Miracle-dz/UniFAR-FTUs huggingface dataset:
Five-year Experience with Crossfire® Highly Cross-linked Polyethylene

Our purpose was to compare the clinical wear performance of highly cross-linked (Crossfire®) polyethylene with conventional (N2Vac™) polyethylene total hip bearings. We implanted 56 hips (47 patients) with Crossfire® acetabular bearing liners and compared their wear performance with 53 conventional polyethylene inserts. Wear and clinical data were collected retrospectively at a minimum 4-year and average 5-year followup. The linear femoral head penetration rate measured from plain radiographs was 0.055 mm/year ± 0.022 mm/year for the Crossfire® polyethylene and 0.138 mm/year ± 0.073 mm/year for the control, a reduction of 60% for the Crossfire® components. Calculated annual wear was 0.036 mm/year for the Crossfire® components and 0.131mm/year for the controls, a reduction of 72%. Radiographic review at most recent followup showed a reduction in erosive osteolytic lesions of the proximal femur for the Crossfire® components compared with controls, also suggesting a reduction in debris release for the Crossfire® components. Complications leading to revision were not seen in the Crossfire® or control groups. These clinical findings suggest that this particular highly cross-linked polyethylene can provide wear reduction and an alternate bearing surface for active patient populations. Level of Evidence: Therapeutic study, Level III (retrospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.
Immunogenicity and safety of hepatitis E vaccine in healthy hepatitis B surface antigen positive adults

A recombinant hepatitis E vaccine, Hecolin®, has been proven safe and effective in healthy adults. As hepatitis B surface antigen (HBsAg) positive individuals have a higher risk of poor prognosis after super-infection with hepatitis E virus (HEV), the safety and immunogenicity of Hecolin® in this population should be assessed. The present study is an extending analysis of data from a large randomized controlled clinical trial of Hecolin®. Healthy participants (n = 14,065) without current or previous evidence of chronic liver disease were randomized to receive Hecolin® or placebo (hepatitis B vaccine) and donated their blood samples before vaccination and subsequently over 31 mo. Most of the adverse events were mild and comparable between participants with and without baseline hepatitis B surface antigen (HBsAg). No vaccine-related serious adverse events were reported. Rates of serious adverse events in HBsAg (+) or HBsAg (-) participants were also comparable between both groups. Almost all participants in the Hecolin® group seroconverted to anti-HEV one month after full vaccination. The antibody response rates and levels were similar in HBsAg (+) and HBsAg (-) participants (98.38%, 19.32 Wu/mL vs. 98.69%, 19.00 Wu/mL). The two-year antibody dynamics of HBsAg (+) participants overlapped perfectly with those of HBsAg (-) participants. In conclusion, the safety and immunogenicity of Hecolin® for HBsAg (+) adults is very similar to that for the general population.
Design of PI+CI Reset Compensators for second order plants

Reset control is a special kind of nonlinear compensation that has been used to overcome limitations of linear time invariant, LTI, compensation. In recent works by the authors a new type of reset compensator, referred to as PI+CI, has been introduced. It basically consists of adding a Clegg integrator, CI, to a Proportional-Integral, PI, compensator, with the goal of improving the closed loop response by using the nonlinear characteristic of this element. It turns out that by resetting a percentage of the integral term of a PI compensator, a significant improvement can be obtained by considerably reducing overshoot percentage and settling time. This work is devoted to the extension of this previous work by deriving new tuning rules for second order plants with and without delay.
Myosin Isoform Expression and MAFbx mRNA Levels in Hibernating Golden‐Mantled Ground Squirrels (Spermophilus lateralis)

