Miracle-dz/UniFAR-FTUs huggingface dataset:
p53 point mutations and thymidylate synthase messenger RNA levels in disseminated colorectal cancer: an analysis of response and survival.

Recent studies suggest that there may be a strong correlation between the p53 status of a tumor and a patient's response to chemotherapy. Therefore, we determined p53 status in 36 patients with disseminated colorectal cancer by cDNA sequencing and immunohistochemical staining, as well as by the gene expression level of thymidylate synthase (TS), the target enzyme of 5-fluorouracil (5-FU), by reverse transcription-PCR. Ten patients (28%) experienced a clinical response to 5-FU chemotherapy. Overall, TS expression and response to chemotherapy were associated: 9 of 18 (50%) patients with TS < or = 3.0 x 10(-3) responded, compared to 1 of 18 (6%) patients with TS > 3.0 x 10(-3) (P = 0.003). p53 mutations were found in 21 of 36 patients (58%) using cDNA cycle sequencing, and p53 protein overexpression was found in 20 of 32 patients (62%) using immunohistochemistry staining. Overall p53 status and response to chemotherapy were associated: 5 of 10 (50%) patients with wild-type p53 or negative p53 staining experienced a response, but only 5 of 26 (19%) patients with mutant p53 or p53 overexpression responded. TS expression, but not expression of p53, was significantly associated with overall survival (P = 0.002). Patients with wild-type p53 had significantly lower TS levels compared to patients with mutated p53 (P = 0.044). In this study, we also present data linking specific p53 point mutations to TS expression levels and resistance to 5-FU. Although the number of patients is relatively small, these results identify p53 status and TS gene expression as associated with response in disseminated colorectal cancer; independent studies are needed to confirm these findings and to provide information leading to a better understanding of the role of 5-FU-based chemotherapy in the treatment of colorectal cancer.
Multi-sided Surfaces with Fullness Control

Multi-sided surfaces are important in several areas of Computer-Aided Geometric Design, including curve network based design, approximation of triangular meshes, hole filling, and so on. In the majority of surface representations, the boundary constraints entirely determine the interior of these patches, however, frequently there is a need to have additional design freedom for shaping the surface. In this paper, we investigate new multi-sided surfaces, where such interior control is possible. As a reference, we take a recent variant of the Gregory patch,8 and compare it with two new representations: (i) a transfinite patch defined by boundary ribbons (curves and cross-derivatives) and a single surface point to set in the middle, and (ii) a recently published, new n-sided Bézier patch,10 defined by a grid of control points. We will discuss the different degrees of freedom for shape adjustment, and illustrate our results by a few examples showing mesh approximation quality.
Men at higher risk of groin injuries in elite team sports: a systematic review

Background Groin injuries are common in sports, particularly multidirectional team sports, but incidence rates across sports other than football (soccer) have been poorly documented. Methods A systematic review (initially using PubMed and SportDiscus databases) was performed to record incidence of groin and groin region injuries in sports. Inclusion criteria included presentation of groin injury incidence data for at least 10 team/squad seasons. Results Data from 31 studies were included. These used varying injury definitions and also considered varying injury categories from general to specific (all groin/hip region injuries, groin injuries, adductor muscle strains, intra-articular hip injuries). When playing the same sport, men had greater injury incidence of groin injury than women (relative risk, RR 2.45, 95% CI 2.06 to 2.92). Sports with high incidences of groin injury included ice hockey and the football codes. There is variation by player position for rate of groin injury in many sports. Hip injuries have become more commonly diagnosed over the past decade in Australian football (p=0.001) and other sports. Conclusions There is moderate evidence that men have a higher risk of groin injury than women when playing the same sport. There is some evidence that hip injuries are being increasingly diagnosed in the subset of ‘groin injuries’ in recent years. It is recommended that injury epidemiology consensus statements aim to include a number of relevant sports to improve injury incidence comparisons among different sports.
Male urogenital disorders.

