Miracle-dz/UniFAR-FTUs huggingface dataset:
Lack of significant genotoxicity of purified soy isoflavones (genistein, daidzein, and glycitein) in 20 patients with prostate cancer.

BACKGROUND Genistein may be useful in the prevention or treatment of prostate cancer; however, it causes genetic damage in cultured human cells. OBJECTIVE The objective was to assess the potential genotoxicity of a purified soy unconjugated isoflavone mixture in men with prostate cancer. DESIGN Twenty patients with prostate cancer were treated with 300 mg genistein/d for 28 d and then with 600 mg/d for another 56 d. In peripheral lymphocytes, DNA strand breaks were assessed as nuclear tail moment, chromosomal damage was assessed as micronucleus frequency (MF), and translocations of the MLL gene (11q23) were assessed by using fluorescence in situ hybridization. Values are also reported for 6 healthy men. The studies were performed under Investigational New Drug application no. 54 137 at a tertiary referral academic medical center. RESULTS No changes in group average or individual nuclear tail moment and MF were observed. We observed a single elevated MF value in one subject that exceeded a clinical threshold set before we initiated the study. A significant decrease in average COMET tail moment was observed on day 28 relative to day 0. We detected no genistein-induced rearrangements of the MLL gene in the 3 subjects we studied with this technique. MF increased significantly in lymphocytes exposed in vitro to unconjugated genistein at concentrations > or = 100 micromol/L. Total genistein never exceeded a peak concentration of 27.1 micro mol/L, and unconjugated genistein never exceeded a peak concentration of 0.32 micromol/L. CONCLUSION Although isoflavones are capable of inducing genetic damage in vitro, a similar effect was not observed in subjects treated with a purified soy unconjugated isoflavone mixture.
Increased n-6 polyunsaturated fatty acids do not attenuate the effects of long-chain n-3 polyunsaturated fatty acids on insulin sensitivity or triacylglycerol reduction in Indian Asians.

BACKGROUND Indian Asians in Western countries have a higher rate of coronary artery disease than do the indigenous white populations, and this higher rate may be influenced by a dietary imbalance of n-6 and n-3 polyunsaturated fatty acids (PUFAs). OBJECTIVE The objective of the study was to test the hypothesis that a high background dietary intake of n-6 PUFA attenuates the effects of fish-oil supplementation on insulin sensitivity and associated blood lipids of the metabolic syndrome. DESIGN Twenty-nine Indian Asian men were recruited to participate in a 12-wk dietary intervention trial. Volunteers were randomly assigned to receive either a moderate or a high n-6 PUFA diet featuring modified oils and spreads over a 6-wk period. After this 6-wk period, both groups were supplemented with 4.0 g fish oil/d (2.5 g eicosapentaenoic acid + docosahexaenoic acid) for an additional 6 wk in combination with the dietary treatment. Volunteers participated in a postprandial study and an insulin sensitivity test after the 6-wk dietary intervention and again after the fish-oil supplementation period. RESULTS There was no significant time x treatment interaction for blood lipids or insulin action after dietary intervention with the moderate or high n-6 PUFA diets in combination with fish oil. After the 6-wk period of fish oil supplementation, fasting and postprandial plasma triacylglycerol concentrations decreased significantly. CONCLUSION The background dietary n-6 PUFA concentration did not modulate the effect of fish-oil supplementation on blood lipids or measures of insulin sensitivity in this ethnic group.
The G protein-coupled receptor Gpr161 regulates forelimb formation, limb patterning and skeletal morphogenesis in a primary cilium-dependent manner

