Miracle-dz/UniFAR-FTUs huggingface dataset:
Numerical Safety Study of Currents Induced in the Patient During Rotations in the Static Field Produced by a Hybrid MRI-LINAC System

MRI-LINAC is a new image-guided radiotherapy treatment system that combines magnetic resonance imaging (MRI) and a linear particle accelerator (LINAC) into a single unit. Moving (i.e., rotating or translating) the patient inside the strong magnetic field of the split MRI-LINAC magnet can potentially induce high levels of electric fields and corresponding current densities in the conducting tissues. The prediction and assessment of patient safety in terms of electromagnetic field exposure have received very little attention for a split cylindrical MRI magnet configuration, especially in the vicinity of the gap region. In this novel numerical study, based on the quasi-static finite-difference method, rotation-induced electric fields and current densities are calculated considering a split 1-T magnet and a tissue-accurate 2-mm-resolution human body model. The patient was modeled in both axial and radial orientations relative to the magnet gap in a number of treatment/imaging scenarios. It was found that rotating the patient in the radial orientation produced an order of magnitude larger field exposure in the central nervous system than when the patient was rotated in the axial orientation. Also, rotating the patient with periods lower than about Trot = 43.3 s may result in field exposures above the limits set out in the international safety guidelines. The novel results of this investigation can provide useful insights into the safe use of the MRI-LINAC technology and optimal orientations of the patient during the treatment.
Diverse Effects of Lead Nitrate on the Proliferation, Differentiation, and Gene Expression of Stem Cells Isolated from a Dental Origin

Lead (Pb2+) exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb2+ toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb2+ concentrations (160, 80, 40, 20, and 10 µM) for 24 hours to identify the adverse effects of Pb2+ on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb2+ treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb2+ continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1) and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb2+ exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.
Hormones and diet, but not body weight, control hypothalamic microglial activity

The arcuate nucleus (ARC) of the hypothalamus plays a key role in sensing metabolic feedback and regulating energy homeostasis. Recent studies revealed activation of microglia in mice with high‐fat diet (HFD)‐induced obesity (DIO), suggesting a potential pathophysiological role for inflammatory processes within the hypothalamus. To further investigate the metabolic causes and molecular underpinnings of such glial activation, we analyzed the microglial activity in wild‐type (WT), monogenic obese ob/ob (leptin deficient), db/db (leptin‐receptor mutation), and Type‐4 melanocortin receptor knockout (MC4R KO) mice on either a HFD or on standardized chow (SC) diet. Following HFD exposure, we observed a significant increase in the total number of ARC microglia, immunoreactivity of ionized calcium binding adaptor molecule 1 (iba1‐ir), cluster of differentiation 68 (CD68‐ir), and ramification of microglial processes. The ob/ob mice had significantly less iba1‐ir and ramifications. Leptin replacement rescued these phenomena. The db/db mice had similar iba1‐ir comparable with WT mice but had significantly lower CD68‐ir and more ramifications than WT mice. After 2 weeks of HFD, ob/ob mice showed an increase of iba1‐ir, and db/db mice showed increase of CD68‐ir. Obese MC4R KO mice fed a SC diet had comparable iba1‐ir and CD68‐ir with WT mice but had significantly more ramifications than WT mice. Intriguingly, treatment of DIO mice with glucagon‐like peptide‐1 receptor agonists reduced microglial activation independent of body weight. Our results show that diet type, adipokines, and gut signals, but not body weight, affect the presence and activity levels of hypothalamic microglia in obesity. GLIA 2013;62:17–25
Managing lapses in cardiac rehabilitation exercise therapy: examination of the problem-solving process.