Hibernating mammals present many unexplored opportunities for the study of muscle biology. The hindlimb muscles of a small rodent hibernator (Spermophilus lateralis) atrophy slightly during months of torpor, representing a reduction in the disuse atrophy commonly seen in other mammalian models. How torpor affects contractile protein expression is unclear; therefore, we examined the myosin heavy‐chain (MHC) isoform profile of ground squirrel skeletal muscle before and after hibernation. Immunoblotting was performed first to identify the MHC isoforms expressed in this species. Relative percentages of MHC isoforms in individual muscles were then measured using SDS‐PAGE (sodium dodecyl sulfate–polyacrylamide gel electrophoresis). The soleus and diaphragm did not display differences in isoforms following hibernation, but we found minor fast‐to‐slow isoform shifts in MHC protein in the gastrocnemius and plantaris. These subtle changes are contrary to those predicted by other models of inactivity but may reflect the requirement for shivering thermogenesis during arousals from torpor. We also measured mRNA expression of the Muscle Atrophy F‐box (MAFbx), a ubiquitin ligase important in proteasome‐mediated proteolysis. Expression was elevated in the hibernating gastrocnemius and the plantaris but was not associated with atrophy. Skeletal muscle from hibernators displays unusual plasticity, which may be a combined result of the intense activity during arousals and the reduction of metabolism during torpor.
DNA of mouse mammary tumor virus‐like virus is present in human tumors influenced by hormones

Mouse mammary tumor virus (MMTV) is a hormonally regulated, oncogenic virus of mice. MMTV‐like virus DNA has previously been detected in human breast cancers, liver disease, and liver cancers. It is hypothesized that local hormonal effects might be of primary importance in determining MMTV‐like virus detection in human tumors. MMTV‐like virus envelope (env) DNA was determined using nested PCR in 89 ovarian, 147 prostate, 50 endometrial, 141 skin, and 51 lung cancers. Viral‐positive sequences were compared with published MMTV‐like viral sequences from human breast cancer, liver cancer and MMTV. Immunohistochemistry for estrogen receptor (ER‐α) and progesterone receptor (PgR) was performed on a subset of tumors. MMTV‐like virus env DNA was detected in ovarian cancers (14/89; 16%), prostate cancers (53/147; 36%), endometrial cancers (5/50; 10%), skin cancers (13/141; 9%) but not in lung cancers (0/51). Phylogenetic analysis of the viral‐positive sequences showed no clustering of the isolates according to tissue type. A significant association was observed between the presence of hormone receptors and detection of MMTV‐like virus in the human cancers screened (P = 0.01). A significant association between MMTV‐like virus and PgR was noted in skin cancers (P = 0.003). Therefore, unlike the mouse model, the detection of MMTV‐like env sequences in human cancers in addition to breast indicates that MMTV‐like viral expression is not breast cancer‐specific and may relate to hormone‐dependent viral expression. J. Med. Virol. 82:1044–1050, 2010. © 2010 Wiley‐Liss, Inc.
Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases.

PURPOSE Our group has previously published the Graded Prognostic Assessment (GPA), a prognostic index for patients with brain metastases. Updates have been published with refinements to create diagnosis-specific Graded Prognostic Assessment indices. The purpose of this report is to present the updated diagnosis-specific GPA indices in a single, unified, user-friendly report to allow ease of access and use by treating physicians. METHODS A multi-institutional retrospective (1985 to 2007) database of 3,940 patients with newly diagnosed brain metastases underwent univariate and multivariate analyses of prognostic factors associated with outcomes by primary site and treatment. Significant prognostic factors were used to define the diagnosis-specific GPA prognostic indices. A GPA of 4.0 correlates with the best prognosis, whereas a GPA of 0.0 corresponds with the worst prognosis. RESULTS Significant prognostic factors varied by diagnosis. For lung cancer, prognostic factors were Karnofsky performance score, age, presence of extracranial metastases, and number of brain metastases, confirming the original Lung-GPA. For melanoma and renal cell cancer, prognostic factors were Karnofsky performance score and the number of brain metastases. For breast cancer, prognostic factors were tumor subtype, Karnofsky performance score, and age. For GI cancer, the only prognostic factor was the Karnofsky performance score. The median survival times by GPA score and diagnosis were determined. CONCLUSION Prognostic factors for patients with brain metastases vary by diagnosis, and for each diagnosis, a robust separation into different GPA scores was discerned, implying considerable heterogeneity in outcome, even within a single tumor type. In summary, these indices and related worksheet provide an accurate and facile diagnosis-specific tool to estimate survival, potentially select appropriate treatment, and stratify clinical trials for patients with brain metastases.
The Toxoplasma Proteins MIC2 and M2AP Form a Hexameric Complex Necessary for Intracellular Survival*