ABSTRACT The role of basal suppression of the sonic hedgehog (Shh) pathway and its interaction with Indian hedgehog (Ihh) signaling during limb/skeletal morphogenesis is not well understood. The orphan G protein-coupled receptor Gpr161 localizes to primary cilia and functions as a negative regulator of Shh signaling by promoting Gli transcriptional repressor versus activator formation. Here, we show that forelimb buds are not formed in Gpr161 knockout mouse embryos despite establishment of prospective limb fields. Limb-specific deletion of Gpr161 resulted in prematurely expanded Shh signaling and ectopic Shh-dependent patterning defects resulting in polysyndactyly. In addition, endochondral bone formation in forearms, including formation of both trabecular bone and bone collar was prevented. Endochondral bone formation defects resulted from accumulation of proliferating round/periarticular-like chondrocytes, lack of differentiation into columnar chondrocytes, and corresponding absence of Ihh signaling. Gpr161 deficiency in craniofacial mesenchyme also prevented intramembranous bone formation in calvarium. Defects in limb patterning, endochondral and intramembranous skeletal morphogenesis were suppressed in the absence of cilia. Overall, Gpr161 promotes forelimb formation, regulates limb patterning, prevents periarticular chondrocyte proliferation and drives osteoblastogenesis in intramembranous bones in a cilium-dependent manner. Summary: Limb- and craniofacial mesenchyme-specific deletion of Gpr161 demonstrates an unexpected role played by cilia in limb/skeletal morphogenesis by basally repressing the sonic hedgehog pathway at times when sonic hedgehog is absent.
Anomia training and brain stimulation in chronic aphasia

Recent studies have reported enhanced performance on language tasks induced by non-invasive brain stimulation, i.e., repetitive transcranial magnetic stimulation (rTMS), or transcranial direct current stimulation (tDCS), in patients with aphasia due to stroke or Alzheimer's disease (AD). The first part of this article reviews brain stimulation studies related to language recovery in aphasic patients. The second part reports results from a pilot study with three chronic stroke patients who had non-fluent aphasia, where real or placebo rTMS was immediately followed by 25 minutes of individualised speech therapy. Real rTMS consisted of high-frequency rTMS over the left dorsolateral prefrontal cortex (BA 8/9) for 25 minutes. Each patient underwent a total of four weeks of intervention. P1 underwent four weeks of real rTMS (5 days/week) where individualised speech therapy was provided for 25 minutes immediately following each rTMS session. P2 and P3 each underwent two weeks of placebo rTMS, followed immediately by individualised speech therapy; then two weeks of real rTMS, followed immediately by individualised speech therapy. Assessments took place at 2, 4, 12, 24 and 48 weeks post-entry/baseline testing. Relative to entry/baseline testing, a significant improvement in object naming was observed at all testing times, from two weeks post-intervention in real rTMS plus speech therapy, or placebo rTMS plus speech therapy. Our findings suggest beneficial effects of targeted behavioural training in combination with brain stimulation in chronic aphasic patients. However, further work is required in order to verify whether optimal combination parameters (rTMS alone or speech therapy alone) and length of rTMS treatment may be found.
Carbohydrate intake, glycemic index, glycemic load, and risk of postmenopausal breast cancer in a prospective study of French women.

BACKGROUND Diets high in carbohydrates may result in chronically elevated insulin concentrations and may affect breast cancer risk by stimulation of insulin receptors or through insulin-like growth factor I (IGF-I)-mediated mitogenesis. Insulin response to carbohydrate intake is increased in insulin-resistant states such as obesity. OBJECTIVE We sought to evaluate carbohydrate intake, glycemic index (GI), and glycemic load (GL) and subsequent overall and hormone-receptor-defined breast cancer risk among postmenopausal women. DESIGN A prospective cohort analysis of dietary carbohydrate and fiber intakes was conducted among 62 739 postmenopausal women from the E3N French study who had completed a validated dietary history questionnaire in 1993. During a 9-y period, 1812 cases of pathology-confirmed breast cancer were documented through follow-up questionnaires. Nutrients were categorized into quartiles and energy-adjusted with the regression-residual method. Cox model-derived relative risks (RRs) were adjusted for known determinants in breast cancer. RESULTS Dietary carbohydrate and fiber intakes were not associated with overall breast cancer risk. Among overweight women, we observed an association between GI and breast cancer (RR(Q1-Q4): 1.35; 95% CI: 1.00, 1.82; P for trend = 0.04). For women in the highest category of waist circumference, the RR(Q1-Q4) was 1.28 (95% CI: 0.98, 1.67; P for trend = 0.10) for carbohydrates, 1.35 (95% CI: 1.04, 1.75; P for trend = 0.01) for GI, and 1.37 (95% CI: 1.05, 1.77; P for trend = 0.003) for GL. We also observed a direct association between carbohydrate intake, GL, and estrogen receptor-negative breast cancer risk. CONCLUSIONS Rapidly absorbed carbohydrates are associated with postmenopausal breast cancer risk among overweight women and women with large waist circumference. Carbohydrate intake may also be associated with estrogen receptor-negative breast cancer.
Metal and dielectric nanoparticle scattering for improved optical absorption in photovoltaic devices

