Miracle-dz/UniFAR-FTUs huggingface dataset:
MHC Class I overexpression on muscles in early juvenile dermatomyositis.

OBJECTIVE To assess muscle expression of MHC Class I complexes (heavy chain and beta2-microglobulin) and to analyze the composition of infiltrating mononuclear cells, specifically cells that bear receptors for class I MHC molecules, in the muscles of children with early juvenile dermatomyositis (JDM). METHODS Light microscopic and immunohistochemical analysis of muscle biopsies from 10 patients with JDM and 3 controls. The mean duration from initial weakness was 2.8 months. At the time of biopsy, 9 patients had not received steroid treatment or immunomodulatory drugs. RESULTS MHC Class I over-expression was evident on muscle fibers in all 10 JDM samples, even in a biopsy reported as normal by conventional histology. MHC class I heavy chain and beta2-microglobulin were over-expressed in an identical distribution. Variable infiltration of T cells and macrophages was seen in the JDM biopsies, with minimal lymphocytic and monocytic infiltration in 4 cases, and none in one. Only very occasional natural killer lymphocytes were identified. Neuronal cell adhesion molecule (NCAM, CD56) staining of regenerating muscle fibers was seen in all samples and these cells were confirmed as being of muscle origin by co-staining for dystrophin. CONCLUSION MHC Class I over-expression is an early event in JDM, and may occur in the absence of lymphocytic infiltration and muscle damage. Immunostaining for MHC Class I could be used routinely in the assessment of muscle histology in juvenile dermatomyositis.
Estimation of Shear Stress-related Blood Damage in Heart Valve Prostheses - in Vitro Comparison of 25 Aortic Valves

The hemodynamics of heart valve prostheses can be reproducibly investigated in vitro within circulatory mock loops. By measuring the downstream velocity and shear stress fields the shear stresses which are clinically responsible for damage to platelets and red blood cells can be determined. The mechanisms of damage and the effects of shear stresses on blood corpuscles were investigated by Wurzinger et al. (3, 4) at the Aerodynamics Institute of the RWTH Aachen. In the present study, the above data are incorporated into a mathematical correlation, which serves as a basic model for the estimation of blood damage. This mathematical model was applied to in vitro investigations of 25 different aortic valve prostheses. The results were compared to clinical findings. In most cases agreement was good, indicating that this model may be directly applied to the clinical situation. This new method facilitates the estimation of clinically expected blood damage from in vitro measurements. It may be useful for the development and evaluation of new valve prostheses. By comparative evaluation of different valve types it also provides additional information to help the implanting surgeon select the optimum valve for his patient.
The Impact of Culture and Sociological and Psychological Issues on Muslim Patients With Breast Cancer in Pakistan

Breast cancer is the most common form of cancer in Muslim women in Pakistan. The impact of the initial diagnosis, culture, religion, and psychosocial and psychological aspects of the disease is not well established. This qualitative study examined the experience and coping strategies used by patients with breast cancer in relation to its impact on their physical, mental health, religious, and family issues. Thirty patients with breast cancer were interviewed. Data were analyzed using thematic analysis. The patient's experience of breast cancer focused on the range of emotions felt throughout the illness trajectory, the importance of religion and family support on coping strategies used to manage the adverse effects of chemotherapy, and also the financial concerns. This is the first study to examine Pakistani Muslim women's views on the lived experience of breast cancer. This article provides clarification of the voiced experiences of women with breast cancer. The data not only highlight the role of religion and family support as essential coping strategies but also emphasize the issues of isolation, aggression, and anger as common responses to chemotherapy. Unique features of this study are women's need to seek spiritual support for their illness and the overriding innate characteristic of maternal responsibility. These cultural features require further analysis and research.
The Prognostic Value of F-18 Fluorodeoxyglucose Bone Marrow Uptake in Patients With Recent Diagnosis of Multiple Myeloma: A Comparative Study With Tc-99m Sestamibi

