Miracle-dz/UniFAR-FTUs huggingface dataset:
Liposome-bound APO2L/TRAIL is an effective treatment in a rabbit model of rheumatoid arthritis.

OBJECTIVE We previously observed that T lymphocytes present in synovial fluid (SF) from patients with rheumatoid arthritis (RA) were sensitive to APO2L/TRAIL. In addition, there was a drastic decrease in the amount of bioactive APO2L/TRAIL associated with exosomes in SF from RA patients. This study was undertaken to evaluate the effectiveness of bioactive APO2L/TRAIL conjugated with artificial lipid vesicles resembling natural exosomes as a treatment in a rabbit model of antigen-induced arthritis (AIA). METHODS We used a novel Ni(2+)-(N-5-amino-1-carboxypentyl)-iminodiacetic acid)-containing liposomal system. APO2L/TRAIL bound to liposomes was intraarticularly injected into the knees of animals with AIA. One week after treatment, rabbits were killed, and arthritic synovial tissue was analyzed. RESULTS Tethering APO2L/TRAIL to the liposome membrane increased its bioactivity and resulted in more effective treatment of AIA compared with soluble, unconjugated APO2L/TRAIL, with substantially reduced synovial hyperplasia and inflammation in rabbit knee joints. The results of biophysical studies suggested that the increased bioactivity of APO2L/TRAIL associated with liposomes was due to the increase in the local concentration of the recombinant protein, augmenting its receptor crosslinking potential, and not to conformational changes in the protein. In spite of this increase in bioactivity, the treatment lacked systemic toxicity and was not hepatotoxic. CONCLUSION Our findings indicate that binding APO2L/TRAIL to the liposome membrane increases its bioactivity and results in effective treatment of AIA.
Molecular Imaging of Gliomas

Gliomas are the most common types of brain tumors. Although sophisticated regimens of conventional therapies are being carried out to treat patients with gliomas, the disease invariably leads to death over months or years. Before new and potentially more effective treatment strategies, such as gene- and cell-based therapies, can be effectively implemented in the clinical application, certain prerequisites have to be established. First of all, the exact localization, extent, and metabolic activity of the glioma must be determined to identify the biologically active target tissue for a biological treatment regimen; this is usually performed by imaging the expression of up-regulated endogenous genes coding for glucose or amino acid transporters and cellular hexokinase and thymidine kinase genes, respectively. Second, neuronal function and functional changes within the surrounding brain tissue have to be assessed in order to save this tissue from therapy-induced damage. Third, pathognomonic genetic changes leading to disease have to be explored on the molecular level to serve as specific targets for patient-tailored therapies. Last, a concerted noninvasive analysis of both endogenous and exogenous gene expression in animal models as well as the clinical setting is desirable to effectively translate new treatment strategies from experimental into clinical application. All of these issues can be addressed by multimodal radionuclide and magnetic resonance imaging techniques and fall into the exciting and fast growing field of molecular and functional imaging. Noninvasive imaging of endogenous gene expression by means of positron emission tomography (PET) may reveal insight into the molecular basis of pathogenesis and metabolic activity of the glioma and the extent of treatment response. When exogenous genes are introduced to serve for a therapeutic function, PET imaging may reveal the assessment of the “location,” “magnitude,” and “duration” of therapeutic gene expression and its relation to the therapeutic effect. Detailed reviews on molecular imaging have been published from the perspective of radionuclide imaging (Gambhir et al., 2000; Blasberg and Tjuvajev, 2002) as well as magnetic resonance and optical imaging (Weissleder, 2002). The present review focuses on molecular imaging of gliomas with special reference on the status and perspectives of imaging of endogenous and exogenously introduced gene expression in order to develop improved diagnostics and more effective treatment strategies of gliomas and, in that, to eventually improve the grim prognosis of this devastating disease.
Prefrontostriatal connections in relation to cortical architectonic organization in rhesus monkeys

