Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibiotic Management of Staphylococcus aureus Infections in US Children's Hospitals, 1999–2008

OBJECTIVES: The objective of this study was to describe trends in antibiotic management for Staphylococcus aureus infections among hospitalized children from 1999 to 2008. METHODS: A retrospective study was conducted by using the Pediatric Health Information Systems database to describe antibiotic treatment of inpatients with S aureus infection at 25 children's hospitals in the United States. Patients who were admitted from 1999 to 2008 with International Classification of Diseases, Ninth Revision, Clinical Modification codes for S aureus infection were included. Trends in the use of vancomycin, clindamycin, linezolid, trimethoprim-sulfamethoxazole, cefazolin, and oxacillin/nafcillin were examined for percentage use and days of therapy per 1000 patient-days. RESULTS: A total of 64813 patients had a discharge diagnosis for S aureus infection. The incidence of methicillin-resistant S aureus (MRSA) infections during this period increased 10-fold, from 2 to 21 cases per 1000 admissions, whereas the methicillin-susceptible S aureus infection rate remained stable. Among patients with S aureus infections, antibiotics that treat MRSA increased from 52% to 79% of cases, whereas those that treat only methicillin-susceptible S aureus declined from 66% to <30% of cases. Clindamycin showed the greatest increase, from 21% in 1999 to 63% in 2008. Similar trends were observed by using days of therapy per 1000 patient-days. CONCLUSIONS: Antibiotic prescribing patterns for the treatment of S aureus infections have changed significantly during the past decade, reflecting the emergence of community-associated MRSA. Clindamycin is now the most commonly prescribed antibiotic for S aureus infections among hospitalized children. The substantial use of clindamycin emphasizes the importance of continuous monitoring of local S aureus susceptibility patterns.
11β-Hydroxysteroid Dehydrogenase Type 1 Regulates Glucocorticoid-Induced Insulin Resistance in Skeletal Muscle

OBJECTIVE Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11β-HSD1 inhibitors improve insulin sensitivity. RESEARCH DESIGN AND METHODS Rodent and human cell cultures, whole-tissue explants, and animal models were used to determine the impact of glucocorticoids and selective 11β-HSD1 inhibition upon insulin signaling and action. RESULTS Dexamethasone decreased insulin-stimulated glucose uptake, decreased IRS1 mRNA and protein expression, and increased inactivating pSer307 insulin receptor substrate (IRS)-1. 11β-HSD1 activity and expression were observed in human and rodent myotubes and muscle explants. Activity was predominantly oxo-reductase, generating active glucocorticoid. A1 (selective 11β-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer307 IRS1 and reduction in total IRS1 protein after treatment with 11DHC but not corticosterone. In C57Bl6/J mice, the selective 11β-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin sensitivity. In KK mice treated with A2, skeletal muscle pSer307 IRS1 decreased and pThr308 Akt/PKB increased. In addition, A2 decreased both lipogenic and lipolytic gene expression. CONCLUSIONS Prereceptor facilitation of glucocorticoid action via 11β-HSD1 increases pSer307 IRS1 and may be crucial in mediating insulin resistance in skeletal muscle. Selective 11β-HSD1 inhibition decreases pSer307 IRS1, increases pThr308 Akt/PKB, and decreases lipogenic and lipolytic gene expression that may represent an important mechanism underpinning their insulin-sensitizing action.
Checking consistency of C and Verilog using predicate abstraction and induction

It is common practice to write C models of circuits due to the greater simulation efficiency. Once the C program satisfies the requirements, the circuit is designed in a hardware description language (HDL) such as Verilog. It is therefore highly desirable to automatically perform a correspondence check between the C model and a circuit given in HDL. We present an algorithm that checks consistency between an ANSI-C program and a circuit given in Verilog using predicate abstraction. The algorithm exploits the fact that the C program and the circuit share many basic predicates. In contrast to existing tools that perform predicate abstraction, our approach is SAT-based and allows all ANSI-C and Verilog operators in the predicates. We report experimental results on an out-of-order RISC processor. We compare the performance of the new technique to bounded model checking (BMC).
CK2 acts as a potent negative regulator of receptor-mediated insulin release in vitro and in vivo

