion of the ischemic and nonischemic brain.
Modifications to a previously devised method for induction of cerebral infarct are herein described. This new surgical approach has made it possible to conduct detailed and sequential ultrastructural analysis of experimental cerebral infarctions.
Metabolic Changes in Response to Acute Cerebral Ischemia Following Bilateral Carotid Artery Ligation in Arteriosclerotic Versus Nonarteriosclerotic Rats
Authors: WEXLER BERNARD C. 
Published: June 2011

Both the left and right carotid arteries of arteriosclerotic and nonarteriosclerotic male and female rats were surgically ligated to induce a state of sudden and severe cerebral ischemia. The animals promptly developed signs of cerebral impairment and were sacrificed 2, 4, 6, 8, 10, 12, 24 and 48 hours later. A similar group of animals was subjected to the same regimen of carotid artery ligation except that a week's time elapsed between the ligation of each carotid artery.
As with unilateral carotid artery ligation, the bilaterally ligated animals manifested fatty metamorphosis of the liver, myocardial infarction and cerebral edema and necrosis, but the severity of these pathological changes was greatly exacerbated with the more severe ischemia.
Serum creatine phosphokinase, glutamic oxalacetic transaminase, triglycerides, free fatty acids, cholesterol, glucose and corticosterone all rose dramatically and in concert with the pathological changes, e.g., fatty liver. Animals with preexisting arterial disease exhibited much greater excursions of these pathophysiological parameters during the cerebral ischemia than did animals with normal arteries. The entire response pattern indicates that cerebral ischemia is a severe stress and is capable of eliciting highly characteristic pathophysiological changes which could be used to assess the severity or course of cerebral ischemia.
Anatomic and Hemodynamic Correlations in Carotid Artery Stenosis
Authors: DEWEESE JAMES A. , MAY ALLYN G. , LIPCHIK ELLIOT O. , ROB CHARLES G. 
Published: June 2011

Pressures were measured in the carotid arteries of 61 patients proximal and distal to atherosclerotic plaques which were carefully studied by angiography and anatomical dissection.
(1) An atherosclerotic plaque causing a constriction of less than 47% luminal diameter leaving a lumen greater than 3.0 mm in diameter never caused pressure drops of greater than 10 mm Hg. Stenoses of greater than 63% luminal diameter leaving lumens less than 1.0 mm in diameter always caused pressure drops.
(2) Atherosclerotic plaques producing defects which narrowed the lumen fell into a distinct pattern:
(a) Type 1 lesions—This basic lesion filled the bulb of the internal carotid artery near its origin, causing a 1 to 2 cm smooth elliptical encroachment on the lumen.
(b) Type 2 lesions—Short localized areas of thickening in addition to the basic lesion caused bar-like defects of the lumen at the origin of the internal carotid artery or near the distal end of the lesion.
(c) Type 3 lesions—Multiple bar-like defects were sometimes seen.
(d) Type 4 lesions—The areas of increased thickening of the lesion were sometimes quite narrow, producing diaphragm-like defects on the lumen.
Although theoretically these various types of stenoses should produce different hemodynamic changes, insufficient numbers of observations were made to corroborate these presumptions.
(3) Angiograms in general mimicked the gross appearance of the plaques and predicted the actual degree of stenosis produced but did not identify many diaphragm defects, ulcerations, or small thrombi.
Experimental Cerebral Infarction. II. Clinicopathological Model of Deep Cerebral Infarction
Authors: MOLINARI GAETANO F. 
Published: June 2011

Injection of silicone rubber cylinders into the internal carotid system permits selective occlusion of the proximal middle cerebral artery segment in the dog. Occlusions of this segment obstruct the mouths of the lenticulostriate arteries and result in deep cerebral hemisphere infarctions.
Surface vessels distal to the occluded segment remain patent and the cortex of the hemisphere is spared, due to efficient collateral circulation.
Hemorrhage in cortical infarctions may occur distal to the point of vascular occlusion and, therefore, may be a function of patent meningocerebral anastomoses.
Hemorrhage into a deep infarction, however, occurred only when there was clinical and pathological evidence of distal migration of the embolus after an initial proximal occlusion.
Infarctions of deep hemisphere structures were otherwise bland or "ischemic," probably because of the paucity of anastomoses among the penetrating blood vessels of the brain.
Temporary Occlusion of the Middle Cerebral Artery in the Monkey: Clinical and Pathological Observations
Authors: CROWELL ROBERT M. , OLSSON YNGVE , KLATZO IGOR , OMMAYA AYUB 
Published: June 2011

