Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase II study of sorafenib and docetaxel in men with metastatic castration resistant prostate cancer (mCRPC).

e16055 Background: Previous trials of the antiangiogenic kinase inhibitor sorafenib in mCRPC have reported PSA elevation accompanying radiographic response, and evidence that sorafenib may potentiate docetaxel (dxl) myelosuppression. To assess the safety, antivascular effects, and activity of sorafenib and dxl in mCRPC, a phase II trial with dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) was conducted. METHODS Eligible men had mCRPC and no prior chemotherapy. Treatment consisted of dxl 75 mg/m2(day 1) and sorafenib (days 2-19) of a 21 day cycle. Patients received 7 days of sorafenib before cycle 1. Six patients received sorafenib 200mg BID and remaining patients received sorafenib 400 mg BID if <4/6 patients had grade 4 neutropenia. DCE-MRI was performed at baseline, days 8 and 28. The primary endpoint was PSA response rate (>50% PSA decline). Secondary endpoints were vascular response rate (>20% decline in area under the gadolinium curve [AUC60]), toxicity rates, and time to progression (TTP). PSA-only progression (2 consecutive PSA rises) was confirmed by a third PSA rise or radiographic progression after a 21-day drug holiday. Sample size of 69 patients in 1 stage was designed to maximize detection of significant correlations between DCE-MRI and clinical outcomes. RESULTS Six of 13 enrolled patients (46%) had a PSA response. A median PSA increase of 37% was observed in 73% of patients after 1 week of sorafenib. The median TTP was 8+ months. Two patients had complete disappearance of bone lesions. Grade 3 adverse events were neutropenia (77%), hand-foot syndrome (23%), anemia (15%), nausea (8%), and rash (8%). A median AUC60 decline of 40% from baseline was observed after 7 days of sorafenib, and only a 6% decline on day 28 during a scheduled sorafenib holiday. CONCLUSIONS Sorafenib 400 mg po bid and dxl 75 mg/m2 are tolerable in men with mCRPC. Elevated PSA values in men treated with sorafenib and dxl does not always reflect disease progression. DCE-MRI can capture sorafenib's impairment of tumor vasculature in osseous metastases and rebound angiogenesis during drug holidays. Bone responses and TTP data provide evidence of encouraging activity. No significant financial relationships to disclose.
Cox Regression Models with Nonproportional Hazards Applied to Lung Cancer Survival Data

TheCoxregressionmodel,whichiswidelyusedfortheanalysisoftreatmentandprognosticefiectswithcensoredsurvivaldata,makestheassumptionofconstanthazardratio. Intheviolationofthisassumption, difierent methods should be used to deal with non-proportionality of hazards. Inthisstudy,thestratifledCoxregressionmodelandextended Coxregressionmodel,whichusestimedependentcovariatetermswith flxed functions of time are discussed. The results are illustrated by an analysis of lung cancer data in order to compare these methods with respect to Cox regression model in the presence of nonproportional hazards.
Ultrasound‐guided parasacral approach to the sciatic nerve block in children

The parasacral (PS) approach to sciatic nerve blockade has the potential for safe and effective use in children, but has never been studied in this population. Its potential advantages include increased posterior cutaneous nerve block reliability, potential for hip joint analgesia, and decreased nerve depth, making ultrasound guidance easier.
Human Sex-Response Cycles

In order to better assess and explain the multiple factors contributing to our patients' sexual difficulties, we need to construct a reasonably simple model of human sexual response that illustrates, first, feedback to the mind as it orchestrates the sexual response and, second, the concept that sexual experiences can be undertaken for reasons that are not strictly sexual but intimacy-based. A simple model is presented that integrates responsive and "spontaneous" sexual desire, the subsequent creation of further stimuli in the form of the emotions experienced, subjective mental excitement, and accurate or inaccurate appreciation of physical, genital, and nongenital changes, all of which continue to modulate the sexual response.
Decreased excretion of antimicrobial proteins and peptides in saliva of patients with oral candidiasis.

