bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization and spending trends for antiretroviral medications in the U.S. Medicaid program from 1991 to 2005
Authors: Jing Yonghua , Klein Patricia , Kelton Christina ML , Li Xing , Guo Jeff J 
Published: October 2007

Abstract

Background
HIV/AIDS incidence and mortality rates have decreased in the U.S. since 1996. Accompanying the longer life spans of those diagnosed with the disease, however, is a tremendous rise in expenditures on medication. The objective of this study is to describe the trends in utilization of, spending on, and market shares of antiretroviral medications in the U.S. Medicaid Program. Antiretroviral drugs include nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and fusion inhibitors (FIs).

Methods
Utilization and payment data from 1991 to 2005 are provided by the Centers for Medicare & Medicaid Services. Descriptive summary analyses were used to assess quarterly prescription numbers and amounts of payment.

Results
The total number of prescriptions for antiretrovirals increased from 168,914 in 1991 to 2.0 million in 1998, and 3.0 million in 2005, a 16.7-fold increase over 15 years. The number of prescriptions for NRTIs reached 1.6 million in 2005. Prescriptions for PIs increased from 114 in 1995 to 932,176 in 2005, while the number of prescriptions for NNRTIs increased from 1,339 in 1996 to 401,272 in 2005. The total payment for antiretroviral drugs in the U.S. Medicaid Program increased from US$ 30.6 million in 1991 to US$ 1.6 billion in 2005, a 49.8-fold increase. In 2005, NRTIs as a class had the highest payment market share. These drugs alone accounted for US$ 787.9 million in Medicaid spending (50.8 percent of spending on antiretrovirals). Payment per prescription for each drug, with the exception of Agenerase®, increased, at least somewhat, over time. The relatively expensive drugs in 2005 included Trizivir® ($1040) and Combivir® ($640), as well as Reyataz® ($750), Lexiva® ($700), Sustiva® ($420), Viramune® ($370), and Fuzeon® ($1914).

Conclusion
The tremendous growth in antiretroviral spending is due primarily to rising utilization, secondarily to the entry of newer, more expensive antiretrovirals, and, finally, in part to rising per-prescription cost of existing medications.
Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development
Authors: Sheng Hui , Zhang Ge , Cheung Wing , Chan Chun , Wang Yi , Lee Kwong , Wang Hong , Leung Kwok , Qin Ling 
Published: October 2007

Abstract

Background
Increased bone marrow lipid deposition in steroid-associated osteonecrosis (ON) implies that abnormalities in fat metabolism play an important role in ON development. The increase in lipid deposition might be explained by elevated adipogenesis of marrow mesenchymal stem cells (MSCs). However, it remains unclear whether there is a close association between elevated adipogenesis and steroid-associated ON development.

Objective
The present study was designed to test the hypothesis that there might be a close association between elevated adipogenesis and steroid-associated ON development.

Methods
ON rabbit model was induced based on our established protocol. Dynamic-MRI was employed for local intra-osseous perfusion evaluation in bilateral femora. Two weeks after induction, bone marrow was harvested for evaluating the ability of adipogenic differentiation of marrow MSCs at both cellular and mRNA level involving adipogenesis-related gene peroxisome proliferator-activated receptor gamma2 (PPARγ2). The bilateral femora were dissected for examining marrow lipid deposition by quantifying fat cell number, fat cell size, lipid deposition area and ON lesions. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON occurrence, the rabbits were divided into ON+ (with at least one ON lesion) group and ON- (without ON lesion) group. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON extension, the ON+ rabbits were further divided into sub-single-lesion group (SON group: with one ON lesion) and sub-multiple-lesion group (MON group: with more than one ON lesion).

Results
Local intra-osseous perfusion index was found lower in either ON+ or MON group when compared to either ON- or SON group, whereas the marrow fat cells number and area were much larger in either ON+ or MON group as compared with ON- and SON group. The adipogenic differentiation ability of MSCs and PPARγ2 expression in either ON+ or MON group were elevated significantly as compared with either ON- or SON group.