In recent years there have been significant advances in the diagnosis and management of male urogenital disorders. Some of these advances have been facilitated by technological revolutions in imaging that have found diagnostic clinical and therapeutic applications. There have also been marked developments in defining the molecular biology of cancers that have provided a wide spectrum of therapeutic opportunities.
Vitamin B12 deficiency in the aged: a population-based study.

BACKGROUND vitamin B12 deficiency is common in the aged, but it is controversial whether only some risk groups should be investigated instead of screening the entire aged population. OBJECTIVES to describe the prevalence of vitamin B12 deficiency in the Finnish aged, and to find out if the subjects especially prone to vitamin B12 deficiency could be identified by the risk factors or clinical correlates. DESIGN a cross-sectional, population-based study of 1048 aged subjects (age 65-100 years) was carried out. Data on lifestyle factors and clinical conditions were collected, physical examinations were conducted and laboratory variables related to vitamin B12 were measured. RESULTS vitamin B12 deficiency had been previously diagnosed in 27 (2.6%) subjects, and a laboratory diagnosis (total vitamin B12 <150 pmol/l, or total vitamin B12 150-250 pmol/l and holotranscobalamin < or =37 pmol/l and homocysteine > or =15 micromol/l) was made for 97 (9.5%) subjects. Low serum total vitamin B12 (<150 pmol/l) was observed in 6.1% and borderline total vitamin B12 (150-250 pmol/l) in 32% of the subjects. Male gender (OR 1.9, 95% CI 1.2-2.9), age > or =75 (OR 2.2, 95% CI 1.4-3.4) and refraining from milk products (OR 2.3, 95% CI 1.2-4.4) increased the probability for vitamin B12 deficiency. Anaemia (OR 1.3, 95% CI 0.7-2.3) or macrocytosis (OR 1.2, 95% CI 0.6-2.7) did not predict vitamin B12 deficiency. CONCLUSION undiagnosed vitamin B12 deficiency is remarkably common in the aged, but no specific risk group for screening can be identified. Thus, biochemical screening of unselected aged population is justified. General practitioners play a key role in diagnosing early vitamin B12 deficiency.
Antibacterial Effects of the Essential Oils of Commonly Consumed Medicinal Herbs Using an In Vitro Model

The chemical composition and antibacterial activity of essential oils from 10 commonly consumed herbs: Citrus aurantium, C. limon, Lavandula angustifolia, Matricaria chamomilla, Mentha piperita, M. spicata, Ocimum basilicum, Origanum vulgare, Thymus vulgaris and Salvia officinalis have been determined. The antibacterial activity of these oils and their main components; i.e. camphor, carvacrol, 1,8-cineole, linalool, linalyl acetate, limonene, menthol, α-pinene, β-pinene, and thymol were assayed against the human pathogenic bacteria Bacillus subtilis, Enterobacter cloacae, Escherichia coli O157:H7, Micrococcus flavus, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella enteritidis, S. epidermidis, S. typhimurium, and Staphylococcus aureus. The highest and broadest activity was shown by O. vulgare oil. Carvacrol had the highest antibacterial activity among the tested components.
Influence of Laser Irradiation on the Constant Composition Kinetics of Enamel Dissolution

The influence of 9.6 µm CO2 laser irradiation on enamel dissolution kinetics was investigated using a constant composition method designed for rate measurements of enamel dissolution as a function of depth, on a micrometer scale. In contrast to lower irradiation intensities (≤1.0 J cm–2), which consistently showed reduced dissolution rates, higher fluences (energy per surface area) resulted in initially increased dissolution rates, which rapidly decreased, after dissolution times corresponding to removal of a few micrometers, to rates similar to those acquired using lower fluences. It was also demonstrated that surface damage during laser irradiation could be limited to the first 1–2 µm by lowering the number of pulses per spot during the irradiation procedure. The constant composition method can be used to measure detailed kinetics of inhibition of acid dissolution of dental enamel that has been treated by low fluence 9.6-µm CO2 laser irradiation.
Clinical immunologic responsiveness in malignant disease. I. Delayed hypersensitivity reaction and the effect of cytotoxic drugs