BACKGROUND Antimicrobial peptides in saliva appear to play a crucial role in the regulation of oral Candida growth, and study on antimicrobial excretion in saliva and oral candidiasis appears useful for the analysis of pathophysiology of oral candidiasis. METHODS To clarify the role of saliva in the regulation of oral Candida growth, the levels of antimicrobial proteins and peptides and their excretion rates were examined in saliva obtained from 50 patients with oral candidiasis and 35 healthy individuals. RESULTS The inhibitory activities of patients' saliva against Candida adhesion with HeLa cells and against Candida growth (radiolabeled glucose incorporation) were lower than those of saliva from the healthy controls. The salivary levels of lactoferrin (Lf; 11 +/- 9 microg/ml), secretory immunoglobulin A (sIgA; 160 +/- 37 microg/ml), beta-defensin 1 (375 +/- 37 ng/ml), and beta-defensin 2 (412 +/- 51 ng/ml) in the patients were largely lower than those in the control group (33 +/- 14 microg/ml, 204 +/- 51 microg/ml, 452 +/- 89 ng/ml, and 530 +/- 142 ng/ml, respectively), although the transferrin (Tf) and secretory component (SC) levels were almost same in both groups, and alpha-defensin 1 was slightly increased in the patient group (660 +/- 115 ng/ml vs. 467 +/- 168 ng/ml). In addition, the excretion rates of the proteins and peptides were largely decreased in the patients (Tf: 14 +/- 2 microg/10 min vs. 34 +/- 7 microg/10 min; Lf: 18 +/- 11 microg/10 min vs. 139 +/- 43 microg/10 min; sIgA: 300 +/- 132 microg/10 min vs. 900 +/- 207 microg/10 min; SC: 112 +/- 46 microg/10 min vs. 292 +/- 64 microg/10 min; alpha-defensin 1: 1223 +/- 431 ng/10 min vs. 2044 +/- 612 ng/10 min; beta-defensin 1: 687 +/- 243 ng/10 min vs. 1985 +/- 295 ng/10 min; and beta-defensin 2: 784 +/- 299 ng/10 min vs. 2288 +/- 278 ng/10 min). CONCLUSION These results conclusively suggest that oral candidiasis is associated with salivary gland hypofunction and that decreases of salivary antibacterial proteins induce Candida overgrowth.
Test Principle Advantages Limitations Sensitivity to antiplatelet drugs Bleeding time In vivo cessation of blood flow Widely

The clinical efficacy of antiplatelet therapy to prevent occlusive arterial events in patients with atherothrombotic disease is well established. The balance of benefits and risks of antiplatelet drugs in various clinical settings has been evaluated over the past decade in large-scale randomized trials [1]. However, for the absolute benefit of an individual patient, it may become useful to monitor the individual’s response to antiplatelet therapy so that either the dosage and/ or the type of drug(s) administered can be titrated or optimized to help control and minimize the risk of either thrombosis or bleeding. There are three families of antiplatelet drugs with proven clinical efficacy: (i) cyclooxygenase-1 inhibitors such as aspirin; (ii) adenosine 5-diphosphate (ADP) inhibitors, such as the thienopyridine compounds prasugrel, clopidogrel and ticlopidine; and (iii) glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonists, such as abciximab, tirofiban and eptifibatide. Both aspirin and thienopyridines selectively inhibit a single pathway of platelet activation: aspirin affects the thromboxane A2 pathway by irreversibly inhibiting cyclooxygenase-1, while thienopyridines affect the ADP pathway by irreversibly antagonizing one of the two platelet ADP receptors P2Y12 [2]. Good antithrombotic efficacy of these drugs, despite their selective mechanism of action, is explained by the fact that both the thromboxaneA2 pathway and the ADP pathway contribute to the amplification of platelet activation and are essential for the full aggregation response of platelets. The identification of GPIIb/IIIa complex importance in mediating platelet aggregation suggests that this receptor could be an attractive target for antiplatelet therapy. The GPIIb/IIIa antagonists have now become an important class of antiplatelet agents that are widely used for the prevention of thrombotic complications in patients undergoing percutaneous coronary interventions or presenting with acute coronary syndromes [3].
A closed slot-line resonator filter

A microwave bandpass filter made from three-dimensional (3-D) slot-line resonators is described. This structure readily lent itself to the design and realization of a 16-pole filter. By concentrating the losses on the resonant element, very high Q can be achieved by using low surface resistance material, such as high temperature superconductor, for the slot-line resonator. The filter is five to ten times smaller than previous generation 3-D filters made using high temperature superconductors.
Application of real-time PCR array to the multiple detection of antibiotic resistant genes in glacier ice samples.

