Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor Proliferation in Squamous Cell Carcinoma of the Vulva

Tumor proliferation is of important prognostic significance for several neoplasms. The very few previous studies on this parameter in vulvar carcinoma have shown contradictory results. The aim of this study was to determine the prognostic significance of tumor proliferation in vulvar carcinoma. Paraffin-embedded tissue of 74 squamous cell carcinomas of the vulva was immunostained for MIB-1, detecting Ki-67, and analyzed for staining patterns and the percentage of positive cells. There were three general staining patterns: a diffuse distribution (diffuse type), a localized staining at the infiltrating tumor border (infiltrating type), and a localized staining in basal parts of infiltrating tumor cell aggregates (basal type). The percentage of positive cells was not correlated with morphologic or clinical parameters, nor was it correlated with disease-free and overall survival. MIB-1 staining types were correlated with tumor type and grading. Tumors of diffuse and infiltrating type seemed to have more frequent lymph node metastasis (p = 0.053) and shorter disease-free survival (p = 0.076). In these tumors, overall survival time was reduced significantly (p = 0.02). In multivariate analysis, MIB-1 staining types were the most important factor for overall survival with an odds ratio of 4.73. In conclusion, distribution and not the percentage of proliferating cells is of prognostic significance in squamous cell carcinoma of the vulva.
An active set solver for min-max robust control

An efficient optimization procedure is proposed for computing robust control laws for linear systems with linear state and input constraints and bounded additive disturbances. We describe an active set method for solving the dynamic programming problem associated with the min-max optimization of a predicted cost. The computational complexity per iteration is shown to depend linearly on the length of the prediction horizon. We consider the continuity of solutions, derive bounds on the closed loop disturbance l2-gain and provide numerical comparisons with a disturbance-affine feedback law.
The safety and tolerability of citalopram

Since citalopram was first approved in 1989, it has been prescribed to an estimated >600 000 patients. An integrated safety database has been prepared, including data from 3107 patients from 24 clinical trials. In placebo-controlled trials, nausea, dry month, somnolence, increased sweating, tremor, diarrhoea, and ejaculation failure, mostly of mild to moderate severity, occurred significantly (p < 0.05) more frequently with citalopram. The excess incidence of these events over placebo was always less than 10%. In pooled comparative studies, citalopram's tolerability profile was similar to that of other selective serotonin reuptake inhibitors (SSRls) and superior to that of tricyclic antidepressants (TCAs). Spontaneous adverse event reports arising from clinical use have confirmed the safety profile defined during the trials programme. Specific monitoring of all serious adverse events from around 10 000 patients receiving citalopram in clinical trials (including small open studies) has indicated a low potential for convulsions and extrapyramidal effects. There is no evidence of withdrawal phenomena on abrupt discontinuation, no clinically relevant effects on cardiac or laboratory parameters, and little or no effect on psychomotor function. When taken in overdose alone, citalopram appears to have a relatively wide margin of safety. Citalopram has been well tolerated in both short-and long-term use, and the profile seen in trials has been confirmed in the clinic.
Control of T lymphocyte activation and IL-2 receptor expression by endogenously secreted lymphokines.

The relative contribution of endogenously secreted lymphokines, TNF-alpha and IL-2, to T cell activation has been studied. Interestingly, a neutralizing anti-TNF-alpha mAb strongly inhibited the proliferation, IL-2R alpha expression, and activation of the nuclear factor (NF)-kappa B induced on human purified T lymphocytes by an immobilized anti-CD3 mAb (imm.anti-CD3). Furthermore, the addition of exogenous TNF-alpha to T cells activated by imm.anti-CD3 or phorbol esters strongly stimulated all those activities. Similarly, neutralizing anti-IL-2R alpha Abs inhibited the cell proliferation and the IL-2R alpha expression induced by imm.anti-CD3, whereas exogenous addition of IL-2 enhanced both activities. However, exogenous addition of IL-2 did not affect NF-kappa B activation. Cyclosporin A, which prevented lymphokine mRNA transcription, inhibited more than 90% of the IL-2R alpha and NF-kappa B levels induced by TCR/CD3-mediated activation. Exogenous TNF-alpha and IL-2 were equally important to the partial recovery of this IL-2R alpha inhibition, and high doses of both lymphokines together completely abolished the inhibitory effect of cyclosporin A. However, only TNF-alpha (but not IL-2) efficiently recovered the nuclear NF-kappa B levels. Those results indicate that the autocrine secretion of TNF-alpha and IL-2, and not the primary stimulus itself, contribute mostly to the regulation of IL-2R; thereby playing a very important role in quantitative control of T cell proliferation and leaving to the specifically TCR/CD3-derived signals the triggering role in T cell activation.
Increasing mean arterial pressure during cardiac surgery does not reduce the rate of postoperative acute kidney injury

