Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of systemic chemotherapy in metastatic hormone-sensitive prostate cancer

Introduction: Patients with metastatic hormone sensitive prostate cancer (mHSPC) have traditionally been treated with androgen deprivation therapy (ADT). Recently, there has been a demonstration of a survival benefit with the addition of docetaxel to ADT from three large randomized controlled trials. This review summarizes these trials, draws comparisons between the trials, and attempts to provide critical evidence-based recommendation on the role of docetaxel in mHSPC. Methods: Of the two published (GETUG-AFU, Chemo-Hormonal therapy vs. Androgen Ablation Randomized Trial for Extensive Disease in prostate cancer [CHAARTED]) and one presented trial (STAMPEDE) an analysis of the study design, patient characteristics, outcomes, variables, and a critical comparison between the trials was performed for making practice recommendations. Results: All the three trials demonstrated statistically significant progression free survival with the addition of docetaxel to ADT in mHSPC. However, while CHAARTED trial demonstrated a significant survival benefit with addition of docetaxel to ADT in patients with high volume mHSPC, GETUG-AFU failed to demonstrate statistically significant survival benefit although there was an absolute difference in survival between the two arms, with lower sample size and statistical power compared to CHAARTED. The largest study, STAMPEDE, reported a 22 month survival benefit in patients with M1 disease with statistical significance; with subgroup analysis of high volume and low volume disease patients yet to be reported. Conclusion: After a careful comparison between the trials, we conclude that systemic docetaxel chemotherapy within 4 months of initiating ADT for metastatic, high-volume HSPC should be considered the standard of care for patients with good performance status.
NMDA Receptors with Incomplete Mg2+ Block Enable Low-Frequency Transmission through the Cerebellar Cortex

The cerebellar cortex coordinates movements and maintains balance by modifying motor commands as a function of sensory-motor context, which is encoded by mossy fiber (MF) activity. MFs exhibit a wide range of activity, from brief precisely timed high-frequency bursts, which encode discrete variables such as whisker stimulation, to low-frequency sustained rate-coded modulation, which encodes continuous variables such as head velocity. While high-frequency MF inputs have been shown to activate granule cells (GCs) effectively, much less is known about sustained low-frequency signaling through the GC layer, which is impeded by a hyperpolarized resting potential and strong GABAA-mediated tonic inhibition of GCs. Here we have exploited the intrinsic MF network of unipolar brush cells to activate GCs with sustained low-frequency asynchronous MF inputs in rat cerebellar slices. We find that low-frequency MF input modulates the intrinsic firing of Purkinje cells, and that this signal transmission through the GC layer requires synaptic activation of Mg2+-block-resistant NMDA receptors (NMDARs) that are likely to contain the GluN2C subunit. Slow NMDAR conductances sum temporally to contribute approximately half the MF-GC synaptic charge at hyperpolarized potentials. Simulations of synaptic integration in GCs show that the NMDAR and slow spillover-activated AMPA receptor (AMPAR) components depolarize GCs to a similar extent. Moreover, their combined depolarizing effect enables the fast quantal AMPAR component to trigger action potentials at low MF input frequencies. Our results suggest that the weak Mg2+ block of GluN2C-containing NMDARs enables transmission of low-frequency MF signals through the input layer of the cerebellar cortex.
Using a Virtual Community to Enhance Cultural Awareness

Purpose: Cultural competence is an expectation of professional practice, yet effectively teaching this concept to nursing students is challenging. The purpose of this study was to assess the use of a virtual community as a teaching application to foster cultural awareness among nursing students. Method: This correlational study involved the collection of two surveys from 342 first-semester students from five baccalaureate nursing programs that used The Neighborhood virtual community during one semester. Descriptive and comparative analyses were performed. Findings and Conclusions: Results suggest that use of the virtual community may have contributed to cultural awareness among student participants. There was a significant correlation between frequency of use and cultural awareness. Virtual communities may represent a useful teaching application for cultural competence in nursing education. Further research is needed to specifically test cultural competence education strategies using a virtual community platform.
Fractionally-spaced equalization: An improved digital transversal equalizer

