Miracle-dz/UniFAR-FTUs huggingface dataset:
Emergence of blaCTX-M-15, blaTEM-169 and blaPER-1 extended-spectrum β-lactamase genes among different Salmonella enterica serovars from human faecal samples

Abstract Background: Broad-spectrum β-lactams are used for empirical therapy of severe infections with non-typhoid Salmonella serotypes; however, activities of these drugs against the strains producing different β-lactamase is not so clear. This study investigated the prevalence of β-lactamase genes among isolates of S. enterica serovars from human faecal samples and determined their diversity in activity against different β-lactams. Methods: Antimicrobial resistance of faecal isolates of S. enterica to extended-spectrum cephalosporins was analysed and MIC values were determined for the strains presenting extended-spectrum β-lactamases (ESBLs) phenotypes. The β-lactamase genes were identified by PCR and sequencing. β-lactamase activity of the Salmonella strains exhibiting ESBL phenotype was detected by biological, iodometric, spectrophotometry and nitrocefin assays. Results: Out of 202 S. enterica isolates, ESBLs phenotype was detected among 3.4% (7/202) of the strains. blaTEM-1 and blaCTX-M-15 were among the frequent β-lactamase genes. Detection of blaTEM-169 in S. enterica serovar Typhimurium and S. enterica serovar Bredeney and blaPER-1 in S. enterica serovar Infantis was a new finding in this experiment. Location of blaCTX-M-15/blaTEM-169/blaPER-1 genes on plasmid was confirmed in a transformation experiment. While crude extracts of the enzymes from each strain showed higher activity against cephalothin and cefotaxime, the lowest activity was detected against ceftazidime. The greatest synergistic activity was seen in a strain of S. enterica that carried blaCTX-M-15 and blaPER-1 genes compared with those presenting blaCTX-M-15/blaTEM-169 or blaCTX-M-15/blaTEM-1 genotypes. Conclusions: The results show dissemination of ESBLs encoding genes and their combined activity among different serovars of S. enterica that are a threat for future treatment options.
A Third‐Generation Bisphosphonate, YM175, Inhibits Osteoclast Formation in Murine Cocultures by Inhibiting Proliferation of Precursor Cells via Supporting Cell‐Dependent Mechanisms

The theory that bisphosphonates inhibit osteoclast formation through their effects on osteoblastic cells remains controversial. To confirm the inhibitory effect of bisphosphonates on osteoclast formation and gain some insights into the underlying mechanisms, we examined the effect of disodium dihydrogen (cycloheptylamino)‐methylenebisphosphonate monohydrate (YM175) on osteoclast‐like multinucleated cell (OCL) formation in various mouse coculture systems. When different origins of osteoclast precursors (bone marrow, spleen, or nonspecific esterase‐positive cells) were cocultured with the same supporting cells (calvarial osteoblasts), YM175 inhibited OCL formation similarly in all cultures. When the same osteoclast precursors (spleen cells) were cocultured with supporting cells of different origin, the results were variable. YM175 inhibited OCL formation almost completely in cocultures with calvarial osteoblasts or osteoblastic cell line KS4, while it did not, or only slightly, inhibit OCL formation in cocultures with stromal cell lines, ST2 or MC3T3‐G2/PA6. Temporal addition of YM175 in cocultures of spleen cells with osteoblastic cells revealed that YM175 was effective when it was present at an early phase of the culture period. Consistent with this observation, YM175 in the presence of osteoblastic cells inhibited proliferation of preosteoclastic cells, but did not inhibit the fusion of mononuclear prefusion osteoclasts. In conclusion, the inhibitory effect of YM175 on OCL formation was confirmed in various murine coculture systems, but the effect was dependent on the types of bone‐derived cells supporting osteoclastogenesis. The findings suggest that YM175 inhibits osteoclastogenesis by inhibiting the proliferation of osteoclast precursors through its action on supporting cells of osteoblast lineage rather than acting directly on osteoclast precursors.
Audit of a fetal central monitoring station in a clinical setting

