Miracle-dz/UniFAR-FTUs huggingface dataset:
N-methyl-D-aspartate-induced excitotoxicity causes myopia in hatched chicks.

OBJECTIVE To characterize the effect of the amacrine cell-selective toxin N-methyl-D-aspartate (NMDA) on ocular growth in chicks. DESIGN Single injections of NMDA in doses ranging from 20 to 2000 nmol in 20 microL of sterile saline were made into the vitreous chamber of one eye of 7-day-old white leghorn chicks (six chicks per group); the contralateral (control) eye was injected with saline. Six NMDA-treated eyes were also deprived of form vision by applying a translucent goggle 7 days after treatment, to determine whether myopia could still be induced or enhanced in NMDA-treated eyes. OUTCOME MEASURES Axial length, equatorial diameter and refractive error, measured immediately after and 7, 14, 21, 28 and 35 days after treatment. RESULTS NMDA-treated eyes became myopic within 7 days of treatment and remained so until at least 35 days after treatment. During this time the eyes continued to grow but could not be induced to become more myopic by depriving them of patterned images. The half-maximal effective dose of NMDA was calculated to be 670 nmol, 7 days after treatment. CONCLUSIONS NMDA-induced excitotoxicity destroys retinal pathways by which patterned visual stimuli restrain ocular growth in the chick.
Licensing of natural killer cells by self‐major histocompatibility complex class I

Summary: Natural killer (NK) cells have potent capacities to immediately kill cellular targets and produce cytokines that may potentially damage normal self‐tissues unless they are kept in check. Such tolerance mechanisms are incompletely understood. Here we discuss recent studies suggesting that NK cells undergo a host major histocompatibility complex (MHC) class I‐dependent functional maturation process, termed ‘licensing’. Ironically, licensing directly involves inhibitory receptors that recognize target cell MHC class I molecules and block activation of NK cells in effector responses. This process results in two types of tolerant NK cells: functionally competent (licensed) NK cells, whose effector responses are inhibited by self‐MHC class I molecules through the same receptors that conferred licensing, and functionally incompetent (unlicensed) NK cells.
Living with a Kidney Transplant: Perceptions and Experiences

The qualitative study was carried out as a part of a larger longitudinal study on renal transplant recipients (RTRs) following a successful transplant in Pakistan. The aim was to explore why recipients with similar physical health status and healthy kidney functioning, differ in perceptions of Quality of life. Using in depth interviews the study participants with the highest and lowest scores on a standardized QoL index were asked to describe their experiences and attributions regarding kidney failure and to describe their health status pre-and post-transplant. The themes emerging from the analysis related to individual differences in the ‘impact’ of transplant on ‘relationships’ with significant others, (family, work and social life) ‘self identity’, ‘social comparisons’, perceptions of ‘health care and medical professionals’, adjustment, acceptance and ‘coping’ with a transplant. The recipients with a positive perception in these aspects tend to report a more satisfied QoL.
Macrophages lacking scavenger receptor A show a decrease in binding and uptake of acetylated low-density lipoprotein and of apoptotic thymocytes, but not of oxidatively damaged red blood cells.

Macrophage binding of oxidatively damaged red blood cells (OxRBC) and apoptotic thymocytes correlates in many instances with a loss of phospholipid bilayer asymmetry, i.e., with an increase in expression of phosphatidylserine on the outer leaflet of the plasma membrane. Oxidatively modified LDL (OxLDL) can compete for the binding of these ligands to macrophages. However, the receptor(s) responsible remains to be identified. The present studies show that mouse peritoneal macrophages totally lacking scavenger receptor A (SRA) bound OxRBC just as effectively as wild-type macrophages, whereas their binding and uptake of acetyl LDL was reduced by more than 80%. Binding of apoptotic thymocytes and binding of OxLDL were also reduced, but only by 20-30%. We conclude that SRA is not involved in the recognition of phosphatidylserine-rich membranes but contributes to the binding of OxLDL and apoptotic thymocytes. The binding of OxRBC was almost totally calcium-dependent, whereas the binding of apoptotic thymocytes was not, suggesting that the mechanisms involved in their uptake by macrophages under these conditions were different.
RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency

