Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased serum leptin concentrations correlate with soluble tumour necrosis factor receptor levels in patients with cirrhosis

Objective Several reports have documented the involvement of hyerleptinaemia in malnutrition associated with liver cirrhosis. However, the mechanisms of elevated leptin levels remains unclear. Serum concentrations of tumour necrosis factor‐α (TNF‐α), and two soluble TNF receptors (sTNF‐RI and sTNF–RII) are increased in patients with liver cirrhosis. In rodents, administration of TNF‐α has been shown to stimulate plasma leptin concentration, suggesting that a cytokine–leptin link may mediate anorexia and weight loss during chronic inflammation. In this study, we investigate the potential interaction of the TNF‐α system with leptin in the development of malnutrition in liver cirrhosis.
Estrogen receptor status, determined by immunohistochemistry, as a predictor of the recurrence of Stage I endometrial carcinoma

The aim of this study was to compare the concordance between immunohistochemical (IHC) and biochemical (RIA) methods for determining hormone receptor status in patients with endometrial carcinoma and to determine whether IHC expression of estrogen and progesterone receptors (ER and PR) has prognostic significance.
Le cabinet ministériel comme espace frontière. Les collaborateurs ministériels passés par la sphère privée sous la présidence de François Hollande

Resume Cet article contribue au debat sur le brouillage de la frontiere public/prive en examinant l’experience des membres de cabinets ministeriels dans la « sphere privee » sous la presidence de Francois Hollande. Il discute l’ouverture au « prive » des viviers de recrutement et les formes variees de « privatisation » des carrieres des collaborateurs de ministres, en reinterrogeant les contours de la categorie « prive ». Il montre que les cabinets constituent un « espace frontiere » dans la mesure ou ils abritent un nombre relativement important d’individus ayant circule entre les spheres publique et privee et cherche a preciser les profils de ces « passeurs ».
Impact of Physical Therapy on Quality of Life and Function After Vaginal Reconstructive Surgery

Objectives Although pelvic floor physical therapy (PFPT) can be beneficial for complaints after vaginal reconstructive surgery, it is not routinely offered to all patients. We sought to evaluate the role of perioperative PFPT in improving quality of life and function after prolapse repairs. Methods This randomized controlled trial compared PFPT to standard care after vaginal reconstructive surgery. The intervention group received PFPT 2 weeks preoperatively and 2, 4, 6, 8, and 12 weeks postoperatively, as well as a physician assessment. Control subjects underwent a physician’s assessment alone at the same time points postoperatively. Both groups completed pelvic organ prolapse quantification examinations, intravaginal electromyography (EMG), voiding diaries, and validated questionnaires at baseline and 12 weeks. The primary outcome was change in the World Health Organization Quality of Life-BREF scale after surgery. Results Forty-nine women completed the study: 24 women in the PFPT group and 25 women in the control group. At 12 weeks, condition-specific questionnaires improved for the entire sample, confirming effectiveness of surgery. Nevertheless, no significant differences were noted between the groups despite therapy with PFPT. However, intravaginal EMG measures were notably affected by the intervention. The PFPT group showed significantly lower averages across all measurements of rest, indicating positive impact on muscle function. Pearson correlations revealed associations with better scores on the World Health Organization Quality of Life-BREF physical domain and greater EMG relaxation, supporting effects from PFPT on quality of life. Conclusions Pelvic symptoms improved in all subjects after vaginal reconstructive surgery. Whereas PFPT did not result in detectable subjective differences in this short-term study, superior muscular function suggested benefit from the intervention.
E-4695, a new C-7 azetidinyl fluoronaphthyridine with enhanced activity against gram-positive and anaerobic pathogens

