Miracle-dz/UniFAR-FTUs huggingface dataset:
An important role for BRCA1 in breast cancer progression is indicated by its loss in a large proportion of non‐familial breast cancers

The presence of BRCA1 protein was determined immunohistochemically in normal and benign breast biopsies, non‐familial breast carcinomas and breast carcinomas from one or more individuals from 8 BRCA1 families. Strikingly, little staining was detected in breast carcinomas from BRCA1 families, regardless of the position or type of mutation, whereas strong immunostaining was observed in 28/28 of non‐malignant breast biopsies. Furthermore, BRCA1 staining was reduced in non‐familial breast carcinomas, since loss of nuclear BRCA1 staining was evident in 19% of non‐familial breast carcinomas whilst a similar proportion (20%) showed absence of either cytoplasmic or nuclear BRCA1 staining. Statistical analysis indicates that breast cancer is characterised by a reduction in levels of nuclear BRCA1 in familial (p < 0.001) and non‐familial breast cancer (p = 0.001). In non‐familial breast cancer absence of nuclear BRCA1, but not cytoplasmic BRCA1, is more common in high grade breast carcinomas (p = 0.03) and in patients with evidence of lymph node involvement (p = 0.05). Correlation between the absence of BRCA1 protein with high grade is consistent with previous findings of a correlation between mutations in the BRCA1 gene and high grade. Our findings provide new evidence in support of BRCA1 as a tumour suppressor protein in non‐familial breast cancer. Int. J. Cancer (Pred. Oncol.) 79:334–342, 1998. © 1998 Wiley‐Liss, Inc.
Role of the Electronic Patient Record in the Development of General Practice in the Netherlands

Abstract From the end of the seventies practice computer systems have been introduced in Dutch general practice. In 1998 90% of the GPs had a practice computer and 60% used it for medical purposes, with good patient acceptance. Collaboration between pioneer GPs, professional organizations, academic institutions and software manufacturers has been of decisive importance. While the practice computer is early recognized as a powerful tool for administrative purposes, it is increasingly supporting clinical and preventive care, quality of care improvement, clinical training of students and vocational training of general practice trainees. Also for scientific research and practice supporting research, automatization has proven to be innovating. Much attention is paid to designing valid databases and database-related research. In addition, practice automatization has opened new perspectives for health policy and management. Further development of technical and methodological issues is needed, and, very importantly, of patients‘ and consumers’ involvement. EPR technology in general practice does not optimally work without good numerator and denominator data, and a good quality patient-doctor relationship over time. While the EPR is a useful tool to facilitate a better performance, it may enable the doctor to focus more on the health care essentials.
The effect of milking machine liner slip on new intramammary infections.

New IMI of cows milked with high and low slip rate milking machine liners were compared. High slip liners used in this study averaged 6.1 initial slips and 7.6 major vacuum fluctuations per cow milking, and low slip liners averaged 3.6 initial slips and 3.1 major vacuum fluctuations per cow milking. Least squares means for new IMI rates per 100 cow days were . 49 in the high slip group and . 27 in the low slip group. Rates of clinical cases per 100 cow days were . 35 in the high slip group and . 20 in the low slip group. New IMI rates for cows entering the trial with an existing infection were . 81 in the high slip group and . 39 in the low slip group. More new IMI tended to occur with cows milked with the high slip liners than with low slip liners.
Genetic diversity of bacteria associated with the hindgut of the terrestrial crustacean Porcellio scaber (Crustacea: Isopoda).

Molecular approaches were used to examine the genetic diversity of bacteria associated with the gut wall of the terrestrial isopod Porcellio scaber and to determine whether an autochthonous microflora exists in the P. scaber hindgut. 16S ribosomal genes were amplified from the total DNA isolated from thoroughly washed papillate regions of the hindgut, where the highest concentrations of bacteria are commonly found. The amplified genes were cloned, sequenced and phylogenetically analysed. The results implied an unexpectedly large diversity of microflora associated with the cuticle of the hindgut. Almost half of the retrieved sequences were found to be less than 80% homologous with any of the known sequences available at DNA data banks. Most of these sequences were clustered in one of three groups, and were clearly distant from the sequences of other bacterial taxa, indicating that they could represent novel bacterial species or even genera. More than two thirds of the sequences were found to be phylogenetically related to sequences from bacteria typically isolated from human and animal intestines, e.g. streptococci, enterococci, and members of the genus Bacteroides. The majority of the remaining sequences were most closely related to typical soil bacteria, e.g. bacilli and pseudomonads. The facts that a large proportion of the retrieved sequences was related to the sequences of bacteria, which are autochthonous to intestinal ecosystems, and that bacteria, specifically attached to the cuticular spines, were observed, indicate that truly autochthonous bacteria may well be present in the hindgut of P. scaber.
Comparative Evaluation of the Effects of Light Intensities and Curing Cycles of QTH, and LED Lights on Microleakage of Class V Composite Restorations.

