Miracle-dz/UniFAR-FTUs huggingface dataset:
Successful Treatment of Primary Central Nervous System Lymphoma without Irradiation in Children: Single Center Experience

Primary CNS lymphoma (PCNSL) is a very uncommon disease in children, and usually treated by chemotherapy, combined with focal or craniospinal radiotherapy (RT). However, adverse effects of RT are a concern. We evaluated the outcomes of childhood PCNSL, treated with systemic and intrathecal chemotherapy, but without RT. For fifteen years, six patients among 175 of non-Hodgkin lymphoma were diagnosed as PCNSL in Seoul National University Children's Hospital and we analyzed their medical records retrospectively. Their male:female ratio was 5:1, and median age was 10.1 yr. The primary sites were the sellar area in three patients, parietal area in one, cerebellum in one, and multiple areas in one. Their pathologic diagnoses were diffuse large B-cell lymphoma in three patients, Burkitt lymphoma in two, and undifferentiated B-cell lymphoma in one. Five were treated with the LMB96 treatment protocol, and one was treated with the CCG-106B protocol. None had RT as a first-line treatment. One patient had a local relapse and received RT and salvage chemotherapy, without success. No patient had treatment-related mortality. Their estimated 5-yr event-free and overall survival rates were both 83.3%. In conclusion, PCNSL is a rare disease in childhood, but successfully treated by chemotherapy without RT.
FACTORS AFFECTING THE SULFIDE STRESS CRACKING PERFORMANCE OF HIGH STRENGTH STEELS

This report summarizes environmental, metallurgical, and stress effects on high strength steel performance in sour environments. A change in any one of these three factors can dramatically alter sulfide stress cracking performance. Environmental factors that have been studied include pH, various acids and salts, concentration of hydrogen sulfide, temperature, and corrosion inhibitors. Metallurgical variables studied include hardness, strength, ductility, microstructure, composition, hydrogen diffusivity, and cold work. The various forms of stressing the test specimens considered are uniform tensile, biaxial, notched specimens, plain strain, and residual stressing. All Environmental variables are interpreted with respect to manufacture and design of tubular goods for deep, sour wells.
Randomized prospective trial of the Angelchik anti‐reflux prosthesis

Fifty‐two patients with reflux oesophagitis resistant to medical treatment were randomized at operation to receive either the Angelchik prosthesis or a fundoplication. All patients were assessed postoperatively by a physician unaware of the nature of the operation. Forty‐two patients have been followed up for 1–2 years; ten patients for 3–9 months. Ninety‐six per cent of the Angelchik patients had satisfactory or excellent results compared with 81 per cent with a fundoplication. There were no failures to control reflux with the Angelchik prosthesis whereas 6 patients (23 per cent) of the fundoplication group have persisting reflux. Operating times for insertion of the prosthesis averaged a little over half that recorded for fundoplication. Complication rates were similar. The results of the trial encourage the use of the prosthesis in patients with gastro‐oesophageal reflux, where medical treatment has failed. The prosthesis should not be used if the gut is opened during operation either inadvertently or deliberately, as in making a suture line or anastomosis, because of the risk of sepsis.
Research and Development, Productivity, and Inflation

R & D, through its effects on the rate of productivity increase, can significantly restrain the rate of inflation in the medium and long run. High rates of inflation damage the workings of the price system and impair the efficiency of practically all economic activities, including R & D. Findings suggest that the percentage increase between 1969 and 1979, in total real R & D expenditures, has been exaggerated due to the inadequacy of the gross national product deflator as applied to R & D.
The CanMEDS initiative: implementing an outcomes-based framework of physician competencies

Background: Outcomes-based education in the health professions has emerged as a priority for curriculum planners striving to align with societal needs. However, many struggle with effective methods of implementing such an approach. In this narrative, we describe the lessons learned from the implementation of a national, needs-based, outcome-oriented, competency framework called the CanMEDS initiative of The Royal College of Physicians and Surgeons of Canada. Methods: We developed a framework of physician competencies organized around seven physician “Roles”: Medical Expert, Communicator, Collaborator, Manager, Health Advocate, Scholar, and Professional. A systematic implementation plan involved: the development of standards for curriculum and assessment, faculty development, educational research and resources, and outreach. Lessons learned: Implementing this competency framework has resulted in successes, challenges, resistance to change, and a list of essential ingredients for outcomes-based medical education. Conclusions: A multifaceted implementation strategy has enabled this large-scale curriculum change for outcomes-based education.
Martin P. Levin Distinguished Mentorship Award: reflections on mentorship in pediatric psychology: key issues and implications.