Patients with advanced malignant disease, not originating from the lymphoreticular tissue, showed marked depression of delayed hypersensitivity reaction to tuberculin, mumps, Candida albicans, and DNCB, as compared to control hospitalized noncancer patients. There were statistical differences in suppression of different primary sites of origin of the neoplasms. Cytotoxic drug therapy enhances this depression of delayed type of hypersensitivity regardless of the drugs used or the response of the patient to them. This suppression was more marked in patients who became leukopenic after the administration of these agents.
Effect of Hemolysis on Nonesterified Fatty Acid and β-Hydroxybutyrate Concentrations in Bovine Blood

Nonesterified fatty acid (NEFA) and b-hydroxybutyrate (BHB) assays are used for evaluating dairy herds for negative energy balance and subclinical ketosis, respectively. Hemolysis is a common artifact in samples submitted to diagnostic laboratories. The effect of hemolysis on NEFA and BHB in bovine serum was determined. Hemolysis was introduced into 26 serum samples by adding serial dilutions of a red cell hemolysate, prepared by repeated freeze-thawing of EDTA-anticoagulated bovine blood. NEFA, BHB, and degree of hemolysis (hemolytic index) were measured by an automated chemistry analyzer. Two endpoint assays that differed by inclusion of a sample blank were used for NEFA measurement. A kinetic enzymatic assay with 2 reagent sources was used for BHB measurement. The assessed methods yielded similar NEFA or BHB results in baseline, nonhemolyzed samples (median NEFA: 0.25 mEq/L, median BHB: 3 mg/dL, median hemolytic index: 8 units). NEFA results were adversely affected by hemolysis, with values increasing significantly with higher degrees of hemolysis. Median values increased above a critical medical decision limit (0.40 mEq/L) at a hemolytic index of 506 units (marked hemolysis). This increase was prevented by inclusion of a sample blank. Result interpretation was affected in individual animals when samples were moderately hemolyzed (median hemolytic index: 258 units). In contrast, BHB results were unaffected by hemolysis with either reagent source. Thus, assays for measuring NEFAs should include a sample blank and NEFA results should not be interpreted in moderately to markedly hemolyzed bovine samples, because result accuracy cannot be assured.
Audit of Women Attending the Aberdeen Genetic Clinic with a Family History of Breast Cancer who Subsequently Develop Cancer

Breast cancer is a common disease. Improved awareness in the general population of the role of genetic factors in the development of disease has resulted in increasing demands upon Genetic services, and consequently further burden on resources for mammographic screening. Inevitably, some of those women who receive breast screening because of their genetic risk will go on to develop breast cancer themselves. We looked at the population of women who had attended the Aberdeen Genetic Clinic because of their family history to determine those who subsequently developed disease.
Femtocell deployed Self Organizing Network for U-Health: Opportunities and challenges

An initiative approach towards uniform integration of Wireless Body Area Network (WBAN) with various outgoing networks can provide a landmark in Ubiquitous Health care (U-Health) development. More interestingly, provided with Self Organizing Network (SON) characteristics, integration of WBAN with femtocell deployed cellular networks, which can bridge WBAN with widely deployed broadband connections as well, could alternatively be one of the simpler but pragmatic solutions for U-Health development. This paper highlights the opportunities of such an integrated network, analyzes both the technical and commercial challenges, and discusses some open issues.
Quercetin selectively inhibits insulin receptor function in vitro and the bioresponses of insulin and insulinomimetic agents in rat adipocytes.