E-4695, (-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-cyclopropyl-1,4- dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid, is a new fluorinated naphthyridine with an azetidine moiety. The MICs of E-4695 at which 90% of the isolates were inhibited (MIC90s) were 0.06 to 0.5 microgram/ml for gram-positive cocci, including species of the genera Staphylococcus, Streptococcus, and Enterococcus, and the MIC90s against gram-negative pathogens such as members of the family Enterobacteriaceae (with the exception of Providencia spp. [MIC90, 8 micrograms/ml]) and Pseudomonas aeruginosa were 0.015 to 0.5 microgram/ml. E-4695 inhibited 90% of the Clostridium perfringens and Bacteroides fragilis isolates at 0.25 and 4 micrograms/ml, respectively. Against gram-positive cocci the potency of E-4695 was 2- to 8-fold higher than that of ciprofloxacin, 4- to 8-fold higher than that of ofloxacin, and 8- to 16-fold higher than that of fleroxacin. Against enteric bacteria and P. aeruginosa the potency of E-4695 was, in general, similar to that of ciprofloxacin and eightfold higher than those of ofloxacin and fleroxacin. E-4695 was four- and eightfold more potent than ciprofloxacin against C. perfringens and B. fragilis isolates, respectively. E-4695 and ciprofloxacin showed similar properties when the effects of pH or magnesium concentration were tested on them. E-4695 and ciprofloxacin had substantial reductions of activity only when pH decreased below 4.8. E-4695 and ciprofloxacin activities were not markedly affected by the presence of 5 or 10 mM Mg2+. The presence of serum and human urine at pH 7.2 decreased the activity of E-4695 between two- and fourfold. After an oral dose of 50 mg/kg of body weight, the maximum level in serum, the biological half-life, and the area under the concentration-time curve from 0 to 10 h for E-4695 were 13.2 microgram/ml, 3.3 h, and 45.6 microgram . h/ml, respectively. The area under the concentration-time curve from 0 to 4 h for ciprofloxacin was 2.3 microgram . h/ml at the same dose. Fifty-percent effective doses (ED50S) against Staphylococcus aureus HS-93 infections in mice were 4.5 mg/kg with E-4695 and 37.6 mg/kg with ciprofloxacin. Infection with Streptococcus pneumoniae 29206 was more effectively treated with E-4695 (ED50, 41,2 mg/kg) than with ciprofloxacin (ED50, 200 mg/kg). The ED50 of E-4695 for infections with Streptococcus pneumoniae 1625 was 132.2 mg/kg; ciprofloxacin was ineffective at 400 mg/kg against this strain. E-4695 was also more potent than ciprofloxacin in treatment of infections caused by gram-negative organisms such as Escherichia coli HM-42 (ED50S, 1.0 and 3.9 mg/kg, respectively). The ED50S of E-4695 and ciprofloxacin were 33.0 and 145.5 mg/kg against P. aeruginosa HS-116 and 9.6 and 18.9 mg/kg against P. aeruginosa B-120, respectively. The therapeutic efficacy of E-4695 may depend not only on its in vitro activity but also on its improved pharmacokinetic properties.
Treatment of erythrodermic psoriasis in HCV+ patient with adalimumab

Erythrodermic psoriasis is a severe and disabling variant of psoriasis. The authors present the case of a 48‐year‐old man with psoriasis and hemophilia presented with a history of hepatitis C virus (HCV) infection treated with pegylated interferon alpha‐2a and ribavirin therapy. At the end of antiviral therapy, skin manifestation progressively worsened, becoming erythrodermic, with lack of efficacy of steroid therapy. The authors decided to start biological therapy with induction dose of adalimumab (Humira, Abbott Laboratories, Abbott Park, Chicago, IL) 80 mg at Week 0 and 40 mg weekly. In our case, this resulted in a highly effective and safe treatment.
Selective inhibition and augmentation of alternative macrophage activation by progesterone

