Miracle-dz/UniFAR-FTUs huggingface dataset:
Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study.

BACKGROUND Neoadjuvant trials conducted using a double HER2 blockade with lapatinib and trastuzumab, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological complete response (pCR) rates, but at the cost of important toxicity. We hypothesised that this toxicity might be due to a specific interaction between paclitaxel and lapatinib. This trial assesses the toxicity and activity of the combination of docetaxel with lapatinib and trastuzumab. PATIENTS AND METHODS Patients with stage IIA to IIIC HER2-positive breast cancer received six cycles of chemotherapy (three cycles of docetaxel followed by three cycles of fluorouracil, epirubicin, cyclophosphamide). They were randomised 1 : 1 : 1 to receive during the first three cycles either lapatinib (1000 mg orally daily), trastuzumab (4 mg/kg loading dose followed by 2 mg/kg weekly), or trastuzumab + lapatinib at the same dose. The primary end point was pCR rate defined as ypT0/is. Secondary end points included safety and toxicity. pCR rate defined as ypT0/is ypN0 was assessed as an exploratory analysis. In June 2012, arm A was closed for futility based on the results from other studies. RESULTS From October 2010 to January 2013, 128 patients were included in 14 centres. The percentage of the 122 assessable patients with pCR in the breast, and pCR in the breast and nodes, was numerically highest in the lapatinib + trastuzumab group (60% and 56%, respectively), intermediate in the trastuzumab group (52% and 52%), and lowest in the lapatinib group (46% and 36%). Frequency (%) of the most common grade 3-4 toxicities in the lapatinib /trastuzumab/lapatinib + trastuzumab arms were: febrile neutropenia 23/15/10, diarrhoea 9/2/18, infection (other) 9/4/8, and hepatic toxicity 0/2/8. CONCLUSIONS This study demonstrates a numerically modest pCR rate increase with double anti-HER2 blockade plus chemotherapy, but suggests that the use of docetaxel rather than paclitaxel may not reduce toxicity. CLINICALTRIALSGOV NCT00450892.
Reproducibility of the Oral Glucose Tolerance Test and the Rice-Meal Test in Mild Diabetics

Reproducibility of 100 gm. oral glucose tolerance test and of Sakaguchi's rice-meal test were studied in sixty untreated mild diabetic patients with fasting blood sugar below 140 mg. per 100 ml. (Hagedorn-Jensen method). The tests were performed twice within a one-week interval. There were considerable variations of blood sugar levels in the same individuals between the duplicate tests. Variations were of similar magnitude after glucose or rice-meal and were smaller for the fasting blood sugar. There was no positive relationship between blood sugar levels after loading and their variability. Such a relationship was, however, clearly demonstrated for the fasting blood sugar levels of 360 newly referred diabetics. Average blood sugar levels and standard deviations for each group remained very stable despite individual variability. Implications of the data on evaluation of the results of these oral tests are discussed.
Genetic and environmental sources of covariation between generalized anxiety disorder and neuroticism.

OBJECTIVE The authors examined the sources of covariation between generalized anxiety disorder and the personality trait of neuroticism. Because women have higher levels of neuroticism and twice the risk of lifetime generalized anxiety disorder of men, gender-specific effects were also explored. METHOD Lifetime generalized anxiety disorder and neuroticism were assessed in more than 8,000 twins from male-male, female-female, and opposite-sex pairs through structured diagnostic interviews. Sex-limited Cholesky structural equation models were used to decompose the correlations between generalized anxiety disorder and neuroticism into genetic and environmental components, including sex-specific factors. RESULTS Genetic correlations between generalized anxiety disorder and neuroticism were high and differed (nonsignificantly) between men and women (1.00 and 0.58, respectively). When nonsignificant gender differences were removed from the models, correlations between generalized anxiety disorder and neuroticism were estimated at 0.80 (95% confidence interval=0.52-1.00). The individual-specific environmental correlation between generalized anxiety disorder and neuroticism was estimated at 0.20 for both genders. CONCLUSIONS There is substantial overlap between the genetic factors that influence individual variation in neuroticism and those that increase liability for generalized anxiety disorder, irrespective of gender. The life experiences that increase vulnerability to generalized anxiety disorder, however, have only modest overlap with those that contribute to an individual's level of neuroticism.
Long-term effects of pyloromyotomy on pyloric motility and gastric emptying in humans