PURPOSE/OBJECTIVE Poor adherence to cardiac rehabilitation (CR) exercise therapy is an ongoing problem. Problem-solving (PS) is an identified cognitive-behavioral strategy to promote exercise adherence. However, PS process has not been examined, and how PS promotes adherence is not known. Using Social Cognitive Theory and Ewart's Social Problem-Solving Model as guiding frameworks, we examined proposed theoretical links between persistence, an indicator of adherence, and (a) PS effectiveness and (b) self-regulatory efficacy. Based on the Model of Social Problem-Solving, 2 distinct components of the PS process (problem-solving and solution implementation), were examined. RESEARCH METHOD/DESIGN Older adult participants (N = 52; 32 men) representing a typical CR sample (mean age = 65.6 years; SD = 10.8) participated in this correlational, observational study. RESULTS Two hierarchical multiple regressions indicated that PS effectiveness and self-regulatory efficacy were significant predictors of anticipated persistence. Relative to PS process, both predictors accounted for: (a) 41% of the variance in anticipated persistence with PS; and (b) 49% of the variance in anticipated persistence with solution implementation. CONCLUSIONS/IMPLICATIONS Proposed theoretical relationships were supported, and both PS effectiveness and self-regulatory efficacy accounted for a greater amount of the variance in anticipated persistence than either alone. Future efforts to improve adherence to rehabilitative exercise could include the use of PS. The 2 distinct components of the PS process may be important for successful adjustment to problems.
The type III secretion system needle tip complex mediates host cell sensing and translocon insertion

Type III secretion systems (T3SSs) are essential virulence determinants of many Gram‐negative bacterial pathogens. The Shigella T3SS consists of a cytoplasmic bulb, a transmembrane region and a hollow ‘needle’ protruding from the bacterial surface. Physical contact with host cells initiates secretion and leads to assembly of a pore, formed by IpaB and IpaC, in the host cell membrane, through which proteins that facilitate host cell invasion are translocated. As the needle is implicated in host cell sensing and secretion regulation, its tip should contain components that initiate host cell contact. Through biochemical and immunological studies of wild‐type and mutant Shigella T3SS needles, we reveal tip complexes of differing compositions and functional states, which appear to represent the molecular events surrounding host cell sensing and pore formation. Our studies indicate that the interaction between IpaB and IpaD at needle tips is key to host cell sensing, orchestration of IpaC secretion and its subsequent assembly at needle tips. This allows insertion into the host cell membrane of a translocation pore that is continuous with the needle.
A tutorial on the universality and expressiveness of fold

In functional programming, fold is a standard operator that encapsulates a simple pattern of recursion for processing lists. This article is a tutorial on two key aspects of the fold operator for lists. First of all, we emphasize the use of the universal property of fold both as a proof principle that avoids the need for inductive proofs, and as a definition principle that guides the transformation of recursive functions into definitions using fold. Secondly, we show that even though the pattern of recursion encapsulated by fold is simple, in a language with tuples and functions as first-class values the fold operator has greater expressive power than might first be expected.
Quantitative proteomics using SILAC: Principles, applications, and developments

SILAC is based on direct addition of selected stable isotope amino acids into the cell culture medium, allowing superior quantitative analysis of the cellular proteome compared to other labeling methods. The great advantages of SILAC lie in its straight‐forward implementation, quantitative accuracy, and reproducibility over chemical labeling or label‐free quantification strategies, favoring its adoption for proteomic research. SILAC has been widely applied to characterize the proteomic changes between different biological samples, to investigate dynamic changes of protein PTMs, to distinguish specific interacting proteins in interaction proteomic analysis, and to analyze protein turnover in the proteome‐wide scale. The present review summarizes the principles of SILAC technology, its applications in biological research, and the present state of this technology.
Developing a high-performance web server in Concurrent Haskell

Server applications, and in particular network-based server applications, place a unique combination of demands on a programming language: lightweight concurrency, high I/O throughput, and fault tolerance are all important. This paper describes a prototype web server written in Concurrent Haskell (with extensions), and presents two useful results: firstly, a conforming server could be written with minimal effort, leading to an implementation in less than 1500 lines of code, and secondly the naive implementation produced reasonable performance. Furthermore, making minor modifications to a few time-critical components improved performance to a level acceptable for anything but the most heavily loaded web servers.
Teacher development by e-learning: Building capacity toward the information society

E-learning has played an increasingly important role in supporting the economic and educational growth of many nations. It also offers opportunities for developing nations to enhance their educational and economic development. Worldwide there is growing demand for teachers who have the skills to prepare students to be successful in a technology-infused, knowledge-based society. E-learning can play a critical role in preparing a new generation of teachers, as well as upgrading the skills of the existing teaching force and pedagogies for learning. The presentation discusses the importance of including e-learning for teacher development as part of a national strategy for educational and economic development; its role in helping to meet the quantitative and qualitative demand for teachers; and the essential conditions that must be met for effective use of e-learning for teacher development.
Hospital-level variation in the use of intensive care.