Significance G protein-coupled receptors (GPCRs) regulate the activity of virtually all cell types including pancreatic β-cells. β-Cell M3 muscarinic receptors (M3Rs) play an essential role in maintaining proper whole-body glucose homeostasis. Activity of the M3R, like that of other GPCRs, is modulated by phosphorylation by various kinases, including GRKs and casein kinase 2 (CK2). The potential physiological relevance of M3R phosphorylation (or of GPCRs in general) by CK2 remains unknown. We here show that CK2-dependent phosphorylation of β-cell M3Rs significantly impairs M3R-mediated increases in insulin release in vitro and in vivo. Our data demonstrate, for the first time to our knowledge, the physiological relevance of CK2 phosphorylation of a GPCR and suggest the novel concept that kinases acting on β-cell GPCRs may represent therapeutic targets. G protein-coupled receptors (GPCRs) regulate virtually all physiological functions including the release of insulin from pancreatic β-cells. β-Cell M3 muscarinic receptors (M3Rs) are known to play an essential role in facilitating insulin release and maintaining proper whole-body glucose homeostasis. As is the case with other GPCRs, M3R activity is regulated by phosphorylation by various kinases, including GPCR kinases and casein kinase 2 (CK2). At present, it remains unknown which of these various kinases are physiologically relevant for the regulation of β-cell activity. In the present study, we demonstrate that inhibition of CK2 in pancreatic β-cells, knockdown of CK2α expression, or genetic deletion of CK2α in β-cells of mutant mice selectively augmented M3R-stimulated insulin release in vitro and in vivo. In vitro studies showed that this effect was associated with an M3R-mediated increase in intracellular calcium levels. Treatment of mouse pancreatic islets with CX4945, a highly selective CK2 inhibitor, greatly reduced agonist-induced phosphorylation of β-cell M3Rs, indicative of CK2-mediated M3R phosphorylation. We also showed that inhibition of CK2 greatly enhanced M3R-stimulated insulin secretion in human islets. Finally, CX4945 treatment protected mice against diet-induced hyperglycemia and glucose intolerance in an M3R-dependent fashion. Our data demonstrate, for the first time to our knowledge, the physiological relevance of CK2 phosphorylation of a GPCR and suggest the novel concept that kinases acting on β-cell GPCRs may represent novel therapeutic targets.
An in vitro model for infection with Leishmania major that mimics the immune response in mice

By using a primary in vitro response specific for Leishmania major, normal T cells from resistant CBA/CaH-T6J and susceptible BALB/c mice commit to a Th1 and a Th2 response, respectively. Since commitment occurred, we measured the production of gamma interferon (IFN-gamma), interleukin-1 (IL-1), IL-2, IL-4, IL-5, IL-10, and IL-12, prostaglandin E2 (PGE2), transforming growth factor beta (TGF-beta), and nitric oxide in the first 7 days of the response to identify factors that are critical for Th1 and Th2 development. While cells from resistant CBA mice produced more IFN-gamma, IL-10, and nitric oxide, cells from susceptible BALB/c mice produced more IL-1alpha, IL-5, PGE2, and TGF-beta. Although substantial amounts of IL-12 were detected, IL-12 did not associate with either Th1 or Th2 development. We did not anticipate that cells from resistant CBA mice would make more IL-10 in vitro. However, this also occurred in vivo since CBA mice produced substantial amounts of IL-10 following infection with L. major. Moreover, adding anti-IL-10 to primary in vitro responses enhanced production of IFN-gamma and nitric oxide by cells from CBA and BALB/c mice. Therefore, IL-10 cannot be regarded as a cytokine that associates with susceptibility to infection with L. major. Finally, the data presented here suggest that a collection of factors that can be produced by accessory cells influence Th commitment (e.g., IL-1, PGE2, and TGF-beta favor Th2 development).
A scikit-based Python environment for performing multi-label classification