OBJECTIVE:The aim of this study was to determine the long term effects of pyloromyotomy for infantile hypertrophic pyloric stenosis (IHPS) on gastric emptying and pyloric motility.METHODS:Concurrent measurements of gastric emptying and antropyloroduodenal pressures were performed in six volunteers (aged 24–26 yr) who had had pyloromyotomy performed in infancy because of IHPS, and in six normal subjects. Subjects were studied on 2 days, once sitting and once in the left lateral position. Gastric emptying of 300 ml 25% dextrose labeled with 20 MBq 99mTc sulfur colloid was measured. Antropyloroduodenal motility was evaluated with a sleeve/multiple sidehole manometric assembly, which was also used to deliver an intraduodenal triglyceride infusion at 1.1 kcal/min for 60 min, starting 30 min after ingestion of the dextrose.RESULTS:In both body positions, gastric emptying and intragastric distribution of the drink did not differ between the two groups. In both groups and postures, the amount emptied was less during intraduodenal lipid infusion. The number (p < 0.01) and amplitude (p < 0.02) of isolated pyloric pressure waves (IPPWs) was greater in the control subjects, whereas basal pyloric pressure was greater in the pyloromyotomy subjects (p < 0.02). In both groups, the rate of gastric emptying in the sitting position was related to the number of IPPWs (r ≥ 0.40, p < 0.05), but not to basal pyloric pressure.CONCLUSIONS:These results indicate that, in adults who have had pyloromyotomy for IHPS in infancy, patterns of pyloric motility are abnormal; pyloric tone is higher, whereas the number and amplitude of phasic pyloric pressure waves are less. In contrast, the overall rate of gastric emptying of a nutrient liquid meal is normal. These observations are consistent with the concept that the stomach has the capacity to compensate for changes in pyloric motility to minimize effects on gastric emptying.
Diffuse lung disease: assessment with helical CT--preliminary observations of the role of maximum and minimum intensity projection images.

PURPOSE To evaluate assessment of diffuse lung disease with helical computed tomography (CT) and maximum intensity projection (MIP) and minimum intensity projection images. MATERIALS AND METHODS Six patients with suspected lung disease (the control group) and 20 patients with documented disease underwent axial helical CT through the upper and lower lung fields. Findings on the MIP and minimum intensity projection images of each helical data set were compared with findings on the thin-section scan obtained at the midplane of the series. RESULTS Owing to markedly improved visualization of peripheral pulmonary vessels (n = 26) and improved spatial orientation, MIP images were superior to helical scans to help identify pulmonary nodules and characterize them as peribronchovascular (n = 2) or centrilobular (n = 7). Minimum intensity projection images were more accurate than thin-section scans to help identify lumina of central airways (n = 23) and define abnormal low (n = 15) and high (ground-glass) (n = 8) lung attenuation. Conventional thin-section scans depicted fine linear structures more clearly than either MIP or minimum intensity projection images, including the walls of peripheral, dilated airways (n = 3) and interlobular septa (n = 3). MIP and minimum intensity projection images added additional diagnostic findings to those on thin-section scans in 13 (65%) of 20 cases. CONCLUSION MIP and minimum intensity projection images of helical data sets may help diagnosis of a wide spectrum of diffuse lung diseases.
The Correlation between Heat-Shock Protein Accumulation and Persistence and Chilling Tolerance in Tomato Fruit