Major Histocompatibility Complex class II (MHC‐II) deficiency is a disease of gene regulation that provides a unique opportunity for the genetic dissection of the molecular mechanisms controlling transcription of MHC‐II genes. Cell lines from MHC‐II deficiency patients have been assigned to three complementation groups (A, B and C) believed to reflect the existence of distinct essential MHC‐II regulatory genes. Groups B and C, as well as an in vitro generated regulatory mutant representing a fourth group (D), are characterized by a specific defect in the binding activity of RFX, a multimeric DNA binding complex that is essential for activation of MHC‐II promoters. RFX5, a subunit of RFX, was recently shown to be mutated in group C. We have now isolated a novel gene, RFXAP (RFX Associated Protein), that encodes a second subunit of the RFX complex. RFXAP is mutated in the 6.1. 6 cell line (group D), as well as in an MHC‐II deficiency patient (DA). This establishes that group D is indeed a fourth MHC‐II deficiency complementation group. Complementation of the 6.1. 6 and DA cell lines by transfection with RFXAP fully restores expression of all endogenous MHC‐II genes in vivo, demonstrating that RFXAP is a novel essential MHC‐II regulatory gene.
Efficacy and tolerability of cancer pain management with controlled-release oxycodone tablets in opioid-naive cancer pain patients, starting with 5 mg tablets.

BACKGROUND We conducted an open-label, dose titration study to assess the efficacy and tolerability of controlled-release oxycodone in the therapy of cancer pain management, starting with a newly developed 5 mg tablet every 12 h. METHODS Twenty-two Japanese cancer patients with pain who had not been taking opioid analgesics over the previous 2 weeks were enrolled. The length of time and the dose needed to attain stable and adequate pain control were evaluated in addition to the assessment of analgesic efficacy and safety during the study period. RESULTS Eighteen patients in the efficacy population (18 out of 20, 90%) attained stable, adequate pain control. Two-thirds of the patients attained stable, adequate pain control without any dose titration. The mean length of time was 1.2 days. In these patients, the pain was significantly reduced in intensity, even at 1 h after the initial dose intake. Fifteen patients (68%) reported at least one side effect, but only one patient had to withdraw from the study because of a side effect. CONCLUSION The results suggest that controlled-release oxycodone tablets offered stable and adequate pain control within a short period of time in most Japanese cancer patients who have not been taking opioid analgesics, and could be effectively titrated against pain from a starting dose of 5 mg every 12 h. This indicates that a lower strength controlled-release oxycodone formulation may make it possible to start and titrate the dose more appropriately and carefully in patients who are sensitive to opioid analgesics.
Changes of DNA Methylation Level and Spatial Arrangement of Primordial Germ Cells in Embryonic Day 15 to Embryonic Day 28 Pig Embryos1

The mammalian germline is generally assumed to undergo extensive epigenetic reprogramming during embryonic development, including a nearly complete erasure of DNA methylation. This assumption does, however, to large degree rely on data from mouse, and despite a well-grounded picture the general nature of these data needs to be validated by investigations of other mammalian species. This study represents such a contribution in the examination of the germline in the domestic pig (Sus scrofa). Semiquantitative immunohistochemistry was used to investigate the level of DNA methylation in the POU5F1-positive primordial germ cells (PGCs) compared with neighboring somatic cells in porcine embryos at Embryonic Day 15 (E15), E17, E20, E21, and E28. We show that, in agreement with the mouse model, a significantly lower level of DNA methylation was observed in the early migrating PGCs. This level was decreasing until a stage coinciding with the entrance of the PGCs to the genital ridge. After this, the methylation level increased. Using whole-mount immunostaining, we determined the spatial arrangement of the porcine PGCs in the period between E15 and E28, allowing some comparison with the migration of the murine germline. The overall conclusion from the obtained data is that the DNA methylation changes in porcine PGCs, as well as the migration of these cells, parallels the picture reported for the mouse.
Global Alignment of Protein-Protein Interaction Networks for Analyzing Evolutionary Changes of Network Frameworks