Abstract Objective. To conduct an audit of the Omniview-SisPorto® central monitoring station (CMS) and determine the effect of the measures undertaken to correct identified problems. Methods. All cardiotocograms (CTGs) recorded in randomly selected days of 2006 and 2009, both in the outpatient clinic and labor ward, were reviewed to assess the following parameters: tracing identification, duration, signal quality, signal loss, acquisition method, and time elapsed between tracing-end and birth. A random sample of cases was compared with original paper recordings and 25% of CTGs were re-retrieved for comparison with first retrieval. Results. Antepartum tracings were identified in 92% of cases. Mean signal quality rose from 96.4% in 2006 to 97.1% in 2009 (p = 0.009). Mean signal loss fell from 7.4% to 5.8% (p = 0.012). Intrapartum CTGs were identified in 44% of cases in 2006 and in 69% in 2009 (p < 0.001). Mean interval between tracing-end and birth decreased from 12.0 to 8.4 min (p < 0.001). Coincidence of variables in tracings retrieved twice increased between 2006 and 2009. All retrieved tracings matched the original paper recordings. Several technical problems identified in 2006 were not found in 2009. Conclusions. The Omniview-SisPorto® system showed reliable recording, storage, and retrieval of CTGs. Auditing of fetal CMSs allows improvement of their performance and use.
Familial Subsets in Idiopathic Parkinson’s Disease

ABSTRACT In the present paper we explore in some detail the hypothesis that the presence of familial aggregations in 10–15% of Parkinson’s disease cases is due in great part to the existence of well-defined familial subsets, rather than to chance occurrences. We describe the clinical and genetic characteristics of the two main subsets: “Essential tremor-related Parkinsonism” and the “Familial akineto-rigid Syndrome” previously identified. The former type of Parkinsonism is associated at random, but with increased frequency, to an autosomal dominant disorder, usually essential tremor but occasionally OPCA. Two possible susceptibility factors were uncovered in this entity: an increased incidence of familial hyperthyroidism (augmentor factor) and a decreased incidence of the generally frequent HLA Haplotypes A1B8 or A2B5 (Protective factors). The other presentation, the “familial akineto-rigid syndrome”, appears to be a definite disease entity with an autosomal recessive mode of inheritance (normal parents, increased incidence of identical parkinsonism in sibs, increased consanguinity rate in parents). This newly defined disorder deserves much further genetic and biochemical analysis.
Recombinant human erythropoietin and overall survival in cancer patients: results of a comprehensive meta-analysis.

BACKGROUND Anemia associated with cancer and cancer therapy is an important clinical and economic factor in the treatment of malignant diseases. METHODS We conducted a systematic literature review to assess the efficacy of erythropoietin to prevent or treat anemia in cancer patients with regard to red blood cell transfusions, hematologic response, adverse events, and overall survival. We searched the Cochrane Library, Medline, EMBASE, and other databases for relevant articles published from January 1985 to December 2001. We included all randomized controlled trials that compared the use of recombinant human erythropoietin (plus transfusion, if needed) with no erythropoietin treatment (plus transfusion, if needed). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated under a fixed-effects model. Clinical and statistical heterogeneity were examined with sensitivity analyses and meta-regression. Statistical tests for effect estimates were two-sided. RESULTS We identified 27 trials involving 3287 adult patients. Patients treated with erythropoietin had a lower relative risk of having a blood transfusion than untreated patients (RR = 0.67, 95% CI = 0.62 to 0.73). Erythropoietin-treated patients with baseline hemoglobin levels lower than 10 g/dL were more likely to have a hematologic response than untreated patients (RR = 3.60, 95% CI = 3.07 to 4.23). The relative risk for thromboembolic complications after erythropoietin treatment was not statistically significantly increased (RR = 1.58, 95% CI = 0.94 to 2.66) compared with that of untreated patients. There is suggestive but inconclusive evidence that erythropoietin may improve overall survival (adjusted data: hazard ratio [HR] = 0.81, 95% CI = 0.67 to 0.99; unadjusted data: HR = 0.84, 95% CI = 0.69 to 1.02). CONCLUSIONS Erythropoietin treatment may reduce the risk for blood transfusions and improve hematologic response in cancer patients. However, our favorable survival outcome is in contrast to two large (N = 351 and 939) recently published randomized controlled trials in which erythropoietin-treated patients had statistically significantly worse survival than untreated patients. Possible reasons for the disparity with our results include differences in study population and design, higher target hemoglobin levels and higher risk of thromboembolic complications, and concerns that erythropoietin may stimulate tumor growth.
Endoglin (CD105) expression in human renal cell carcinoma