OBJECTIVE To determine the extent to which hospitals vary in the use of intensive care, and the proportion of variation attributable to differences in hospital practice that is independent of known patient and hospital factors. DATA SOURCE Hospital discharge data in the State Inpatient Database for Maryland and Washington States in 2006. STUDY DESIGN Cross-sectional analysis of 90 short-term, acute care hospitals with critical care capabilities. DATA COLLECTION/METHODS: We quantified the proportion of variation in intensive care use attributable to hospitals using intraclass correlation coefficients derived from mixed-effects logistic regression models after successive adjustment for known patient and hospital factors. PRINCIPAL FINDINGS The proportion of hospitalized patients admitted to an intensive care unit (ICU) across hospitals ranged from 3 to 55 percent (median 12 percent; IQR: 9, 17 percent). After adjustment for patient factors, 19.7 percent (95 percent CI: 15.1, 24.4) of total variation in ICU use across hospitals was attributable to hospitals. When observed hospital characteristics were added, the proportion of total variation in intensive care use attributable to unmeasured hospital factors decreased by 26-14.6 percent (95 percent CI: 11, 18.3 percent). CONCLUSIONS Wide variability exists in the use of intensive care across hospitals, not attributable to known patient or hospital factors, and may be a target to improve efficiency and quality of critical care.
aPKC enables development of zonula adherens by antagonizing centripetal contraction of the circumferential actomyosin cables

Atypical protein kinase C (aPKC) generally plays crucial roles in the establishment of cell polarity in various biological contexts. In mammalian epithelial cells, aPKC essentially works towards the transition of primordial spot-like adherens junctions (AJs) into continuous belt-like AJs, also called zonula adherens, lined with perijunctional actin belts. To reveal the mechanism underlying this aPKC function, we investigated the functional relationship between aPKC and myosin II, the essential role of which in epithelial-junction development was recently demonstrated. Despite its deleterious effects on junction formation, overexpression of a dominant-negative mutant of aPKC (aPKCλ kn) did not interfere with the initial phase of myosin-II activation triggered by the formation of Ca2+-switch-induced cell-cell contacts. Furthermore, cells overexpressing aPKCλ kn exhibited myosin-II-dependent asymmetric organization of F-actin along the apicobasal axis, suggesting that aPKC contributes to junction development without affecting the centripetal contraction of the circumferential actomyosin cables. Time-lapse analyses using GFP-actin directly revealed that the circumferential actomyosin cables were centrifugally expanded and developed into perijunctional actin belts during epithelial polarization, and that aPKCλ kn specifically compromised this process. Taken together, we conclude that aPKC is required for antagonizing the myosin-II-driven centripetal contraction of the circumferential actin cables, thereby efficiently coupling the myosin-II activity with junction development and cell polarization. The present results provide novel insights into not only the site of action of aPKC kinase activity but also the role of actomyosin contraction in epithelial polarization.
Cost-effectiveness of N-butyl-2-cyanoacrylate (histoacryl) glue injections versus transjugular intrahepatic portosystemic shunt in the management of acute gastric variceal bleeding