Glacier environments harbor cold-tolerant bacteria (Amato et al., 2007; Christner et al., 2003; Segawa et al., 2005). However, a variety of bacteria such as soil and enteric bacteria have been detected from these highly oligotrophic and psychrophilic environments (Segawa et al., 2005; Sheridan et al., 2003). The origin of these bacteria remains unknown. These bacteria may have been supplied at least in part from animals by means such as bird droppings (Sjolund et al., 2008). There are other plausible transmissions, such as local and global atmospheric circulation. In the case of the global atmospheric circulation, a glacier environment may receive bacteria originating from hu-man industrial activities, although most glaciers are located at a distance from such sites of human activi-ties. Emergence of antibiotic resistant bacteria has been considered as a human impact on the environment (Cabello, 2006; Chee-Sanford et al., 2001; Goni-Urriza et al., 2000). The prevalence of antibiotic resistant genes in the glacier environment can be used as an indicator of human impact on the global environment. In this experiment, the prevalence of antibiotic resis-tant genes in glacier ice samples taken from various locations in the northern hemisphere (Alaska, Central Asia) and Antarctica were evaluated by real time PCR array approach using a Taqman probe system. We collected samples of the glacial ice (1 cm in depth) or cryoconite hole samples (Table 1) using a sterilized stainless steel scoop or sterilized syringe, re-spectively. The samples were stored in 50-ml sterile plastic conical tubes (Iwaki, Tokyo). All samples were kept frozen and transported to the Tokyo Institute of Technology, Japan or National Institute of Polar Re-search, Japan. Bacterial DNA was extracted as follows within a Class 100 Clean bench (Sanyo, Tokyo, Model MCV-131BNS) at the National Institute of Polar Research (Tokyo). Ice samples were melted and a portion (1‒
Enumeration of acetogens by a colorimetric most-probable-number assay

Anaerobic O demethylation by acetogenic bacteria often is the first step in the mineralization of methoxylated aromatic compounds in anoxic environments. In this reaction, an ether bond is cleaved and the resulting methyl group is metabolized via the acetyl coenzyme A pathway (acetogenesis). Anaerobic O demethylation was used to assess acetogen populations. Environmental samples were diluted in anaerobic medium containing a methoxylated aromatic substrate (vanillate) and titanium(III), and acetogen titers were estimated by the most-probable-number (MPN) method. Complex formation between Ti(III) and vicinal hydroxyl groups of the aromatic products of anaerobic O demethylation results in the development of a yellow color in the medium, which can be detected by eye and monitored spectrophotometrically. High-performance liquid chromatography analysis of the yellow MPN tubes showed that they contained the product of anaerobic O demethylation of vanillate (protocatechuate). This assay was used to enumerate O-demethylating acetogen populations in environmental samples.
Paradoxical aspects of parkinsonian tremor

Although resting tremor is the most identifiable sign of Parkinson's disease, its underlying basis appears to be the most complex of the cardinal signs. The variable relationship of resting tremor to other symptoms of PD has implications for diagnosis, prognosis, medical and surgical treatment. Structural lesions very rarely cause classic resting tremor, with likely contributions to tremor by a network of neurons both within and outside the basal ganglia. Patients with only resting tremor show dopaminergic deficits with radioligand imaging, but severity of tremor correlates poorly in such dopamine imaging studies. Correlation of tremor severity to changes in radioligand studies is also limited by the use of mostly qualitative measures of tremor severity. A complex pharmacologic basis of parkinsonian resting tremor is supported by treatment studies. Although levodopa is clearly effective for resting tremor, several agents have shown efficacy that appears to be superior or additive to that of levodopa including anticholinergics, clozapine, pramipexole, and budipine. Although the thalamus has the greatest body of evidence supporting its role as an effective target for surgical treatment of tremor, recent studies suggest that the subthalamic nucleus may be a reasonable alternative target for patients with Parkinson's disease and severe tremor as the predominant symptom. © 2007 Movement Disorder Society
Screening childhood cancer survivors with the brief symptom inventory‐18: classification agreement with the symptom checklist‐90‐revised