Introduction: We hypothesized that the optimization of renal haemodynamics by maintaining a high level of mean arterial blood pressure (MAP) during cardiopulmonary bypass (CPB) could reduce the rate of acute kidney injury (AKI) in high-risk patients. Methods: In this randomized, controlled study, we enrolled 300 patients scheduled for elective cardiac surgery under cardiopulmonary bypass. All had known risk factors of AKI: serum creatinine clearance between 30 and 60 ml/min for 1.73m2 or two factors among the following: age >60 years, diabetes mellitus, diffuse atherosclerosis. After a standardized fluid loading, the MAP was maintained between 75-85 mmHg during CPB with norepinephrine (High Pressure, n=147) versus 50-60 mmHg in the Control (n=145). AKI was defined by a 30% increased of serum creatinine (sCr). We further tested others definitions for AKI: RIFLE classification, 50% rise of sCr and the need for haemodialysis. Results: The pressure endpoints were achieved in both the High Pressure (79 ± 6 mmHg) and the Control groups (60 ± 6 mmHg; p<0.001). The rate of AKI did not differ by group (17% vs. 17%; p=1), whatever the criteria used for AKI. The length of stay in hospital (9.5 days [7.9-11.2] vs. 8.2 [7.1-9.4]) and the rate of death at day 28 (2.1% vs. 3.4%) and at six months (3.4% vs. 4.8%) did not differ between the groups. Conclusion: Maintaining a high level of MAP (on average) during normothermic CPB does not reduce the risk of postoperative AKI. It does not alter the length of hospital stay or the mortality rate.
Quantification of pesticides in food crops using QuEChERS approaches and GC-MS/MS

ABSTRACT The analysis of pesticides in food products requires accurate measurements for which standardised protocols have been developed. This paper reports the validation of QuEChERS (quick, easy, cheap, effective, rugged, and safe)-based methods applied to three different food samples (brown rice, red pepper and mandarin orange) analysed using gas chromatography-tandem mass spectrometry (GC-MS/MS). The validation of the analytical methods used to measure 113 pesticides, including various insecticides, fungicides and herbicides, was conducted in three food matrices and at three spiking levels by three different laboratories. The set of validated results was interpreted, statistically analysed and visualised using principal component analysis (PCA). Notably, the matrix effects in GC-MS analysis for most of the tested pesticides from different matrices were lowered to practical values (less than 30%) appropriate for routine analysis. This allowed for the quantification of pesticides in the samples using standard and analyte protectants (APs) in the reagent method blank as a screening measure, providing an alternative to matrix-matched calibration. Alternatively, the use of only one standardised calibration (grape matrix) in combination with APs also allowed for the qualitative and semi-quantitative analysis of pesticides in different matrices. The inclusion of APs reduced the differences in the matrix-induced enhancement effects of various samples. The use of an internal standard (IS) to correct the matrix effects was also noted. The normalisation of the analyte peak with triphenyl phosphate (TPP) as an IS resulted in a slight improvement of validation values such as precision and linearity in only one laboratory, but it lowered the value of matrix effects in all three laboratories.
Neuroblastomas with Discordant Genotype-Phenotype Relationships: Report of Four Cases with MYCN Amplification and Favorable Histology