Conclusion
These findings support our hypothesis that there is a close association between elevated adipogenesis and steroid-associated osteonecrosis development.
Revealing cell cycle control by combining model-based detection of periodic expression with novel cis-regulatory descriptors
Authors: Andersson Claes R , Hvidsten Torgeir R , Isaksson Anders , Gustafsson Mats G , Komorowski Jan 
Published: October 2007

Abstract

Background
We address the issue of explaining the presence or absence of phase-specific transcription in budding yeast cultures under different conditions. To this end we use a model-based detector of gene expression periodicity to divide genes into classes depending on their behavior in experiments using different synchronization methods. While computational inference of gene regulatory circuits typically relies on expression similarity (clustering) in order to find classes of potentially co-regulated genes, this method instead takes advantage of known time profile signatures related to the studied process.

Results
We explain the regulatory mechanisms of the inferred periodic classes with cis-regulatory descriptors that combine upstream sequence motifs with experimentally determined binding of transcription factors. By systematic statistical analysis we show that periodic classes are best explained by combinations of descriptors rather than single descriptors, and that different combinations correspond to periodic expression in different classes. We also find evidence for additive regulation in that the combinations of cis-regulatory descriptors associated with genes periodically expressed in fewer conditions are frequently subsets of combinations associated with genes periodically expression in more conditions. Finally, we demonstrate that our approach retrieves combinations that are more specific towards known cell-cycle related regulators than the frequently used clustering approach.

Conclusion
The results illustrate how a model-based approach to expression analysis may be particularly well suited to detect biologically relevant mechanisms. Our new approach makes it possible to provide more refined hypotheses about regulatory mechanisms of the cell cycle and it can easily be adjusted to reveal regulation of other, non-periodic, cellular processes.
Extracellular survivin up-regulates adhesion molecules on the surface of leukocytes changing their reactivity pattern
Authors: Mera Simona , Magnusson Mattias , Tarkowski Andrej , Bokarewa Maria 
Published: October 2007

AbstractRheumatoid arthritis (RA) is an autoimmune disease with joints as a principal target of inflammation. We have shown recently that the extracellular expression of the antiapoptotic protein survivin is associated with a destructive course of RA. Here, we address the potential impact of extracellular survivin on peripheral blood leukocytes (PBL). The binding of survivin to the surface of human PBL as well as the expression of adhesion molecules were assessed by FACS. The expression of adhesion molecules on leukocytes as a function of circulating survivin was analyzed in blood of 24 patients with RA and compared with eight healthy individuals. We show that extracellular survivin expresses immunomodulatory properties. It binds to the surface of the majority of granulocytes and a significant part of lymphocytes and monocytes inducing the activation of α-chains of β-integrins and their ligand ICAM-1. Survivin-induced expression of α-chains of β2-integrins is regulated by p38 MAPK and PI-3K but not by the NF-κB signaling pathway. Clinical relevance of our findings is supported by the in vivo association of high circulating survivin levels with an increased expression of CD11c on monocytes and granulocytes in RA patients. The results of our study demonstrate that extracellular survivin affects the phenotype of leukocytes having a possible impact on homing of inflammatory cells during arthritis.
17β-Estradiol: a novel hormone for improving immune and cardiovascular responses following trauma-hemorrhage
Authors: Choudhry Mashkoor A , Chaudry Irshad H 
Published: October 2007

Abstract17β-Estradiol (i.e., estrogen or E2) is a female sex steroid, which plays an essential role in female reproductive physiology. However, several lines of evidence indicate that in addition to its role in reproductive physiology, E2 is critical for maintaining many other organ functions in stress conditions. These include immune, cardiovascular, and neuronal functions, as well as regulation of skin, bone, and lipid metabolism. Studies have examined the role of E2 as an adjunct in post-trauma responses, and this article will review whether E2 as an adjunct to fluid resuscitation following trauma-hemorrhage plays any role in improving/restoring immune and cardiovascular functions.
HMGB1 preconditioning: therapeutic application for a danger signalõ
Authors: Klune J R , Billiar T R , Tsung A 
Published: October 2007