To evaluate the prognostic potential of endoglin (CD105) expression in human renal cell carcinoma (RCC), as endoglin is a cell membrane glycoprotein expressed in tumour‐associated vascular endothelium and a marker of angiogenesis; intratumoral microvessel density assessed by endoglin staining has prognostic significance in some neoplasms.
Individual Characteristics, Family Factors, and Classroom Experiences as Predictors of Low-Income Kindergarteners’ Social Skills

There has been increasing awareness of the need for research and theory to take into account the intersection of individual characteristics and environmental contexts when examining predictors of child outcomes. The present longitudinal, multi-informant study examined the cumulative and interacting contributions of child characteristics (language skills, inattention/hyperactivity, and aggression) and preschool and family contextual factors in predicting kindergarten social skills in 389 low-income preschool children. Child characteristics and classroom factors, but not family factors, predicted teacher-rated kindergarten social skills, while child characteristics alone predicted change in teacher-rated social skills from preschool to kindergarten. Child characteristics and family factors, but not classroom factors, predicted parent-rated kindergarten social skills. Family factors alone predicted change in parent-rated social skills from preschool to kindergarten. Individual child characteristics did not interact with family or classroom factors in predicting parent- or teacher-rated social skills, and support was therefore found for an incremental, rather than an interactive, predictive model of social skills. The findings underscore the importance of assessing outcomes in more than one context, and of considering the impact of both individual and environmental contextual factors on children’s developing social skills when designing targeted intervention programs to prepare children for kindergarten.
A COMPARISON OF THE COST-EFFECTIVENESS OF STROKE CARE PROVIDED IN LONDON AND COPENHAGEN

Objectives: This study compared the relative cost-effectiveness of stroke care provided in London and Copenhagen. Methods: Hospitalized stroke patients at centers in London (1995–96) and Copenhagen (1994–95) were included. Each patient's use of hospital and community health services was recorded for 1 year after stroke. Center-specific unit costs were collected and converted into dollars using the Purchasing Power Parity Index. An incremental cost-effectiveness ratio (ICER) was calculated comparing a Copenhagen model of stroke care to a London model, using regression analysis to adjust for case-mix differences. Results: A total of 625 patients (297 in Copenhagen, 328 in London) were included in the analysis. Most patients in London (85%) wereadmitted to general medical wards, with 26% subsequently transferred to a stroke unit. In Copenhagen, 57% of patients were directly admitted to a stroke or neurology unit, with 23% then transferred to a separate rehabilitation hospital. The average length of total hospital stay was 11 days longer in Copenhagen. Patients in Copenhagen were less likely to die than those in London; for patients with cerebral infarction the hazard ratio after case-mix adjustment was 0.53 (95% CI from 0.35 to 0.80). However, a lower proportion of patients with hemorrhagic stroke died in London. The ICER of using the Copenhagen compared with the London model of care ranged from $21,579 to $37,444 per life-year gained for patients with cerebral infarctions. Conclusions: The ICERs of the Copenhagen compared with the London model of care were within a range generally regarded as cost-effective.
Low‐dose vasopressin increases glomerular filtration rate, but impairs renal oxygenation in post‐cardiac surgery patients

Background: The beneficial effects of vasopressin on diuresis and creatinine clearance have been demonstrated when used as an additional/alternative therapy in catecholamine‐dependent vasodilatory shock. A detailed analysis of the effects of vasopressin on renal perfusion, glomerular filtration, excretory function and oxygenation in man is, however, lacking. The objective of this pharmacodynamic study was to evaluate the effects of low to moderate doses of vasopressin on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2) and renal oxygen extraction (RO2Ex) in post‐cardiac surgery patients.
Advantages of histamine H4 receptor antagonist usage with H1 receptor antagonist for the treatment of murine allergic contact dermatitis