scikit-multilearn is a Python library for performing multi-label classification. The library is compatible with the scikit/scipy ecosystem and uses sparse matrices for all internal operations. It provides native Python implementations of popular multi-label classification methods alongside a novel framework for label space partitioning and division. It includes modern algorithm adaptation methods, network-based label space division approaches, which extracts label dependency information and multi-label embedding classifiers. It provides python wrapped access to the extensive multi-label method stack from Java libraries and makes it possible to extend deep learning single-label methods for multi-label tasks. The library allows multi-label stratification and data set management. The implementation is more efficient in problem transformation than other established libraries, has good test coverage and follows PEP8. Source code and documentation can be downloaded from this http URL and also via pip. The library follows BSD licensing scheme.
Heme Oxygenase-1 Protein Localizes to the Nucleus and Activates Transcription Factors Important in Oxidative Stress*

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is an integral membrane protein of the smooth endoplasmic reticulum. However, we detected an HO-1 immunoreactive signal in the nucleus of cultured cells after exposure to hypoxia and heme or heme/hemopexin. Under these conditions, a faster migrating HO-1 immunoreactive band was enriched in nuclear extracts, suggesting that HO-1 was cleaved to allow nuclear entry. This was confirmed by the absence of immunoreactive signal with an antibody against the C terminus and the lack of a C-terminal sequence by gas chromatographymass spectrometry. Incubation with leptomycin B prior to hypoxia abolished nuclear HO-1 and the faster migrating band on Western analysis, suggesting that this process was facilitated by CRM1. Furthermore, preincubation with a cysteine protease inhibitor prevented nuclear entry of green fluorescent protein-labeled HO-1, demonstrating that protease-mediated C-terminal cleavage was also necessary for nuclear transport of HO-1. Nuclear localization was also associated with reduction of HO activity. HO-1 protein, whether it was enzymatically active or not, mediated activation of oxidant-responsive transcription factors, including activator protein-1. Nevertheless, nuclear HO-1 protected cells against hydrogen peroxide-mediated injury equally as well as cytoplasmic HO-1. We speculate that nuclear localization of HO-1 protein may serve to up-regulate genes that promote cytoprotection against oxidative stress.
Cutting Edge: IRF8 Regulates Bax Transcription In Vivo in Primary Myeloid Cells

A prominent phenotype of IRF8 knockout (KO) mice is the uncontrolled expansion of immature myeloid cells. The molecular mechanism underlying this myeloproliferative syndrome is still elusive. In this study, we observed that Bax expression level is low in bone marrow preginitor cells and increases dramatically in primary myeloid cells in wt mice. In contrast, Bax expression level remained at a low level in primarymyeloid cells in IRF8 KO mice. However, in vitro IRF8 KO bone marrow-differentiated myeloid cells expressed Bax at a level as high as that in wild type myeloid cells. Furthermore, we demonstrated that IRF8 specifically binds to the Bax promoter region in primary myeloid cells. Functional analysis indicated that IRF8 deficiency results in increased resistance of the primary myeloid cells to Fas-mediated apoptosis. Our findings show that IRF8 directly regulates Bax transcription in vivo, but not in vitro during myeloid cell lineage differentiation.
Social Isolation and Aging in Zambia: Examining the Possible Predictors

This research paper examined social isolation and aging in Zambia by examining possible predictors. The paper produces evidence on risk factors likely to engender social isolation among the elderly population of Zambia. Snowball sampling was undertaken to select 690 adults aged 60 and over in communities as well as those living in homes for the aged. A structured questionnaire was used to solicit information from respondents. Results show that old people in Zambia experience forms of social isolation which exhibit themselves (but not limited to) through such factors as loss of appetite, stress, moody, hopeless, useless, unhappy, and lonely. On balance, however, the direction of association and the number of statistically significant findings suggest that associations between variables examined and risk factors associated with social isolation amongst older people in this analysis could explain the overall situation occuring currently in Zambia and probably other developing countries. In view of this, this study recommends that further work is needed to identify and explain details of factors of social isolation using techniques such as focus group discussions as well as in-depth interviews with key informants. Such approaches may even help to explain why, for example, sex seems not to be significant in determining indicators of social isolation.
On the Distribution of Class Groups of Number Fields