Prefrontostriatal connections were investigated in rhesus monkeys using the autoradiographic technique to examine whether there are systematic relationships with regard to the architectonic organization of the prefrontal cortex. On the basis of progressive laminar elaboration, the different regions of the prefrontal cortex can be grouped into two architectonic trends. The dorsal trend, which begins in the medial proisocortical areas, can be followed through the dorsolateral prefrontal cortex, culminating in the dorsal arcuate region. The ventral trend, which originates in the orbital proisocortex, can be traced through the inferior prefrontal convexity to the ventral arcuate region. The results show that the main connections from the prefrontal cortex to the striatum are to the head and body of the caudate nucleus. These connections are topographically organized. Medial and dorsal prefrontal areas project predominantly to the dorsal and central portion of the head and body of the caudate nucleus, whereas orbital and inferior prefrontal areas are related mainly to the ventral and central portion. Moreover, prefrontostriatal connections have a medial‐lateral topography. Medial and orbital prefrontal areas project medially in the head and body of the caudate nucleus, whereas the dorsal and ventral arcuate regions project laterally, adjacent to the internal capsule. The prefrontal regions above and below the principal sulcus project mainly to the intermediate sector of the head and body of the nucleus. However, there appears to be some degree of overlap of corticostriatal projections from the dorsal and ventral prefrontal regions, as well as within each trend. Relatively minor projections are directed to the putamen as well as to the tail of the caudate nucleus from certain subregions of the prefrontal cortex. Thus the distribution of prefrontostriatal connections seems to reflect the architectonic organization of the prefrontal cortex. Possible functional aspects of prefrontostriatal connectivity are considered in the light of behavioral and physiological studies.
Stroke in Childhood: Outcome and Recurrence Risk by Mechanism in 59 Patients

This paper describes 59 patients, 3 months to 16 years of age, who were seen consecutively in the same center for cerebral arterial infarction. It focuses on the mechanism of stroke. The pathophysiologic process could be established for 78% of the children. Arteriopathic stroke (31 patients, or 53%) was the most common. The arteriopathies were either progressive (moyamoya in 4 patients, or 7%) or nonprogressive (27 patients, or 46%). The latter form occurred in two patterns: dissection of cervicocephalic arteries (12 patients, or 20%) and transient cerebral arteriopathy of unknown origin but probably angiitis (15 patients, or 25%). Cardiac or transcardiac embolic stroke occurred in 12% of the series and systemic diseases in 14%. There was a favorable outcome in 70% of patients having stroke due to nonprogressive arterial disease and stroke due to unidentified mechanisms. In contrast, only 26% of patients with embolic stroke, systemic disease, or moyamoya had a favorable outcome. Recurrences were more frequent and severe in this latter group. It is concluded that it is important to determine the mechanism of childhood stroke, because it strongly influences outcome, the recurrence risk, and treatment choice. (J Child Neurol 2000;15:290-294).
MASS/RADIUS CONSTRAINTS ON THE QUIESCENT NEUTRON STAR IN M13 USING HYDROGEN AND HELIUM ATMOSPHERES

The mass and radius of the neutron star (NS) in low-mass X-ray binaries can be obtained by fitting the X-ray spectrum of the NS in quiescence, and the mass and radius constrains the properties of dense matter in NS cores. A critical ingredient for spectral fits is the composition of the NS atmosphere: hydrogen atmospheres are assumed in most prior work, but helium atmospheres are possible if the donor star is a helium white dwarf. Here we perform spectral fits to XMM-Newton, Chandra, and ROSAT data of a quiescent NS in the globular cluster M13. This NS has the smallest inferred radius from previous spectral fitting. Assuming an atmosphere composed of hydrogen, we find a significantly larger radius, more consistent with those from other quiescent NSs. With a helium atmosphere (an equally acceptable fit), we find even larger values for the radius.
IL-22 Increases Permeability of Intestinal Epithelial Tight Junctions by Enhancing Claudin-2 Expression