BACKGROUND The purpose of this study was to evaluate the effects of light intensity and curing cycles of QTH and LED lights on the microleakage of Class V composite restorations. MATERIALS AND METHODS Eighty freshly extracted human maxillary premolars were used for this study. Standardized Class V cavities were prepared and they were restored with microhybrid resin composite. According to the curing protocol, the teeth were then divided into 4 groups (n=20): QTH curing (standard and soft start modes), and LED (standard and soft start modes) irradiations. Microleakage was evaluated by immersion of the samples in 50% silver nitrate solution. The samples were then sectioned, evaluated under a stereomicroscope, and scored for microleakage. RESULTS The results of the present in-vitro study showed mean dye leakage scores of 1.9, 1.2, 1.45 and 0.90 for Group I (QTH-Standard mode), Group II (QTH-Soft Start mode), Group III (LED-Standard mode) and Group IV (LED-Soft Start mode) respectively. CONCLUSION It was thus concluded that the soft start polymerization showed a highly significant difference as compared to the standard curing modes of QTH and LED lights, respectively.
Validation of the freezing of gait questionnaire in patients with Parkinson's disease

To revalidate the Freezing of Gait Questionnaire (FOG‐Q), patients with Parkinson's disease (PD) were randomly assigned to receive rasagiline (1 mg/day) (n = 150), entacapone (200 mg with each dose of levodopa) (n = 150), or placebo (n = 154). Patients were assessed at baseline and after 10 weeks using the FOG‐Q, Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), and Parkinson's Disease Questionnaire (PDQ‐39). FOG‐Q dimensionality, test–retest reliability, and internal reliability were examined. Convergent and divergent validities were assessed by correlating FOG‐Q with UPDRS, BDI, and PDQ‐39. Comparisons between FOG‐Q item 3 and UPDRS item 14 were also made. Principal component analysis indicated that FOG‐Q measures a single dimension. Test–retest reliability and internal reliability of FOG‐Q score was high. FOG‐Q was best correlated to items of the UPDRS relating to walking, general motor issues, and mobility. Correlations between baseline and endpoint suggested that FOG‐Q item 3 is at least as reliable as UPDRS item 14. At baseline, 85.9% of patients were identified as “Freezers” using FOG‐Q item 3 (≥1) and 44.1% using UPDRS item 14 (≥1) (P < 0.001). FOG‐Q was a reliable tool for the assessment of treatment intervention. FOG‐Q item 3 was effective as a screening question for the presence of FOG. © 2007 Movement Disorder Society
Maternal Protein Restriction Suppresses the Newborn Renin-Angiotensin System and Programs Adult Hypertension in Rats

Restriction of maternal protein intake during rat pregnancy produces offspring that are hypertensive in adulthood, but the mechanisms are not well understood. Our purpose was to determine whether this adult hypertension could be programmed during development by suppression of the fetal/newborn renin-angiotensin system (RAS) and a consequent reduction in nephron number. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Birth weight was reduced by 13% (p < 0.0005), and the kidney/body weight ratio was reduced in LP pups. Renal renin mRNA levels were significantly reduced in newborn LP pups; renal renin concentration and renin immunostaining were suppressed. Renal tissue angiotensin II levels were also suppressed in newborn LP (0.079 ± 0.002 ng/mg, LP versus 0.146 ± 0.016 ng/mg, NP, p < 0.01). Mean arterial pressure in conscious, chronically instrumented adult offspring (21 wk) was higher in LP (135 ± 1 mm Hg, LP versus 126 ± 1 mm Hg, NP, p < 0.00007), and GFR normalized to kidney weight was reduced in LP (p < 0.04). The number of glomeruli per kidney was lower in adult LP offspring (21,567 ± 1,694, LP versus 28,917 ± 2,342, NP, p < 0.03), and individual glomerular volume was higher (1.81 ± 0.16 106 μm3, LP versus 1.11 ± 0.10 106 μm3, NP, p < 0.005); the total volume of all glomeruli per kidney was not significantly different. Thus, perinatal protein restriction in the rat suppresses the newborn intrarenal RAS and leads to a reduced number of glomeruli, glomerular enlargement, and hypertension in the adult.
Effect of Ag grain size on high temperature joint formation in Ag-In system