MYCN amplification prevents cellular differentiation and promotes mitotic and karyorrhectic activities in neuroblastomas. Hence, MYCN-amplified tumors typically show an appearance of neuroblastoma of either an undifferentiated or a poorly differentiated subtype with a high mitosis-karyorrhexis index. In addition, they are classified as part of the unfavorable histology group, according to the International Neuroblastoma Pathology Classification. Large cell type and/or presence of prominent nucleoli is also reported to be an additional hallmark of MYCN amplification. However, there are few neuroblastomas having MYCN amplification and favorable histology. Four cases of MYCN amplification and favorable histology were identified in our file of 63 cases of neuroblastoma. The patients (M:F = 3:1) were diagnosed between 6 and 13 months of age, and all had adrenal primary tumors and were treated with high-dose therapy and autologous stem cell rescue. Three patients (stages 1, 3, and 4) are alive and well 7 years, 26 months, and 19 months after diagnosis, respectively. One patient with stage 4 disease died 8 months after diagnosis. Their tumors showed the same histologic feature of neuroblastoma: poorly differentiated subtype with a low mitosis-karyorrhexis index; they were not qualified as large cell type and had no prominent nucleoli. MYCN amplification of those tumors was confirmed by fluorescence in situ hybridization in all 4 cases, but MYCN protein expression was not demonstrated by immunohistochemistry (4 cases) and MYCN mRNA was not detected by reverse transcriptase polymerase chain reaction (1 case). Those cases showed a discrepant genotype-phenotype that was not simply a laboratory observation but could indicate the concept that that MYCN amplification did not automatically equate to a poor prognosis in this group of patients.
Development of a radioimmunoassay for Escherichia coli heat-stable enterotoxin: comparison with the suckling mouse bioassay

Escherichia coli strains which produce heat-stable enterotoxin (ST) are usually identified by demonstrating the production of ST. At present, ST can be detected only by bioassay methods. Recently, we purified E. coli ST, which enabled us to develop a radioimmunoassay for ST. Radioiodination of ST was performed by the lactoperoxidase method, which resulted in a high specific activity and retained the biological activity of St. Anti-ST antisera were raised in goats by injecting the goats with pure ST coupled to bovine immunoglobin G. Antibody titers ranged from 1:8,000 to 1:40,000. Using these reagents, we examined assay conditions thoroughly and found that a 14- to 18-h incubation at 4 degrees C in sodium acetate buffer with an ionic strength of 120 mM (pH 6.2) gave maximal sensitivity and reproducibility. Free ST was separated from antibody-bound ST by dextran-coated charcoal. This radioimmunoassay accurately and reproducibly measured ST in the range from 50 to 500 pg of ST per tube and could quantitate ST accurately in complex bacteriological media. This assay was specific for STa, measured human and porcine STa equally well, and did not cross-react with STb, with several other enterotoxins, or with various gastrointestinal peptides. Intact disulfide bridges in the ST molecule were required for immunoreactive activity.
HAMLET (human α‐lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death

HAMLET, a complex of partially unfolded α‐lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double‐membrane‐enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3‐I) to granular (LC3‐II) staining in LC3‐GFP‐transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3‐methyladenine. HAMLET also caused accumulation of LC3‐II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin‐1 and Atg5. Suppression of Beclin‐1 and Atg5 improved the survival of HAMLET‐treated tumor cells and inhibited the increase in granular LC3‐GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET‐induced tumor cell death. © 2008 Wiley‐Liss, Inc.
Phylogeography and postglacial dispersion of the chub (Leuciscus cephalus) in Europe