Purpose: We assessed the prognostic value of F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow of patients with multiple myeloma (MM) in comparison with Tc-99m methoxy-isobutyl-isonitrile (MIBI). Methods: The extent and intensity of FDG and MIBI uptake in the bone marrow of 18 patients with a recent diagnosis of MM were assessed by visual score and by calculating the mean SUV (mSUV) for FDG and the femora/thigh ratio (TG/BKG, [Target/Background ratio]) for MIBI images. These parameters were correlated with clinical indexes of disease using hemoglobin and beta-2-microglobulin levels and plasma cell infiltrate (PCI) percentage. The mean values of the visual score, mSUV, and TG/BKG levels were compared in patients deceased after a relatively short follow-up (n = 9; group A) and in patients with a longer survival or were alive at the end of the study (n = 9; group B). Results: Significant correlations of mSUV and TG/BKG values with PCI percentages and beta-2-microglobulin were found (P < 0.05). The extent of FDG and MIBI bone marrow uptake was greater in patients of group A (P < 0.01). Higher values of mSUV (P < 0.01) and TG/BKG (P < 0.05) were also observed in patients of group A. These results were consistent with the differences (not statistically significant) in hemoglobin, albumin, beta-2-microglobulin levels, and PCI percentages observed in the 2 groups. Conclusion: Our study demonstrates that an increase of FDG bone marrow uptake may predict a more aggressive disease, as much as MIBI uptake. Therefore, an additional analysis of FDG bone marrow images should be performed in patients undergoing PET studies during the initial staging of MM.
Role of adenosine kinase in cochlear development and response to noise

Adenosine signalling has an important role in cochlear protection from oxidative stress. In most tissues, intracellular adenosine kinase (ADK) is the primary route of adenosine metabolism and the key regulator of intracellular and extracellular adenosine levels. The present study provides the first evidence for ADK distribution in the adult and developing rat cochlea. In the adult cochlea, ADK was localized to the nuclear or perinuclear region of spiral ganglion neurons, lateral wall tissues, and epithelial cells lining scala media. In the developing cochlea, ADK was strongly expressed in multiple cell types at birth and reached its peak level of expression at postnatal day 21 (P21). Ontogenetic changes in ADK expression were evident in the spiral ganglion, organ of Corti, and stria vascularis. In the spiral ganglion, ADK showed a shift from predominantly satellite cell immunolabelling at P1 to neuronal expression from P14 onward. In contrast to the role of ADK in various aspects of cochlear development, the ADK contribution to the cochlear response to noise stress was less obvious. Transcript and protein levels of ADK were unaltered in the cochlea exposed to broadband noise (90–110 dBSPL, 24 hr), and the selective inhibition of ADK in the cochlea with ABT‐702 failed to restore hearing thresholds after exposure to traumatic noise. This study indicates that ADK is involved in purine salvage pathways for nucleotide synthesis in the adult cochlea, but its role in the regulation of adenosine signalling under physiological and pathological conditions has yet to be established. © 2010 Wiley‐Liss, Inc.
Autoradiographic Localization and Quantitation of β1- and β2-Adrenoceptors in the Human Atrioventricular Conducting System: A Comparison of Patients with Idiopathic Dilated Cardiomyopathy and Ischemic Heart Disease

The density and distribution of β1- and β2-adrenoceptors in the atrioventricular conducting system and interatrial and interventricular septa from human hearts with idiopathic dilated cardiomyopathy and ischemic heart disease was determined by quantitative autoradiography using (-) [125I]cyanopindolol and the selective β1-adrenoceptor antagonist CGP 20712A and the selective β2-adrenoceptor antagonist ICI 118 551. Both β1- and β2-adrenoceptors were present in the atrioventricular node, bundle of His, interatrial and interventricular septa. No differences in the density or proportions of β1- and β2-adrenoceptors in the atrioventricular node, bundle of His, interatrial septum and interventricular septum were observed between hearts with idiopathic dilated cardiomyopathy or ischemic heart disease (P > 0.05) so further analysis did not distinguish between the two aetiologies. The density of β1-adrenoceptors was lower in the bundle of His (5.0 ± 1.7 fmol/mg protein) than in the atrioventricular node (22.2 ± 5.7 fmol/mg protein, P < 0.05), the interatrial septum (29.6 ± 4.5 fmol/mg protein, P < 0.001) and interventricular septum (24.9 ± 5.2 fmol/mg protein, P < 0.005, n = 8 for all values). The atrioventricular node, interatrial and interventricular septa had similar densities of β1-adrenoceptors (P = 0.060, ANOVA). The distribution of β2-adrenoceptors in the atrioventricular node (21.5 ± 4.1 fmol/mg protein), bundle of His (12.9 ± 2.6 fmol/mg protein) and atrial (16.7 ± 2.3 fmol/mg protein) and septal myocardium (13.8 ± 2.5 fmol/mg protein, n = 8 for all values) was uniform (P = 0.18, ANOVA). The percentage of β1- and β2-adrenoceptors in the atrioventricular node, bundle of His, interatrial and interventricular septa was uneven (P < 0.001, ANOVA). There was a higher proportion of β2-adrenoceptors in the bundle of His (72 ± 6%) than in the atrioventricular node (51 ± 3%, P < 0.01), interatrial septum (36 ± 1%, P < 0.001) and interventricular septum (36 ± 1%, P < 0.001).
Demographic corrections appear to compromise classification accuracy for severely skewed cognitive tests