I regard this award as a significant honor, and I would like to acknowledge the Society of Pediatric Psychology (SPP), the extraordinary generosity of the Levin family, and the efforts of my own mentors, most especially Dick Lanyon, Bruce Cushna, Gail Gardner, and Don Routh. This occasion has afforded me the opportunity to reflect on mentoring on a personal level and to address the implications of mentoring for the field of pediatric psychology. To provide context concerning my current mentorship experience, at this time I am mentoring faculty psychologists and physicians at various stages of their careers, graduate students, and fellows. In my current position as director of a division of behavioral pediatrics and psychology within a department of pediatrics in an academic medical center, I provide research mentorship to students in a graduate program that specializes in pediatric psychology (Drotar, 1998) and mentorship for students’ clinical work in a department of pediatrics (Drotar & Zagorski, 2001). This discussion focuses on three key questions that have been drawn from these experiences. What are the challenges to the career development of pediatric psychologists? What characteristics of effective mentoring relationships will help our students best meet these challenges? What strategies are needed to enhance the quality of mentorship in the field of pediatric psychology? This discussion of mentoring is intended primarily for those with academic careers as pediatric psychologists.
Cathepsin S Inhibition Attenuates Neuropathic Pain and Microglial Response Associated with Spinal Cord Injury

Loss of function is usually considered the major consequence of spinal cord injury (SCI). However, chronic pain severely compromises the quality of life of many SCI patients. Recently, microglial cells in enhanced response states have been proposed to contribute to chronic pain following SCI. Here we report that following contusion injury, the microglial cysteine protease cathepsin S (CatS) is critical for the maintenance of SCI-induced neuropathic pain and spinal microglial response. Following SCI, significant mechanical and thermal hypersensitivity developed in both hind-paws. Prolonged intrathecal administration of the CatS inhibitor LHVS (morpholinurea-leucine-homophenylalanine- vinyl sulfone-phenyl), commencing day 26 post-SCI, resulted in significant attenuation of established mechanical and thermal pain behaviours compared to vehicle. This attenuation was evident as early as 24hrs following treatment initiation, and was maintained throughout the 7 day duration of drug administration. In addition, following the 7 day treatment period LHVS significantly attenuated the SCI-induced response of microglial in the lumbar dorsal horn of the spinal cord. We suggest that following SCI, CatS expressed by spinal microglia, is critical for the maintenance of below the level pain induced by contusion injury and suggest that CatS inhibition constitutes a novel therapeutic approach for the treatment of chronic pain associated with SCI.
Preoperative therapeutic exercise in frail elderly scheduled for total hip replacement: a randomized pilot trial

Objective: To evaluate the feasibility and preliminary effectiveness of therapeutic exercise before total hip replacement in frail elderly. Design: A single-blind, randomized clinical pilot trial. Setting: Outpatient physiotherapy department. Subjects: Frail elderly with hip osteoarthritis awaiting total hip replacement. Interventions: A short (3—6 weeks) tailor-made, therapeutic exercise programme was compared with usual care. Main measures: Feasibility was assessed through patient satisfaction, adherence, occurrence of adverse events and the number of eligible non-volunteers. Preliminary preoperative effectiveness was assessed with performance and self-reported measures of pain, functioning, physical activity and quality of life. Postoperatively we measured functional recovery and length of hospital stay. Results: Sixty-two eligible patients were approached of whom 21 (mean age 76 years) agreed to participate. Exercisers (n = 10), rated the intervention as very good 8.9 (8—10) (10-point rating scale). No serious adverse events occurred. Forty-one (66%) eligible patients did not participate, mainly because of logistic considerations, resulting in selection bias. The intervention group (trainings sessions participated 91%) showed relevant preoperative improvements on the chair-rise time (delta —2.9 seconds; 95% confidence interval (CI) —6.2 to 0.4) and timed-up-and-go (delta —4.4 seconds; 95% CI —9.3 to 0.5). Postoperatively, no significant differences were seen. Conclusions: A short, tailor-made, exercise programme is well tolerated and appreciated in elderly patients awaiting total hip replacement. However, a larger randomized clinical trial in the same setting is not warranted, because of the high number of eligible non-volunteers.
INCESTUOUS MATE PREFERENCE BY A SIMULTANEOUS HERMAPHRODITE WITH STRONG INBREEDING DEPRESSION

