Miracle-dz/UniFAR-FTUs huggingface dataset:
Activities of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin, against Haemophilus influenzae and Moraxella catarrhalis

ABSTRACT Ceftobiprole, a broad-spectrum pyrrolidinone-3-ylidenemethyl cephem currently in phase III clinical trials, had MICs between 0.008 μg/ml and 8.0 μg/ml for 321 clinical isolates of Haemophilus influenzae and between ≤0.004 μg/ml and 1.0 μg/ml for 49 clinical isolates of Moraxella catarrhalis. Ceftobiprole MIC50 and MIC90 values for H. influenzae were 0.06 μg/ml and 0.25 μg/ml for β-lactamase-positive strains (n = 262), 0.03 μg/ml and 0.25 μg/ml for β-lactamase-negative strains (n = 40), and 0.5 μg/ml and 2.0 μg/ml for β-lactamase-negative ampicillin-resistant strains (n = 19), respectively. Ceftobiprole MIC50 and MIC90 values for β-lactamase-positive M. catarrhalis strains (n = 40) were 0.12 μg/ml and 0.5 μg/ml, respectively, whereas the ceftobiprole MIC range for β-lactamase-negative M. catarrhalis strains (n = 9) was ≤0.004 to 0.03 μg/ml. Ceftriaxone MICs usually were generally at least twofold lower than those of ceftobiprole, whereas amoxicillin-clavulanate MICs usually were higher than those of ceftobiprole. Azithromycin and telithromycin had unimodal MIC distributions against H. influenzae, with MIC90 values of azithromycin and telithromycin of 2 μg/ml and 4 μg/ml, respectively. Except for selected quinolone-nonsusceptible H. influenzae strains, moxifloxacin proved highly active, with MIC90 values of 0.12 μg/ml. Time-kill analyses showed that ceftobiprole, ceftriaxone, cefpodoxime, amoxicillin-clavulanate, azithromycin, telithromycin, and moxifloxacin were bactericidal at 2× MIC by 24 h against all 10 H. influenzae strains surveyed. Only modest increases in MICs were found for H. influenzae or M. catarrhalis clones after 50 serial passages in the presence of subinhibitory concentrations of ceftobiprole, and single-passage selection showed that the selection frequency of H. influenzae or M. catarrhalis clones with elevated ceftobiprole MICs is quite low.
Home Ownership and Social Mobility

This paper extends the literature on social mobility to investigate intergenerational links in home ownership, an important marker of wealth. Repeated cross sectional data show that home ownership rates have fallen rapidly over time, and in particular amongst younger people in more recent birth cohorts. We then hone in on two British birth cohorts for whom we have information on parental home ownership. Comparing the intergenerational transmission of home ownership for individuals in the 1958 and 1970 British birth cohorts, we find that home ownership for 42 year olds from the 1970 birth cohorts (in 2012) shrunk disproportionately among those whose parents did not own their own home when they were children. Using housing measures in an intergenerational setting, and bearing in mind that housing is the most important component of wealth for most people, our results reinforce a picture of falling social mobility in Britain.
Intestinal-enriched Krüppel-like Factor (Krüppel-like Factor 5) Is a Positive Regulator of Cellular Proliferation*

Intestinal-enriched Krüppel-like factor (IKLF or KLF5) belongs to the family of mammalian Krüppel-like transcription factors. Previous studies indicate that expression of IKLF is enriched in the proliferating crypt epithelial cells of the intestinal tract. However, the biological function of IKLF is unknown. In the current study, we have shown that the level of IKLF mRNA was nearly undetectable in serum-deprived NIH3T3 fibroblasts but became acutely and significantly increased upon the addition of fetal bovine serum or the phorbol ester, PMA. This induction required protein synthesis because it was prevented by cycloheximide. Transfection of IKLF into NIH3T3 cells resulted in the formation of foci in a manner similar to that caused by the activated Ha-ras oncogene. Constitutive expression of IKLF in transfected NIH3T3 cells significantly increased the rate of proliferation when compared with cells transfected with an empty vector. The growth ofIKLF-transfected cells was no longer inhibited by cell-cell contact or by low serum content. Moreover, these cells proliferated in an anchorage-independent fashion. We conclude thatIKLF encodes a delayed early response gene product that positively regulates cellular proliferation and may give rise to a transformed phenotype when overexpressed.
Conserved cellular function and stress‐mediated regulation among members of the proteolipid protein family