Demographic corrections for cognitive tests should improve classification accuracy by reducing age or education biases, but empirical support has been equivocal. Using a simulation procedure, we show that creating moderate or extreme skewness in cognitive tests compromises the classification accuracy of demographic corrections, findings that appear replicated within clinical data for the few neuropsychological test scores with an extreme degree of skew. For most neuropsychological tests, the dementia classification accuracy of raw and demographically corrected scores was equivalent. These findings suggest that the dementia classification accuracy of demographic corrections is robust to slight degrees of skew (i.e., skewness <1.5).
The immuno‐epidemiology of pregnancy‐associated Plasmodium falciparum malaria: a variant surface antigen‐specific perspective

Women living in areas of intense P. falciparum transmission have acquired substantial protective immunity to malaria when they reach childbearing age. Nevertheless, pregnancies in such areas are associated with substantial malaria‐related morbidity and mortality, particularly among women of low parity. The parity‐dependency of susceptibility to malaria in pregnant women suggests that protective immunity to this type of malaria can be developed. However, until recently it has been poorly understood why the clinical protection against malaria, which young women in endemic areas acquire well before their first pregnancy, is suddenly rendered inadequate when they become pregnant, only to be regained during the course of a few pregnancies. In this article, I discuss some recent immuno‐epidemiological studies of pregnancy‐associated malaria, which, in combination with the generally improved understanding of how protective immunity to P. falciparum malaria operates and is acquired, have provided important insights into this enigma.
Macrophage‐T cell interaction in experimental visceral leishmaniasis: failure to express costimulatory molecules on Leishmania‐infected macrophages and its implication in the suppression of cell‐mediated immunity

The most important immunopathological consequence of infection with Leishmania seen in murine and human hosts is the suppression of T cell‐mediated immune responses to both mitogens and leishmanial antigens. It has been suggested that this suppression is mediated by macrophages, either by defective antigen processing and presentation or by the elaboration of suppressive mediators like prostaglandins. Optimum activation of T helper cells requires not only T cell receptor occupancy by the antigen‐Ia complex, but also costimulatory signals provided by the antigen‐presenting cells. We investigated the status of several costimulatory molecules on infected macrophages from both genetically susceptible BALB/c and resistant C57BL/6 mice. Our results demonstrate that upon parasitization, the macrophages become unable to deliver costimulatory signals to T helper cells, and that this effects is mediated by prostaglandins, as the inhibition of its synthesis by indomethacin recovered the defect. Upon infection with L. donovani, B7‐1 expression was decreased, while ICAM‐1 was marginally increased in BALB/c macrophages and there was no significant change in the expression of B7‐1 and ICAM‐1 in Leishmania‐infected C57BL/6 macrophages. Expression of VCAM‐1 did not change during infection. This selective alteration in the expression of costimulatory molecules on L. donovani‐infected BALB/c macrophages was caused by the living parasite, as shown by the fact that killing of the parasites by stibogluconate led to no alteration in the levels of costimulatory molecules. We found that the change in B7‐1 expression on the surface of infected macrophages resulted in the inhibition of delayed‐type hypersensitivity‐mediating functions of T helper cells from BALB/c mice. The results described in this study not only throw light on the possible mechanism of leishmanial pathogenesis, but also open up the possibility of immunotherapy of leishmaniasis by selective manipulation of costimulatory molecules.
Role of Glycoprotein B of Herpes Simplex Virus Type 1 in Viral Entry and Cell Fusion