Progesterone is the female sex hormone necessary for the maintenance of pregnancy, and is known to modulate macrophage activation. However, studies have concentrated exclusively on the ability of progesterone to negatively regulate the innate and classical pathways of activation, associated with nitric oxide (NO) and interleukin (IL)‐12 production. Our aim was to examine the ability of progesterone to modulate alternative macrophage activation. Bone marrow cells were isolated and differentiated from male BALB/c mice, exposed to varying concentrations of progesterone and stimulated with lipopolysaccharide (LPS) (innate activation), IL‐4 (alternative activation) or LPS in combination with IL‐4. Our present study demonstrates that progesterone not only down‐regulates inducible nitric oxide synthase 2 (iNOS) activity in macrophages but also arginase activity, in a dose‐dependent manner, independent of the stimuli, whether it is induced by LPS (innate activation), IL‐4 (alternative activation) or LPS in combination with IL‐4. The ability of progesterone to down‐modulate IL‐4‐induced cell surface expression of the mannose receptor further suggested a negative regulation of alternative macrophage activation by this hormone. Analysis of mRNA expression, by quantitative reverse transcription–polymerase chain reaction (qRT–PCR), of genes associated with innate and alternative macrophage activation revealed that progesterone down‐regulated LPS‐induced macrophage nos2, argI and p40 (IL‐12/IL‐23) expression and IL‐4‐induced argI, mrc‐1 and fizz1 expression. However, progesterone up‐regulated IL‐4‐induced macrophage expression of ym1, while dectin‐1 expression remained unaltered. Following treatment of macrophages with LPS and IL‐4 in combination a similar pattern was observed, with the exception that progesterone up‐regulated macrophage expression of fizz1 as well as ym1 and did not modify mrc‐1 expression. Our data demonstrate for the first time that a hormone has the ability to regulate selectively the expression of different genes associated with alternative macrophage activation.
Overview of dosimetric and biological perspectives on radiosurgery of multiple brain metastases in comparison with whole brain radiotherapy.

Purpose Treatment option of stereotactic radiosurgery versus whole brain radiotherapy for multiple brain metastases (>10) is an ongoing debate. Detailed dosimetric and biological information are presented in this study to investigate the possible clinical outcomes.Materials and Methods: Nine patients with multiple brain metastases (11-25) underwent stereotactic radiosurgery. Whole brain radiotherapy plans are retrospectively designed with the same MR image set and the same structure set for each patient using the standard opposing lateral beams and fractionation (3 Gy × 10). Physical doses and biologically effective doses are calculated for each lesion target and the CNS normal tissues and they are compared between whole brain radiotherapy and stereotactic radiosurgery in the context of clinical efficacy and published toxicities. Results Tumor biologically effective dose is higher in radiosurgery than in whole brain radiotherapy by factors of 3.2-5.3 in maximum dose and of 2.4-3.1 in mean dose. Biologically effective mean dose in radiosurgery is 1.3-34.3% for normal brain, 0.7-31.6% for brainstem, 0.5-5.7% for chiasm, 0.2-5.7% for optic nerves and 0.6-18.1% for hippocampus of that in whole brain radiotherapy over nine cases presented here. We also presented the dose-volume relationship for normal brain to address the dosimetric concerns in radiosurgery. Conclusions Dose-volume metrics presented in this study are essential to understanding the safety and efficacy of whole brain radiotherapy and/or radiosurgery for multiple brain metastases. Whole brain radiotherapy has resulted in higher incidence of radiation-related toxicities than radiosurgery. Even for patients with more than 10 brain metastases, the CNS normal tissues receive significantly lower doses in radiosurgery. Mean normal brain dose in SRS is found to correlate with the total volume of lesions rather than the number of lesions treated.
Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice

Zinc co-crystallizes with insulin in dense core secretory granules, but its role in insulin biosynthesis, storage and secretion is unknown. In this study we assessed the role of the zinc transporter ZnT8 using ZnT8-knockout (ZnT8−/−) mice. Absence of ZnT8 expression caused loss of zinc release upon stimulation of exocytosis, but normal rates of insulin biosynthesis, normal insulin content and preserved glucose-induced insulin release. Ultrastructurally, mature dense core insulin granules were rare in ZnT8−/− beta cells and were replaced by immature, pale insulin “progranules,” which were larger than in ZnT8+/+ islets. When mice were fed a control diet, glucose tolerance and insulin sensitivity were normal. However, after high-fat diet feeding, the ZnT8−/− mice became glucose intolerant or diabetic, and islets became less responsive to glucose. Our data show that the ZnT8 transporter is essential for the formation of insulin crystals in beta cells, contributing to the packaging efficiency of stored insulin. Interaction between the ZnT8−/− genotype and diet to induce diabetes is a model for further studies of the mechanism of disease of human ZNT8 gene mutations.
Bacteriophages of Erwinia amylovora