A phylogeographic analysis of mitochondrial DNA variation was performed in order to test the hypothesis of a postglacial recolonization of mid‐ and north‐European rivers from a Danubian refuge. Over 345 chub specimens from European rivers covering most of the species’ native range were investigated using 600 bp of the cytochrome b gene. Chub in European rivers belong to four highly divergent mitochondrial groups (lineages) differing by mean divergence estimates from 5.2% to 7.89%. These four lineages have a largely allopatric distribution, implying four geographical sets: two Mediterranean, and two north‐European sets. This pattern provided strong evidence for: (i) the eradication of this species from most of Europe during maximum ice extent; (ii) its survival in four refugia (Adriatic side of the Balkans, eastern Greece (Aegean Rivers), southern tributaries of the Danube, and periphery of Black and Caspian Seas); (iii) a differential postglacial recolonization of mid‐ and northern Europe from the last two refugia only; (iv) the occurrence of this recolonization in two steps for the Danubian (western) lineage that entered western Europe (Rhine–Rhone–Loire drainages) during the Riss–Würm interglacial period and survived the last glaciation there before colonizing Garonne, UK and German drainages up to the Elbe during the Holocene; and (v) the occurrence of this recolonization in a single step for the Ponto‐Caspian (eastern) lineage that entered the Baltic area as far as the Oder in the Holocene. Both lineages came into contact in the River Elbe without evident mixing.
Arsenicosis and stigmatisation

Arsenicosis is believed to have debilitating effects on social relations, but with arsenic poisoning previously associated directly with economic and cognitive impacts, the degree to which stigmatisation is influenced by socio-economic or health status has not been established in the literature. Based on face-to-face interviews with 100 arsenic outpatients from specialist arsenic clinics in rural Bangladesh, this study represents an early quantitative analysis of factors predicting social impacts of arsenicosis. Physical health status, average years of schooling, family size and the presence of non-government organisation (NGO) and government-run arsenic-awareness campaigns significantly predicted social impacts. We found that the presence of awareness-raising activities was by far the most significant predictor of social impacts after other key variables, including gender and income, thus underscoring the importance of public health interventions in mitigating the impact of stigmatised diseases. The study confirms previous qualitative findings that ostracism is a pervasive problem for arsenicosis patients, and that public health interventions can be a valuable counter to such social problems.
Long-term outcomes following repair or replacement in degenerative mitral valve disease.

BACKGROUND We studied whether mitral valvuloplasty (MVP) was superior to mitral valve replacement (MVR) in patients with degenerative mitral regurgitation (MR), and analyzed the independent risk factors for survival and reoperation. METHODS 326 patients with degenerative MR underwent MVP (n = 241), mitral valve replacement (MVR) (n = 78) or emergent MVR due to failure of repair (EMVR). Clinical data were analyzed retrospectively. RESULTS Thirty-day mortality was lower after MVP (2.5 %) compared to MVR (9.0 %) ( P < 0.05). Late survival at 1 and 5 years in the MVP group was 94.4 % and 84.3 % versus 80.4 % and 64.6 % in the MVR group ( P < 0.05), respectively. After adjusting the baseline characteristics by the propensity score method, a significant survival benefit was found for patients who underwent MVP. Multivariable analysis showed that MVR was an independent predictor of thirty-day mortality and survival. There was no significant difference in thirty-day mortality and survival between the EMVR and MVR groups. The need for reoperation was not significantly different between the MVP and MVR groups. In the MVP group, the risk factors for survival and reoperation were identified. CONCLUSIONS MVP is superior to MVR for the treatment of degenerative MR despite the impact of repair failure. Age less than 60 years, ring size to body surface area greater than 19.0, absence of a prosthetic ring and residual MR at the end of surgery (≥ 1/4) reduce the durability of MVP.
Immunomodulatory agents and risk of postpartum multiple sclerosis relapses.

OBJECTIVE To determine whether treatment with an interferon beta or glatiramer acetate shortly after delivery reduces the otherwise increased risk of postpartum relapses of multiple sclerosis. METHODS In a retrospective cohort of 112 women with multiple sclerosis and live births from Kaiser Permanente Southern California, complete medical and pharmacy records of the mothers and infants were reviewed. Propensity score-adjusted hazard ratios (HR) of time to first postpartum relapse were calculated. RESULTS Of 80 women who breastfed little or not at all, 55 (69%) resumed treatment within 1 year postpartum, of whom 26 (47%) relapsed within 6 months postpartum. Resuming treatment within 2 weeks postpartum did not decrease the risk of relapse in the 2 years postpartum compared with women who resumed treatment later in the postpartum year (propensity score-adjusted HR = 1.3, 95% confidence interval = 0.5-3.4, p = 0.6). There was no difference in relapse rates between the groups in the first 6 months postpartum. However, later in the postpartum year those who resumed treatment early had fewer relapses (p = 0.08, Poisson regression). CONCLUSIONS Among women who breastfeed little or not at all, starting treatment with interferon beta or glatiramer acetate within two weeks postpartum does not reduce the risk of postpartum relapse of multiple sclerosis but may reduce the risk of subsequent relapses in the postpartum year.
Floor space covered by broiler chickens kept at stocking densities according to Council Directive 2007/43/EC