Chronic stress causes morphological alterations in the hippocampus of rodents and tree shrews, including atrophy of CA3 dendrites and loss of synapses. The molecular mechanisms underlying these structural changes remain largely unknown. We have previously identified M6a as a stress responsive gene and shown that M6a is involved in filopodium/spine outgrowth and, likely, synapse formation. M6a belongs to the proteolipid protein (PLP) family, all of their members having four transmembrane domains that allow their localization at the plasma membrane. In the present work, we analyzed other members of this family, the closely related M6b as well as PLP and its splice variant DM20. We found that chronic restraint stress in mice reduces M6b and DM20, but not PLP, mRNA levels in the hippocampus. In addition, M6b and DM20, but again not PLP, induce filopodium formation in primary cultures of hippocampal neurons. Several M6b protein isoforms were studied, all of them having similar effects except for the one lacking the transmembrane domains. Our results reveal a conserved cellular function and a stress‐mediated regulation among members of the proteolipid protein family, suggesting an involvement of proteolipid proteins in the stress response. © 2009 Wiley‐Liss, Inc.
LONG-TERM EFFECTS ON WOMEN OF ASSISTED REPRODUCTION

The long-term health sequelae for women from assisted reproductive technology (ART) have not been studied extensively. There are a number of reasons that women's health may be compromised after ART procedures, including the consequences of the increased incidence of multiple births, operative deliveries, and preterm infants, the possible adverse effects of the drug regimens used for ovarian stimulation, and the instrumentation involved in ART procedures. In this paper we review the existing literature in these areas. It emphasizes the effects of the drugs used for ovarian stimulation, and in particular the incidence of cancer among women who have undergone ART. The review indicates that there is cause for concern about the long-term effects on women from ART treatments. It highlights the lack of research undertaken in almost all areas related to women's long-term health after ART. In the area of ART and cancer, it draws attention to the lack of conclusive evidence in relation to the posited association between fertility treatments and cancer, resulting from the limited number of very large studies and the need for longer follow-up periods. We make a number of recommendations regarding further research that is needed to address the current shortcomings in the published literature.
Risk-managed industry momentum and momentum crashes

This paper investigates Barroso and Santa-Clara’s [J. Financ. Econ., 2008, 116, 111–120] risk-managed momentum strategy in an industry momentum setting. We investigate several traditional momentum strategies including that recently proposed by Novy-Marx [J. Financ. Econ., 2012, 103, 429–453]. We moreover examine the impact of different variance forecast horizons on average pay-offs and also Daniel and Moskowitz’s [J. Financ. Econ., 2016, 122, 221–247] optionality effects. Our results show in general that neither plain industry momentum strategies nor the risk-managed industry momentum strategies are subject to optionality effects, implying that these strategies have no time-varying beta. Moreover, the benefits of risk management are robust across volatility estimators, momentum strategies and subsamples. Finally, the ‘echo effect’ in industries is not robust in subsamples as the strategy works only during the most recent subsample.
Effect of Meeting Leapfrog Volume Thresholds on Complication Rates Following Complex Surgical Procedures

Background:There is limited published data on the relationship between hospital volume and postoperative complications. The objectives of the current study are to examine the association between hospital volume and complications and also to examine the association between complications and in-hospital mortality following 5 complex surgical procedures. Methods:The Nationwide Inpatient Sample for years 2000 to 2003 was used. Patients who underwent coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), elective abdominal aortic aneurysm repair (AAA), pancreatectomy (PAN), and esophagectomy (ESO) as primary procedures were selected. Hospital volumes were calculated as suggested by the Leapfrog Group evidence-based hospital referral criteria. The association between hospital volume and complications were examined by multivariable logistic regression analyses, adjusting for patient and hospital characteristics. Results:A total of 261551 CABG, 573072 PCI, 35104 AAA, 4931 PAN, and 2473 ESO procedures were selected for analysis. A total of 580 hospitals performed the CABG procedures during the study period in this dataset. The corresponding numbers of hospitals for PCI, AAA, PAN, and ESO were 714, 1207, 758, and 555 respectively. In-hospital complication rates following CABG, PCI, AAA, PAN, and ESO were 26.45%, 6.74%, 23.81%, 39.28%, and 46.30%, respectively. High-volume hospitals for all the procedures were associated with lower odds for in-hospital mortality when compared with low-volume hospitals (P < 0.05). High-volume hospitals were associated with significantly lower odds for at least one complication following 3 of the 5 procedures (PCI, AAA, and PAN) and specifically for significantly lower odds for respiratory complications following CABG, AAA, and PAN, digestive complications following PAN, hemorrhage/hematoma complications following PCI, and septicemia following PCI and PAN when compared with low-volume hospitals (P < 0.05). Conclusion:Lower mortality rates in high-volume hospitals can be partly, though not completely, attributed to lower complication rates. Future studies must focus on identifying other potential pathways for reduced mortality in high-volume hospitals.
Temporal Association Between Reflux-like Behaviors and Gastroesophageal Reflux in Preterm and Term Infants