ABSTRACT Fifty bacteriophage isolates of Erwinia amylovora, the causal agent of fire blight, were collected from sites in and around the Niagara region of southern Ontario and the Royal Botanical Gardens, Hamilton, Ontario. Forty-two phages survived the isolation, purification, and storage processes. The majority of the phages in the collection were isolated from the soil surrounding trees exhibiting fire blight symptoms. Only five phages were isolated from infected aerial tissue in pear and apple orchards. To avoid any single-host selection bias, six bacterial host strains were used in the initial isolation and enrichment processes. Molecular characterization of the phages with a combination of PCR and restriction endonuclease digestions showed that six distinct phage types, described as groups 1 to 6, were recovered. Ten phage isolates were related to the previously characterized E. amylovora PEa1, with some divergence of molecular markers between phages isolated from different sites. A study of the host ranges of the phages revealed that certain types were unable to efficiently lyse some E. amylovora strains and that some isolates were able to lyse the epiphytic bacterium Pantoea agglomerans. Representatives from the six molecular groups were studied by electron microscopy to determine their morphology. The phages exhibited distinct morphologies when examined by an electron microscope. Group 1 and 2 phages were tailed and contractile, and phages belonging to groups 3 to 6 had short tails or openings with thin appendages. Based on morphotypes, the bacteriophages of E. amylovora were placed in the order Caudovirales, in the families Myoviridae and Podoviridae.
Rhythmic syllable-related activity in a songbird motor thalamic nucleus necessary for learned vocalizations

Birdsong is a complex behavior that exhibits hierarchical organization. While the representation of singing behavior and its hierarchical organization has been studied in some detail in avian cortical premotor circuits, our understanding of the role of the thalamus in adult birdsong is incomplete. Using a combination of behavioral and electrophysiological studies, we seek to expand on earlier work showing that the thalamic nucleus Uvaeformis (Uva) is necessary for the production of stereotyped, adult song in zebra finch (Taeniopygia guttata). We confirm that complete bilateral lesions of Uva abolish singing in the ‘directed’ social context, but find that in the ‘undirected’ social context, such lesions result in highly variable vocalizations similar to early babbling song in juvenile birds. Recordings of neural activity in Uva reveal strong syllable-related modulation, maximally active prior to syllable onsets and minimally active prior to syllable offsets. Furthermore, both song and Uva activity exhibit a pronounced coherent modulation at 10Hz—a pattern observed in downstream premotor areas in adult and, even more prominently, in juvenile birds. These findings are broadly consistent with the idea that Uva is critical in the sequential activation of behavioral modules in HVC.
Can China’s Energy Intensity Constraint Policy Promote Total Factor Energy Efficiency? Evidence from the Industrial Sector

As part of the country’s efforts to achieve green development, China implemented a mandatory energy intensity reduction target in its 11th “Five-Year Plan (FYP)” in 2006, and then began to roll out a series of relevant measures. However, existing studies have paid little attention to the actual effects of China’s energy intensity constraint policy (EICP). In this paper, using panel data from China’s 36 industrial sub-sectors covering the years from 2001 to 2014, we adopt the difference-in-differences (DID) method to investigate for the first time the EICP’s (marginal) effect on total factor energy efficiency growth (TFEEG). We also estimate the superposition effect caused by the introduction of a carbon intensity constraint policy (CICP) on TFEEG, through the difference-in-difference-in-differences (DDD) strategy. Finally, using counterfactual, re-grouping and quasi-DID analyses, we conduct a series of robustness tests of the empirical results. The results show that the TFEEG in China’s industrial sector experienced an overall declining trend between 2001 and 2014. The implementation of the EICP has had a significantly negative effect on the improvement of the TFEEG of sub-sectors with higher levels of energy intensity. After the implementation of the EICP, the TFEEG rate of these sub-sectors declined by 4.31%, compared to the rate of the other sub-sectors. The results of a series of robustness tests indicate that such a negative effect is credible. The marginal effect in the first two years after the implementation of the EICP was significantly negative, while the superposition effect of the introduction of a CICP on industrial TFEEG remained negative. Thus, the Chinese government should reinforce the implementation of energy-saving policies by introducing additional market-oriented auxiliary policies to propel the green development transformation of China’s industrial sector.
What Forms the Migrating Pattern for Innovation Adoption? The Case of Mobile Data Services