Toxoplasma gondii parasites gain entry into host cells through a process that depends on apically stored adhesins that are strategically released during invasion. One of these adhesins, microneme protein 2 (MIC2), is a type one transmembrane protein that binds to an accessory protein known as MIC2-associated protein (M2AP). Together the MIC2·M2AP complex participates in host cell attachment and invasion. The short cytoplasmic C-domain of MIC2 is implicated in protein trafficking and mediating an association with the parasite cytoskeleton. To define the role of the cytoplasmic domain of MIC2, proteins lacking the C-domain were expressed in transgenic T. gondii. Surprisingly, protein trafficking and secretion were not affected. We hypothesized that mutant mic2 lacking the C-domain might be escorted to the micronemes by association with endogenous wild-type MIC2 possessing functional transmembrane and cytoplasmic domains. To investigate this interaction, native blue gels and gel filtration were employed to identify a stable macromolecular MIC2·M2AP complex of ∼450 kDa. Our findings reveal that MIC2 and M2AP proteins form stable hexamers consisting of three αβ dimers. Resolution of this complex has implications for how MIC2·M2AP associates with host cell receptors and the cytoskeleton to facilitate parasite motility and invasion.
Dimer recognition and secretion by the ESX secretion system in Bacillus subtilis

Significance Bacteria use a wide range of secretion mechanisms to export proteins from the cytoplasm. These secretion pathways differ in the nature of substrate recognition signal and the mode of substrate translocation. This work elucidates fundamental properties of substrate secretion by the early secretory antigen 6 kDa (ESX) system. We use systematic mutagenesis and targeted crosslinking of an ESX substrate from Bacillus subtilis to provide, to our knowledge, the first experimental evidence for secretion of an intact dimeric complex requiring a composite recognition signal formed by both members of the complex. Protein secretion typically involves translocation of unfolded polypeptides or transport of monomeric folded proteins. Here we provide, to our knowledge, the first experimental evidence for secretion of an intact multimeric complex requiring a signal formed by both members of the complex. Using systematic mutagenesis of a substrate involved in early secretory antigen 6 kDa (ESX) secretion in Bacillus subtilis, we demonstrate that export of the substrate requires two independent motifs. Using mixed dimers, we show that these motifs must form a composite secretion signal in which one motif is contributed by each subunit of the dimer. Finally, through targeted crosslinking we show that the dimer formed in the cell is likely secreted as a single unit. We discuss implications of this substrate recognition mechanism for the biogenesis and quality control of secretion substrates and describe its likely conservation across ESX systems.
Sensitivity to Δ9-tetrahydrocannabinol is selectively enhanced in beta-arrestin2−/− mice

Little is known about the roles of &bgr;-arrestins in the regulation of brain CB1 cannabinoid receptors. This study investigated the role of &bgr;-arrestin2 in cannabinoid behavioral effects using &bgr;-arrestin2−/− mice and their wild-type counterparts. A variety of cannabinoid ligands from different chemical classes that exhibit a variety of efficacies for activation of CB1 receptors were investigated, including Δ9-tetrahydrocannabinol, CP55940, methanandamide, JWH-073, and O-1812. Δ9-tetrahydrocannabinol produced both greater antinociception and greater decreases in body temperature in &bgr;-arrestin2−/− compared with &bgr;-arrestin2+/+ mice. No significant differences were, however, present in either assay for the other CB1 agonists. Antagonist radioligand binding indicated no difference in the density of cannabinoid CB1 receptors in the cerebellum, cortex, or hippocampus of &bgr;-arrestin2+/+ and −/− mice. These data demonstrate that &bgr;-arrestin2 may regulate cannabinoid CB1 receptor sensitivity in an agonist-specific manner.
Changes for Children

of the republic.1 The concept of the melting pot married the fact that America was settled by waves of immigrants from different parts of the world with the hope that, in America, traditional distinctions and prejudices would be put aside and a new homogenous "race" formed. With the passage of time, the country gradually raised barriers against immigration and turned its attention more toward resolving the problems of its domestic and, by then, largely native-born population. Today, fueled in part by recent new waves of immigration and increased awareness of ethnic identities, the issue of the racial, cultural, and/or ethnic makeup of American society is again very much a topic of discussion and concern.
What can increase the default risk in local governments?