Abstract Inbreeding depression and its consequences for mate choice have been extensively studied in free-living animals. However, very little is known about its significance for parasites, although it is well recognized that the mating systems of parasites can have important implications for their epidemiology and evolution. In this article, we show that the cestode Schistocephalus solidus shows incestuous mate preference despite evidence for very strong inbreeding depression. When given the simultaneous choice between mating with a sibling and an unrelated partner, on average, the cestode preferred its sibling. To explain this surprising result, we present three hypotheses that suggest different benefits to fitness of incestuous mating, which could, alone or in concert, outweigh the cost of inbreeding depression.
Extreme apprenticeship method: key practices and upward scalability

Programming is a craft that can be efficiently learned from people who already master it. Our previous work introduced a teaching method we call Extreme Apprenticeship (XA), an extension to the cognitive apprenticeship model. XA is based on a set of values that emphasize doing and best programming practices, together with continuous feedback between the master and the apprentice. Most importantly, XA is individual instruction that can be applied even in large courses. Our initial experiments (n = 67 and 44) resulted in a significant increase in student achievement level compared to previous courses. In this paper, we reinforce the validity of XA by larger samples (n = 192 and 147) and a different lecturer. The results were similarly successful and show that the application of XA can easily suffer if the core values are not fully adhered to.
MURF2B, a Novel LC3-Binding Protein, Participates with MURF2A in the Switch between Autophagy and Ubiquitin Proteasome System during Differentiation of C2C12 Muscle Cells

The ubiquitin proteasome system and macroautophagy are proteolytic pathways essential in the maintenance of cellular homeostasis during differentiation and remodelling of skeletal muscle. In both pathways, proteins to be degraded are tagged with polyubiquitin. In skeletal muscles, the MURF2 proteins display E3 ubiquitin ligase structure suggesting that they may covalently attach ubiquitin polypeptides to still unknown target proteins. So far only MURF2A isoforms were studied and shown to interact with p62/SQSTM1, a protein implicated in macroautophagic and ubiquitin proteasome system degradations. Here, we analyzed the MURF2B and MURF2A proteins and show that the ratio of the isoforms changes during differentiation of muscle C2C12 cells and that the shift of the isoforms expression follows the sequential activation of autophagic or proteasomal degradation. We also show that MURF2B has a functional domain needed for its interaction with LC3, a protein needed for autophagic vesicles formation. Using specific MURF2 RNAi cells we observed that MURF2A and MURF2B are both needed for the formation of autophagosomes and that in the absence of MURF2B, the cells expressing MURF2A display an activated ubiquitin proteasome system implicated in the degradation of p62/SQSTM1 by UPS. Altogether, our results indicate that MURF2A and MURF2B proteins could participate in the molecular switch between the two ubiquitin degradative pathways.
Mast Cells: Potential Positive and Negative Roles in Tumor Biology