After many experiments in developing fluxless Ag-In joints, we realize that the success of producing a joint relates to microstructure of the Ag layer. Ag with small grains results in rapid growth of solid Ag2In intermetallic compounds through grain boundary diffusion. Thus, a joint is not obtained because of lack of molten phase, (L). To coarsen Ag grains, an annealing step is added to the Ag-plated Cu substrate. This step makes Ag grains 200 times coarser compared to the as-plated Ag. The coarsened microstructure slows down the Ag2In growth. Consequently, the (L) phase stays at molten state with sufficient time to react with the Ag layer on Si chip to produce a joint. Nearly perfect joints are produced on Ag-plated Cu substrates. The resulting joints consist of pure Ag, Ag-rich solid solution, Ag2In, and Ag3In. The melting temperature exceeds 650°C. Using the present process, high temperature joints of high thermal conductivity are made between Si chips and Cu substrates at low bonding temperature (200°C). We foresee the Ag-In system as an important system to explore for various fluxless bonding applications. This system provides the possibilities of producing joints of wide composition choices and wide melting temperature range. Present study provides preliminary but useful information on how the microstructure of Ag affects the bonding results.
Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components.

AIMS Cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) are both expressed in the intestinal mucosa and present a barrier to oral drug delivery. CYP3A4 and P-gp share both overlapping tissue distribution and substrate specificity. Grapefruit juice interactions with CYP3A4 substrates are well documented and occur as a consequence of down regulation of intestinal CYP3A4. The aim of the present study was to screen grapefruit juice components against the CYP3A4-mediated metabolism and P-gp mediated transport of the HIV-1 protease inhibitor saquinavir. METHODS Five grapefruit juice components: quercetin, naringin, naringenin, 6', 7'-dihydroxybergamottin and bergamottin were screened as potential inhibitors of the metabolism of saquinavir by human liver microsomes. The known CYP3A4 inhibitor ketoconazole was also screened for inhibitory potential. These compounds were also screened as modulators of P-gp activity by assessing the directional transport of saquinavir across Caco-2 cell monolayers which express P-gp. The effect of verapamil, a known modulator of P-gp function, was also determined in these cell lines. RESULTS On preincubation, 6', 7'-dihydroxybergamottin and bergamottin inhibited the metabolism of saquinavir, with IC50 values of 0.33+/-0.23 muM and 0.74+/-0.13 muM, respectively (n=3). Ketoconazole achieved an IC50 of 0. 55+/-0.12 muM (n=4). The other compounds studied failed to reach IC50 at concentrations of up to 100 muM. The transport of saquinavir in the basolateral-->apical (BL-->AP) direction exceeded that in the apical -->basolateral direction (AP-->BL), with apparent permeability coefficients of 199.2+/-15.8x10-7 cm s-1 and 8.00+/-1. 13x10-7 cm s-1, respectively (n=3) which is indicative of a polarized efflux mechanism. The ratio of BL-->AP/AP-->BL for saquinavir was 25, but in the presence of verapamil and ketoconazole this ratio was reduced to 3.6 and 4.0, respectively (n=3), indicating extensive inhibition of P-gp mediated saquinavir efflux. Of the grapefruit juice components studied only naringin and 6', 7'-dihydroxybergamottin had any appreciable effect, reducing the ratio to 7.6 and 7.1, respectively (n=3); but this was due solely to increased AP-->BL transport. CONCLUSIONS Grapefruit juice components inhibit CYP3A4-mediated saquinavir metabolism and also modulate, to a limited extent, P-gp mediated saquinavir transport in Caco-2 cell monolayers. The in vivo effects of grapefruit juice coadministration are most likely the result of effects on CYP3A4 (inhibition and down regulation) and only to a minor extent on modulation of P-gp function.
Is thirty-day hospital mortality really lower for black veterans compared with white veterans?