AbstractHigh mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as a late mediator of lethality in sepsis and as an early mediator of inflammation following injury. In contrast to the proinflammatory role of HMGB1, recent evidence suggests beneficial applications of HMGB1 in injury states. One such application is the use of HMGB1 as a preconditioning stimulus. Preconditioning is a phenomenon whereby a low level of stressful stimuli confers protection against subsequent injury. Preconditioning has been demonstrated in multiple species, can be induced by various stimuli, and is applicable in different organ systems. Only with the recent introduction of the concept of endogenous molecules, such as HMGB1, as signals and mediators for inflammation during injury states has the use of endogenous molecules been investigated for this use. This review will focus on the use of endogenous molecules, specifically HMGB1, as a preconditioning stimulus and its mechanism of protection, as well as other protective applications for HMGB1.
Sperm release strategies in marine broadcast spawners: the costs of releasing sperm quickly
Authors: Marshall Dustin J. , Bolton Toby F. 
Published: October 2007

SUMMARY
When under competition for fertilisations, males are thought to increase their reproductive success by releasing as many sperm as possible into the reproductive arena and in many species, this prediction holds. For marine invertebrates, which utilise the ancestral strategy of broadcast spawning eggs and sperm, however, it appears that males tend to release their sperm more slowly than females release their eggs. Marine invertebrate eggs typically have a relatively slow permanent block to polyspermy (whereby eggs become impermeable to further sperm attachment), and for several minutes after fertilisation, sperm can continue to attach to a fertilised egg. We hypothesised that releasing sperm slowly minimises the `wastage' of sperm on already fertilised eggs. We simulated different sperm release rates in a flume using the broadcast spawning polychaete, Galeolaria caespitosa. Sperm release rates strongly affected overall fertilisation success: higher release rates resulted in lower fertilisation rates. Laboratory studies confirmed that the `permanent' block to polyspermy in G. caespitosa took less than a minute to form but this lag was sufficient to result in some sperm wastage. Thus upstream, fertilised eggs that have not formed a permanent block to polyspermy can remove sperm from the pool that would otherwise fertilise downstream sibling eggs. We suggest that while electrical blocks to polyspermy evolved in response to excess sperm, permanent blocks to polyspermy could have evolved in response to sperm limitation (insufficient sperm).
When does a notch behave like a crack?
Authors: Dini D , Hills D A 
Published: October 2007

The characteristic asymptotic fields at the tip of sharp, semi-infinite cracks and notches are first compared with corresponding features present in selected finite bodies (edge cracks and notches). This gives an explicit view of the gradual divergence of the semi-infinite and finite problem solutions as the observation point becomes remote from the tip. Hence, upper bounds for the local plastic zone to be characterized by the singular field are known. Asymptotic solutions for semi-infinite rounded features are introduced, whose remote fields may be matched to the sharp singular fields through the medium of the corresponding generalized stress intensity factor. Thus the semi-infinite sharp and rounded problems converge remotely but diverge as the apex of the feature is approached. This comparison sets a lower bound for loads at which the outer boundary of the plastic zone is characterized by the singular field. Thus, the range of loads for the plastic zones to be controlled by the singular solutions are derived. We then proceed to compare critically the nature of the semi-infinite sharp notch and semi-infinite crack states of stress, defining the circumstances in which these are alike. All these elements considered together enable the closeness of various notch plastic zones to that of the classical semi-infinite crack to be gauged.
Effect of inlet port on the flow in the cylinder of an internal combustion engine
Authors: Yasar A , Sahin B , Akilli H , Aydin K 
Published: October 2007