Many innovation adoption studies examine users' pre- and post-adoption innovation behaviors. However, the emergence of a gap between the post-adoption of the old generation and the pre-adoption of the new generation leaves room for discussion. This paper surveys Taiwanese mobile phone users and conducts an empirical study to map how 2G mobile data services (MDS) users go about adopting 3G MDS. The investigation of migrating patterns provides managerial and marketing benefits since most innovative products and services have been multi-generationally revolutionized. Our findings suggest that users make comparisons between generations which alter their concepts and intentions. There is an attitude difference between the pre- and post-users' perceived enjoyment of the entertainment services provided by 3G MDS. While satisfaction and system quality are insufficient to encourage users to switch, the latter factor has a mediating effect through its perceived usefulness and enjoyment in terms of influencing users' migrating patterns.
Temperature responses of mesophyll conductance differ greatly between species.

The temperature responses of mesophyll conductance (gm ) were investigated for nine species using carbon isotope techniques combining tunable diode laser spectroscopy and gas exchange measurements. Species included the evergreen trees Eucalyptus pauciflora and Quercus engelmannii; the tropical evergreen tree Lophostemon confertus; as well as the herbaceous species Nicotiana tabacum, Oryza sativa, Triticum aestivum, Gossypium hirsutum, Glycine max and Arabidopsis thaliana. Responses varied from a two- to threefold increase in mesophyll conductance between 15 and 40 °C observed for N. tabacum, G. hirsutum, G. max and E. pauciflora to almost no change in L. confertus and T. aestivum. To account for the different temperature responses between species, we suggest that there must be variation in both the activation energy for membrane permeability and the effective pathlength for liquid phase diffusion. Stomatal conductance was relatively independent of increases in leaf temperature and concomitant increases in leaf to air vapour pressure difference. Two exceptions were Eucalyptus and Gossypium, where stomatal conductance increased with temperature up to 35 °C despite increasing leaf to air vapour pressure. For a given species, temperature responses of stomatal and mesophyll conductance were independent of one another.
The long-duration response to l-dopa in the treatment of early PD

Objective: To investigate the long-duration response (LDR) to l-dopa resulting from different regimens of l-dopa. Background: In clinical practice, l-dopa is usually administered without considering the LDR due to the drug. Moreover, it has not been established whether in early PD a multiple daily intake of small doses of l-dopa may induce a sustained LDR. Methods: Twenty-four patients with early PD underwent a double-blind, crossover trial, comparing three different 15-day treatment periods with l-dopa: treatment A (250 mg every 24 hours); treatment B (250 mg every 8 hours); and treatment C (125 mg every 8 hours). After completion, 20 patients underwent a subsequent open-label randomized trial with prolonged treatments (250 mg every 24 hours or 125 mg every 8 hours) up to 3 months. LDR was measured at the end of each treatment. Results: All patients achieved a sustained LDR after treatments A and B, whereas only 17% of patients reached a sustained LDR after treatment C. Overall, the LDRs resulting from treatments A and B had similar magnitude and were larger than the LDR deriving from treatment C. After 3 months of prolonged treatments, only three of 10 patients treated with 125 mg every 8 hours increased their LDR, whereas all 10 patients treated with 250 mg every 24 hours had a maximal and stable LDR. Conclusions: Sustained LDR to l-dopa is dependent on the amount of the single doses of the drug. A regimen scheduling small, divided doses during the day, as done in clinical practice, is a questionable therapy for the achievement of a sustained LDR.
Trajectory formation of step-tracking wrist movements predicted by an optimal control model

In this study, we apply an optimal motor control model to the step-tracking wrist movement task. The motor control model was originally proposed for arm reaching movement and succeeded in predicting experimentally observed features in movement kinematics. As is the case with arm reaching movement, step-tracking wrist movement includes redundancy in trajectory formation. Therefore, step-tracking wrist movement can be a good test bed for computational models of neural motor control. We show that our model can predict spatiotemporal patterns in movement kinematics of the wrist movements. In addition, we discuss the mechanism that determines the characteristic of the movement kinematics from motor control and biomechanical viewpoints.