OBJECTIVE To examine the source of observed lower risk-adjusted mortality for blacks than whites within the Veterans Affairs (VA) system by accounting for hospital site where treated, potential under-reporting of black deaths, discretion on hospital admission, quality improvement efforts, and interactions by age group. DATA SOURCES Data are from the VA Patient Treatment File on 406,550 hospitalizations of veterans admitted with a principal diagnosis of acute myocardial infarction, stroke, hip fracture, gastrointestinal bleeding, congestive heart failure, or pneumonia between 1996 and 2002. Information on deaths was obtained from the VA Beneficiary Identification Record Locator System and the National Death Index. STUDY DESIGN This was a retrospective observational study of hospitalizations throughout the VA system nationally. The primary outcome studied was all-location mortality within 30 days of hospital admission. The key study variable was whether a patient was black or white. PRINCIPAL FINDINGS For each of the six study conditions, unadjusted 30-day mortality rates were significantly lower for blacks than for whites (p<.01). These results did not vary after adjusting for hospital site where treated, more complete ascertainment of deaths, and in comparing results for conditions for which hospital admission is discretionary versus non-discretionary. There were also no significant changes in the degree of difference by race in mortality by race following quality improvement efforts within VA. Risk-adjusted mortality was consistently lower for blacks than for whites only within the population of veterans over age 65. CONCLUSIONS Black veterans have significantly lower 30-day mortality than white veterans for six common, high severity conditions, but this is generally limited to veterans over age 65. This differential by age suggests that it is unlikely that lower 30-day mortality rates among blacks within VA are driven by treatment differences by race.
The potential of house flies to act as a vector of avian influenza subtype H5N1 under experimental conditions

The objective of the present study was to determine the potential for house flies (Musca domestica L.) (Diptera: Muscidae) to harbour the avian influenza (AI) H5N1 virus. Laboratory‐reared flies were experimentally fed with a mixture containing the AI virus. Exposed flies were washed with brain–heart infusion broth and followed by 70% alcohol before preparation of whole fly homogenate. The homogenate was inoculated into six 10‐day‐old embryonated chicken eggs (ECEs). Allantoic fluids were collected to determine the virus using the haemagglutination (HA) test, reverse transcription‐polymerase chain reaction (RT‐PCR) or quantitative real‐time RT‐PCR (RRT‐PCR). In the first experiment, ECEs that were inoculated with the 50 AI virus exposed fly homogenates died within 48 h and HA and RT‐PCR were positive for AI virus. In the second experiment, ECEs that were inoculated with only one fly died with positive HA test and RT‐PCR. In the last experiment, a group of exposed flies was collected at 0, 6, 12, 24, 36, 48, 72 and 96 h post‐exposure. Fly homogenates of each time point were tested by virus titration in ECEs and RRT‐PCR. Virus titres declined in relation to exposure time. Furthermore, RRT‐PCR results were positive at any time point. The present study shows that the flies may harbour the AI virus and could act as a mechanical vector of the AI virus.
Facial emotion labeling deficits in children and adolescents at risk for bipolar disorder.

OBJECTIVE Research has revealed facial emotion labeling deficits in children and adolescents with bipolar disorder. To assess whether such impairments may be an endophenotype for bipolar disorder, the authors examined facial emotion identification proficiency in children who were at risk for bipolar disorder because they had a first-degree relative with the illness. METHOD The facial expressions subtests of the Diagnostic Analysis of Nonverbal Accuracy scale were administered to 52 patients with bipolar disorder, 24 at-risk youths, and 78 control subjects, all 4-18 years of age. RESULTS Compared with the control group, both the bipolar and at-risk groups made more errors identifying facial emotions. The number of errors did not differ significantly between the bipolar and at-risk groups. CONCLUSIONS Deficits in facial emotion labeling may be a risk marker for bipolar disorder. Further study is needed to determine the neural mechanisms involved, as well as to explore other emotional processing impairments in youths at risk for bipolar disorder and to identify genetic associations.
Rae1 interaction with NuMA is required for bipolar spindle formation