It is controversially discussed whether the stocking densities set by the EU Directive 2007/43/EC allow a species-appropriate housing of broiler chickens. To calculate the exact area broilers occupy due to their physical size and shape, planimetric measurements using a colour-contrast method were carried out. In total, 1949 photographs of standing and 1482 of squatting chickens, taken from a top view, were analysed. A computer program counted the pixels representing the previously weighed animal in the photograph and calculated the animal area. The average area covered by chickens with 400 g live weight was 116.64±13.12 cm2 in a standing and 138.61±12.92 cm2 in a squatting position. These areas increased linearly as a function of live weight to 452.57±58.89 cm2 (R2=0.90 standing) and 513.54±42.70 cm2 (R2=0.82 squatting) at the end of the study (3200 g live weight). Squatting chickens occupied more space compared with a standing position in most of the tested weight classes (P<0.05). Depending on target weights, stocking densities and body positions, broilers occupied 48.5–77.7 per cent of 1 m2. Thus, from a physical point of view, simultaneous resting is possible at any stocking density provided by the EU Directive and at common target weights.
Differences in lumbopelvic control and occupational behaviours in female nurses with and without a recent history of low back pain due to back injury

Low back pain is highly prevalent in nurses. This study aimed to determine which physical fitness, physical activity (PA) and biomechanical characteristics most clearly distinguish between nurses with [recently injured (RInj)] and without [not recently injured (NRInj)] a recent back injury. Twenty-seven (8 RInj, 19 NRInj) female nurses completed questionnaires (pain, work, PA), physical fitness, biomechanical and low back discomfort measures, and wore an accelerometer for one work shift. Relative to NRInj nurses, RInj nurses exhibited reduced lumbopelvic control (41.4% more displayed a moderate loss of frontal plane position), less active occupational behaviours (less moderate PA; less patient lifts performed alone; more sitting and less standing time) and more than two times higher low back discomfort scores. Despite no physical fitness differences, the lumbopelvic control, occupational behaviours and discomfort measures differed between nurses with and without recent back injuries. It is unclear whether poor lumbopelvic control is causal or adaptive in RInj nurses and may require further investigation. Practitioner Summary: It is unclear which personal modifiable factors are most clearly associated with low back pain in nurses. Lumbopelvic control was the only performance-based measure to distinguish between nurses with and without recent back injuries. Future research may investigate whether reduced lumbopelvic control is causal or adaptive in recently injured nurses.
Evolutionary genetics of fluctuating asymmetry in the peacock butterfly(Inachis io)

Fluctuating asymmetry (FA) and trait size were analysed for two pupal and two adult traits in the peacock butterfly (Inachis io L.). Natural families were raised in the field and the laboratory. The amount of FA relative to trait size was lower for the measured pupal traits. Although there were clear differences in trait sizes between the sexes and between the laboratory and field, no differences in FA were detected. Individuals that died in the pupal stage or hatched with crippled wings did not differ in their amount of FA from healthy adults. Differences for the trait sizes between families were large and significant and the heritabilities (h2) were high. For FA most differences between families were not significant and h2s were close to and not different from 0. Only for one of the pupal traits was a significant difference detected between families but its h2 (0.15) was not significantly different from 0. Differences in survival between families were not related to their average FA. Although half of the phenotypic correlations between trait sizes were significantly different from 0, only one correlation between FA (for the adult traits) was significant, albeit weakly (r=0.11). Some of the genetic correlations between trait sizes were strong and significant, but genetic correlations between FA were practically absent because of the low amounts of genetic variation for FA. A purely random cause of FA seems more likely for these traits than any influence of sex, environment, quality or genes.