Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacological Studies with 5-Fluorocytosine

A cylinder plate bioassay for 5-fluorocytosine (5-FC) is described which permits determination of 5-FC concentrations in biological fluids in the presence of amphotericin B. Using this assay, we determined serum concentrations in 12 patients after a single dose of drug and in 8 patients receiving daily 5-FC at 6-hr intervals (4 to 120 days). Drug was detectable in serum as early as 0.5 hr and concentrations were measurable as long as 24 hr after a dose, regardless of renal function. Peak concentrations occurred 6 hr after the initial drug dose, but were seen between 1 and 2 hr after a dose in all patients receiving a minimum of 4 days of therapy. Mild to moderate renal impairment produced marked increases in peak 5-FC concentrations in the serum of a group of eight patients on three different dosage schedules. Five patients were studied before and after amphotericin B-induced renal insufficiency. Peak concentrations increased from 14 to 142% concomitant with the change in renal function. Parallel studies in rabbits confirmed the results in our patients. 5-FC half-life in the serum of 10 rabbits increased from 3.35 ± 0.27 to 24.63 ± 0.70 hr after experimentally induced acute renal failure. Concentrations of 5-FC in the cerebrospinal fluid of five patients ranged from 17 to 62 μg/ml and were 74.4 ± 5.6% of simultaneously determined serum concentrations. The effect of renal function on 5-FC concentrations in cerebrospinal fluid was similar to that seen with serum.
Lumiracoxib 400 mg once daily is comparable to indomethacin 50 mg three times daily for the treatment of acute flares of gout.

OBJECTIVES To demonstrate non-inferiority of lumiracoxib 400 mg once daily (o.d.) compared with indomethacin 50 mg three times daily (t.i.d.) in the treatment of acute gout, and to compare the safety and tolerability of these treatments. METHODS In this 1-week, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study, patients with a clinical diagnosis of gout, an acute attack of gout in four or more joints within the 48 h prior to evaluation, and at least moderate pain intensity in the target joint were randomized to treatment with lumiracoxib 400 mg o.d. (n = 118) or indomethacin 50 mg t.i. d. (n = 117). The primary efficacy endpoint was the mean change in pain intensity from baseline over days 2-5, assessed on a 5-point Likert scale, where non-inferiority could be claimed if the lower limit of the confidence interval (CI) was greater than -0.5. The patient's and physician's global assessment of response to treatment, and physician's assessment of tenderness, swelling and erythema of the study joint were also assessed. RESULTS The estimated difference between treatments for the change from baseline in pain intensity over days 2-5 was -0.004 (95% CI -0.207 to 0.199, P > 0.05), indicating that lumiracoxib 400 mg o.d. had comparable efficacy to indomethacin 50 mg t.i. d. for the primary efficacy variable. There was no significant difference between treatments in any of the secondary efficacy variables. Adverse events were reported by 10.2% of patients treated with lumiracoxib and 22.2% of those receiving indomethacin. CONCLUSIONS Lumiracoxib is as effective as indomethacin for treatment of acute gout and may have a better safety and tolerability profile.
New Frontiers in Calvarial Reconstruction: Integrating Computer-Assisted Design and Tissue Engineering in Cranioplasty

Summary: Repair of large and complex calvarial defects remains a particular challenge for reconstruction. The paucity of techniques and materials emphasizes the need for alternative bone formation strategies. Recent integrative approaches suggest that successful reconstruction requires interdisciplinary teams, with surgeons interacting with imaging experts, materials scientists, and engineers. In this review, the authors present an overview of current materials used in calvarial reconstruction. Subsequently, progress in computer-designed prostheses, tissue engineering, and osteoinduction strategies is discussed. Finally, the authors discuss their experience with the integration of computer-aided fabrication of customized implants and tissue engineering for calvarial reconstruction.
Spectrum and frequency of FZD4 mutations in familial exudative vitreoretinopathy.