Heating tomato fruit (Lycopersicon esculentum) for 48 h at 38[deg]C prevented chilling injury from developing after 21 d at 2[deg]C, whereas unheated fruit developed high levels of injury. Although the overall protein pattern as seen by Coomassie blue staining was similar from heated and unheated fruit, some high- and many low-molecular-mass proteins were observed in the heated fruit that were absent or present in reduced amounts in unheated fruit. When fruit were injected with [35S]methionine at harvest and then heated, they accumulated high levels of specific radiolabeled proteins that could still be detected after 21 d at 2[deg]C. If the fruit were held at 20[deg]C after heating, the label in the proteins declined rapidly and these fruit were also sensitive to chilling injury. Hsp70 antibody reacted more strongly with proteins from heated and chilled fruit than with proteins from chilled fruit. Hsp18.1 antibody reacted strongly with proteins from heated fruit but not with those from unheated fruit. A 23-kD protein, highly labeled in heated fruit but not in unheated fruit, had its amino terminus sequenced. To our knowledge, this is the first report showing a relationship between the persistence of heat-shock proteins and chilling tolerance in a plant tissue.
Improving empirical antibiotic treatment: prospective, nonintervention testing of a decision support system

Leibovici L, Gitelman V, Yehezkelli Y, Poznanski O, Milo G, Paul M & Ein‐dor P (Rabin Medical Centre, Petah‐Tiqva, Sackler Faculty of Medicine, and Faculty of Management, Tel‐Aviv University, Ramat‐Aviv, Tel‐Aviv, Israel). Improving empirical antibiotic treatment: prospective, nonintervention testing of a decision support system. J Intern Med 1997; 242: 395–400.
The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering.

In the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), a 19% lower incidence of coronary heart disease (CHD) in cholestyramine-treated men was accompanied by mean falls of 8% and 12% in plasma total (TOTAL-C) and low-density lipoprotein (LDL-C) cholesterol levels relative to levels in placebo-treated men. When the cholestyramine treatment group was analyzed separately, a 19% reduction in CHD risk was also associated with each decrement of 8% in TOTAL-C or 11% in LDL-C levels (P less than .001). Moreover, CHD incidence in men sustaining a fall of 25% in TOTAL-C or 35% in LDL-C levels, typical responses to the prescribed dosage (24 g/day) of cholestyramine resin, was half that of men who remained at pretreatment levels. Adherence to medication was associated with reduced incidence of CHD only when accompanied by falls in TOTAL-C and LDL-C levels. Small increases in high-density lipoprotein cholesterol levels, which accompanied cholestyramine treatment, independently accounted for a 2% reduction in CHD risk. Thus, the reduction of CHD incidence in the cholestyramine group seems to have been mediated chiefly by reduction of TOTAL-C and LDL-C levels.
CD8+ Cytotoxic T Lymphocyte Activation by Soluble Major Histocompatibility Complex-Peptide Dimers*

CD8+ cytotoxic T lymphocyte (CTL) can recognize and kill target cells that express only a few cognate major histocompatibility complex class I-peptide (pMHC) complexes. To better understand the molecular basis of this sensitive recognition process, we studied dimeric pMHC complexes containing linkers of different lengths. Although dimers containing short (10–30-Å) linkers efficiently bound to and triggered intracellular calcium mobilization and phosphorylation in cloned CTL, dimers containing long linkers (≥80 Å) did not. Based on this and on fluorescence resonance energy transfer experiments, we describe a dimeric binding mode in which two T cell receptors engage in an anti-parallel fashion two pMHC complexes facing each other with their constant domains. This binding mode allows integration of diverse low affinity interactions, which increases the overall binding and, hence, the sensitivity of antigen recognition. In proof of this, we demonstrated that pMHC dimers containing one agonist and one null ligand efficiently activate CTL, corroborating the importance of endogenous pMHC complexes in antigen recognition.
MALATTIA LEVENTINESE/DOYNE HONEYCOMB RETINAL DYSTROPHY IN A CHINESE FAMILY WITH MUTATION OF THE EFEMP1 GENE