Glycoprotein B (gB) of herpes simplex virus type 1 is an envelope protein that is essential for viral growth. We previously reported the isolation of two gB-null viruses, which form gB-free virions in nonpermissive cells. In the present study, these gB-free virions were shown to bind to the cell surface at the same rate as the wild-type virus. They failed, however, to form plaques and to synthesize virus-specific proteins upon infection. Their plating efficiency was significantly enhanced by treatment with polyethylene glycol, a membrane fusion agent. Therefore, gB is required in a stage after viral attachment but before the expression of the virus-specific proteins. A gB-null syncytial virus was isolated, which contained a gB defect and a syncytial mutation in another genetic locus. It caused complete fusion of gB-transformed cells but no fusion on untransformed cells, indicating the essential role of gB in virus-induced cell fusion. Mutations located at two independent sites in the cytoplasmic domain of gB were transferred to viral DNA and shown to confer a syncytial phenotype to the virus. A transient-expression assay was developed to determine the ability of a set of plasmids containing addition and nonsense mutations in the gB gene to complement the cell-fusion defect in the gB-null syncytial virus. Mutations in plasmids, including those located in the extracytoplasmic domain of gB, were identified that reduced the fusion activity of gB. Therefore, gB contains different functional regions responsible for fusion induction and its inhibition.
MITOSIS IN CHLAMYDOMONAS REINHARDTII BASAL BODIES AND THE MITOTIC APPARATUS

Cell division in Chlamydomonas reinhardtii was described by Johnson and Porter (1968). In their paper, they state (p. 409): ". they (referring to basal bodies) are not found at the poles of the mitotic apparatus as are the centrioles of animal cells and certain plant cells" (present author's
Pediatric phase I and pharmacokinetic study of erlotinib followed by the combination of erlotinib and temozolomide: a Children's Oncology Group Phase I Consortium Study.

PURPOSE We conducted a phase I and pharmacokinetic study of the epidermal growth factor receptor (EGFR) inhibitor erlotinib as a single agent and in combination with temozolomide in children with refractory solid tumors. PATIENTS AND METHODS Erlotinib was administered orally once daily to cohorts of three to six children for a single 28-day course. Patients then received the combination of daily erlotinib and temozolomide daily for 5 days for all subsequent 28-day courses. An oral erlotinib solution was administered during the dose-finding phase and a tablet formulation was subsequently studied at the maximum-tolerated dose (MTD). Pharmacokinetic studies and ERBB-receptor expression and signaling studies were performed. RESULTS Forty-six patients, median age 11.5 years, received erlotinib at doses of 35, 50, 65, 85, or 110 mg/m(2)/d. At 110 mg/m(2)/d, two of four patients had dose-limiting toxicity (DLT) consisting of rash and hyperbilirubinemia, whereas one of six patients developed dose-limiting rash at 85 mg/m(2)/d. The most frequent non-DLTs included diarrhea, rash, and hyperbilirubinemia. The combination of erlotinib and temozolomide was well tolerated. The median apparent erlotinib clearance was 3.1 L/h/m(2) and the median terminal half-life was 8.7 hours. One patient with a neurocytoma had stable disease for 19 months, two patients with neuroblastoma remained on study for 23 and 24 months, and one patient with myoepithelioma had a mixed response. CONCLUSION The recommended phase II dose of erlotinib in recurrent pediatric solid tumors is 85 mg/m(2)/d, either alone or in combination with temozolomide.
α-Synuclein structural features inhibit harmful polyunsaturated fatty acid oxidation, suggesting roles in neuroprotection