Objectives: Multichannel intraluminal impedance studies (MII-pH) have become the criterion standard for the diagnosis of gastroesophageal reflux (GER). Several clinical signs and symptoms that are attributed to GER during infancy may not be related to true reflux. Our objective was to correlate the observed reflux-like behaviors to reflux events on MII-pH studies. Methods: This is a retrospective study on infants being evaluated for GER with MII. During the MII-pH study, the infants were observed for clinical behaviors. Symptom Index (SI), symptom sensitivity index (SSI), and symptom association probability were used to correlate symptoms with reflux events. Results: Of 58 infants (40 preterm, 18 term) included in the study, only 6 infants (10%) had an abnormal MII-pH study. Irritability (32 infants), bradycardia (20), and desaturation (18) were the common signs and symptoms. A total of 2142 (755 acidic and 1386 nonacidic) reflux episodes and 953 clinical reflux behaviors were recorded. The incidence and pattern of GER was similar in preterm and term infants. There was no significant difference in GER episodes and acid exposure in preterm infants fed orally or via nasogastric tube. The symptom association probability was abnormal in only 6 (19%), 1 (5%), and 5 (28%) infants with irritability, bradycardia, and desaturation, respectively. Conclusions: The prevalence of GER as detected by MII-pH was low (10%) in symptomatic preterm and term infants. The incidence and pattern of GER was similar in preterm and term infants. The majority of suspected clinical reflux behaviors did not correlate with reflux events.
The use of prophylaxis in 2663 children and adults with haemophilia: results of the 2006 Canadian national haemophilia prophylaxis survey

Summary. Prophylaxis is standard of care for boys with severe haemophilia A. Indications for prophylaxis in adulthood, non‐severe haemophilia A, haemophilia B and haemophilia with inhibitors are less well defined. This survey, conducted in 2006, aimed to describe prophylaxis use in patients of all ages and severities with haemophilia A or haemophilia B in Canada. Data on 2663 individuals (2161 haemophilia A; 502 haemophilia B), including 78 inhibitor‐positive patients, were returned by 22/25 Canadian haemophilia treatment centres. This represented 98% of the Canadian haemophilia population. Frequency of prophylaxis use, defined as infusion of factor VIII/IX concentrate at least once weekly for ≥45 weeks of the year, was highest in individuals with severe haemophilia A (69%). It was lower in individuals with severe haemophilia B (32%), moderate haemophilia A (18%) or B (5%) and mild haemophilia A (1%) or B (1%). Among individuals with severe haemophilia A, the frequency of prophylaxis use was 84% in children (≤18 years) and 55% in adults (>18 years). Thirteen per cent of inhibitor‐positive individuals were receiving prophylaxis with bypassing agents. Comparison with data obtained from a 2002 Canadian survey showed a greater use of prophylaxis in children ≤5 years of age with severe haemophilia A (73% vs. 49%). Prophylaxis is no longer confined to children with severe haemophilia A, but is used in a significant proportion of adults with severe haemophilia A and individuals with severe haemophilia B or moderate haemophilia A. Prophylaxis is being started earlier in boys with severe haemophilia A.
Body Fat and Overweight Among Children and Adolescents with Diabetes Mellitus

Body composition was assessed in 68 children and adolescents with diabetes mellitus. Body fat was measured by skinfold thickness and the results were compared with those obtained by bioelectrical impedance methods (r = 0.76, p < 0.001). Percentage body fat from skinfold thickness estimations was 12–38%. Girls appeared to be most at risk of obesity during puberty with mean body fat 31%, significantly greater than in prepubertal girls (22%, p = 0.001) and pubertal boys (21%, p < 0.001). Body fat increased progressively through puberty in girls, with those in late puberty (stages 4 and 5) having significantly more percentage body fat than those in earlier puberty (stages 2 and 3, p < 0.001). Those in late puberty also received significantly more insulin per kilogram body weight (p = 0.05) and had higher HbA1 levels (p < 0.05) than prepubertal girls.
The involvement of two p450 enzymes, CYP83B1 and CYP83A1, in auxin homeostasis and glucosinolate biosynthesis.