Concern has been expressed by international organisations and in previous studies about the financial situation of local governments, and the question of debt has been identified as a crucial element in efforts to overcome the current financial crisis. However, the variables that can affect the financial soundness of these governments have not been sufficiently studied, despite their direct relation to the credit risk premium. In this article, we aim to identify risk factors for default by local governments, and provide useful information to municipal financial managers. We conducted an empirical study of 148 Spanish municipalities and analysed data from four years, applying a random effects logistic regression model. Our findings reveal that a lower population density, less dependent population, falling levels of per capita income and the presence of progressive local government are all risk factors for default by local governments. Furthermore, our findings indicate that the general financing structure variable and debt composition and maturity variable do influence the risk of default by local governments. Points for practitioners The findings of this article can provide useful information for managers and politicians responsible for the financial management of local governments, in particular, by enabling them to better understand the risk premiums assigned by banks. Specifically, by identifying the risk factors for default, this article highlights the warning signs of this risk, so that suitable arguments may be expressed in negotiating loan repayment schedules and interest rates, and in designing financial viability and restructuring plans.
Refined composite multivariate multiscale entropy based on variance for analysis of resting-state magnetoencephalograms in Alzheimer's disease

Alzheimer's disease (AD) is one of the fastest growing neurological diseases. Multiscale entropy with coarse-graining based on mean (MSEμ) has been widely used to characterize AD. Alternatively, multiscale entropy based on variance (MSEσ<sup>2</sup>) has been recently proposed to quantify the dynamics of volatility (variance) of univariate signals. Here, we extend the MSEσ<sup>2</sup> to multivariate signals to take into account both the time and spatial domains for discrimination of resting-state magnetoencephalogram (MEG) recordings of 36 AD patients from those of 26 normal controls. We also consider the usefulness of the refined composite mvMSEσ<sup>2</sup> (RCmvMSEσ<sup>2</sup>) to understand if the RCmvMSEσ<sup>2</sup> can better discriminate AD group from control subjects in comparison with mvMSEσ<sup>2</sup>. The results show mvMSEσ<sup>2</sup> and RCmvMSEσ<sup>2</sup>, unlike exiting multiscale-based methods, lead to significant differences between control and AD patients at all scale factors. The results obtained by the mvMSEσ<sup>2</sup> and RCmvMSEσ<sup>2</sup> are similar. Thus, refined composite technique might not enhance the detection of different pathological states, especially when signals are not too noisy and short. Finally, our findings show that the mvMSEσ<sup>2</sup> and RCmvMSEσ<sup>2</sup> can be useful tools for the analysis of real signals to characterize different kinds of dynamics.
Provision of dental care for special care patients: the view of Irish dentists in the Republic of Ireland.

STATEMENT OF PROBLEM Part 2 of the Disability Act 2005 requires that all people with a disability are entitled to a needs assessment and, by implication, provision of identified care needs. This process started with children aged 0-6 in 2007 and will roll out to all people with disabilities by 2011. Oral health is part of that needs assessment but it may be that dentists are not in a position to provide that care, by virtue of a lack of education, training or facilities. The majority of dental care delivered would seem, from information gathered as part of this study, to be of an emergency nature. This study aimed to identify the shortfalls in service provision, and their potential causes, to inform what it is hoped will be a positive directive on special care dentistry (SCD) in the proposed National Oral Health Strategy. PURPOSE OF STUDY To assess the provision of dental services for special care patients (SCPs) by dental practitioners in Ireland. To review the educational background of primary dental care providers in SCD. MATERIALS AND METHODS A postal and online questionnaire was sent to every third dentist on the Dental Register in Ireland. An analysis of data was performed using Statistical Programme for Social Sciences (SPSS). RESULTS There were 782 questionnaires distributed. Of the 274 (35% response rate) dentists returning questionnaires, 236 were deemed suitable for inclusion; those dentists working in general practice or the Health Service Executive (HSE) only were included. Treatment provided by dental practitioners included emergency services (775), extractions (72%) and restorative intervention (72%). Oral hygiene instruction for the carers of SCPs was provided by 52% of respondents. Of those surveyed, 25% claimed an awareness of the Disability Act 2005. Qualitative analysis of a definition of SCD and the perceived barriers to care were recorded. Additional fees for the treatment of SCPs were deemed necessary by 78% of respondents. An experience of training in SCD was recorded by 41%, and 65% of dentists expressed a willingness to partake in some/further training. CONCLUSIONS While the treatment of SCPs was reported by the majority of respondents (66%), the most common service provided was the management of dental emergencies. The need for a greater emphasis on preventive care was highlighted. Knowledge of the Disability Act 2005 was limited and responsible agencies need to increase awareness of the requirements for professional groups, like dentists, under the Act.
Composite score of reflux symptoms in diagnosis of gastroesophageal reflux disease.