α-Synuclein (aS) is a protein abundant in presynaptic nerve terminals in Parkinson disease (PD) and is a major component of intracellular Lewy bodies, the pathological hallmark of neurodegenerative disorders such as PD. Accordingly, the relationships between aS structure, its interaction with lipids, and its involvement in neurodegeneration have attracted great interest. Previously, we reported on the interaction of aS with brain polyunsaturated fatty acids, in particular docosahexaenoic acid (DHA). aS acquires an α-helical secondary structure in the presence of DHA and, in turn, affects DHA structural and aggregative properties. Moreover, aS forms a covalent adduct with DHA. Here, we provide evidence that His-50 is the main site of this covalent modification. To better understand the role of His-50, we analyzed the effect of DHA on aS-derived species: a naturally occurring variant, H50Q; an oxidized aS in which all methionines are sulfoxides (aS4ox); a fully lysine-alkylated aS (acetyl-aS); and aS fibrils, testing their ability to be chemically modified by DHA. We show, by mass spectrometry and spectroscopic techniques, that H50Q and aS4ox are modified by DHA, whereas acetyl-aS is not. We correlated this modification with aS structural features, and we suggest a possible functional role of aS in sequestering the early peroxidation products of fatty acids, thereby reducing the level of highly reactive lipid species. Finally, we show that fibrillar aS loses almost 80% of its scavenging activity, thus lacking a potentially protective function. Our findings linking aS scavenging activity with brain lipid composition suggest a possible etiological mechanism in some neurodegenerative disorders.
Shakespeare and the Idea of Late Writing: Authorship in the Proximity of Death

Introduction 1. Shakespeare and the idea of late writing 2. The Shakespearean caesura: genre, chronology, style 3. The invention of late Shakespeare: subjectivism and its discontents 4. Last words / late plays: the possibility and impossibility of late Shakespeare in early modern culture and theatre 5. How old is 'late'? : late Shakespeare, old age, King Lear 6. The Tempest and the uses of late Shakespeare in the theatre: Gielgud, Rylance, Prospero.
The Timing of Neurodevelopmental Abnormality in Schizophrenia: An Integrative Review of the Neuroimaging Literature

Abstract In this paper we will review recent neuroimaging research in schizophrenia, with an aim to critically evaluate several recent proposals concerning the nature and the timing of the neuroanatomic abnormalities underlying the disorder. Specifically, enlargement of cerebrospinal fluid spaces, deficits in cortical gray matter, and reduced volume of mesiotemporal structures have all been reported in patients in the first episode of schizophrenia, their first-degree relatives, and individuals with schizotypal personality disorder, supporting the possibility that these abnormalities reflect a genetically mediated neurodevelopmental disorder. These findings from the empirical literature will be synthesized from the perspective of dual cytoarchitectonic trends theory of neurodevelopment, as well as in relation to current conceptions of the schizophrenia prodrome. We believe that the evidence shows that sufficient groundwork has been laid to begin longitudinal neuroimaging studies of adolescents at clinical risk for schizophrenia, in order to more definitively determine the pathophysiology of the disorder. Such information could have significant implications in terms of understanding the prediction, treatment, and ultimately the prevention of schizophrenia.
Contribution of education, occupation and cognitively stimulating activities to the formation of cognitive reserve

The cognitive reserve (CR) concept posits that there is individual variability in processing task demands and coping with neurodegenerative diseases. This variability can be attributed to the protective effects derived from continuous cognitive stimulation throughout life, including formal education, engagement in cognitively stimulating activities and occupation. These can result in protection against age-related cognitive decline and reduce the risk of developing Alzheimer’s disease. The aim of this review is to summarize the main features of CR formation and to discuss the challenges in carrying out CR research in developing countries.
Scheduling correlated broadcast data considering access frequencies with temporal variations

Recently, there has been an increasing interest in the research of push-based information systems that deliver data using broadcast in both wired and wireless environments. In push-based systems, since a server can meet all requests for broadcast data pending in a system with one broadcast, a larger throughput can be expected when there exists a large number of clients. In this paper to reduce the response time of data access, we propose a new scheduling strategy of broadcast program considering an environment where clients issue requests for multiple data items consecutively with think-time. The proposed strategy reduces the average response time by broadcasting the optimal data item at present according to clients' access characteristics such as access frequencies, correlations among data items, and think-time.