Recent technological advances have yielded protein-protein interaction (PPI) networks across multiple species. To interpret these networks, comparison methods to characterize interactions across species have gained importance. However, the methodologies of most such studies have been limited to the relationships of protein complexes or pathways between different species because methodologies for network comparisons are limited. In this study, we introduce a novel comparison problem of biological networks, focusing on the framework structure of the networks, and compare these structures to find changes and conservations in the smaller networks. For this purpose, we define an alignment score between two networks based on the validity of the framework structure in each species and on the conservation of homologous genes in the networks. We propose an algorithm to find a high-score alignment based on k-means clustering. Experiments using D. melanogaster and C. elegans PPI networks show that our algorithm identified the network conservation on genes belonging to cancer-related pathways.
Common challenge topics in pediatric transplantation

This special issue is dedicated to the common challenge topics in pediatric transplantation. It contains 11 chapters, ranging from clinical research in pediatric transplantation to translational research (from bench to bedside). It includes comprehensive reviews from renowned scientists, clinicians and surgeons from five countries from the International Pediatric Transplantation Association (IPTA), Harvard University, the University of Miami and the University of São Paulo Medical School. The clinical management of specific issues, such as sensitized patients and ABO blood type-incompatible transplantation, is addressed. In addition, the challenges facing this patient population and the future perspectives for clinical research are discussed.
Stroke at high altitude: Indian experience.

UNLABELLED Stroke is a common medical emergency. There is limited knowledge about stroke at high altitude. We present the clinical profile of 30 cases of stroke at high altitude seen at our center between November 1998 to July 2000. A detailed neurological and systemic examination was carried out. Cases were investigated with blood counts, lipid profile, cardiac evaluation, and CT scan/MRI. Coagulation parameters were studied in some cases. Strokes formed 13.7/1000 of hospital admissions from high altitude area, compared to 1.05/1000 in nonhigh altitude area. All our cases from high altitude area were males (serving soldiers of armed forces). Their mean high altitude stay was 10.2 months, and they were all located at heights greater than 4270 m. Age ranged from 22 to 48 years (mean 33.4 yr). Except for smoking (in four cases), they had no preexisting risk factors. Twenty-two cases were of ischemic stroke, 2 of intracerebral hemorrhage, 4 of TIA/RIND (transient ischemic attack/reversible ischemic neurological deficit), and 2 had cerebral venous thrombosis. Out of 30 cases, 28 were of "stroke in young" (<45 yr) and were compared with cases in the same age group from nonhigh altitude areas. Polycythemia with Hb ranging from 16.2 to 22 g.dL(-1) was seen in 21 of these 28 cases (75%). Protein C and S deficiency was found in 1 case in each group. CT scan showed massive infarcts involving at least 50% of one cerebral hemisphere in 12 cases. Multiple infarcts were seen in one case. CONCLUSION Long-term stay at high altitude is associated with higher risk of stroke. Although all types of stroke were seen, ischemic stroke was the commonest. Massive infarcts were common. Polycythemia was an important risk factor.
Estimation of serum levels of GM-CSF, IL-1 , and Complement Components C3 and C4 in Patients with Chronic HCV

Hepatitis C virus infection is a frequent cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. It is epidemic around the globe and is estimated to afflict 150-200 million people worldwide. It results in chronic disease in 85% of cases (1). The pathogenesis of HCV-induced hepatic injury could be attributed to either direct cytopathic damage by HCV and/or immune-mediated hepatic injury, especially via cellular immunity (2). However, it is likely that the interactions between HCV and the host immune system have the major role in the pathogenesis (3).
Generation of blood group specificity: New insights from structural studies on the complexes of A‐ and B‐reactive saccharides with basic winged bean agglutinin