AIM To evaluate the significance of the composite score of reflux symptoms in the diagnosis of gastroesophageal reflux disease (GERD), and to determine the relationship of the composite score with reflux esophagitis (RE) and pathological gastroesophageal reflux (PGER). METHODS Upper digestive endoscopy and /or 24-h esophageal pH monitoring were performed in 244 subjects. Of these, 54 were consecutive patients attending our clinic with symptoms suggestive of GERD, and 190 were randomly selected from 2532 respondents who participated in our previous general population-based study on GERD. A standardized questionnaire was used to classify both the frequency and severity of typical symptoms of GERD (heartburn, acid and food regurgitation) using a 4-score scale, and the composite score of main reflux symptoms (score index: SI, range from 0 to 18) were calculated for every subject. RE was diagnosed according to the Savary-Miller criteria. Subjects with abnormal pH-metry (DeMeester score more than 14.7) were considered to have PGER. GERD patients were defined as the subjects with RE and/or PGER. RESULTS The sensitivity of SI in the diagnosis of GERD was inversely associated with SI, but the specificity tended to increase with increased SI. With the cut-off of 8, the SI achieved the highest accuracy of 70.0%, with a sensitivity of 78.6% and a specificity of 69.2% in diagnosing GERD, followed by the cut-off of 3, which had an accuracy of 62.1%, a sensitivity of 96.4% and a specificity of 34.6%. The prevalence of RE, PGER and GERD was strongly associated with increased SI (P<0.01), but there was no significant association between the severity of RE and SI (P>0.05). Among patients with RE, 69.2% had PGER, and 30.8% were confirmed to have negative findings of pH monitoring. Among patients with PGER, 52.9% were identified to have RE and 47.1% had negative endscopic findings in esophagus. CONCLUSION According to the composite score of main reflux symptoms, the diagnosis of GERD can be made without further tests in most cases. However, 24-h esophageal pH monitoring and upper digestive endoscopy are still indicated in patients with mild and atypical symptoms.
Postmenopausal changes in production of type 1 and type 2 cytokines and the effects of hormone replacement therapy

ObjectiveAn appropriate defense against infective agents or malignant cells is attributed to the exquisitely balanced T helper 1 type (cellular) and T helper 2 type (humoral) immune reactions. We investigated the effect of hormone replacement therapy (HRT) on postmenopausal changes in the production of interferon (IFN)-&ggr; and interleukin (IL)-10, a type 1 and a type 2 cytokine, respectively. DesignBoth cytokines were measured by ELISA in the supernatant of lipopolysaccharide-stimulated whole blood cells from 72 untreated and 44 HRT-treated women. Thirteen women were examined before and during HRT. ResultsThe production of IFN-&ggr; in women in their 40s and in postmenopausal women was significantly higher compared with that of younger women. However, IFN-&ggr; fell to the lowest level in the late postmenopausal stage, whereas the production of IL-10 increased gradually with age and in parallel with the postmenopausal period. Thus, in women in the mid-and late postmenopausal period, excessive production of type 2 cytokine (IL-10) compared with type 1 cytokine (IFN-&ggr;) occurred. The IFN-&ggr; levels of women on HRT were significantly lower than those of untreated women in the early and mid-postmenopausal stages, and IL-10 levels of women on HRT were significantly lower than those of untreated women in the mid-and late postmenopausal stages. HRT induced a significant decrease in the production of IL-10 and tended to lower the level of IFN-&ggr;. ConclusionsProduction of IL-10 is augmented in postmenopausal women. HRT probably prevents postmenopausal women from an aberration of the immune system by improving the balance of type 1 and type 2 immune reactions.