Mast cells are immune cells that reside in virtually all vascularized tissues. Upon activation by diverse mechanisms, mast cells can secrete a broad array of biologically active products that either are stored in the cytoplasmic granules of the cells (e.g., histamine, heparin, various proteases) or are produced de novo upon cell stimulation (e.g., prostaglandins, leukotrienes, cytokines, chemokines, and growth factors). Mast cells are best known for their effector functions during anaphylaxis and acute IgE-associated allergic reactions, but they also have been implicated in a wide variety of processes that maintain health or contribute to disease. There has been particular interest in the possible roles of mast cells in tumor biology. In vitro studies have shown that mast cells have the potential to influence many aspects of tumor biology, including tumor development, tumor-induced angiogenesis, and tissue remodeling, and the shaping of adaptive immune responses to tumors. Yet, the actual contributions of mast cells to tumor biology in vivo remain controversial. Here, we review some basic features of mast cell biology with a special emphasis on those relevant to their potential roles in tumors. We discuss how using in vivo tumor models in combination with models in which mast cell function can be modulated has implicated mast cells in the regulation of host responses to tumors. Finally, we summarize data from studies of human tumors that suggest either beneficial or detrimental roles for mast cells in tumors. Cancer Immunol Res; 1(5); 269–79. ©2013 AACR.
Naturalistic Decision Making in Forensic Science: Toward a Better Understanding of Decision Making by Forensic Team Leaders

Abstract: This study uses the naturalistic decision‐making (NDM) perspective to examine how Dutch forensic team leaders (i.e., the officers in charge of criminal forensic research from the crime scene until the use of laboratory assistance) make decisions in real‐life settings and identifies the contextual factors that might influence those decisions. First, a focus group interview was conducted to identify four NDM mechanisms in day‐to‐day forensic decision making. Second, a serious game was conducted to examine the influence of three of these contextual mechanisms. The results uncovered that forensic team leaders (i) were attracted to obtain further information when more information was initially made available, (ii) were likely to devote more attention to emotionally charged cases, and (iii) used not only forensic evidence in the decision making but also tactical, unverified information of the police inquiry. Interestingly, the measured contextual influences did not deviate significantly from a control group of laypeople.
Extracellular protease from the antarctic yeast Candida humicola

The psychrotrophic, dimorphic yeast Candida humicola, isolated from Antarctic soil, secretes an acidic protease into the medium. The secretion of this protease by C. humicola was found to be dependent on the composition of the medium. In YPD or yeast nitrogen base medium containing either amino acids or ammonium sulfate as the nitrogen source, the activity of the protease in the medium was low (basal level). However, when yeast nitrogen base medium was depleted of amino acids or ammonium sulfate and supplemented with proteins, the activity of the enzyme increased. The secretion of the enzyme was greater during exponential growth at low temperatures than during growth at higher temperatures. The purified protease had a molecular mass of 36,000 Da and was inhibited by pepstatin, iodoacetamide, and sodium dodecyl sulfate. Despite the prevalent cold temperatures in Antarctica, this extracellular protease of the psychrotrophic yeast C. humicola was active at temperatures ranging from 0 to 45 degrees C, with an optimum activity at 37 degrees C.
Estimating Empirical Codon Hidden Markov Models

Empirical codon models (ECMs) estimated from a large number of globular protein families outperformed mechanistic codon models in their description of the general process of protein evolution. Among other factors, ECMs implicitly model the influence of amino acid properties and multiple nucleotide substitutions (MNS). However, the estimation of ECMs requires large quantities of data, and until recently, only few suitable data sets were available. Here, we take advantage of several new Drosophila species genomes to estimate codon models from genome-wide data. The availability of large numbers of genomes over varying phylogenetic depths in the Drosophila genus allows us to explore various divergence levels. In consequence, we can use these data to determine the appropriate level of divergence for the estimation of ECMs, avoiding overestimation of MNS rates caused by saturation. To account for variation in evolutionary rates along the genome, we develop new empirical codon hidden Markov models (ecHMMs). These models significantly outperform previous ones with respect to maximum likelihood values, suggesting that they provide a better fit to the evolutionary process. Using ECMs and ecHMMs derived from genome-wide data sets, we devise new likelihood ratio tests (LRTs) of positive selection. We found classical LRTs very sensitive to the presence of MNSs, showing high false-positive rates, especially with small phylogenies. The new LRTs are more conservative than the classical ones, having acceptable false-positive rates and reduced power.
A Comprehensive Immunoreceptor Phosphotyrosine-based Signaling Network Revealed by Reciprocal Protein–Peptide Array Screening*