Purpose: To characterize the clinical features and molecular genetic findings in a Chinese pedigree with Malattia leventinese/Doyne honeycomb retinal dystrophy. Methods: All patients underwent ophthalmologic examinations, including Snellen best-corrected visual acuity, fundus photography, fundus autofluorescence imaging, fundus fluorescein angiography, and optical coherence tomography. Genomic DNA was isolated from blood samples. All exons of EFEMP1 were amplified by polymerase chain reaction and sequenced. Possible structural and functional impacts of the protein because of amino acid substitution were predicted by bioinformatics analysis. Results: A heterozygous missense mutation comprising C > T in exon 10 of EFEMP1 was identified in all patients of the pedigree; this resulted in an amino acid substitution at position 345 (Arg345Trp, R345W). Clinically, six patients from the Chinese family were ascertained with varying degrees of early onset drusen. Besides the drusen, choroidal neovascularization and retinal pigment epithelium changes were noted in some patients. Increased autofluorescence corresponding to the drusen was detected in the R345W mutation patients. Intrafamilial patients with Malattia leventinese/Doyne honeycomb retinal dystrophy seem to be phenotypically variable in visual loss, ophthalmoscopic findings, autofluorescence imaging, and optical coherence tomography changes. The amino acid change may have an effect on protein structure and function through bioinformatics analysis. Conclusion: The R345W mutation in EFEMP1 caused Malattia leventinese/Doyne honeycomb retinal dystrophy in a Chinese family. This is the first report, as per our knowledge, of the R345W mutation in EFEMP1 in a Chinese pedigree of this disease.
Mephedrone, Methylone and 3,4‐Methylenedioxypyrovalerone (MDPV) Induce Conditioned Place Preference in Mice

During the last decade, there has been a worldwide increase in popularity and abuse of synthetic cathinones. Common ingredients of the so‐called bath salts include mephedrone, methylone and 3,4‐methylenedioxypyrovalerone (MDPV). Relatively little information about the pharmacology and addiction potential of these drugs is available. We used the conditioned place preference (CPP) paradigm to explore the reinforcing effects of three different synthetic cathinones. The primary aim of this study was to investigate whether mephedrone, methylone and MDPV induce CPP in mice. The secondary aims were to investigate a possible dose–response CPP and whether the synthetic cathinones induce higher CPP than amphetamine at equal dose. C57BL/6 mice were conditioned to mephedrone, methylone, MDPV and amphetamine at doses of 0.5, 2, 5, 10 or 20 mg/kg (i.p.). During the conditioning, the mice received two training sessions per day for 4 days. All four tested drugs showed a significant place preference compared with controls. Mice conditioned with MDPV (5 and 10 mg/kg) displayed a greater preference score compared to mice conditioned with amphetamine (5 and 10 mg/kg). Our findings show that mephedrone, methylone and MDPV produce CPP equal or higher than amphetamine strongly suggesting addictive properties. Given the public health concern of abuse, future pharmacological studies are necessary to fully understand the effects of these drugs.
Study on PI sliding mode controller for paralleled dc-dc converter

A new control scheme for current distribution in parallel connected DC/DC converters was presented in this paper, which combined the proportional integral sliding mode (SM) control with the Master-Slave current sharing technology to achieve both current sharing and a better robustness in a parallel dc-dc converter. And the stability condition of the closed-loop system was analyzed by using small signal method. A parallel buck converter experiment platform based on FPGA was constructed. And the experimental results of the given proposed method are compared with the traditional double closed loop PI control. Experimental results were presented, showing good dynamic performance of the proposed control scheme.
Broadband neurophysiological abnormalities in the medial prefrontal region of the default‐mode network in adults with ADHD