The Brief Symptom Inventory‐18 (BSI‐18) is an 18‐item symptom checklist used as a brief distress screening in cancer and other medical patients. This study evaluated the validity of the BSI‐18 in a sample of 221 adult survivors of childhood cancers ages 18–55 (median = 26). Validity of the BSI‐18 was compared to the Symptom Checklist‐90‐Revised (SCL‐90‐R). Results indicated the BSI‐18 scales had acceptable internal consistency (alpha >0.80) and were highly correlated with the corresponding SCL‐90‐R subscales (correlations from 0.88 to 0.94). When subjects were classified as case positive (significantly distressed) using the BSI‐18 manual case‐rule, classification agreement with the SCL‐90‐R was poor as evidenced by low sensitivity (41.78%). An alternative BSI‐18 case‐rule previously developed for cancer patients using the General Severity Index (GSI; GSI t‐score ⩾57) demonstrated better sensitivity (83.54%). ROC analysis indicated the BSI‐18 had strong diagnostic utility relative to the SCL‐90‐R (AUC = 0.98) and several possible GSI cut‐off scores were evaluated. The optimal cut‐of score was a t‐score ⩾50 which had a sensitivity of 97.47% and a specificity of 85.21%. Results support use of the BSI‐18 with adult survivors of childhood cancer but indicate an alternative case‐rule must be used. Copyright © 2006 John Wiley & Sons, Ltd.
Cytotoxicity of Adenovirus-Antibody Aggregates: Sensitivity to Different Cell Strains, and Inhibition by Hexon Antiserum and by Complement

Adenovirus-antibody aggregates under defined conditions are cytotoxic in vitro. All members of adenovirus groups I, II, and III caused toxicity upon aggregation. The toxicity of the clusters is exerted by the virions. Toxicity is temperature dependent and may be caused by a mechanism similar to that used in viral penetration. Cells permitting direct viral penetration were all sensitive to the toxic aggregates. The toxicity seems to be related to hexon antigens on the surface of the virions since antihexon sera neutralized the toxicity. No evidence was obtained showing that pentons are required for this kind of cytotoxicity. Adenovirus types 3, 5, and 9 were used in the experiment. Cytotoxicity was estimated by the 51Cr release assay. Complement factors could be excluded as mediators of the cytolytic reactions. Instead, complement was shown to prevent the formation of toxic aggregates or to neutralize the toxicity of preformed ones.
bZIP67 Regulates the Omega-3 Fatty Acid Content of Arabidopsis Seed Oil by Activating FATTY ACID DESATURASE3[W][OPEN]

This work explores the regulation of polyunsaturated fatty acid content in Arabidopsis seed oil. It shows that a transcriptional complex containing the basic Leu zipper protein bZIP67 and LEAFY COTYLEDON1-LIKE is responsible for activation of FATTY ACID DESATURASE3, which encodes an enzyme whose activity determines the level of omega-3 polyunsaturated fatty acids. Arabidopsis thaliana seed maturation is accompanied by the deposition of storage oil, rich in the essential ω-3 polyunsaturated fatty acid α-linolenic acid (ALA). The synthesis of ALA is highly responsive to the level of FATTY ACID DESATURASE3 (FAD3) expression, which is strongly upregulated during embryogenesis. By screening mutants in LEAFY COTYLEDON1 (LEC1)–inducible transcription factors using fatty acid profiling, we identified two mutants (lec1-like and bzip67) with a seed lipid phenotype. Both mutants share a substantial reduction in seed ALA content. Using a combination of in vivo and in vitro assays, we show that bZIP67 binds G-boxes in the FAD3 promoter and enhances FAD3 expression but that activation is conditional on bZIP67 association with LEC1-LIKE (L1L) and NUCLEAR FACTOR-YC2 (NF-YC2). Although FUSCA3 and ABSCISIC ACID INSENSITIVE3 are required for L1L and bZIP67 expression, neither protein is necessary for [bZIP67:L1L:NF-YC2] to activate FAD3. We conclude that a transcriptional complex containing L1L, NF-YC2, and bZIP67 is induced by LEC1 during embryogenesis and specifies high levels of ALA production for storage oil by activating FAD3 expression.
Reduction of Mortality with Antithrombin III in Septicemic Rats: A Study of Klebsiella pneumoniae Induced Sepsis