In eukaryotic cells, the faithful segregation of daughter chromosomes during cell division depends on formation of a microtubule (MT)-based bipolar spindle apparatus. The Nuclear Mitotic Apparatus protein (NuMA) is recruited from interphase nuclei to spindle MTs during mitosis. The carboxy terminal domain of NuMA binds MTs, allowing a NuMA dimer to function as a “divalent” crosslinker that bundles MTs. The messenger RNA export factor, Rae1, also binds to MTs. Lowering Rae1 or increasing NuMA levels in cells results in spindle abnormalities. We have identified a mitotic-specific interaction between Rae1 and NuMA and have explored the relationship between Rae1 and NuMA in spindle formation. We have mapped a specific binding site for Rae1 on NuMA that would convert a NuMA dimer to a “tetravalent” crosslinker of MTs. In mitosis, reducing Rae1 or increasing NuMA concentration would be expected to alter the valency of NuMA toward MTs; the “density” of NuMA-MT crosslinks in these conditions would be diminished, even though a threshold number of crosslinks sufficient to stabilize aberrant multipolar spindles may form. Consistent with this interpretation, we found that coupling NuMA overexpression to Rae1 overexpression or coupling Rae1 depletion to NuMA depletion prevented the formation of aberrant spindles. Likewise, we found that overexpression of the specific Rae1-binding domain of NuMA in HeLa cells led to aberrant spindle formation. These data point to the Rae1–NuMA interaction as a critical element for normal spindle formation in mitosis.
Guanine nucleotide-sensitive inhibition of L-type Ca2+ current by lysosphingolipids in RINm5F insulinoma cells.

The lysosphingolipids sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPPC) reportedly increase free cytosolic Ca2+ concentration ([Ca2+]i) in a variety of cell types, apparently by activating G protein-coupled plasma membrane receptors. We investigated whether and how sphingolipids modulate Ca2+ homeostasis in the insulinoma cell line RINm5F. The addition of SPPC and glucopsychosine (GPS) did not affect basal [Ca2+]i but inhibited the KCl (30 mM)-induced increase in [Ca2+]i in a pertussis toxin-insensitive and concentration-dependent manner (EC50 approximately 5 micro M). Similar inhibitory effects were observed with dihydro-SPPC and psychosine, whereas SPP and various N-acylated sphingolipids (at 10 micro M each) had little or no effect on the KCl-induced [Ca2+]i increase. Because in RINm5F cells the primary pathway for depolarization-induced [Ca2+]i increase are L-type Ca2+ channels, we studied whether sphingolipids reduce L-type Ca2+ current (ICa.L). When added to the bath, GPS and SPPC, but not SPP (10 micro M each), rapidly reduced maximal ICa.L by approximately 35%, similar to the alpha2-adrenoceptor agonist clonidine (30 micro M). However, when applied internally, GPS had no effect on ICa. L. When the electrode solution contained the stable GDP analog guanosine-5'-O-(2-thio)diphosphate (1 and 10 mM), the inhibitory effect of GPS was abolished. In conclusion, a novel cellular action of lysosphingolipids is observed in RINm5F cells (i.e., a guanine nucleotide-sensitive inhibition of L-type Ca2+ currents). The pharmacological profile of this inhibition is unique and unlike any known lysosphingolipid receptor-mediated action.
Identification of building double-bounces feature in very high resoultion SAR data for earthquake damage mapping

Nowadays very high resolution (VHR) Synthetic Aperture Radar (SAR) systems can provide near real time earthquake damage maps with an high degree of details to stakeholders in charge of managing the emergency phase. However, the increased resolution introduces new challenges to interpret and detect changes in urban areas caused by seismic events. In metric resolution SAR sensors a building appears as a complex of image structures associated to different scattering mechanisms, preventing the use of pixel-based algorithms. In this paper we propose an object oriented approach, focusing the attention on the double-bounce return from buildings, trying to detect damages looking at changes of these particular image patterns. The identification of double-bounce regions is performed using open and close morphological filters and assuming linear structuring elements with different orientation and length. The change detection analysis based on a pre- and a post-event image is carried out using four change detection indicators, such as: intensity ratio, interferometric coherence, intensity correlation and Kullback-Leibler divergence. All change features are extracted using all pixels within each identified object, i.e., double-bounce regions. The test case is the earthquake that hit L'Aquila city (Italy) on April 6, 2009, while the dataset is composed of two X-band COSMO-SkyMed SAR images acquired before and after the event. A macro-seismic survey map was available to evaluate the obtained results.