We report here that quercetin, a naturally occurring bioflavonoid, is an effective blocker of insulin receptor tyrosine kinase-catalyzed phosphorylation of exogenous substrate. The ID50 was estimated to be 2 +/- 0.2 microM in cell-free experiments, using a partially purified insulin receptor and a random copolymer of glutamic acid and tyrosine as a substrate. Insulin-stimulated autophosphorylation of the receptor itself was not blocked by quercetin (up to 500 microM). In intact rat adipocytes, quercetin inhibited insulin-stimulating effects on glucose transport, oxidation, and its incorporation into lipids. Inhibition of lipogenesis (50%) occurred at 47 +/- 4 microM, whereas full inhibition was evident at 110 +/- 10 microM quercetin. In contrast, the effect of insulin in inhibiting lipolysis remained unaltered in quercetin-treated adipocytes. The inhibitor was devoid of general adverse cell affects. Basal activities and the ability of lipolytic agents to stimulate lipolysis were not affected. Inhibition by quercetin enabled us to evaluate which insulinomimetic agents are dependent on tyrosine phosphorylation of endogenous substrates for stimulating glucose metabolism. Quercetin blocked lipogenesis mediated by insulin, wheat germ agglutinin, and concanavalin A. The lipogenic effect of Zn2+ and Mn2+ was partially blocked, whereas that of vanadate was not affected at all. (ABSTRACT TRUNCATED AT 250 WORDS)
Wide-range ZVS asymmetric half-bridge converter with clamping switches for small DC offset current

In this paper, a new wide range zero-voltage switching asymmetric half-bridge (AHB) converter with clamping switches for small DC offset current is proposed. Since the hold-up time requirement makes the conventional AHB converter operates asymmetrically in nominal state, a large DC offset current degrades the performance of AHB converters. In order to overcome this problem, the proposed AHB converter operates symmetrically in nominal state and two clamp switches that replace the clamp diodes, operate in hold-up state for additional gain. From the results, it can reduce the DC offset current of transformer and relieves the drawbacks that caused by asymmetric operation. In addition, a large external inductor of the proposed converter makes the wider zero-voltage switching (ZVS) range. Therefore, the proposed converter achieves the high overall efficiency and the smaller DC offset current than the conventional AHB converter. To verify these advantages of the proposed converter, the experiment was implemented with 340~400V input voltage, 500W (12V/41.67A) output power system at 100 kHz.
Brain region-specific monoaminergic correlates of neuropsychiatric symptoms in Alzheimer's disease.

Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are present during the disease course of nearly all AD patients and consist of psychosis, agitation/aggression, and depression, among others. Given their detrimental consequences regarding life expectancy, cognition, and socio-economic costs, it is essential to elucidate their neurochemical etiology to facilitate the development of novel and effective pharmacotherapeutics. This study attempted to identify brain region-specific monoaminergic correlates of NPS by measuring the levels of eight monoamines and metabolites in nine relevant postmortem brain regions of 40 behaviorally characterized AD patients, i.e., dopamine (DA), serotonin (5-HT), (nor)epinephrine and their respective metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid, 5-hydroxy-3-indoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), using RP-HPLC-ECD. Likewise, Mini-Mental State Examination (MMSE) score correlates of monoaminergic neurotransmitter alterations were calculated. As a result, MMSE scores, used as a measure of dementia severity, correlated positively with hippocampal 5-HIAA levels as well as with 5-HT levels of the superior temporal gyrus and cerebellar cortex. Furthermore, hippocampal 5-HIAA levels inversely correlated with agitation scores, whereas thalamic MHPG levels comparably did with the presence of hallucinations. Finally, in the cerebellar cortex, DOPAC/DA ratios, indicative of DA turnover, correlated with physically agitated behavior while MHPG levels correlated with affective disturbances. These findings support the assumption that specific NPS features in AD might be (in)directly related to brain region-specific monoaminergic neurotransmitter alterations. Additionally, the effect of AD pathology on neurochemical alterations in the cerebellum requires further examination due to its important but underestimated role in the neurochemical pathophysiology of NPS in AD.
A Label-Free Approach to Identify Inhibitors of α4β7-Mediated Cell Adhesion to MadCAM