The influence of electromagnetic scattering by Au and silica nanoparticles placed atop silicon photovoltaic devices on absorption and photocurrent generation has been investigated. The nanoparticles produce substantial increases in power transmission into the semiconductor and consequently photocurrent response from ∼500to>1000nm. Increases in power conversion efficiency under simulated solar irradiation of up to 8.8% are observed experimentally, and numerical simulations provide quantitatively accurate predictions of these observed enhancements. Additional simulations indicate that these concepts can be applied to a broad range of photovoltaic device structures, including those based on low-index materials for which conventional antireflection coatings are problematic.
Three Huge Pulmonary Arteriovenous Malformations: Endovascular Embolization with the Amplatzer Vascular Plug

Pulmonary arteriovenous malformations are abnormal direct communications between pulmonary arteries and pulmonary veins. Transcatheter embolotherapy is the preferred treatment method because of its less invasive nature. There are several methods for the treatment of pulmonary arteriovenous malformations, such as detachable occlusion balloon and coil embolization. The Amplatzer Vascular Plug is a new alternative embolization device which is a self expandable cylindirical nitinol wire mesh used for embolization of the pulmonary arteriovenous malformations. We described two cases (with three huge pulmonary arteriovenous malformations) treated with the Amplatzer Vascular Plug. (Tur Toraks Der 2011; 12: 168-71)
Preclinical PET imaging of HIP/PAP using 1'-18F-fluoroethyl-β-D-lactose

Purpose This study aims at preclinical evaluation of a recently reported lactose analogue, 1'-18F-fluoroethyl-β-D-lactose (18F-FEL), in binding to hepatocarcinoma-intestine-pancreas and pancreatitis-associated protein (HIP/PAP) in vitro and in vivo. Methods In this study, a multifunctional module was employed for the automated synthesis of 18F-FEL. Additional radiochemical purity, biodistribution, in vitro and in vivo competition, metabolic stability and micro-PET studies were performed using T3M4 and SK-BR-3 xenografts. Expression of HIP/PAP in T3M4 and SK-BR-3 tumor sections and cell lines were tested with immunohistochemistry (IHC) and western blot analysis. Results The synthesis of 18F-FEL was completed in 30 min, with a radiochemical yield of 20 ± 5% and specific activity of 14.2 ± 7.1 GBq/μmol. 18F-FEL exhibited high HIP/PAP-binding affinity with a half maximal inhibitory concentration (IC50) of 22.0 ± 4.0 nM. 18F-FEL demonstrated high stability and specific tumor accumulation, which was reduced by approximately 80% in a PET competition assay by co-injection of β-D-lactose. High expression of HIP/PAP was detected in T3M4 tumors and cell line, but negative result was found for SK-BR-3 cell line. Conclusion 18F-FEL has a high binding property to HIP/PAP, high stability and excellent pharmacokinetics in vivo and therefore warrants further evaluation in a proof-of-concept study in humans.
Origami MEMS and NEMS

In a manner reminiscent of macroscale bending and folding techniques such as origami, the out-of-plane assembly of lithographically micro- and nanopatterned thin films, can be used to fabricate three-dimensional (3D) micro- and nanostructured devices. These 3D devices, including microelectronic circuits, sensors, antennas, metamaterials, robotic, and biomimetic constructs, enable new functionalities and are challenging to fabricate by other methods. In this article, we summarize important features of this set of techniques and the devices assembled thereof, with a focus on functional constructs that have been formed by bending, folding, or buckling. At small size scales, manipulation using manual or even wired probes face daunting practical challenges in terms of cost, scalability, and high-throughput manufacturability; hence we emphasize techniques that manipulate strain in thin films so that they can spontaneously assemble into programmed 3D geometries without the need for any wires or probes.
Changes in maternal upper arm fat stores are predictors of variation in infant birth weight.