Previous investigations of the default‐mode network (DMN) in persons with attention‐deficit/hyperactivity disorder (ADHD) have shown reduced functional connectivity between the anterior and posterior aspects. This finding was originally demonstrated in adults with ADHD, then in youth with ADHD, and has been tentatively linked to ultra low frequency oscillations within the DMN. The current study evaluates the specificity of DMN abnormalities to neuronal oscillations in the ultra low frequency range, and examines the regional specificity of these DMN aberrations in medicated and unmedicated adults with, and those without ADHD. An individually matched sample of adults with and without ADHD completed 6‐minute sessions of resting‐state magnetoencephalography (MEG). Participants with ADHD were known responders to stimulant medications and completed two sessions (predrug/postdrug). MEG data were coregistered to the participant's MRI, corrected for head motion, fitted to a regional‐level source model, and subjected to spectral analyses to extract neuronal population activity in regions of the DMN. The unmedicated adults with ADHD exhibited broadband deficits in medial prefrontal cortices (MPFC), but not other DMN regions compared to adults without ADHD. Unmedicated patients also showed abnormal cross‐frequency coupling in the gamma range between the MPFC and posterior cingulate areas, and disturbed balance within the DMN as activity in posterior regions was stronger than frontal regions at beta and lower frequencies, which dissipated at higher γ‐frequencies. Administration of pharmacotherapy significantly increased prefrontal alpha activity (8–14 Hz) in adults with ADHD, and decreased the cross‐frequency gamma coupling. These results indicate that neurophysiological aberrations in the DMN of patients with ADHD are not limited to ultra slow oscillations, and that they may be primarily attributable to abnormal broadband activity in the MPFC. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.
Nerve growth factor exposure promotes tubular epithelial–mesenchymal transition via TGF-β1 signaling activation

Abstract Clinical studies showed that renal expression and serum levels of nerve growth factor (NGF) are increased in renal diseases characterized by progressive fibrosis, a pathologic process in which TGF-β1 mediates most of the key events leading to tubular epithelial–mesenchymal transition (EMT). However, the pathogenic role of high NGF levels has not yet been elucidated. In this study, we found that in tubular renal cells, HK-2, NGF transcriptionally up-regulated TGF-β1 expression and secretion and enhanced cell motility by activating EMT markers via its receptors, TrkA and p75NTR. Interestingly, we observed that TGF-β1–SMAD pathway activation and the up-regulation of EMT markers NGF-induced were both prevented when knockdown of TGF-β1 gene occurred and that the pretreatment with an antibody anti-NGF reversed the nuclear translocation of pSMAD3/SMAD4 complex. Collectively, our results demonstrated that NGF promotes renal fibrosis via TGF-β1-signaling activation, suggesting that in kidney diseases high NGF serum levels could contribute to worsen renal fibrosis.
Mechanical properties of Ti-6Al-4V specimens produced by shaped metal deposition

Abstract Shaped metal deposition is a novel technique to build near net-shape components layer by layer by tungsten inert gas welding. Especially for complex shapes and small quantities, this technique can significantly lower the production cost of components by reducing the buy-to-fly ratio and lead time for production, diminishing final machining and preventing scrap. Tensile testing of Ti-6Al-4V components fabricated by shaped metal deposition shows that the mechanical properties are competitive to material fabricated by conventional techniques. The ultimate tensile strength is between 936 and 1014 MPa, depending on the orientation and location. Tensile testing vertical to the deposition layers reveals ductility between 14 and 21%, whereas testing parallel to the layers gives a ductility between 6 and 11%. Ultimate tensile strength and ductility are inversely related. Heat treatment within the α+β phase field does not change the mechanical properties, but heat treatment within the β phase field increases the ultimate tensile strength and decreases the ductility. The differences in ultimate tensile strength and ductility can be related to the α lath size and orientation of the elongated, prior β grains. The micro-hardness and Young’s modulus are similar to conventional Ti-6Al-4V with low oxygen content.
A rapid procedure for the preparation of highly purified pyruvate decarboxylase from brewer's yeast.

A rapid purification procedure for pyruvate decarboxylase (E.C. 4.1.1.1.) from fresh cells of brewer's yeast (Saccharomyces carlsb.) is reported. The preparation of a crude enzyme (30-45 U/mg) by the use of fractionation steps with protamine sulfate, acetone, and ammonium sulfate takes about 6-7 h. A stable pyruvate decarboxylase (70-85 U/mg) was obtained from such preparations after purification on CM Sephadex C 50 after another 2-3 h. Stability and structural properties are compared for enzymes prepared from fresh and dried yeast.