Traditionally, cell adhesion assays are performed in a manual workstation format using fluorescence-based readouts. Herein, the authors describe a label-free homogeneous assay to identify inhibitors of α4β7 integrin-mediated cell adhesion to its ligand, the mucosal addressin cell adhesion molecule (MadCAM), using the SRU BIND platform. The biosensor is optically based and comprises a subwavelength polymer grating. The assay was validated using standard compounds and an α4 blocking antibody and correlated very closely with the manual assay format when running a battery of test compounds of varying potencies. Cell adhesion was strictly dependent on the presence of divalent cations where Mg2+ was greater than Ca2+ at promoting cell adhesion. This homogeneous and label-free format exhibited low variability with a calculated Z′ of 0.6. In addition to measuring α4β7-mediated 8866 cell adhesion to MadCAM, the authors also demonstrate that this platform can measure adhesion of Jurkat cells expressing α4β1 to the vascular cell adhesion molecule. Thus, the SRU BIND platform is widely applicable to measuring cell adhesion events mediated by other integrins binding to their receptors in an assay format that is amenable to high-throughput screening.
In vitro culture and mtDNA fate of ibex–rabbit nuclear transfer embryos

Rabbit oocyte can be used as the recipient in interspecies somatic cell nuclear transfer (iSCNT). This work was undertaken in order to study the developmental competence of Capra ibex somatic cells reprogrammed by rabbit oocytes and the fate of mitochondria in iSCNT embryos. Metaphase II (MII) oocytes from superovulated rabbit were used as nuclear recipients. The nuclear donors were Capra ibex somatic cells with different proliferative status: population doubling time (PDL)=15±2 (group 1), 35±2 (group 2), 55±2 (group 3) and 70±2 (group 4). Oocytes reconstructed with electrical pulses (2.1 kV/cm, 10 μs, 2 times) were activated (1.4 kV, 20 μs, 2 times) and then cultured in Medium199 containing 10% fetal bovine serum at 38.5 °C, 5% CO2 in air. In groups 1, 2, 3 and 4, the fusion rates were 35.83%, 66.03%, 65.40% and 35.35%, respectively. Similar cleavage rates were observed among the four groups. However, the developmental potential to morula/blastocyst from early nuclear donor embryos (16.42%/10.45%) was significantly higher (p < 0.05) than in terminal donor embryos (9.52%/3.81%). Polymerase chain reaction analysis of the mitochondrial (mt) DNA cytb gene demonstrated that mtDNAs from ibex and rabbit could be detected at various developmental stages before implantation. In conclusion, our results provide some original information about rescuing Capra ibex using the iSCNT technique. These results indicate that: (1) enucleated rabbit oocytes make Capra ibex fibroblast nuclei reprogramme; (2) the proliferative status of donor cells affects the efficiency of iSCNT; and (3) rabbit ooplasm rescues the donor-derived mtDNAs, resulting in mtDNA heteroplasmy before implantation.
Prion protein in Caenorhabditis elegans

The infectious agent of prion diseases is believed to be nucleic acid-free particles composed of misfolded conformational isomers of a host protein known as prion protein (PrP). Although this “protein-only” concept is generally accepted, decades of extensive research have not been able to elucidate the mechanisms by which PrP misfolding leads to neurodegeneration and infectivity. The challenges in studying prion diseases relate in part to the limitations of mammalian prion models, which include the long incubation period post-infection until symptoms develop, the high expense of maintaining mammals for extended periods, as well as safety issues. In order to develop prion models incorporating a genetically tractable simple system with a well-defined neuronal system, we generated transgenic C. elegans expressing the mouse PrP behind the pan-neuronal ric-19 promoter (Pric-19). We show here that high expression of Pric-19::PrP in C. elegans can result in altered morphology, defective mobility, and shortened lifespan. Low expression of Pric-19::PrP, however, does not cause any detectable harm. Using the dopamine neuron specific promoter Pdat-1, we also show that expression of the murine BAX, a pro-apoptotic member of the Bcl-2 family, causes dopamine neuron destruction in the nematode. However, co-expression of PrP inhibits BAX-mediated dopamine neuron degeneration, demonstrating for the first time that PrP has anti-BAX activity in living animals. Thus, these distinct PrP-transgenic C. elegans lines recapitulate a number of functional and neuropathological features of mammalian prion models, and provide an opportunity for facile identification of genetic and environmental contributors to prion-associated pathology.