Dysfunction of the epithelial barrier is a hallmark of inflammatory intestinal diseases. The intestinal epithelial barrier is maintained by expression of tight junctions that connect adjacent epithelial cells and seal the paracellular space. IL-22 is critical for the maintenance of intestinal barrier function through promoting antipathogen responses and regeneration of epithelial tissues in the gut. However, little is known about the effects of IL-22 on the regulation of tight junctions in the intestinal epithelium. In this study we report that IL-22 signals exclusively through the basolateral side of polarized Caco-2 cell monolayers. IL-22 treatment does not affect the flux of uncharged macromolecules across cell monolayers but significantly reduces transepithelial electrical resistance (TEER), indicating an increase of paracellular permeability for ions. IL-22 treatment on Caco-2 monolayers and on primary human intestinal epithelium markedly induces the expression of Claudin-2, a cation–channel-forming tight junction protein. Furthermore, treatment of IL-22 in mice upregulates Claudin-2 protein in colonic epithelial cells. Knocking down Claudin-2 expression with small interfering RNA reverses the reduction of TEER in IL-22–treated cells. Moreover, IL-22–mediated upregulation of Claudin-2 and loss of TEER can be suppressed with the treatment of JAK inhibitors. In summary, our results reveal that IL-22 increases intestinal epithelial permeability by upregulating Claudin-2 expression through the JAK/STAT pathway. These results provide novel mechanistic insights into the role of IL-22 in the regulation and maintenance of the intestinal epithelial barrier.
Granulocyte colony stimulating factors: How different are they? How to make a decision?

Two granulocyte colony stimulating factors (G-CSFs) are available for clinical use in Europe: filgrastim (Neupogen®) and lenograstim (Granocyte®). The purpose of this literature review is to study how they differ, the clinical implications of these differences (especially in terms of efficacy) and the economic impact of these differences. From a chemical point of view the two molecules are not identical. Their amino acid sequence is different and one is glycosylated, whereas the other is not. The important question to ask is what these structural differences mean for the patient. It appears that glycosylation has important consequences in terms of efficacy. Several recent comparative studies, both in vitro and in vivo, in animals and in humans, reinforce this idea which was often shared intuitively by physicians. In economical terms, in hospitals where the exact dosages are used (150 μg/m2 or 19.2 million units (MU)/m2 for Granocyte, and 5 μg/kg or 0.5 MU/kg for Neupogen), the choice of G-CSF must be made according to the daily cost of treatment which, for an average patient, means comparing the price of 325 μg of Neupogen and of 255 μg of Granocyte. This is in fact equal to comparing the price per MU of each product. In hospitals where one vial per patient per day is used whatever be their weight or body surface area, the price per MU and the price per vial should be considered together, puting into perspective the potential therapeutic benefit for patients, one vial of Granocyte 34 containing more MU than one vial of Neupogen 30.
A comparison of fixed-bearing and mobile-bearing total knee arthroplasty at a minimum follow-up of 4.5 years.

BACKGROUND Durable long-term independent results with the Low Contact Stress rotating-platform (mobile-bearing) and the Insall Burstein-II (fixed-bearing) total knee prostheses have been reported, but no studies describing either the mid-term or long-term results and comparing the two prostheses are available, to our knowledge. METHODS Thirty-two patients who had bilateral arthritis of the knee with similar deformity and preoperative range of motion on both sides and who agreed to have one knee replaced with a mobile-bearing total knee design and the other with a fixed-bearing design were prospectively evaluated. Comparative analysis of both designs was done at a mean follow-up period of six years, minimizing patient, surgeon, and observer-related bias. Clinical and radiographic outcome, survival, and complication rates were compared. RESULTS Patients with osteoarthritis had better function scores and range of motion compared with patients with rheumatoid arthritis. However, with the numbers available, no benefit of mobile-bearing over fixed-bearing designs could be demonstrated with respect to Knee Society scores, range of flexion, subject preference, or patellofemoral complication rates. Radiographs showed no difference in prosthetic alignment. Two knees with a mobile-bearing prosthesis required a reoperation: one had an early revision because of bearing dislocation and another required conversion to an arthrodesis to treat a deep infection. CONCLUSIONS We found no advantage of the mobile-bearing arthroplasty over the fixed-bearing arthroplasty with regard to the clinical results at mid-term follow-up. The risk of bearing subluxation and dislocation in knees with the mobile-bearing prosthesis is a cause for concern and may necessitate early revision. LEVEL OF EVIDENCE Therapeutic Level II.
Anti-tuberculosis drug resistance in community and prison patients, Orel Oblast, Russian Federation.