The relationship between changes in maternal subcutaneous fat and infant birth weight was studied in 608 low income women. A loss of upper arm fat area (> 6.4 cm2), measured from 28 wk gestation to 4-6 wk postpartum, was associated with greater birth weight (+144 g, P < 0.01). However, when pregravid weight was low (< 25th percentile for age), a loss of upper arm fat area was associated with a birth weight lower by more than 300 g than that for women with higher pregravid weights who also lost fat, indicating that maternal stores among those with low weight may have been relatively depleted. Continued gains in upper arm fat area (> 5 cm2) from 28 wk gestation to the postpartum period was also associated with a lower birth weight (-123 g, P < 0.02). The mothers who gained upper arm fat late in pregnancy or continued to accrue fat in the postpartum period had the largest gestational weight gains, bore infants who were smaller, and retained the most weight postpartum. Thus, change in upper arm fat is a significant predictor of variation in infant birth weight.
Active Search for Computer‐aided Drug Design

We consider lead discovery as active search in a space of labelled graphs. In particular, we extend our recent data‐driven adaptive Markov chain approach, and evaluate it on a focused drug design problem, where we search for an antagonist of an αv integrin, the target protein that belongs to a group of Arg−Gly−Asp integrin receptors. This group of integrin receptors is thought to play a key role in idiopathic pulmonary fibrosis, a chronic lung disease of significant pharmaceutical interest. As an in silico proxy of the binding affinity, we use a molecular docking score to an experimentally determined αvβ6 protein structure. The search is driven by a probabilistic surrogate of the activity of all molecules from that space. As the process evolves and the algorithm observes the activity scores of the previously designed molecules, the hypothesis of the activity is refined. The algorithm is guaranteed to converge in probability to the best hypothesis from an a priori specified hypothesis space. In our empirical evaluations, the approach achieves a large structural variety of designed molecular structures for which the docking score is better than the desired threshold. Some novel molecules, suggested to be active by the surrogate model, provoke a significant interest from the perspective of medicinal chemistry and warrant prioritization for synthesis. Moreover, the approach discovered 19 out of the 24 active compounds which are known to be active from previous biological assays.
Carcinoma in Situ of the Bladder

Central to the earlier detection and effective treatment of bladder cancer is the understanding of the basic principle that in situ cancer, evolving from epithelial atypia or hyperplasia, is the early phase in the development of invasive bladder cancer. While it may be asymptomatic, irritative bladder symptoms such as frequency, urgency, and dysuria irrespective of bacteriuria are usually evident and should be evaluated with exfoliative urinary cytology to detect the presence of this cancer. Properly collected and skillfully interpreted cytologic examination of the urine is probably the most accurate screening test for this and other important varieties of bladder cancer. Improved technologic features of cystoscopy have aided in the identification of in situ cancer, particularly when multiple random cold biopsy specimens of all quadrants, including the trigone, of the bladder and of the prostatic urethra are employed. Such investigative methods recognize that in situ cancer is a generalized urothelial malignancy that very often involves ureteral, prostatic as well as all bladder mucosa. Despite the pathologic observation that this cancer shows an intense cellular activity, the temporal aspect of its transition from a superficial cancer to an invasive one remains unpredictable, although clearly finite. Treatment is controversial. Radical cystectomy should effect cure if recommended early and before it becomes clinically apparent that the disease is already invasive in some urothelial locations. If the cancer appears to be localized to a relatively small (5 cm) area of the bladder and the patient's symptoms are not excessive, intravesical chemotherapy using such preparations as Thio‐tepa, mitomycin, Adriamycin, or epodyl may result in a temporary, sometimes complete, remission.
Commentary: When does understanding phenotypic evolution require identification of the underlying genes?

Adaptive evolution is fundamentally a genetic process. Over the past three decades, characterizing the genes underlying adaptive phenotypic change has revealed many important aspects of evolutionary change. At the same time, natural selection is often fundamentally an ecological process that can often be studied without identifying the genes underlying the variation on which it acts. This duality has given rise to disagreement about whether, and under what circumstances, it is necessary to identify specific genes associated with phenotypic change. This issue is of practical concern, especially for researchers who study nonmodel organisms, because of the often enormous cost and labor required to “go for the genes. ” We here consider a number of situations and questions commonly addressed by researchers. Our conclusion is that although gene identification can be crucial for answering some questions, there are others for which definitive answers can be obtained without finding underlying genes. It should thus not be assumed that considerations of “empirical completeness” dictate that gene identification is always desirable.
Occupancy of glycoprotein IIb/IIIa by B-6 vitamers inhibits human platelet aggregation.