PURPOSE Mutations in the frizzled-4 gene (FZD4) have recently been associated with autosomal dominant familial exudative vitreoretinopathy (FEVR) in families linking to the EVR1 locus on the long arm of chromosome 11. The purpose of this study was to screen FZD4 in a panel of 40 patients with FEVR to identify the types and location of mutations and to calculate what proportion of this heterogeneous condition is attributable to FZD4 mutations. METHODS PCR products were generated from genomic DNA with primers designed to amplify the coding sequence of FZD4. The PCR products were screened for mutations by single-strand conformational polymorphism-heteroduplex analysis (SSCP-HA) and by direct sequencing. RESULTS In total, eight mutations were identified, seven of which were novel. Three were deletions (c957delG, c1498delA, and c1501-1502delCT), one was a nonsense mutation (Q505X), and four were missense mutations (G36D, M105T, M157V, and S497F). CONCLUSIONS Eight mutations have been identified in the FZD4 gene in a cohort of 40 unrelated patients with FEVR. This result indicates that FZD4 mutations are responsible for only 20% of FEVR index cases and suggests that the other FEVR loci may account for more cases than previously anticipated.
Future Reserves 2020: perceptions of cohesion, readiness and transformation in the British Army Reserve

ABSTRACT The British Army Reserve, and in particular its logistics component, is currently undergoing profound organisational transformation as part of the Future Reserves 2020 (FR20) program. Yet, to date there has been no sustained quantitative analysis of perceptions of cohesion, readiness and morale in the Army Reserve. Moreover, there has been little quantitative examination of FR20’s impact to date. This paper addresses these gaps in the literature by undertaking an examination of the above variables using survey data from a representative sample of AR logistics soldiers collected longitudinally. It finds that cohesion is highly important in explaining variance in perceptions of readiness and morale, and that perceptions of cohesion, readiness and morale are relatively high in the force. Nevertheless, the data indicates that FR20 has failed to increase these significantly over time. Similarly, it finds that confidence in FR20 delivering increased military capability is also declining. These findings are important for understanding FR20’s impact to date and future trajectory.
Deficiency of Cardiolipin Synthase Causes Abnormal Mitochondrial Function and Morphology in Germ Cells of Caenorhabditis elegans*

Background: Cardiolipin is required for maintaining optimal mitochondrial function. Results: Cardiolipin depletion selectively obstructed proliferation, mitochondrial function, and morphology in germ cells. Conclusion: The contribution of cardiolipin to mitochondrial function and morphology varies among the different cell types in vivo. Significance: This provides a biological basis for understanding the different sensitivities of organelles to changes in the lipid environment. Cardiolipin (CL) is a major membrane phospholipid specifically localized in mitochondria. At the cellular level, CL has been shown to have a role in mitochondrial energy production, mitochondrial membrane dynamics, and the triggering of apoptosis. However, the in vivo role of CL in multicellular organisms is largely unknown. In this study, by analyzing deletion mutants of a CL synthase gene (crls-1) in Caenorhabditis elegans, we demonstrated that CL depletion selectively caused abnormal mitochondrial function and morphology in germ cells but not in somatic cell types such as muscle cells. crls-1 mutants reached adulthood but were sterile with reduced germ cell proliferation and impaired oogenesis. In the gonad of crls-1 mutants, mitochondrial membrane potential was significantly decreased, and the structure of the mitochondrial cristae was disrupted. Contrary to the abnormalities in the gonad, somatic tissues in crls-1 mutants appeared normal with respect to cell proliferation, mitochondrial function, and mitochondrial morphology. Increased susceptibility to CL depletion in germ cells was also observed in mutants of phosphatidylglycerophosphate synthase, an enzyme responsible for producing phosphatidylglycerol, a precursor phospholipid of CL. We propose that the contribution of CL to mitochondrial function and morphology is different among the cell types in C. elegans.
Body dissatisfaction, weight criticism, and self-reported physical activity in preadolescent children.