The right middle cerebral artery (MCA) was exposed in monkeys via a retro-orbital microsurgical approach. In 43 animals a temporary occlusive clip was placed on the MCA origin for one to 24 hours. In 20 animals, the origin of the MCA was permanently occluded.
Clinical evaluation of the monkeys one to three days postoperatively showed that one to two-hour clipping caused no or mild neurological deficits, four-hour clipping caused mild to moderate deficits, six to eight-hour clipping caused moderate to severe deficits, and 24-hour clipping produced severe deficits or death, a result equivalent to that produced by permanent occlusion. Gross and microscopical evaluation of the brains showed that one to two-hour clipping usually caused no or mild damage, four-hour clipping caused mild to moderate damage (often with capsular sparing), and six to eight-hour clipping and 24-hour clipping produced severe extensive infarction not different from that caused by permanent occlusion. Six to eight-hour clipping and 24-hour clipping were associated with a high incidence of hemorrhagic infarction, but other clipping times were not. The results suggest that reestablishment of flow by surgical means within a few hours after MCA occlusion in selected patients might result in significant restoration of neurological function. If flow renewal were done within about four hours, an increased incidence of hemorrhagic infarction might be avoided.
The Detection of Carotid Artery Obstruction: A Correlation With Arteriography
Authors: WISE GARY , BROCKENBROUGH E. C. , MARTY RAYMOND , GRIEP ROBERT 
Published: June 2011

Intravenous radioisotope arteriography, carotid compression ocular plethysmography, and supraorbital Doppler studies were more accurate than ophthalmodynamometry in the detection of the presence or absence of carotid artery obstruction in 35 patients. Abnormal results were present in patients with carotid obstruction who did not have a carotid bruit.
The isotope method provides information about relative blood flow through the two carotid arteries. Ocular plethysmography and supraorbital Doppler studies provide information about collateral circulatory pathways in patients with carotid obstruction.
Currently, they are most useful clinically in patients who are erroneously thought to have only intracranial vascular disease since abnormal results suggest an extracranial carotid lesion. These methods will not reveal abnormalities in patients with small, ulcerated carotid plaques which are a source of embolic material but which are not decreasing carotid blood pressure and flow.
Demonstration of Alpha and Beta Adrenergic Receptors in Canine Cerebral Vasculature
Authors: LOWE ROBERT F. , GILBOE DAVID D. 
Published: June 2011

The cerebral vascular effects of various adrenomimetic agents were examined in 12 isolated canine brains perfused with blood at constant flow. Changes in cerebral vascular resistance (CVR) and the magnitude of pressor or depressor responses observed following drug injection were examined.
The presence of alpha adrenergic receptors in this vascular bed is indicated by the increased CVR observed when phenylephrine, norepinephrine, and epinephrine were administered and by the reduced or reversed pressor actions of these compounds following treatment with the alpha adrenergic blocking drug phenoxybenzamine HCl.
The presence of beta adrenergic receptors in this vascular bed is indicated by the decreased CVR noted when isoproterenol was given and by the reduced depressor actions of this compound following treatment with the beta adrenergic blocking drug propranolol. Further evidence for the presence of beta adrenergic receptors is demonstrated by the vasomotor reversal to epinephrine which was observed following alpha suppression with phenoxybenzamine.
As catecholamine blood levels in intact dogs are low in comparison to those achieved in these studies, it appears doubtful that circulating catecholamines play an important physiological role in the regulation of CVR. Possible explanations are considered for the lower response of the cerebral vasculature to catecholamines when this response is compared to that observed in other vascular beds.
Current Status of the Epidemiology of Brain Infarction Associated with Occlusive Arterial Disease
Authors: KANNEL WILLIAM B. 
Published: June 2011

Although large gaps in our knowledge concerning the epidemiology of cerebrovascular disease are apparent, careful inspection of all existing data now makes it possible to see certain patterns emerging which suggest certain risk factors for stroke.
While the problem of differential diagnosis of the various categories of cerebrovascular disease presents a major obstacle to obtaining an undistorted picture of the epidemiological features of stroke from death certificate mortality data, the addition of evidence from prospective studies, including those in Framingham, Massachusetts, reveals that various types of arterial occlusion with cerebral infarction are by far the most prevalent type of stroke. Any specific origin of atherosclerosis remains obscure, as possible etiological candidates including dietary alterations in salt, fat and refined carbohydrate, sedentary living, excessive calories promoting obesity, the cigarette habit and even the mineral content of water in addition to marital status have all been incriminated. However uncertain the final answer is, certain precursors for atherosclerosis, such as hypertension, diabetes, and hyperlipidemia, are important. Of these, hypertension is clearly the most important contributor to stroke incidence. Certain combinations of items carry more risk than do the same items singly. For example, the risk of a brain infarction in diabetics with hypertension is probably about six times that of normal subjects. In persons under 50 at the time of measurement risk of cerebral infarction is possibly ten times higher in those with hypertension and elevated lipids than in those without either elevated. This compounding of risk has pathogenetic, preventive and public health implications. For purposes of stroke screening alone the most efficient and practical method would be to determine casual blood pressure, although it must be stated that as yet there is uncertainty concerning the change in the risk if such blood pressure is treated.