Here we describe and demonstrate, via analysis and simulation, the performance improvement of voice-grade modems which use a Fractionally-Spaced Equalizer (FSE) instead of a conventional synchronous equalizer. The reason for this superior performance is that the fse adoptively realizes the optimum linear receiver; consequently it can effectively compensate for more severe delay distortion than the conventional adaptive equalizer, which suffers from aliasing effects. An additional advantage of the FSE is that data transmission can begin with an arbitrary sampling phase, since the equalizer synthesizes the correct delay during adaptation. We show that an FSE combined with a decision feedback section, which can mitigate the effect of severe amplitude distortion, can compensate for a wide range of linear distortion. At 9.6 kbit/s, the FSE provides a 2 to 3 dB gain in output signal-to-noise ratio, relative to the synchronous equalizer, over worst-case private-line channels. This translates to a theoretical improvement of approximately two orders of magnitude in bit error rate.
Energetics of Transport through the Nuclear Pore Complex

Molecular transport across the nuclear envelope in eukaryotic cells is solely controlled by the nuclear pore complex (NPC). The NPC provides two types of nucleocytoplasmic transport: passive diffusion of small molecules and active chaperon-mediated translocation of large molecules. It has been shown that the interaction between intrinsically disordered proteins that line the central channel of the NPC and the transporting cargoes is the determining factor, but the exact mechanism of transport is yet unknown. Here, we use coarse-grained molecular dynamics simulations to quantify the energy barrier that has to be overcome for molecules to pass through the NPC. We focus on two aspects of transport. First, the passive transport of model cargo molecules with different sizes is studied and the size selectivity feature of the NPC is investigated. Our results show that the transport probability of cargoes is significantly reduced when they are larger than ∼5 nm in diameter. Secondly, we show that incorporating hydrophobic binding spots on the surface of the cargo effectively decreases the energy barrier of the pore. Finally, a simple transport model is proposed which characterizes the energy barrier of the NPC as a function of diameter and hydrophobicity of the transporting particles.
Exploring the relationship between social class, mental illness stigma and mental health literacy using British national survey data

The relationship between social class and mental illness stigma has received little attention in recent years. At the same time, the concept of mental health literacy has become an increasingly popular way of framing knowledge and understanding of mental health issues. British Social Attitudes survey data present an opportunity to unpack the relationships between these concepts and social class, an important task given continuing mental health inequalities. Regression analyses were undertaken which centred on depression and schizophrenia vignettes, with an asthma vignette used for comparison. The National Statistics Socio-economic Classification, education and income were used as indicators of class. A number of interesting findings emerged. Overall, class variables showed a stronger relationship with mental health literacy than stigma. The relationship was gendered such that women with higher levels of education, especially those with a degree, had the lowest levels of stigma and highest levels of mental health literacy. Interestingly, class showed more of an association with stigma for the asthma vignette than it did for both the depression and schizophrenia vignettes, suggesting that mental illness stigma needs to be contextualised alongside physical illness stigma. Education emerged as the key indicator of class, followed by the National Statistics Socio-economic Classification, with income effects being marginal. These findings have implications for targeting health promotion campaigns and increasing service use in order to reduce mental health inequalities.
Estradiol supplementation enhances submaximal feed-forward drive of growth hormone (GH) secretion by recombinant human GH-releasing hormone-1,44-amide in a putatively somatostatin-withdrawn milieu.

To test the clinical hypothesis that an estrogen-enriched milieu enhances GHRH action, we administered placebo (Pl) and estradiol-17 beta (E(2)) orally for 23 d to six postmenopausal women in a prospectively randomized, double-masked, within-subject crossover design with 6 wk intervening. The GHRH stimulation protocol entailed consecutive i.v. infusion of L-arginine and a single i.v. pulse of saline or one of five randomly ordered doses of recombinant human GHRH-1,44-amide (0.03, 0.1, 0.3, 1.0, or 3.0 microg/kg) in a total of 12 separate morning, fasting sessions. GH secretion was monitored by sampling blood every 10 min for 6 h; chemiluminescence assay of GH concentrations; deconvolution analysis of stimulated GH release; and nonlinear dose-response reconstruction. Supplementation with E(2), compared with Pl: 1) increased (mean +/- SEM) E(2) concentrations from 18 +/- 3 (Pl) to 164 +/- 12 pg/ml (to convert to picomoles per liter, multiply by 3.57) (P < 0.001); 2) decreased IGF-I concentrations from 181 +/- 14 to 120 +/- 11 microg/liter (P < 0.01); 3) elevated mean GH concentrations from 0.27 +/- 0.06 to 0.59 +/- 0.08 microg/liter (P = 0.014); 4) potentiated GH secretion stimulated by L-arginine alone by 1.43-fold (P = 0.012); 5) reduced the ED(50) of GHRH from 0.27 +/- 0.02 to 0.13 +/- 0.01 microg/kg (P < 0.01), denoting enhanced GHRH potency; and 6) heightened the maximal slope of the dose-response function from 1.1 +/- 0.1 to 1.4 +/- 0.05 [( microg/liter) ( microg/kg)(-1)] (P < 0.05), signifying augmented pituitary sensitivity. The foregoing facilitative mechanisms were specific because E(2) replacement did alter maximal L-arginine/GHRH-induced GH secretion, indicating unchanged secretagogue efficacy. In conclusion, inasmuch as E(2) also attenuates inhibition of GH secretion by infused somatostatin and potentiates stimulation of GH secretion by GH-releasing peptide-2, we postulate that estrogenic steroids drive pulsatile GH production in part via mechanisms that include all three of GHRH, somatostatin, and putatively GH-releasing peptide/ghrelin signaling.
New species and records of linyphiid spiders from Laos (Araneae, Linyphiidae).