Cells of the immune system communicate with their environment through immunoreceptors. These receptors often harbor intracellular tyrosine residues, which, when phosphorylated upon receptor activation, serve as docking sites to recruit downstream signaling proteins containing the Src Homology 2 (SH2) domain. A systematic investigation of interactions between the SH2 domain and the immunoreceptor tyrosine-based regulatory motifs (ITRM), including inhibitory (ITIM), activating (ITAM), or switching (ITSM) motifs, is critical for understanding cellular signal transduction and immune function. Using the B cell inhibitory receptor CD22 as an example, we developed an approach that combines reciprocal or bidirectional phosphopeptide and SH2 domain array screens with in-solution binding assays to identify a comprehensive SH2-CD22 interaction network. Extending this approach to 194 human ITRM sequences and 78 SH2 domains led to the identification of a high-confidence immunoreceptor interactome containing 1137 binary interactions. Besides recapitulating many previously reported interactions, our study uncovered numerous novel interactions. The resulting ITRM-SH2 interactome not only helped to fill many gaps in the immune signaling network, it also allowed us to associate different SH2 domains to distinct immune functions. Detailed analysis of the NK cell ITRM-mediated interactions led to the identification of a network nucleated by the Vav3 and Fyn SH2 domains. We showed further that these SH2 domains have distinct functions in cytotoxicity. The bidirectional protein-peptide array approach described herein may be applied to the numerous other peptide-binding modules to identify potential protein–protein interactions in a systematic and reliable manner.
Increased serum glycated albumin level is associated with the presence and severity of coronary artery disease in type 2 diabetic patients.

BACKGROUND Glycated albumin is the predominant circulating Amadori-type glycated protein in vivo and plays a major role in the development of diabetic vascular complications. The aim of this study was to assess the relationship between increased serum glycated albumin level and the presence and severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS In a total of 320 consecutive patients with T2DM, coronary angiography revealed normal coronary arteries in 83 patients (control group) and significant coronary stenosis (> or = 70% luminal diameter narrowing) in 237, of whom 51 patients had 1-vessel disease (Group I), 80 had 2-vessel disease (Group II), and 106 had 3-vessel disease (Group III). Serum glycated albumin, hemoglobin A(1c) (HbA(1c)) and tumor necrosis factor (TNF)-alpha levels, lipid profile, and renal function were measured. Logistic regression analysis was performed to determine the relative risk of serum glycated albumin level for the presence and severity of CAD. Multivariate stepwise linear regression analysis was done to identify independent determinants of the glycated albumin level. Serum glycated albumin (21.2+/-5.3% vs 19.4+/-4.3%, p=0.005) and TNF-alpha levels (123 +/-115 pg/ml vs 65+/-59 pg/ml, p<0.001) were significantly higher in patients with CAD than in controls, but serum HbAlc level did not significantly differ between them (7.6+/-1.3% vs 7.4+/-1.2%, p=0.19). There was a significant difference in serum glycated albumin level between Groups I and III (19.5+/-3.3% vs 21.8+/-5.7%, p<0.001). The serum glycated albumin level correlated with the number of diseased arteries (Spearman r=0.205, p<0.001), and was closely related to serum levels on admission of glucose (r=0.495, p<0.001), TNF-alpha (r=0.123, p=0.028), blood urea nitrogen (r=0.167, p=0.004), triglycerides (r=0.129, p=0.021), and HbA(1c) (r=0.795, p<0.001). Multivariate analysis indicated that serum levels of glucose (p<0.0001), TNF-alpha (p=0.001), blood urea nitrogen (p=0.004) and triglycerides (p=0.035) were independent determinants for glycated albumin. Logistic regression analysis revealed that glycated albumin > or = 19% (odds ratio (OR) 2.9, p<0.001) was an independent predictor for CAD and glycated albumin > or = 21% (OR 2.3, p=0.032) for 3-vessel disease prediction. The area under the receiver-operating characteristic curve for glycated albumin (0.620, 95% confidence interval (CI) 0.548 to 0.691, p=0.001) was superior to that for HbA(1c) (0.543, 95% CI 0.473 to 0.613, p=0.243). CONCLUSIONS An increased serum level of glycated albumin is associated with the presence and severity of CAD, and may be useful in screening patients with T2DM.