Histamine facilitates development of eczematous lesions in chronic allergic contact dermatitis. In addition to the well‐known corticosteroid treatments, H1 receptor (H1R) antagonists also have been used. This study observed effects of histamine H4 receptor (H4R) antagonist usage with H1R antagonist in a murine chronic allergic contact dermatitis model, developed by repeated percutaneous challenge to the dorsal skin with 2,4,6‐trinitro‐1‐chlorobenzene (TNCB). The H1R antagonist olopatadine hydrochloride and/or the H4R antagonist JNJ7777120 was then administered. Combination therapy was more effective than H1R antagonist monotherapy. Serum IgE and levels of interleukin (IL)‐4, IL‐5 and IL‐6 (Th2 cytokines) in eczematous lesions decreased with combined therapy. Combined therapy with H1R and H4R antagonists counteracts the disadvantages of each as monotherapeutic agents and potentially represents a new strategy for the treatment of chronic allergic contact dermatitis.
Regenerative phenotype in mice with a point mutation in transforming growth factor β type I receptor (TGFBR1)

Regeneration of peripheral differentiated tissue in mammals is rare, and regulators of this process are largely unknown. We carried out a forward genetic screen in mice using N-ethyl-N-nitrosourea mutagenesis to identify genetic mutations that affect regenerative healing in vivo. More than 400 pedigrees were screened for closure of a through-and-through punch wound in the mouse ear. This led to the identification of a single pedigree with a heritable, fast, and regenerative wound-healing phenotype. Within 5 wk after ear-punch, a threefold decrease in the diameter of the wound was observed in the mutant mice compared with the wild-type mice. At 22 wk, new cartilage, hair follicles, and sebaceous glands were observed in the newly generated tissue. This trait was mapped to a point mutation in a receptor for TGF-β, TGFBR1. Mouse embryonic fibroblasts from the affected mice had increased expression of a subset of TGF-β target genes, suggesting that the mutation caused partial activation of the receptor. Further, bone marrow stromal cells from the mutant mice more readily differentiated to chondrogenic precursors, providing a plausible explanation for the enhanced development of cartilage islands in the regenerated ears. This mutant mouse strain provides a unique model to further explore regeneration in mammals and, in particular, the role of TGFBR1 in chondrogenesis and regenerative wound healing.
All Tools are Informational Now: How Information and Persuasion Define the Tools of Government

The toolbox of governments increasingly resembles a set of information cues and prompts whereby public actors use their authority to define messages to be received by various publics and organisational actors. Citizens and other targets of government policy, such as organisations and interest groups, may be influenced by the content of messages, the framing of the argument or request, and whether the information presents a default in the presentation of choices, so that citizens or other actors are guided to choose certain outcomes and not others. The traditional tools of government, law and finance, need a supportive informational context to be effective, which is increasingly being realised by governments and other public sector organisations. Recent developments in British government show that the distinction between nudge-like interventions and the traditional policy instruments cannot be sustained. These informational tools have increased the capacity of government; they can help alleviate the problems of too great a reliance on top-down forms of intervention and mitigate the crowding out of motivation. In short, an informational approach to the use of the tools of government can complement and enhance more traditional forms of intervention.
Individual wage growth: the effects of industry experience and firm tenure