Recent linyphiid collections from Laos as well as some additional specimens from Thailand and West Malaysia are examined. Six species and two genera are described as new to science: Bathyphantes paracymbialis n. sp. , Nematogmus asiaticus n. sp. , Theoa hamata n. sp. ; Asiagone n. gen. is erected for Asiagone signifera n. sp. (type species) and A. perforata n. sp. ; Laogone n. gen. is established for Laogone cephala n. sp. The following new synonyms are proposed: Gorbothorax Tanasevitch, 1998 n. syn. = Nasoona Locket, 1982; Paranasoona Heimer, 1984 n. syn. and Millplophrys Platnick, 1998 n. syn. = Atypena Simon, 1894; Gorbothorax ungibbus Tanasevitch, 1998 n. syn. = Oedothorax asocialis Wunderlich, 1974; Hylyphantes birmanicus (Thorell, 1895) n. syn. = H. graminicola (Sundevall, 1830). The following new combinations are proposed: Atypena cirrifrons (Heimer, 1984) n. comb. ex from Paranasoona; A. pallida (Millidge, 1995) and A. crocatoa (Millidge, 1995) both n. comb. ex Millplophrys; Nasoona asocialis (Wunderlich, 1974) n. comb. ex Oedothorax Bertkau, 1883; N. asocialis (Wunderlich, 1974), N. comata (Tanasevitch, 1998), N. conica (Tanasevitch, 1998), N. setifera (Tanasevitch, 1998) and N. wunderlichi (Brignoli, 1983), all n. comb. ex Gorbothorax. Eight linyphiid species are newly recorded from Laos: A. cirrifrons (Heimer, 1984), Bathyphantes floralis Tu & Li, 2006, Hylyphantes graminicola (Sundevall, 1830), Nasoona asocialis, N. crucifera (Thorell, 1895), Nasoonaria sinensis Wunderlich & Song, 1995, Neriene birmanica (Thorell, 1887), and N. oxycera Tu & Li, 2006. The linyphiid spider fauna of Laos currently contains 15 species and is unusually highly specific. All species, except the Palearctic H. graminicola, are probably represented by Southeastern Asian or Oriental autochthons.
Correlates of depression in a representative nationwide sample of adolescents (15-19 years) and young adults (20-24 years).

BACKGROUND The authors investigated correlates of depression in a general population sample of adolescents (15-19 years) and young adults (20-24 years). METHODS As part of the Finnish Health Care Survey a random sample of 509 adolescents (281 females, 228 males) and 433 young adults (224 females, 209 males) was interviewed in 1996. DSM-IIR major depressive episode (MDE) was assessed by the University of Michigan Composite International Diagnostic Interview Short Form (UM-CIDI SF). RESULTS In multivariable regression analysis, current smoking (odds ratio (OR) 5.54; 95% confidence interval (CI) 1.44, 21.3) and chronic illness (OR 3.77; 95% CI: 1.04, 13.7) associated with MDE among adolescents. Among young adults, drunkenness at least twice a month (OR 4.48; 95% CI: 1.44, 14.0) or once a month (OR 2.79; 95% CI: 1.14, 6.83), not being married nor cohabiting (OR 3.50; 95% CI: 1.35, 9.08) and infrequent physical exercise (OR 4.01; 95% CI: 1.18, 14.0) were related to MDE. Female MDE associated with not being married nor cohabiting (OR 3.56; 95% CI: 1.23, 10.1) and living in southern Finland (OR 2.30; 95% CI: 1.06, 5.02). Drunkenness at least twice a month was related to MDE among males (OR 4.54; 95% CI: 1.27, 16.3). CONCLUSIONS Attention should be paid to compromised health and health-related behaviour associating with MDE in youth. Specifically, the association between smoking and major depression in early adolescence should be borne in mind, and drinking habits or frequency of drunkenness should be carefully noted.
Geometry, electronic structures and optical properties of phosphorus nanotubes