OBJECTIVE To examine the associations among physical activity, weight criticism during physical activity, and body dissatisfaction in a sample of pre-adolescent children. METHODS A community sample of 376 fifth- and sixth-grade students (M age = 10.8, SD = 0.65) completed measures of physical activity, weight criticism during physical activity, and body dissatisfaction. RESULTS Girls who reported experiencing high levels of weight criticism and high body dissatisfaction engaged in significantly fewer vigorous activities than girls who experienced criticism in the absence of body dissatisfaction. These results were not evident among boys. CONCLUSIONS These findings highlight the importance of body dissatisfaction in girls' propensity to engage in physical activity, and lend preliminary support to obesity prevention efforts that address body dissatisfaction and weight criticism among girls.
The likelihood of homoploid hybrid speciation

New species may be formed through hybridization and without an increase in ploidy. The challenge is for hybrid derivatives to escape the homogenizing effects of gene flow from parental species. The mechanisms hypothesized to underlie this process were modelled using a computer simulation. The model is of recombinational speciation, in which chromosomal rearrangements between parental species result in poor fertility of F1 hybrids, but through recombination, novel homozygous types are formed that have restored fertility. In simulations, stable populations bearing the recombinant karyotypes originated frequently and were maintained when the fertility of F1 hybrids was high. However, this high rate of origination was offset by low genetic isolation, and lower F1 hybrid fertility increased the evolutionary independence of derived populations. In addition, simulations showed that ecological and spatial isolation were required to achieve substantial reproductive isolation of incipient species. In the model, the opportunity for ecological isolation arose as a result of adaptation to extreme habitats not occupied by parental species, and any form of spatial isolation (e.g. founder events) contributed to genetic isolation. Our results confirmed the importance of the combination of factors that had been emphasized in verbal models and illustrate the trade-off between the frequency at which hybrid species arise and the genetic integrity of incipient species.
Topographical and Synaptic Organization of the GABA‐Containing Pallidosubthalamic Projection in the Rat

The anterograde transport of Phaseolus vulgaris‐leucoagglutinin (PHA‐L) was combined with postembedding immunocytochemistry for gamma‐aminobutyric acid (GABA) to study the topography, the synaptic organization and the neurotransmitter content of the pallidosubthalamic projection in the rat. After injections of PHA‐L in different parts of the globus pallidus a rich plexus of anterogradely labelled fibres and terminals was found in the ipsilateral subthalamic nucleus. The immunoreactive elements were distributed according to a mediolateral and rostrocaudal topography. Injections of PHA‐L restricted to the lateral two‐thirds of the globus pallidus gave rise to a massive anterograde labelling confined to the lateral half of the subthalamic nucleus. On the other hand, injections of PHA‐L strictly confined to the medial part of the globus pallidus resulted in anterograde labelling that occupied the ventromedial pole of the subthalamic nucleus. In some cases a few retrogradely labelled cells were found in the subthalamic nucleus after PHA‐L injections in the globus pallidus. The perikarya and the primary dendrites of these labelled cells were sometimes surrounded by anterogradely labelled terminals suggesting a close reciprocal connection between the globus pallidus and the subthalamic nucleus. Electron microscopic analysis of the PHA‐L‐labelled terminals revealed that they contain many mitochondria, numerous small round or slightly pleomorphic vesicles and occasionally one or two large dense core vesicles. They form symmetrical synaptic contacts predominantly with the proximal dendrites (39%) and less frequently with the perikarya (31%) and the distal dendrites (30%) of the subthalamic cells. Quantitative measurements showed that the pallidosubthalamic varicosities have a diameter ranging from 0.7 to 4.5 μm and a mean cross‐sectional area of 0.79 ± 0.26 μm2 (Mean ± SD). Postembedding immunocytochemistry for GABA revealed that the PHA‐L‐immunoreactive pallidosubthalamic axon terminals display GABA immunoreactivity. The results of our study demonstrate that the pallidosubthalamic projection is organized according to a mediolateral and rostrocaudal topography and that the proximal dendrites of the subthalamic cells are the major targets of the GABA‐immunoreactive pallidosubthalamic terminals. This suggests that the globus pallidus exerts a powerful control over the subthalamic cells through an inhibitory GABAergic pathway.
Apparent ileal and total-tract nutrient digestion by pigs as affected by dietary nondigestible oligosaccharides.