The first committed step in the biosynthesis of indole glucosinolates is the conversion of indole-3-acetaldoxime into an indole-3-S-alkyl-thiohydroximate. The initial step in this conversion is catalyzed by CYP83B1 in Arabidopsis (S. Bak, F.E. Tax, K.A. Feldmann, D.A. Galbraith, R. Feyereisen [2001] Plant Cell 13: 101-111). The knockout mutant of the CYP83B1 gene (rnt1-1) shows a strong auxin excess phenotype and are allelic to sur-2. CYP83A1 is the closest relative to CYP83B1 and shares 63% amino acid sequence identity. Although expression of CYP83A1 under control of its endogenous promoter in the rnt1-1 background does not prevent the auxin excess and indole glucosinolate deficit phenotype caused by the lack of the CYP83B1 gene, ectopic overexpression of CYP83A1 using a 35S promoter rescues the rnt1-1 phenotype. CYP83A1 and CYP83B1 heterologously expressed in yeast (Saccharomyces cerevisiae) cells show marked differences in their substrate specificity. Both enzymes convert indole-3-acetaldoxime to a thiohydroximate adduct in the presence of NADPH and a nucleophilic thiol donor. However, indole-3-acetaldoxime has a 50-fold higher affinity toward CYP83B1 than toward CYP83A1. Both enzymes also metabolize the phenylalanine- and tyrosine-derived aldoximes. Enzyme kinetic comparisons of CYP83A1 and CYP83B1 show that indole-3-acetaldoxime is the physiological substrate for CYP83B1 but not for CYP83A1. Instead, CYP83A1 catalyzes the initial conversion of aldoximes to thiohydroximates in the synthesis of glucosinolates not derived from tryptophan. The two closely related CYP83 subfamily members therefore are not redundant. The presence of putative auxin responsive cis-acting elements in the CYP83B1 promoter but not in the CYP83A1 promoter supports the suggestion that CYP83B1 has evolved to selectively metabolize a tryptophan-derived aldoxime intermediate shared with the pathway of auxin biosynthesis in Arabidopsis.
Cost analysis of the treatments for patients with advanced Parkinson's disease: SCOPE study

Abstract Objective: To perform a comparative long-term analysis of the associated healthcare costs for the therapeutic options in advanced Parkinson’s Disease (PD): deep brain stimulation (DBS), continuous duodenal levodopa-carbidopa infusion (CDLCI), and continuous subcutaneous apomorphine infusion (CSAI). Methods: Resource use associated with the pre-treatment period, procedure, and follow-up was assessed for the three therapies from the perspective of the Spanish national healthcare system. Resources consumption was measured with a Healthcare Resources Questionnaire (at nine advanced PD centres). Unit costs (Euro-Spain 2010) were applied to measure resource use to obtain the average total cost for each therapy over 5 years. Results: Mean cumulative 5-year cost per patient was significantly lower with DBS (€88,014) vs CSAI (€141,393) and CDLCI (€233,986) (p < 0.0001). DBS was associated with the lowest cumulative costs from year 2, with a yearly average cost of €17,603 vs €46,797 for CDLCI (p = 0.001) and €28,279 for CSAI (p = 0.008). For every patient treated annually with CDLCI, two could be treated with DBS (or €29,194 could be saved) and for every patient treated with CSAI, €10,676 could be saved with DBS. The initial DBS investment (32.2% of the total 5-year costs) was offset by decreases in anti-Parkinsonian drugs and follow-up costs. CDLCI and CSAI required constant drug use (i.e., levodopa and carbidopa for CDLCI, apomorphine for CSAI), representing ∼95% of their total 5-year cost. Limitations: All costs were based on a questionnaire, not on actual clinical data. The study is not a cost-effectiveness analysis as there is a lack of comparable outcomes data. An expert panel was used due to the complexity and variability in the treatment of advanced PD. The sample size was relatively small. Conclusions: Overall, DBS requires less use of health resources than CDLCI or CSAI in advanced PD patients, mostly pharmacological. The initial DBS investment was offset at year 2 by reductions in the ongoing consumption of anti-Parkinsonian medication. For every patient treated annually with CDLCI or CSAI, substantial cost savings could be made with DBS.
Perceived discrimination and chronic health in adults from nine ethnic subgroups in the USA