SETTING Orel Oblast, Russian Federation. OBJECTIVES To determine baseline levels of anti-tuberculosis drug resistance in Orel Oblast. DESIGN Drug susceptibility testing (DST) records from 1 July 1999 to 30 June 2000 for patients with sputum acid-fast bacilli smear-positive pulmonary tuberculosis were reviewed. Treatment and incarceration status were obtained from the tuberculosis register. Patients with 1 month or less of prior treatment were defined as new cases; those previously treated for more than 1 month were defined as retreatment cases. RESULTS Of 246 smear-positive isolates, 212 (86%) had DST performed. Of these, 190 (90%) were from new and 22 (10%) from retreatment cases; 171 (81%) were from community and 41 (19%) were from prison patients. Any drug resistance was more common among prison than community patients (44% vs. 30%, P = 0.05). MDR-TB was found in 14 (6.6%) of 212 isolates, and was more prevalent in prison compared with community patients (12% vs. 5%, P = 0.05). Retreatment cases were more likely than new cases to have MDR-TB (prevalence ratio [PR] = 8.5, 95%CI = 3.3-22.3), although the PR was higher for prison than for community retreatment cases (10.0 vs. 5.8). CONCLUSIONS New cases with MDR-TB were less prevalent in Orel Oblast compared with other survey sites in Russia. Any drug resistance and MDR-TB were associated with prior treatment, especially in the prison population. Continued monitoring of trends in drug resistance following DOTS implementation is needed.
Risk factors for clinically significant macular edema in a multi-ethnics population with type 2 diabetes.

AIM To determine the risk factors of clinically significant macular edema (CSME) in patients with non-proliferative diabetic retinopathy (NPDR) in a multi-ethnics Malaysian population. METHODS We performed a case control study in which 150 patients with bilateral NPDR and CSME in either eye were compared to 150 patients with bilateral NPDR and no CSME in both eyes. CSME and NPDR were graded according to Early Treatment of Diabetic Retinopathy Study criteria. Student's t-test, odds ratio and multiple logistic regression analysis were performed to analyze the duration of diabetes, body mass index (BMI), blood pressure(BP), total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TG), fasting blood glucose (FBG), HbA1c, full blood count, serum creatinine and proteinuria between the two groups. RESULTS Both groups were matched in terms of age, gender and ethnicity. Duration of diabetes, total serum cholesterol, serum LDL, FBG, HbA1c and serum creatinine were significantly higher in the CSME group (P<0.05). The hemoglobin, packed cell volume were significantly lower in the CSME group (p<0.05). There was no significant difference for serum HDL, TG, BMI, systolic and diastolic BP. Multiple logistic regression analysis showed that total serum cholesterol and HbA1c had significantly high odds of developing CSME. CONCLUSION HbA1c and total cholesterol are the two most important risk factors associated with CSME in patients with NPDR.
What Determines the Sacrifice Ratio? A Bayesian Model Averaging Approach

Existing empirical studies on the sacrifice ratio (measuring the output cost of disinflation) consider a large number of potential explanatory variables including the length of disinflation, various institutional settings, economic conditions, and the political climate. Some results are robust across different studies, while others are not. We address the presence of model uncertainty by using the Bayesian model averaging method to identify the important determinants of the sacrifice ratio, without relying on ad hoc model selection. Our results show that the length of disinflation is the most important variable. This supports the ‘cold turkey’ argument for faster disinflation.
Reduced rates of HIV acquisition during unprotected sex by Kenyan female sex workers predating population declines in HIV prevalence