We propose a modification of the predictions of the Cohen-Lenstra heuristic for class groups of number fields in the case that roots of unity are present in the base field. As evidence for this modified formula we provide a large set of computational data that show close agreement with it. Furthermore, our predicted formula agrees with results on class groups of function fields in positive characteristic for which the base field contains appropriate roots of unity.
Spatial Distribution of Innovation Activities in Czech Republic, 2010-2012

Innovation is widely considered as an engine of economic growth, competitiveness and job creation. As such it has become a hot policy topic over the last years, especially on regional and national levels. Thus, it is vital to analyze and evaluate innovation activities, whether they are dispersed or concentrated in space. This article address the question: are innovations spatially clustered or not? In this article, we obtain a clear picture of the geographical distribution of innovation activities carried out by companies in Czech Republic during 20102012. Visual and statistical analysis of firm-level survey data concerning innovation activities of 5,449 (22% of the statistical population) Czech companies has been performed. Using four newly calculated innovation measures, their overall scores in Local Administrative Units 1 and consequent geovisualization allowed us revealing clusters of innovating districts and evaluating their spatial patterns. The main findings are that low innovative regions are located mainly (1) in the borderlands, (2) in rural areas, and (3) in mountainous areas. On the other hand, highly innovative regions tend to be in major cities and their neighborhoods, which indicates a positive spillover effect.
Genetic Isolation between the Western and Eastern Pacific Populations of Pronghorn Spiny Lobster Panulirus penicillatus

The pronghorn spiny lobster, Panulirus penicillatus, is a circumtropical species which has the widest global distribution among all the species of spiny lobster, ranging throughout the entire Indo-Pacific region. Partial nucleotide sequences of mitochondrial DNA COI (1,142–1,207 bp) and 16S rDNA (535–546 bp) regions were determined for adult and phyllosoma larval samples collected from the Eastern Pacific (EP)(Galápagos Islands and its adjacent water), Central Pacific (CP)(Hawaii and Tuamotu) and the Western Pacific (WP)(Japan, Indonesia, Fiji, New Caledonia and Australia). Phylogenetic analyses revealed two distinct large clades corresponding to the geographic origin of samples (EP and CP+WP). No haplotype was shared between the two regional samples, and average nucleotide sequence divergence (Kimura's two parameter distance) between EP and CP+WP samples was 3.8±0.5% for COI and 1.0±0.4% for 16S rDNA, both of which were much larger than those within samples. The present results indicate that the Pacific population of the pronghorn spiny lobster is subdivided into two distinct populations (Eastern Pacific and Central to Western Pacific), with no gene flow between them. Although the pronghorn spiny lobster have long-lived teleplanic larvae, the vast expanse of Pacific Ocean with no islands and no shallow substrate which is known as the East Pacific Barrier appears to have isolated these two populations for a long time (c.a. 1MY).
Phylogeography of the Cactophilic Drosophila and Other Arthropods Associated with Cactus Necroses in the Sonoran Desert

Studies on the population genetics, phylogenetic relationships, systematics and evolution of arthropods that inhabit necrotic tissue of cacti in the Sonoran Desert of North America are reviewed. These studies have focused upon several species of insects (orders Diptera and Coleoptera) and arachnids (order Pseudoscorpiones). For most taxa studied, little genetic structure and high dispersal ability are found in populations inhabiting the mainland and Baja California peninsula regions of the Sonoran Desert, consistent with the availability of the rotting cactus microhabitat which is patchily distributed and ephemeral. There is evidence, however, that the Gulf of California, which bisects the Sonoran Desert, has played a role in limiting gene flow and promoting speciation in several taxa, including histerid beetles, whereas other taxa, especially Drosophila nigrospiracula and D. mettleri, apparently are able to freely cross the Gulf, probably by taking advantage of the Midriff Islands in the northern Gulf as dispersal “stepping stones”. Genetic evidence has also been found for historical population expansions dating to the Pleistocene and late Pliocene in several taxa. Overall, these studies have provided important insights into how arthropods with different life history traits, but generally restricted to a necrotic cactus microhabitat, have evolved in an environmentally harsh and tectonically active region. In addition, they suggest some taxa for further, and more detailed, hypothesis driven studies of speciation.
Evaluation of surgery for Parkinson's disease: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