ABSTRACTThe management of bleeding gastric varices has not been standardized. Although transjugular intrahepatic portosystemic shunt (TIPS) is used in most centers, endoscopic treatment with N-butyl-2-cyanoacrylate (cyanoacrylate) glue has recently been shown to be effective. Cost-effectiveness analyses of these methods are lacking.METHODS:We performed a retrospective review of patients with bleeding gastric varices treated either by TIPS or cyanoacrylate glue injection. Economic analysis was based on direct costs for a fixed financial year. The two groups were compared for a period of 6 months follow-up, to liver transplantation, or death for each patient.RESULTS:Between January, 1995 and December, 1999, 20 patients with bleeding gastric varices had TIPS; 23 patients had cyanoacrylate glue injection from January, 2000 to October, 2001. There were no significant differences between the two groups in patient characteristics, transfusion requirement, and gastric variceal anatomy. In the TIPS group, 15/20 patients had the procedure performed within 24 h of hemorrhage, and 90% of stent insertions were successful. Complications consisted of two cases of pulmonary edema, two cases of severe encephalopathy, and a 15% stenosis rate at 6 months. In the glue group, there were 3 ± 1.5 endoscopies and 2 ± 1 injections per patient, with a 96% initial hemostasis. There was one case of (glue) pulmonary embolism and one blocked front endoscope lens, which required repair. The initial rebleed rate was significantly lower in patients who had TIPS (15% vs 30%, p = 0.005). The inpatient stay was shorter in the glue group (13 ± 1 vs 18 ± 2 days, p = 0.05), but there was no difference in the overall mortality rate. The median cost within 6 months of initial gastric variceal bleeding was $4,138 ($3,009–$8,290) for glue versus $ 11,906 ($8,200–$16,770) for TIPS (p < 0.0001). CONCLUSION:In this comparable group of patients, cyanoacrylate glue injection was more cost effective than TIPS in the management of acute gastric variceal bleeding. A prospective, randomized trial would be required to confirm our analysis.
Nitroblue tetrazolium reduction and bone resorption by osteoclasts in vitro inhibited by a manganese‐based superoxide dismutase mimic

Oxygen‐derived free radicals are produced by osteoclasts. Oxygen radical formation occurs at the osteoclast/bone surface interface. This location next to bone implies that oxygen radicals, including but not limited to superoxide, are needed for bone resorption. Compounds that scavenge superoxide are being developed as pharmaceutical agents to inhibit the damaging effects of oxygen radical formation on tissues. One such scavenger is the Desferal‐manganese complex (DMnC). DMnC reduced the amount of formazan staining produced by the interaction of oxygen radicals with nitroblue tetrazolium (NBT) in both individual mouse calvarial osteoclasts in tissue explants and isolated osteoclasts. As a result of the reduced concentrations of oxygen radicals, DMnC inhibited bone resorption by calvarial explants and isolated osteoclasts. Superoxide dismutase (SOD) inhibited NBT reduction and bone resorption by isolated osteoclasts but to a lesser degree than DMnC. Inhibition of bone resorption in the isolated osteoclast system increased in parallel to the concentration of DMnC in cultures. Desferal without Mn had no effect on bone resorption by isolated osteoclasts. These results support the hypothesis that osteoclasts produce oxygen radicals as part of the process of bone resorption.
Comparative Effectiveness of Therapeutic Hypothermia After Out-of-Hospital Cardiac Arrest: Insight from a Large Data Registry.

This study was done to determine the effectiveness of therapeutic hypothermia (TH) after out-of-hospital cardiac arrest (OHCA) among a large cohort of adults in the Cardiac Arrest Registry to Enhance Survival (CARES), with an emphasis on subgroups with a nonshockable first documented rhythm. This was an IRB approved retrospective cohort study. All adult index events at participating sites from November 2010 to December 2013 were study eligible. All patient data elements were provided. Summary statistics were calculated for all patients with and without TH. For multivariate adjustment, a multilevel (i.e., hierarchical), mixed-effects logistic regression (MLR) model was used with hospitals treated as random effects. Propensity score matching (PSM) on both shockable and nonshockable patients was done as a sensitivity analysis. After predefined exclusions, our final sample size was 6369 records for analysis: shockable=2992 (47.0%); asystole=1657 (26.0%); pulseless electrical activity=1249 (19.6%); other unspecified nonshockable=471 (7.4%). Unadjusted differences in neurological status at hospital discharge with and without TH were similar (p=0.295). After multivariate adjustment, TH had either no association with good neurological status at hospital discharge or that TH was actually associated with worse neurological outcome, particularly in patients with a nonshockable first documented rhythm (i.e., for NS patients, MLR odds ratio for TH=1.444; 95% CI [1.039, 2.006] p=0.029, and OR=1.017, p=0.927 via PSM). Highlighting our limitations, we conclude that when TH is indiscriminately provided to a large population of OHCA survivors with a nonshockable first documented rhythm, evidence for its effectiveness is diminished. We suggest more uniform and rigid guidelines for application.
[Total white blood cell count, erythrosedimentation rate and C-reactive protein for the detection of serious bacterial infections in 0- to 90-day-old infants with fever without a source].