Using a first principles approach, we investigated the geometry, electronic structures, and optical properties of phosphorus nanotubes (PNTs). Two possible 1D configurations, the so-called α-PNTs and β-PNTs, are proposed, which are structurally related to blue and black phosphorus monolayers, respectively. Hereby, we predict that both armchair and zigzag geometries can be synthesized in α-PNTs, but the zigzag form of β-PNT is highly unfavorable because of large strain and conformation energies. The band gap of α-PNTs is expected to be ∼2.67 eV, and this is insensitive to the chirality when the tube’s inner diameter is larger than 1.3 nm, while the armchair β-PNTs have a much smaller band gap. Interestingly, we find nearly flat band structures in the zigzag α-PNT system. This may indicate that an excited particle–hole pair has a huge effective mass. We also find asymmetric optical properties with respect to the polarization direction. The armchair α-PNT for parallel polarization shows a large refractive index of 2.6 near the ultraviolet wavelength, and also we find that the refractive index can be even smaller than 1 in certain frequency ranges. The zigzag tubes show very weak reflectivity for parallel polarization, while the armchair tube displays high reflectivity.
Over‐expression of metallothionein predicts chemoresistance in breast cancer

Metallothionein (MT) plays a role in fundamental cellular processes such as proliferation, apoptosis and differentiation. We examined MT expression in women with invasive breast ductal carcinoma who underwent mastectomy/lumpectomy without neo‐adjuvant treatment. We showed that MT was over‐expressed in 87.9% of breast cancer tissues examined, with the mean percentage of positive cells at 30%. There were two patterns of MT expression: predominantly cytoplasmic in 75.9% and nuclear in 24.1% of MT‐positive cases. Higher MT scores were associated with poorer histological grade (p = 0.009) but were independent of age, tumour size and oestrogen receptor status. For patients who were treated with adjuvant chemotherapy (cyclophosphamide/methotrexate/5 fluorouracil‐ or doxorubicin‐based regimes), those with high MT expression had a significantly lower recurrence‐free survival (p = 0.048), suggesting a role of MT in predicting disease recurrence. Down‐regulation of MT in MCF‐7 cells by silencing the MT‐2A gene (the most abundantly expressed of the 10 known functional MT isoforms) increased chemosensitivity of the cells to doxorubicin. To examine the mechanisms underlying these clinical data, we used siRNAs to decrease MT‐2A mRNA expression and protein expression. In MT down‐regulated cells challenged with the IC50 concentration of doxorubicin, we observed a significant reduction in cell viability. Cell cycle analysis also revealed a corresponding increase in apoptosis in the MT down‐regulated cells following doxorubicin exposure, showing that down‐regulation of MT increased susceptibility to doxorubicin cytotoxicity. The data suggest that MT could be a potential marker of chemoresistance and a molecular therapeutic target. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Monitoring arterio‐venous differences of glucose and lactate in the anesthetized rat with or without brain damage with ultrafiltration and biosensor technology

Continuous monitoring of arterio‐venous glucose and lactate differences may serve as a diagnostic tool to assess normal brain function and brain pathology. We describe a method and some results obtained with arterio‐venous measurements of glucose and lactate in the blood of the halothane‐anesthetized rat and after brain injury. The method is based on low flow rate ultrafiltration for continuous collection of blood filtrate combined with flow injection analysis and biosensors for the detection of glucose and lactate. We measured the glucose and lactate concentration every minute in the jugular vein and the aorta at control conditions and during and after inflation of an embolectomy‐balloon for 2 min. Net cerebral lactate efflux and glucose uptake was seen under control conditions and at low blood lactate levels. During brain injury both lactate release and glucose uptake were reduced and there was a net lactate influx at high arterial lactate levels. These results indicate that the flux of lactate in and out of the brain is not only dependent on the lactate concentration in the brain, but on blood levels as well, possibly because of bi‐directional flux through the monocarboxylate transporter type 1. © 2001 Wiley‐Liss, Inc.
K+ Channels Which Contribute to the Acetylcholine‐Induced Hyperpolarization in Smooth Muscle of the Guinea‐Pig Submucosal Arteriole