Basic winged bean agglutinin binds A‐blood group substance with higher affinity and B‐blood group substance with lesser affinity. It does not bind the O substance. The crystal structures of the lectin, complexed with A‐reactive and B‐reactive di and tri saccharides, have been determined. In addition, the complexes of the lectin with fucosylated A‐trisaccharides and B‐trisaccharides and with a variant of the A‐trisaccharide have been modeled. These structures and models provide valuable insights into the structural basis of blood group specificities. All the four carbohydrate binding loops of the lectin contribute to the primary combining site while the loop of variable length contributes to the secondary binding site. In a significant advance to the current understanding, the interactions at the secondary binding site also contribute substantially, albeit in a subtle manner, to determine the blood group specificity. Compared with the interactions of the B‐trisaccharide with the lectin, the third sugar residue of the A‐reactive trisacharide forms an additional hydrogen bond with a lysine residue in the variable loop. In the former, the formation of such a hydrogen bond is prevented by a shift in the orientation of third sugar resulting from an internal hydrogen bond in it. The formation of this bond is also facilitated by an interaction dependent change in the rotamer conformation of the lysyl residue of the variable loop. Thus, the difference in the interactions at the secondary site is generated by coordinated movements in the ligand as well as the protein. A comparison of the crystal structure and the model of the complex involving the variant of the A‐trisaccharide results in the delineation of the relative contributions of the interactions at the primary and the secondary sites in determining blood group specificity. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Trauma Informed Care on an Inpatient Pediatric Psychiatric Unit and The Emergence of Ethical Dilemmas as Nurses Evolved Their Practice

Two case studies are presented reflecting the ethical dilemmas experienced by nurses who were striving to improve their practice in the provision of patient care. The cases are described in the context of finding alternatives to cohesive interventions such as chemical restraints and physical restraints. A summary of the literature on ethical dilemmas that was relevant to the issues arising in these cases is included. Discussion of the use of the American Nursing Association's (ANA, ) Nursing Code of Ethics with Interpretive Statements is highlighted for its relevance and support of the nurses experiencing the ethical dilemmas.
Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98.

PURPOSE Because cytogenetic data are essential for risk stratification of childhood acute myeloid leukemia (AML), the impact of chromosomal aberrations is crucial. PATIENTS AND METHODS Data of a large group of patients younger than 18 years treated according to study AML-Berlin-Frankfurt-Münster (BFM) 98 (n = 454), including their cytogenetics, were analyzed. RESULTS The favorable outcome in the subgroups of patients with t(8;21), inv(16), and t(15;17), with an overall survival of 91% (SE, 4%), 92% (SE, 6%), and 87% (SE, 5%), respectively, was confirmed. Within this group, the 5-year probability of event-free survival (pEFS) of all 17 children with t(8;21) and additional aberrations apart from del(9q) or -X/-Y was 100%. As expected, the cytogenetic finding of a complex karyotype (n = 35; pEFS, 33%; SE, 8%) or a monosomy 7 (n = 12; pEFS, 17%; SE, 11%) was associated with a poor outcome. Compared with remaining patients with cytogenetic data (pEFS, 48%; SE, 2%), prognosis in patients with an MLL rearrangement (n = 91) was inferior (pEFS, 34%; SE, 5%; P = .0005). Particularly, children with t(9;11) and additional aberrations (n = 13; pEFS, 31%; SE, 14%) and MLL rearrangements other than t(9;11) and t(11;19) (n = 41; pEFS, 24%; SE, 7%) had an unfavorable outcome. Nine patients with aberrations in 12p showed an adverse prognosis (pEFS, 11%; SE, 10%). The outcome of patients with aberrations of chromosome 5 (n = 13) was better than expected (pEFS, 50%; SE, 13%). CONCLUSION Because the prognostic value of rare recurrent chromosomal aberrations still has to be elucidated, these data will contribute to future risk stratification for the treatment of pediatric AML.
[Long-term outcome after penetrating keratoplasty for bullous keratopathy - influence of preoperative visual acuity on final outcome].