The effects of two types of nondigestible oligosaccharides (NDO), fructooligosaccharides (FOS), and transgalactooligosaccharides (TOS) were studied on growing and weanling pigs' nutrient digestion. Dietary NDO were included at the expense of purified cellulose. Twenty-five 57-d-old growing pigs, averaging 15.9+/-. 6 kg on d 0 of the experiment, were fed a corn-based control diet or the control with 6.8 or 13.5 g of FOS/kg or 4.0 or 8.0 g of TOS/kg (five pigs per diet). Feces were collected on d 28 to 32, and small-intestinal digesta were collected (slaughter technique) on d 42 to 47 of the experiment. Feeds, feces, and digesta were analyzed for DM, inorganic matter, CP, ether extract, and crude fiber. Dietary NDO did not significantly affect apparent fecal and small intestinal digestion of nutrients in growing pigs. After being fed a NDO-free diet through d 10 after weaning, 38-d-old weanling pigs (n = 20), averaging 10.4+/-. 8 kg on d 0 of the experiment, were fed a control diet (based on cornstarch, casein, and oat husk meal) or the control with 10 or 40 g of FOS or TOS/kg (four pigs per diet). Feces and urine were collected on d 13 to 17, and ileal digesta were collected via a postvalve T-cecum cannula on d 33 to 37 of the experiment. Feeds, feces, and digesta were analyzed for DM, inorganic matter, CP, ether extract, starch, NDF, ADF, ADL, Ca, P, Mg, Fe, Cu, and Zn. Nonstarch neutral-detergent soluble carbohydrates (NNSC) completed the mass balance for the carbohydrates. Urine was analyzed for N and minerals. The apparent fecal digestion of NNSC increased in the NDO-supplemented diets. The TOS-fed pigs tended (P<.10) to have a higher apparent fecal digestion of CP than the FOS-fed and control pigs but excreted more N via the urine (P<.01). Nitrogen and mineral balances were not affected. The FOS was nearly completely degraded prececally. Mean fiber digestion was lower at the fecal compared with the ileal level, as was the extent of NDO effects. This indicates that fiber digestion requires more than 2 wk to adapt to dietary NDO. Apparent ileal digestion of hemicellulose increased for the NDO-supplemented diets (P<.05), but that of NNSC decreased (P<.001). Thus, under the well-controlled conditions of this experiment, dietary NDO hardly affected nutrient digestion in well-kept growing and weanling pigs. However, digestion of dietary nonstarch carbohydrates may be affected.
Different antibody patterns and different prognoses in patients with scleroderma with various extent of skin sclerosis.

Ninety patients who fulfilled the ARA criteria for systemic sclerosis were divided into 6 groups on the basis of cutaneous areas of sclerosis. Anticentromere antibody (ACA) was found in 14 of 28 patients of the first 2 groups, the first group being pure sclerodactyly, and the second sclerodactyly plus minimal sclerotic lesions (eyelids, neck, armpits). In the other 4 groups (62 patients) in whom skin sclerosis was more diffuse, ACA was found in one case. Fluorescent antinuclear antibodies (FANA) with a diffusely grainy pattern, those with a nucleolar pattern and the anti-Scl-70 antibody were present in all 6 groups, but were significantly more frequent in the last 4 groups than in Groups 1 and 2. The cumulative survival rate as well as disease duration were found to be significantly longer in the first 2 groups designated "limited cutaneous systemic sclerosis," than in the 5th and 6th groups, i.e., patients in whom the trunk also was involved: "diffuse cutaneous systemic sclerosis. " The cumulative survival rate and disease duration of patients with skin sclerosis of the face and limbs, but not of trunk, were not significantly different either from those of patients with limited cutaneous systemic sclerosis or from those of patients with diffuse cutaneous systemic sclerosis. Thus these patients show the same antibody pattern as diffuse cutaneous systemic sclerosis, but the prognosis not significantly different from the other 2 subsets. We suggest they constitute a distinct subset of systemic sclerosis for which we propose the name "intermediate cutaneous systemic sclerosis. "
Predictors of long-term survival in patients with lung cancer included in the randomized Spanish Lung Cancer Group 0008 phase II trial using concomitant chemoradiation with docetaxel and carboplatin plus induction or consolidation chemotherapy.