1 Membrane potentials were recorded from submucosal arterioles (diameter, 30–80 μm) of the guinea‐pig small intestine, using conventional microelectrode techniques. In control solution the resting membrane potential was about −73 mV, and the addition of 0.5 mm Ba2+ depolarized the membrane to about −43 mV. 2 ACh (10 nm to 10 μM), or substance P (0.1 μM), caused a membrane hyperpolarization in preparations which had been depolarized by Ba2+ but not in control preparations. ACh produced a sustained hyperpolarization, whereas substance P produced a transient hyperpolarization, without being affected by either nitroarginine (0.1 mm) or indomethacin (10 μM). 3 In the presence of 50 μM BAPTA (acetoxymethyl ester form), the membrane potentials were not altered in the control solution or in the presence of Ba2+, but Ba2+ caused a smooth depolarization of the membrane. Following this procedure, both ACh and substance P caused membrane depolarization instead of hyperpolarization, suggesting that the ACh‐ and substance P‐induced hyperpolarization in arteriolar smooth muscle are intracellular [Ca2+] dependent. 4 In short segments (200–500 μM) of arteriole, the time constant of electrotonic potentials produced by passing current pulses through the recording electrode was about 75 ms. The addition of Ba2+ increased both the input resistance and the time constant. 5 The hyperpolarizations produced by ACh or substance P were associated with a reduction in the amplitude and the time constant of electrotonic potential. 6 The reversal potential for the ACh‐induced hyperpolarization, estimated from the current‐voltage relationship, was about −86 mV, a value close to the equilibrium potential for K+. 7 In the presence of 50 nM charybdotoxin the hyperpolarization produced by ACh became transient and was reduced in amplitude: the residual response was further reduced by apamin (0.1 μM). The response produced by substance P was also reduced by 50 nM charybdotoxin: again the residual response was sensitive to 0.1 μM apamin. The hyper‐polarizations produced by either ACh or substance P were insensitive to glibenclamide (10 μM) and 4‐aminopyridine (1 mm). 8 It is suggested that in submucosal arterioles of the guinea‐pig ileum, ACh‐ or substance P‐induced hyperpolarizations of smooth muscle result from activation of both charybdotoxin‐sensitive and apamin‐sensitive K+ channels, with the former being predominant. The results are discussed in relation to the possible involvement of one or more endothelium‐dependent hyperpolarizing factors in ACh‐ and substance P‐induced hyperpolarization.
Reduction in circulating pro-angiogenic and pro-inflammatory factors is related to improved outcomes in patients with advanced pancreatic cancer treated with gemcitabine and intravenous omega-3 fish oil.

BACKGROUND Pancreatic cancer is a rapidly progressive disease which is often only amenable to palliative treatment. Few patients respond to palliative chemotherapy, so surrogate markers indicating which patients are likely to respond to treatment are required. There is a well-established link between pro-inflammatory circulating cytokines and growth factors (CAF), and the development of neoplasia. Agents that may modulate these factors are of interest in developing potential novel therapeutic applications. METHODS As part of a single-arm phase II trial in patients with advanced pancreatic cancer (APC) treated with gemcitabine and intravenous (i.v.) omega-3 rich lipid emulsion (n-3FA), serum samples were analysed for 14 CAF using a multiplex cytokine array. Baseline serum concentrations were correlated with overall (OS) and progression-free survival (PFS), and changes in concentration correlated with time and outcomes for CAF responders were analysed. RESULTS Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) concentrations reduced significantly with treatment over time. Low baseline interleukin (IL)-6 and -8 were correlated with improved OS. PDGF responders showed a tendency towards improved OS and FGF responders a significantly improved PFS. DISCUSSION Treatment with gemcitabine plus i.v. n-3FA may reduce concentrations of CAF which may be associated with an improved outcome. Baseline IL-6 and -8 may be surrogate markers for outcome in patients with APC treated with this regimen.