PURPOSE The aim of this study was to analyse the long-term functional results of penetrating keratoplasty for pseudophacic bullous keratopathy and Fuchs endothelial dystrophy and to analyse the potential influence of the preoperative visual acuity on the final outcome. PATIENTS AND METHODS This retrospective study describes the postoperative results of 413 patients. 154 of them with bullous keratopathy and 259 patients with Fuchs dystrophy. All received penetrating excimer laser keratoplasty (PK). The results include the examination of the patients 1 / 3 / 5 / 8 / > 9 years postoperatively. For analysis the patients were divided in two groups: group I includes patients with a visual acuity ≤ 0.1 and group II with a visual acuity > 0.1. The trephination was performed using a 193 nm excimer laser. The transplanted cornea was fixed by using a double running cross-stitch suture. The outcome measures included best corrected visual acuity (CCV), keratometric equivalent (KEQ), keratometric astigmatism (AST), spherical equivalent (SEQ), refractive cylinder (CYL), best corrected visual acuity (BCVA), surface regularity index (SRI), surface asymmetry index (SAI), potential visual acuity (PVA), pachymetry (PAC), endothelial cell count (ECC), intraocular tension (TEN), topographic equivalent (T-EQ) and topographic astigmatism (T-AST). RESULTS 5 / 8 years postoperatively CCV was 0.55 / 0.58; KEQ was 43.75 / 45.64 D; SEQ - 0.88 /- 1.88 D; AST was 3.91 / 4.41 D; CYL was 3.09 / 3.40 D; ECC was 1230 / 1080 cells/mm (2); TEN was 13.61 / 14.36 mmHg; PAC was 593.21 / 579.50 µm; SRI was 1.08 / 0.89; SAI was 1.31 / 1.10; PVA was 0.77 / 0.83; T-EQ was 44.78 / 44.92 D and T-AST was 4.85 / 3.92 D. The outcome of patients with a preoperative visual acuity of ≤ 0.1 was significantly worse than the group with the visual acuity of > 0.1. CONCLUSION This study shows that the long-term results after penetrating keratoplasty for pseudophacic bullous keratopathy and Fuchs endothelial dystrophy are good. Patients with preoperative visual acuity of ≤ 0.1 had worse final results.
Graphene Surface Plasmons With Dielectric Metasurfaces

An approach to capture light efficiently into graphene surface plasmons by patterning the sinusoidal dielectric metasurfaces above and below the graphene sheet is proposed. The presence of plasmonic resonance is demonstrated by means of an analytical model based on the transformation optics through the extraction of effective graphene conductivity, which is further revealed via a numerical study of the optical spectra as a function of grating parameters at the subwavelength scale. Besides, the resonant position is found to be sensitive to the dielectric contacted with graphene. These findings can deepen our understanding of plasmon resonances and pave the way to the design of graphene plasmonic devices like refractive index sensors.
Reporting of time-to-event end points and tracking of failures in randomized trials of radiotherapy with or without any concomitant anticancer agent for locally advanced head and neck cancer.

PURPOSE For multiple reasons, including complexities in anatomy and management, locally advanced squamous cell carcinomas of the head and neck (SCCHNs) represent a challenging disease for the reporting of end points and the tracking of failures. METHODS We retrieved all randomized trials published in English that began accrual on or after 1978 and enrolled previously untreated patients with nonmetastatic SCCHN receiving primary radiotherapy with or without any concomitant anticancer agent. The reporting of time-to-event end points and the tracking of failures in these trials were analyzed. Failures were defined as events meeting a prespecified end point definition. RESULTS Forty trials involving a total of 125 time-to-event end points were identified. A total of 17 different types of end points were reported. Locoregional control and overall survival accounted for 70% of primary end points. Except for survival, the definitions used for all other end points were heterogeneous. Among 72 end points tracking locoregional failures, 29% did not define the term, whereas 64% specified the absence of complete response as a failure. Overall, the specification of details related to elective neck dissection or salvage surgery to define locoregional failures was deficient. Furthermore, it was rarely stated whether residual disease found during these procedures represents a failure. The methods and timing specifications to assess failures were frequently missing in published reports. The tracking of other types of failure beyond the first failure was reported in only one trial. CONCLUSION These results support the need to standardize the selection, definition, and reporting of time-to-event end points in clinical trials of locally advanced SCCHN.
Channel dependence analysis for slicing Promela

Accurate channel analysis and communication dependence information is necessary for source code analysis tools to be useful in the concurrent specification and programming language domain. We present channel analysis along with an application thereof and describe its implications for the development and understanding of programs written in concurrent languages. We describe how communication dependences within a concurrent program can be computed and then used in combination with control and flow dependences to construct a representation that allows for efficient program slicing.