In this study, the characteristics of flow emerging from the inlet of the intake port in the cylinder were investigated experimentally. A particle image velocimetry (PIV) technique was used to measure the velocity distribution in order to observe and analyse the flow behaviour. High-image-density PIV provided acquisition of patterns of instantaneous and averaged vorticity and velocity, revealing the detail of the flow characteristics in the cylinder cavity. With this measuring technique, it is possible to study the effect of intake valve geometry on the flow behaviours. The results showed that the flow structure changed substantially along the cylinder stroke due to the geometry of the intake valve port.
Differentiation between ‘good’, ‘borderline’, and ‘poor’ ASTM lubricant standards by ring zone sampling and multivariate data analysis
Authors: Aruna M A , G Datoo A N , Fox M F 
Published: October 2007

The relative degradation of lubricant formulations corresponding to ASTM sequence IIIF and VG, ‘good’, ‘borderline’, and ‘poor’ test lubricants was investigated by piston ring zone sampling from an operating petrol engine over 25 hour test runs. Chemical/physical analyses of the lubricant samples for each formulation gave a data base that was examined by several multivariate techniques. Very clear separation is obtained between the ‘good’, ‘borderline’, and ‘poor’ lubricant formulations. Further analyses of base oil and additive pack contributions to the data base show that the ‘good/pass’ lubricant formulation maintains a close cohesive grouping of physical and chemical properties throughout the test. The ‘poor/fail’ lubricant formulation properties move towards the ‘good/pass’ formulation as the test proceeds. The ‘borderline’ lubricant formulation loses additive pack effectiveness after ∼ 60 per cent of the test duration, thereafter giving erratic database result ‘outliers’. Ring zone sampling of lubricant formulations, their chemical/physical analyses together with chemometrics is an effective, rapid, and cost effective method for separating the ASTM sequence III and V performance levels of ‘good’, ‘borderline’, and ‘poor’ lubricant formulations.
Cancer incidence and causes of death among total hip replacement patients: A review based on Nordic cohorts with a special emphasis on metal-on-metal bearings
Authors: Visuri TI , Pukkala E , Pulkkinen P , Paavolainen P 
Published: October 2007

All patients with total hip arthroplasty (THA) are exposed to soluble or particulate forms of Co and Cr. Adverse effects of these wear products are not known. Data from Nordic registries is used to estimate adverse effects on a large scale, based mostly on metal-on-polyethylene bearings. Cancer incidence was in line with the general population when the patients were operated on for all indications and significantly decreased when the indication was primary osteoarthritis. Stomach cancer and colorectal cancers were significantly reduced and prostate cancer and skin melanoma significantly increased. There was no significant excess of cancer in target organs, i.e. liver, kidney, or haematopoietic cancers. THA patients had reduced mortality and extended life expectancy compared with standard Nordic populations. All-site cancer incidence of the first-generation metal-on-metal McKee-Farrar patients operated on for primary osteoarthritis was in line with the general population after follow-up for up to 28 years. General mortality of these patients was also reduced and they also had an extended life expectancy. Temporary increases in haematopoietic cancers at different follow-up periods were seen in some cohorts. This malignancy deserves a special record linkage monitoring while large numbers of young patients are provided with the second generation of metal-on-metal prostheses.
Biological effects of clinically relevant wear particles from metal-on-metal hip prostheses
Authors: Brown C , Fisher J , Ingham E 
Published: October 2007