PURPOSE The aim of this study was to analyze prognostic variables associated with long-term survival in patients with stage III non-small-cell lung cancer enrolled in a Spanish Lung Cancer Group (SLCG) phase II trial. PATIENTS AND METHODS Between May 2001 and June 2006, 139 patients were enrolled. The initial design included 3 arms: sequential chemotherapy (CT) followed by standard thoracic radiation therapy (TRT; RT), concomitant CT/TRT followed by consolidation CT, or induction CT followed by CT/TRT. Based on the results of the Radiation Therapy Oncology Group 9410 trial, the sequential arm was closed. Induction or consolidation therapy comprised docetaxel plus gemcitabine. Concomitant treatment comprised docetaxel plus carboplatin plus 60 Gy TRT. A univariate and a Cox proportional hazard regression analysis of the following 11 variables were performed: age, sex, Eastern Cooperative Oncology Group performance status (PS), histology, forced expiratory volume in 1 second, disease stage, nodal status, hemoglobin level, completion of RT treatment, completion of induction or consolidation plus concomitant treatment, and RT delay. RESULTS With a median follow-up of 23 months for living patients, median survival was 13.07 months for the consolidation arm and 14.65 months for the induction arm. The 4-year survival rates were 25.37% and 32.35%, respectively. Only RT treatment completion (P < .0001) and induction or consolidation plus concomitant treatment completion (P < .0001) were associated with longer survival. CONCLUSION Based on this retrospective analysis of patients enrolled in the SLCG 0008 randomized phase II study, age, sex, PS, and clinical parameters are not good predictors of overall survival; however, completion of treatment is needed to achieve long-term results.
Paget's disease of the vulva: clinicopathologic study of type 1 cases treated at a single institution

The aim of this study was to evaluate clinicopathologic characteristics of primary cutaneous Paget's disease of the vulva. Between 1986 and 2005, 22 patients with primary cutaneous Paget's disease of the vulva (type 1) were treated at Tohoku University Hospital. Medical records were reviewed for pathologic diagnosis, patient age, associated neoplasms, type(s) of eczema, symptom duration, treatment, surgical procedures, recurrence, and length of follow-up. Patient age ranged from 51 to 85 years (median 71.5 years). Median duration of symptoms was 24 months (range 2–60 months). Type 1a (intraepithelial) Paget's disease accounted for 18 patients, with 3 type 1b (invasive) cases and 1 type 1c (intraepithelial disease with underlying adenocarcinoma) case. Mean length of follow-up was 53.7 months, and median follow-up was 49 months (range 6–199 months). Only two patients had an associated internal malignancy: T-cell leukemia and breast cancer. Mapping biopsy was performed in 14 of the 18 type 1a cases. All patients were free of disease at the surgical margins and are alive without recurrence. The four patients with type 1b or 1c disease had lymph node metastases. Two has died of disease, and two are alive with no recurrence. The rate of secondary malignancy seems to be low in primary cutaneous Paget's disease of the vulva. Mapping biopsy with careful examination of characteristic skin surface may be useful for surgery of type 1a cases. Inguinal lymphadenectomy is recommended in cases with question of invasion or known underlying adenocarcinoma.
Scrutinizing the Emotional Nature of Intuitive Coherence Judgments

Abstract Dual‐system models propose that cognitive processing can occur either intuitively or deliberately. Unlike deliberate decision strategies, intuitive ones are assumed to have an emotional component attached to the decision process. We tested if intuitive decisions are indeed accompanied by an emotional response while deliberate decisions are not. Specifically, we conducted a psychophysiological study in which participants were instructed to decide either intuitively or deliberately if three simultaneously presented words were semantically coherent or incoherent (triad task). The degree of emotionality of these two decision strategies (intuitive vs. deliberate) was compared using changes in electrodermal activity (EDA) and the reaction time (RT) effect of an affective priming paradigm as primary measurements. Based on a valence‐arousal model, our results revealed that intuitive and deliberate judgments do not differ as to their emotional valence but that they do differ in emotional arousal. Most notably, sympathetic activation during intuitive judgments was significantly lower compared to sympathetic activation during deliberate judgments. Our results reflect that a relaxed state of mind—manifested in low sympathetic activity—could underlie the holistic processing that is assumed to facilitate the proliferation of semantic associations during coherence judgments. This suggests that coherence judgments made under an (instructed) intuitive decision mode have a specific psychophysiological signature and that arousal is the differentiating component between intuitive and deliberate decision strategies. © 2016 The Authors Journal of Behavioral Decision Making Published by John Wiley & Sons Ltd.