This paper estimates the wage and mobility effects of experience in an industry. It uses a simultaneous equation model that accounts for the potential endogeneity of job tenure and industry experience in the wage determination process and allows for nonlinearities in the effects of interest. The empirical model is estimated using a large panel of Italian workers for the years 1986-2004. Results show that wage returns to industry experience are much higher than wage returns to job seniority. The hypotheses of exogeneity of job seniority and industry experience can be tested and are rejected. ∗The author would like to thank Simon Woodcock for his excellent supervision, as well as Benoit Dostie and Jennifer Hunt for helpful comments and suggestions based on earlier versions of this work. The author would also like to acknowledge the participants at the 2009 Comparative Analysis of Enterprise (Micro) Data CAED Conference (Tokyo, Japan), at the 2009 CEA conference (Toronto, Canada) and at the 2009 IZA Summer School (Buch, Germany) for comments and discussions on an earlier version of this work. Researchers at the LABORatorio R. Revelli (Moncalieri, Turin, Italy) and in particular Claudia Villosio and Roberto Quaranta have been of great help with the dataset and for assisting the author during his work as a visiting researcher. All remaining errors are of the author.
Bimodal targeting of cytochrome P450s to endoplasmic reticulum and mitochondria: the concept of chimeric signals

Targeting signals are critical for proteins to find their specific cellular destination. Signals for protein targeting to the endoplasmic reticulum (ER), mitochondria, peroxisome and nucleus are distinct and the mechanisms of protein translocation across these membrane compartments also vary markedly. Recently, however, a number of proteins have been shown to be present in multiple cellular sites such as mitochondria and ER, cytosol and mitochondria, plasma membrane and mitochondria, and peroxisome and mitochondria suggesting the occurrence of multimodal targeting signals in some cases. Cytochrome P450 monooxygenases (CYPs), which play crucial roles in pharmacokinetics and pharmacodynamics of drugs and toxins, are the prototype of bimodally targeted proteins. Several members of family 1, 2 and 3 CYPs have now been reported to be associated with mitochondria and plasma membrane in addition to the ER. This review highlights the mechanisms of bimodal targeting of CYP1A1, 2B1, 2E1 and 2D6 to mitochondria and ER. The bimodal targeting of these proteins is driven by their N‐terminal signals which carry essential elements of both ER targeting and mitochondria targeting signals. These multimodal signals have been termed chimeric signals appropriately to describe their dual targeting property. The cryptic mitochondrial targeting signals of CYP2B1, 2D6, 2E1 require activation by protein kinase A or protein kinase C mediated phosphorylation at sites immediately flanking the targeting signal and/or membrane anchoring regions. The cryptic mitochondria targeting signal of CYP1A1 requires activation by endoproteolytic cleavage by a cytosolic endoprotease, which exposes the mitochondrial signal. This review discusses both mechanisms of bimodal targeting and toxicological consequences of mitochondria targeted CYP proteins.
Human Resource Development (HRD) and Foreign Remittances The case of South Asia

The South Asian region has experienced substantial economic growth during the past decade. This has also been complemented by a rising middle class, which not only acts as an impetus to growth but also adds to the innovation and entrepreneurship potential available within the region. While a growing number of people in the labour force age group represent a growing potential for increased output by the private sector, there are Key points
Joint network topology optimization and multicell beamforming using mixed integer programming

Coordinated multi-point processing (CoMP) is a promising technique to manage intercell interference and to enhance system performance in cellular networks with single frequency reuse. However, the operational costs of CoMP, such as the associated control signaling and communication overhead and the increase of network complexity, could prevent the practical implementation of CoMP. To ensure that CoMP provides performance improvement to cellular networks at reasonable costs, we consider in this paper the problem of joint multicell basestation assignment and beamformer design (JBAB). We study this problem through a mixed integer second order cone programming (MI-SOCP) approach. We propose a novel MI-SOCP formulation of the JBAB problem and an improved MI-SOCP reformulation with desirable features. Based on the new formulations, we develop a computationally efficient heuristic algorithm that generates close-to-optimal feasible solutions of the JBAB problem. Interestingly, we demonstrate via simulations that our improved MI-SOCP formulation results in dramatically reduced run-time performance of the MI-SOCP solvers. The numerical results also show that the fast heuristic algorithm outperforms the existing methods in terms of both total transmitted power and percentage of feasible solutions obtained while guaranteeing a prescribed signal-to-interference-plus-noise-ratio (SINR) level at each mobile station (MS). In addition, the proposed algorithm yields network topologies that require almost the same transmitted power as that found by the branch-and-bound procedure implemented in IBM ILOG CPLEX in ensuring a predefined SINR target at each MS.