The problems of osteolysis and late aseptic loosening associated with ultra-high molecular weight polyethylene (UHMWPE) particles has lead to a renewed interest in metal-on-metal prostheses. Wear particles generated by modern Co-Cr-on-Co-Cr prostheses are nanometre in size (range: 10-120 nm; mean: about 40 nm), an order of magnitude smaller than the size of UHMWPE known to be critical for activation of osteolytic cytokines by macrophages. Co-Cr wear particles will induce osteolytic cytokine production by human macrophages, but only at high volumetric concentrations. Unlike UHMWPE, Co-Cr particles are not inert. Co-Cr particles have the potential to release metal ions; they may be toxic to cells, induce deoxyribonucleic acid damage or cause host hypersensitivity. The nanometre size range of Co-Cr wear particles means that they may be disseminated widely in the body. The potential for metal-on-metal bearings to induce adverse effects clinically will be dependent upon the rate of wear. What constitutes a safe wear rate for modern metal-on-metal bearings is unknown. However, the wear of metal-on-metal prostheses is critically dependent upon the design and, in particular, the carbon content of the alloy, the radial clearance, and the head diameter. Thus, the potential for adverse biological reactions associated with metal-on-metal bearings can be reduced by selection of appropriately designed implants.
Hip resurfacing arthroplasty: The evolution of contemporary designs
Authors: Grigoris P , Roberts P , Panousis K , Jin Z 
Published: October 2007

Metal-on-metal hip resurfacing is considered by many as the most significant recent development in hip arthroplasty. It preserves proximal femoral bone stock, optimizes stress transfer to the proximal femur, and offers inherent stability and optimal range of movement. The early results of hip resurfacing in the 1970s and 1980s were poor and the procedure was largely abandoned by the mid-1980s. The expectation that these prostheses would be easy to revise was not often fulfilled. The large diameter of the articulation combined with thin polyethylene cups or liners resulted in accelerated wear and the production of large volumes of biologically active particulate debris, leading to bone loss and implant loosening. Failure has been attributed to other factors, mainly avascular necrosis of the femoral head. However, this concern has not been confirmed by retrieval studies. The failure of early hip resurfacings was essentially a consequence of the use of inappropriate materials, poor implant design, inadequate instrumentation, and crude surgical technique. It was not an inherent problem with the procedure itself. The renaissance of metal-on-metal articulations for total hip arthroplasty enabled the introduction of new hip resurfacings and most of the major implant manufacturers have already introduced such systems. Early results are encouraging and complications commonly seen in the 1970s and 1980s, such as early implant loosening and femoral neck fracture, now appear to be rare. Whilst early results should be regarded with caution, modern metal-on-metal hip resurfacing potentially offers the ultimate bone preservation and restoration of function in appropriately selected young patients.
Metal-on-metal hip joint tribology
Authors: Dowson D , Jin Z-M 
Published: October 2007

The basic tribological features of metal-on-metal total hip replacements have been reviewed to facilitate an understanding of the engineering science underpinning the renaissance of these hard-on-hard joints. Metal-on-polymer hip replacements operate in the boundary lubrication regime, thus leading to the design guidance to reduce the femoral head diameter as much as is feasible to minimize frictional torque and volumetric wear. This explains why the gold-standard implant of this form from the past half-century had a diameter of only 22.225 mm (7/8 in). Metal-on-metal implants can operate in the mild mixed lubrication regime in which much of the applied load is supported by elastohydrodynamic films. Correct tribological design leads to remarkably low steady state wear rates. Promotion of the most effective elastohydrodynamic films calls for the largest possible head diameters and the smallest clearances that can reasonably be adopted, consistent with fine surface finishes, good sphericity and minimal structural elastic deformation of the cup on its foundations. This guidance, which is opposite in form to that developed for metal-on-polymer joints, is equally valid for solid (monolithic) metallic heads on metallic femoral stems and surface replacement femoral shells. Laboratory measurements of friction and wear in metal-on-metal joints have confirmed their potential to achieve a very mild form of mixed lubrication. The key lies in the generation of effective elastohydrodynamic lubricating films of adequate thickness compared with the composite roughness of the head and cup. The calculation of the film thickness is by no means easy, but the full procedure is outlined and the use of an empirical formula that displays good agreement with calculations based upon the full numerical solutions is explained. The representation of the lambda ratio, A, embracing both film thickness and composite roughness, is described.