INTRODUCTION Total white blood cell count (WBC), erythrosedimentation rate (ESR) and C-reactive protein (CRP) are frequently used by primary care physicians attending infants < 90 days old with fever without localizing signs to distinguish those with a serious bacterial infection (SBI). The main objective of this study was to obtain the diagnostic values of these parameters in infants with fever. PATIENTS AND METHODS We analyzed previously healthy infants aged 0 to 90 days old and fever with no source of infection admitted to the emergency room and/or hospitalized. The main outcome measure was the presence or absence of a SBI (urinary tract infection, bacteremia, meningitis, pneumonia, enteritis) and diagnostic values of WBC, ESR and CRP. RESULTS A total of 103 infants met the inclusion criteria. Of these, 22 infants (21.3%) had a SBI, the most common being urinary tract infection. Absolute neutrophil count (ANC) and WBC had an area under the ROC curve (AUC) of 0.6 (95% CI: 0.46-0.73) and 0.55 (95% CI: 0.44-0.68) respectively. An ANC>or=10,000/microl had a sensitivity and specificity of 9% (95% CI: 1-21) and 92.5% (95% CI: 86-98) respectively. A WBC>or=15,000/microl had a sensitivity and specificity of 13.6% (95% CI: 1-28) and 85% (95% CI: 77-93) respectively. CRP showed an AUC of 0.71 (95% CI: 0.55-0.86) and a best cut-off point of 2 mg/dL (sensitivity 53% [95% CI: 29-76] and specificity of 85% [95% CI: 75-94]). ESR>or=20 mm/hour had an AUC, sensitivity and specificity of 0.53 (95% CI: 0.37-0.7), 38% (95% CI: 16-62) and 75% (95% CI: 65-85) respectively. CONCLUSIONS None of these parameters alone, commonly used by physicians, is a reliable diagnostic tool to rule out SBI in infants<90 days old with fever without source of infection.
Diagnostic and clinical importance of interleukin‐2 receptor alpha chain expression on non‐T‐cell acute leukaemia cells

The expression of interleukin‐2 receptors (IL‐2R) was examined in 328 adult patients with non‐T‐cell (non‐T) acute leukaemia and blast crisis of chronic myelocytic leukaemia (CML.BC) using two monoclonal antibodies, anti‐Tac for IL‐2R α chain (IL‐2Rα) and Mikβ1 for IL‐2R β chain (IL‐2Rβ). Leukaemic cells in the following cases were positive for anti‐Tac; 28/192 of acute myelocytic leukaemia (AML), 24/44 CML‐BC, 4/28 CD19(+)CD10(‐) acute lympho‐blastic leukaemia (ALL), and 20/64 common ALL (c‐ALL). IL‐2Rβ was not detected on leukaemic cells of any case examined. Eleven of IL‐2Rα(+) AML were derived from myelodysplastic syndrome. None of the IL‐2Rα positive leukaemic cells responded to exogenous recombinant human IL‐2 (rhIL‐2) in culture. In addition, IL‐2Rα expression on non‐T leukaemic cells was closely correlated with coexpressing different lineage markers and the presence of the Philadelphia abnormality. Marked increase of serum soluble IL‐2Rα was demonstrated in the IL‐2Rα(+) patients examined. Clinically, the IL‐2Rα(+) patients showed significantly lower response to chemotherapy and poorer prognosis than IL‐2Rα(‐) patients. Our results clearly indicate the diagnostic importance of IL‐2Rα expression in non‐T acute leukaemia with a close relation to the particular cellular characteristics and the prognosis.