Objectives: Female sex workers (FSWs) form a core group at high risk of both sexual HIV acquisition and secondary transmission. The magnitude of these risks may vary by sexual risk taking, partner HIV prevalence, host immune factors and genital co-infections. We examined temporal trends in HIV prevalence and per-act incidence, adjusted for behavioral and other variables, in FSWs from Nairobi, Kenya. Methods: An open cohort of FSWs followed since 1985. Behavioral and clinical data were collected six monthly from 1985 to 2005, and sexually transmitted infection (STI) diagnostics and HIV serology performed. A Cox proportional hazards model with time-dependent covariables was used to estimate infection risk as a function of calendar time. Results: HIV prevalence in new FSW enrollees peaked at 81% in 1986, and was consistently below 50% after 1997. Initially uninfected FSWs remained at high risk of acquiring HIV throughout the study period, but the rate of HIV acquisition during unprotected sex with a casual client declined by over four-fold. This reduction correlated closely with decreases in gonorrhea prevalence, and predated reductions in the Kenyan HIV population prevalence by over a decade. Conclusions: The per-act rate of HIV acquisition in high-risk Nairobi FSWs fell dramatically between 1985 and 2005. This decline may represent the impact of improved STI prevention/therapy, immunogenetic shifts in at-risk women, or changes in the proportion of HIV exposures occurring with clients who had acute HIV infection. Declining HIV incidence in high-risk cohorts may predict and/or be causally related to future reductions in population prevalence.
Context, complexity, and cognitive processing in schizophrenia

Background. Cohen et al.'s (1990, 1999) concept of context has been employed to explain various schizophrenic cognitive deficits. Braver et al.'s (2001) modified definition allows us to link context to cognitive complexity and explain a range of our experimental findings. Method. Saccadic and manual responses to experimental paradigms involving familiar and unfamiliar versions of tasks varying in stimulus–response compatibility, response familiarity, and temporal factors were used. These include comparison of acoustic and visually driven saccades and antisaccades, manual and saccadic pattern reproduction, and colour (cognitively guided) saccades with two delay intervals. Results. In one experiment, schizophrenic participants, unlike controls, made fewer errors on the auditory compared to the visual antisaccade task, suggesting that prepotent responses are more easily inhibited when stimulus–response compatibility is reduced. In a second experiment in which a left–right response sequence is reproduced manually or saccadically, schizophrenic performance is impaired when the novel and thus more complex saccadic response is required. In the third experiment, a colour signal is interpreted to determine the correct direction of a saccade. With two different blocked delay intervals, shortening the delay results in schizophrenic performance decline, suggesting difficulty adjusting to temporal context changes. Conclusion. These results, together with our previous findings (Schooler et al., 1997a; Zahn et al., 1998) suggest schizophrenic context processing deficits become increasingly evident as contexts become more complex. These results may be due to microgaps in schizophrenic individuals’ maintenance of context.
Essays on currency carry trades

This thesis investigates pricing models of currency carry trades. The main contribution of Chapter 2 is the use of an empirical method to summarise risk information and construct factor models. Carry trades partially share same risk characteristics with other asset markets, but some carry trade specific risk factors are also proposed. Therefore, a method to summarise overlapping information is proposed, and the type of information that is dominant in the risk factors is investigated. The important contribution of Chapter 3 is the provision of evidence of a a relationship between commodity prices and carry trade returns. Commodity prices co-move due to consumer income shocks whereas each commodity group has heterogeneity. The adopted approach takes into account these commonalities and heterogeneity. Furthermore, the overlap between commodity related information and financial market information is tested. Chapter 4 contributes with estimates of conditional factor models for carry trades. These models assume that alphas and betas are conditioned on economic states, and are time-varying. The analysis estimates alphas and betas by a nonparametric method and that allows smooth change in these parameters. Finally, the most important contribution in Chapter 5 is the investigation and provision of evidence of time variation in risk prices. Expected returns are decomposed into betas and risk prices. If expected returns change over time, then betas and/or risk prices vary over time. Recently developed dynamic factor models are adopted and used to investigate the impact of time-varying risk prices on pricing errors.