Vitamin B-6 inhibits platelet aggregation. However, the effect of the occupancy of GPIIb/IIIa, a major receptor responsible for aggregation on platelet membranes, by B-6 vitamers on platelet aggregation is unknown. This study was carried out to quantify GPIIb/IIIa occupancy in platelets treated with B-6 vitamers [pyridoxal-5-phosphate (PLP); pyridoxal (PL); pyridoxine (PN); pyridoxamine (PM)], using a monoclonal antibody-based assay, by flow cytometry. Antibody binding was compared with inhibition of platelet aggregation. PLP, PL, PN and PM occupied GPIIb/IIIa with dissociation constants of 1.83 +/- 1.15, 19.43 +/- 7.86, 3.63 +/- 1.67 and 10.89 +/- 2.93 mmol/L, respectively. Occupancy of GPIIb/IIIa by the four B-6 vitamers was negatively correlated with platelet aggregation (r = -0.90 to -0.94, P < 0.001). The concentrations of the four B-6 vitamers that inhibited maximal platelet aggregation were in the order of PLP < PN or =80% of the GPII/IIIa receptor. Platelet aggregation was inhibited by B-6 vitamers via the occupancy of GPIIb/IIIa with the potency of PLP > PN > PM > PL.
DEVONIAN SEDIMENTARY ROCKS TECTONICALLY INCORPORATED INTO THE BRNO MASSIF, EASTERN MARGIN OF THE BOHEMIAN MASSIF

Devonské sedimentární horniny tektonicky začleněné do brněnského masivu, východní okraj Českého masivu Devonská klastika severního okolí Brna jsou součástí sj. orientované zóny Babího lomu, která probíhá středem brněnského masivu. I když devon tvoří zdánlivě samostatný relikt, byly na jižním svahu kopce Strážná (369 m n. m.) nalezeny klíčové informace pro řešení stavby celé zóny Babího lomu: 1) Horninový sled devonských klastik je na dané lokalitě dostatečně variabilní (břidlice, prachovce, pískovce, křemenné a petromiktní slepence), což umožňuje dobře rozpoznat vrstevnatost i směr do nadloží. 2) Vrstevnatost devonských hornin se v z. části reliktu uklání k V a směrem na V se překlápí přes vertikální orientaci do pozice překocené s úklonem k Z. 3) Omezení devonských hornin je z části primární – transgresivní (na JZ s reliktním fosilním zvětráním podloží), z části tektonické (východní a sz. omezení). Uvedená pozorování lze v kombinaci se strukturně geologickými informacemi z okolí vysvětlit následující interpretací: 1) Devonské vrstvy tvoří překocenou vrásu. S největší pravděpodobností se jedná o antiklinálu s osní plochou ukloněnou k Z. 2) Vrásová stavba vznikla zřejmě v důsledku deformace vlekem podél násunového zlomu a tvoří spodní část tektonické šupiny. 3) Svrchní část této šupiny reprezentují horniny hřbetu Babího lomu. Následné křehké postižení vedlo k rozdělení struktury a posunutí částí do různých úrovní za vzniku dnešního obrazu geologické stavby.
Identification of patient deterioration in vital-sign data using one-class support vector machines

Adverse hospital patient outcomes due to deterioration are often preceded by periods of physiological deterioration that is evident in the vital signs, such as heart rate, respiratory rate, etc. Clinical practice currently relies on periodic, manual observation of vital signs, which typically occurs every 2-to-4 hours in most hospital wards, and so patient deterioration may go unidentified. While continuous patient monitoring systems exist for those patients who are confined to a hospital bed, the false alarm rate of conventional systems is typically so high that the alarms generated by them are ignored. This paper explores the use of machine learning methods for automatically identifying patient deterioration, using data acquired from continuous patient monitors. We compare generative and discriminative techniques (a probabilistic method using a mixture model, and a support vector machine, respectively). It is well-known that parameter tuning affects the performance of such methods, and we propose a method to optimise parameter values using “partial AUC”. We demonstrate the performance of the proposed method using both synthetic data and patient vital-sign data collected from a recent observational clinical study.
CONSENSUS ALGORITHM DESIGN FOR DISTRIBUTED ESTIMATION

In this paper we study the problem of designing optimal consensus algorithms for distributed estimation of dynamical systems. In particular, we show that for fixed estimation gain, the problem of finding optimal consensus matrix is convex and can be efficiently performed numerically. We also provide some numerical examples to common scenarios, like symmetric geometric random graphs, which are representative models for wireless sensor networks.