Summary Experimental gram-negative sepsis was induced in the rat by Klebsiella pneumoniae. Although bacteria are susceptible to the treatment with the antibiotic Tobramycin, DIC could not be prevented. DIC was manifested by a leuko- and thrombocytopenia, decreases in fibrinogen and AT III and an increase of the aPTT. In this model the therapeutic treatment with human AT III was evaluated. To determine the optimal concentration of AT III a prestudy in a LPS induced DIC in the rat was performed. It was shown that a bolus i. v. injection of 500 U/kg improved survival and DIC, and was thus chosen for the Klebsiella sepsis model. The infectious load was adjusted to yield a mortality rate of 90-100% in the untreated Klebsiella group and a reduction to about 40-50% of the mortality rate by Tobramycin. It was found that AT III reduced mortality in the Klebsiella induced sepsis not only when given prophylactically but was effective even when administrated in a late stage of the DIC, i. e. 3 or 5 h post infection.
Decentralized Direct MRAC of a Self-Balancing Robot Mounted on a Ball

In this paper, a decentralized direct model reference adaptive control (MRAC) scheme is proposed in order to achieve the control for both ball and body dynamics of a self–balancing robot mounted on a ball, also known as ballbot. The nonlinear model for the ballbot is decomposed in the ball dynamics and body dynamics subsystems. Thus, a second order system is defined for each nonlinear dynamical subsystem. Under the assumption that a linear–in–the–parameters model for each second order system can be defined, then each subsystem is represented by a parameterized model from which a local direct MRAC is designed. The performance of our decentralized adaptive control scheme is validated via simulation results taking into account parametric variations, noise in the measurements and external perturbations.
Irradiation of silicon particle detectors with MeV-protons

Silicon particle detectors are used in several applications and will clearly require better hardness against particle radiation in the future large scale experiments than can be provided today. To achieve this goal, more irradiation studies with defect generating bombarding particles are needed. Protons can be considered as important bombarding species, although neutrons and electrons are perhaps the most widely used particles in such irradiation studies. Protons provide unique possibilities, as their defect production rates are clearly higher than those of neutrons and electrons, and, their damage creation in silicon is most similar to the that of pions. This thesis explores the development and testing of an irradiation facility that provides the cooling of the detector and on-line electrical characterisation, such as current-voltage (IV ) and capacitance-voltage (CV ) measurements. This irradiation facility, which employs a 5-MV tandem accelerator, appears to function well, but some disadvantageous limitations are related to MeV-proton irradiation of silicon particle detectors. Typically, detectors are in non-operational mode during irradiation (i.e., without the applied bias voltage). However, in real experiments the detectors are biased; the ionising proton generates electron-hole pairs, and a rise in rate of proton flux may cause the detector to breakdown. This limits the proton flux for the irradiation of biased detectors. In this work, it is shown that, if detectors are irradiated and kept operational, the electric field decreases the introduction rate of negative space-charges and current-related damage. The effects of various particles with different energies are scaled to each others by the non-ionising energy loss (NIEL) hypothesis. The type of defects induced by irradiation depends on the energy used, and this thesis also discusses the minimum proton energy required at which the NIEL-scaling is valid.
RNA virus fitness

RNA viruses constitute the most abundant group of pathogens of man, animals and plants. They share high mutation rates which are in the range 10−3 to 10−5 misincorporations per nucleotide site and round of copying. This is due to the absence or low efficiency of proofreading‐repair or postreplicative repair activities associated with replicating RNA. Populations of RNA viruses are extremely heterogeneous and form dynamic mutant swarms termed viral quasispecies. This genetic organisation implies that any individual mutant has only a fleeting existence; that is, RNA viral genomes are statistically defined but individually indeterminate. RNA viruses are able to accommodate their average nucleotide sequences to changes in environment. A parameter used to quantitate adaptation is fitness, or the relative ability of a virus to produce infectious progeny. Repeated transfers of one or a few particles (bottleneck events) generally lead to fitness losses. In contrast, large population passages allow competitive optimisation of mutant genomes and fitness gains. Of relevance to medical practice is the ability of viral quasispecies to overcome selective pressures imposed by vaccines and antiviral agents. Particularly dramatic have been the systematic isolations of HIV‐1 mutants resistant to antiretroviral inhibitors in treated individuals. In addition to the ability of HIV‐1 quasispecies to generate many mutant genomes in short times, calculations of mutation frequencies in the pol gene of HIV‐1 populations have documented that mutations related to resistance to antiretroviral inhibitors preexist in the mutant swarms of HIV‐1 quasispecies. It is not possible at present to anticipate whether a suitable drug cocktail may be capable of sustained inhibition of HIV‐1 replication without selection of mutants resistant to the combination of antiviral agents. © 1997 John Wiley & Sons, Ltd.