Objective. This comparative analysis examines the association between chronic cardiovascular, respiratory and pain conditions, race, ethnicity, nativity, length of residency, and perceived discrimination among three racial and nine ethnic subgroups of Asian Americans (Vietnamese, Filipino, and Chinese), Latino-American (Cuban, Portuguese, and Mexican), and Afro-Caribbean American (Haitian, Jamaican, and Trinidadian/Tobagonian) respondents. Design. Analysis used weighted Collaborative Psychiatric Epidemiology Surveys–merged data from the National Latino and Asian American Study and the National Survey of American Life. Logistic regression analysis was conducted to determine which groups within the model were more likely to report perceived discrimination effects. Results. Afro-Caribbean subgroups were more likely to report perceived discrimination than Asian American and Latino-American subgroups were. Logistic regression revealed a significant positive association with perceived discrimination and chronic pain only for Latino-American respondents. Conclusion. Significant differences in reports of perceived discrimination emerged by race and ethnicity. Caribbean respondents were more likely to report high levels of perceived discrimination; however, they showed fewer significant associations related to chronic health conditions compared to Asian Americans and Latino-Americans. Examination of perceived discrimination across ethnic subgroups reveals large variations in the relationship between chronic health and discrimination by race and ethnicity. Examining perceived discrimination by ethnicity may reveal more complex chronic health patterns masked by broader racial groupings.
Neuropeptide Y suppresses absence seizures in a genetic rat model primarily through effects on Y2 receptors

Neuropeptide Y (NPY) potently suppresses absence seizures in a model of genetic generalized epilepsy, genetic absence epilepsy rats of Strasbourg (GAERS). Here we investigated the Y‐receptor subtype(s) on which NPY exerts this anti‐absence effect. A dual in vivo approach was used: the cumulative duration of seizures was quantified in adult male GAERS in 90‐min electroencephalogram recordings following intracerebroventricular (i.c.v.) injection of: (i) subtype‐selective agonists of Y1 ([Leu31Pro34]NPY, 2.5 nmol), Y2 (Ac[Leu28,31]NPY24–36, 3 nmol), Y5 receptors [hPP1−17,Ala31,Aib32]NPY, 4 nmol), NPY (3 nmol) or vehicle; and following (ii) i.c. v. injection of antagonists of Y1 (BIBP3226, 20 nmol), Y2 (BIIE0246, 20 nmol) and Y5 (NPY5RA972, 20 nmol) receptors or vehicle, followed by NPY (3 nmol). Injection of the Y1‐ and Y5‐selective agonists resulted in significantly less mean seizure suppression (37.4% and 53.9%, respectively) than NPY (83.2%; P < 0.05), while the Y2 agonist had similar effects to NPY (62.3% suppression, P = 0.57). Food intake was not increased following injection of the Y2 agonist, while significant increases in food intake were seen following NPY and the other Y‐subtype agonists. Compared with vehicle, NPY injection suppressed seizures following the Y1 and Y5 antagonists (45.3% and 80.1%, respectively, P < 0.05), but not following the Y2 antagonist (5.1% suppression, P = 0.46). We conclude that NPY Y2 receptors are more important than Y1 and Y5 receptors in mediating the effect of NPY to suppress absence seizures in a genetic rat model. Y2 receptor agonists may represent targets for novel drugs against genetic generalized epilepsies without resulting in appetite stimulation.
Screening of Protective Antigens of Japanese Encephalitis Virus by DNA Immunization: a Comparative Study with Conventional Viral Vaccines

ABSTRACT In this study, we evaluated the relative role of the structural and nonstructural proteins of the Japanese encephalitis virus (JEV) in inducing protective immunities and compared the results with those induced by the inactivated JEV vaccine. Several inbred and outbred mouse strains immunized with a plasmid (pE) encoding the JEV envelope protein elicited a high level of protection against a lethal JEV challenge similar to that achieved by the inactivated vaccine, whereas all the other genes tested, including those encoding the capsid protein and the nonstructural proteins NS1-2A, NS3, and NS5, were ineffective. Moreover, plasmid pE delivered by intramuscular or gene gun injections produced much stronger and longer-lasting JEV envelope-specific antibody responses than immunization of mice with the inactivated JEV vaccine did. Interestingly, intramuscular immunization of plasmid pE generated high-avidity antienvelope antibodies predominated by the immunoglobulin G2a (IgG2a) isotype similar to a sublethal live virus immunization, while gene gun DNA immunization and inactivated JEV vaccination produced antienvelope antibodies of significantly lower avidity accompanied by a higher IgG1-to-IgG2a ratio. Taken together, these results demonstrate that the JEV envelope protein represents the most critical antigen in providing protective immunity.