To the Editor: I write to comment on the report of the Task Force on Surgery for Parkinson’s Disease—particularly on the recommendations regarding bilateral deep brain stimulation of the subthalamic nucleus.1 I interpret “investigational” to mean that reasonable uncertainties exist. What is it about subthalamic nucleus stimulation that is uncertain? Reports from two major groups showed a highly significant reduction in parkinsonian symptoms. Assuming sound experimental design and appropriate statistical methods, is there any reasonable doubt that the subjects in these groups experienced symptom improvement? The answer is no. Most statistical tests are weighted against a type I error which is finding a difference when one does not truly exist. In one study,2 the changes in the Unified Parkinson Disease Rating Scales parts II and III were improved in the off-medication condition with a p < 0.001. 2 Power …
Adaptive integral position control using RBF neural networks for brushless DC linear motor drive

The paper presents an adaptive integral position controller usingRBF (Radial Basis Function) neural networks (NNs) for a brushless DC linear motor. By assuming that the upper bounds of the nonlinear friction and force ripple, an RBF NN is used for approximating the friction, the force ripple and the load; an adaptive backstepping control with integral action is then proposed to achieve position tracking of the linear motor. The parameter adjustment rules for the overall controller are derived via the Lyapunov stability theory. Based on the LaSalle-Yoshizawa lemma, the proposed controller is proven asymptotically stable. Experimental results are conducted to show the efficacy and usefulness of the proposed control method.
Early Histologic Changes Following Polymethylmethacrylate Injection (Vertebroplasty) in Rabbit Lumbar Vertebrae

Study Design. An ex vivo histologic study in rabbits. Objective. To evaluate the early histologic effects of polymethylmethacrylate (PMMA) injection on bone and intraosseous neural tissue following vertebroplasty in rabbit lumbar vertebrae. Summary of Background Data. Vertebroplasty with PMMA is performed to treat painful osteoporotic vertebral fractures. Early pain relief has been consistently documented, but its mechanism has not been elucidated. Among the mechanisms of pain relief may be the immediate stabilizing effects of the cement, and the exothermic reaction during curing, which may lead to intraosseous neural ablation. It has been well established that PMMA can induce thermal osteonecrosis after arthroplasty, but the potential for osteonecrosis after vertebroplasty has not been established. Previous studies have suggested that temperature elevations during cement curing may induce thermal bone necrosis. However, this cause-and-effect relationship has not yet been histologically studied in an animal model. Methods. Vertebroplasty with PMMA was performed at 2 levels in 12 New Zealand rabbits (24 levels); trochar insertion without PMMA injection was performed at 3 levels each of 2 control animals (6 levels). Sacrifice was performed 24 hours after the procedure. Histologic examination was performed to evaluate the presence of bone or intraosseous neural tissue necrosis. Results. Half of the levels with PMMA showed evidence of necrosis at the bone-cement interface. Almost all (11 of 12) showed only focal necrosis, with only 1 specimen showing necrosis along the entire periphery of the PMMA. The other 12 specimens and all control levels displayed no bone necrosis. There was no evidence of intraosseous neural tissue necrosis in control or PMMA-injected specimens. Conclusion. Injection of PMMA in rabbit lumbar vertebral bodies produces early, focal bone necrosis in only half of cases, suggesting that competency of the cement-bone interface is reasonable in most cases. No evidence of intraosseous neural tissue damage was found.