Miracle-dz/UniFAR-FTUs huggingface dataset:
Aneuploidy and proliferation in keratinocytic intraepidermal neoplasias

Abstract: Cutaneous squamous (pre)malignancies can be classified according to the keratinocytic intraepidermal neoplasia (KIN) classification. Aneuploidy can be seen as the result of chromosomal aberrations leading to altered DNA content and has been strongly associated with malignancy. Hyperproliferation is also strongly associated with tumorigenesis. The aim of the study was to analyse the presence and the amount of aneuploidy and proliferation in the progression from intraepithelial neoplasm to microinvasive carcinoma (miSCC). For this purpose, nuclei were isolated from 116 formalin‐fixed KIN lesions from 68 patients in which DNA content was measured by flow cytometry. Proliferation was assessed by immunohistochemical staining for Ki67 as well as by flow cytometry. Aneuploidy was increasingly found in higher KIN lesions, but not in normal skin. However, in miSCC aneuploidy was relatively less frequently found. DNA indices (mean ± SE) of KIN III‐lesions (1.57 ± 0.05) were significantly lower compared with KIN I/II lesions (1.71 ± 0.05). Ki67 expression was strongly positively correlated with KIN grade, and proved to be a good adjunct in the classification of KINs. Thus, aneuploidy occurred more frequently in higher KIN lesions, indicating cumulative damage during KIN progression. The lower frequency of aneuploidy in miSCC compared with KIN III may point at alternative routes towards invasive carcinoma besides serial progression through all three KIN stages. Ki67 expression appears a valuable marker in the classification of KINs.
Treatment of pediatric open femoral fractures with external fixator versus flexible intramedullary nails.

BACKGROUND In children, inappropriate treatment of open femoral fractures may induce several complications. A few studies have compared the external fixator with flexible intramedullary nails in high-grade open femoral fractures of children. The present study aims at comparing results of these two treatment methods in open femoral fractures. METHODS In this descriptive analytical study, 27 patients with open femoral fractures, who were treated using either the external fixator (n=14) or TEN nails (n=13) method from 2006-2011, were studied. Some patients were treated with a combination method of TEN and pin. The results were evaluated considering infection, union, malunion, and refracture and the patients were followed up for two years. RESULTSS Mean time required for fracture union was 3.89 (range: 2-5.8) and 3.61 (range: 2-5.6) months for the external fixator and TEN groups, respectively. The difference was not statistically significant and there was not any significant difference between the two groups considering infection of the fractured area. Osteomyelitis was not observed in any group. There was an infection surrounding the external fixator pin in 4 cases (28.5%) and so this required changing the location of the pin. In the TEN group, one case (7.6%) of painful bursitis was observed at the entry point of TEN and so the pin was removed earlier than usual. There were two cases (14.2%) of femoral refracture in the external fixator group. Malunion requiring correction was not observed in any of the groups. There were no complications observed in five patients treated with a combined method of pin and flexible intramedullary nails. CONCLUSION Both external fixator and intramedullary nail methods are effective ways in treating high grade open femoral fractures in children and final treatment results are similar. Combining pins and flexible intramedullary nails is effective in developing more stability and is not associated with more complications.
Vitamin D status and parathyroid hormone in obese children before and after weight loss.

OBJECTIVE The roles of vitamin D and parathyroid hormone (PTH) are discussed controversially in obesity, and studies of these hormones in obese children are limited. Therefore, we studied the relationships between PTH, 1,25-dihydroxy-vitamin D (1,25-OH Vit D), 25-hydroxy-vitamin D (25-OH Vit D), weight status, and insulin sensitivity before and after weight loss in obese children. METHODS Fasting serum PTH, 1,25-OH Vit D, 25-OH Vit D, inorganic phosphate, calcium, alkaline phosphatase (AP), insulin, glucose, and weight status (SDS-BMI and percentage body fat) were determined in 133 obese children (median age 12.1 years) and compared with 23 non-obese children. Furthermore, these parameters were analyzed in 67 obese children before and after participating in a 1-year obesity intervention program. RESULTS Obese children had significantly (P < 0.001) higher PTH and lower 25-OH Vit D concentrations compared with non-obese children, while calcium, phosphate, AP, and 1,25-OH Vit D did not differ significantly. Changes of PTH (r = 0.23, P = 0.031) and 25-OH Vit D (r = -0.27, P = 0.013) correlated significantly with changes of SDS-BMI, but not with changes of insulin sensitivity (homeostasis model assessment; HOMA-B%). Reduction of overweight in 35 children led to a significant (P < 0.01) decrease of PTH concentrations and an increase in 25-OH Vit D levels. CONCLUSIONS PTH levels were positively and 25-OH Vit D concentrations were negatively related to weight status. Since these alterations normalized after weight loss, these changes are consequences rather than causes of overweight. A relationship between PTH, vitamin D, and insulin sensitivity based on the HOMA index was not found in obese children. Further longitudinal clamp studies are necessary to study the relationship between vitamin D and insulin sensitivity.
Bundling and Competition for Slots: On the Portfolio Effects of Bundling

We consider competition among sellers when each of them sells a portfolio of distinct products to a buyer having limited slots. We study how bundling affects competition for slots. Under independent pricing, equilibrium often does not exist and hence the outcome is often inefficient. When bundling is allowed, each seller has an incentive to bundle his products and an efficient equilibrium always exists. Furthermore, in the case of digital goods, all equilibria are efficient if slotting contracts are prohibited. We also identify portfolio effects of bundling and analyze the consequences on horizontal mergers. Finally, we derive clear-cut policy implications.
13‐cis‐retinoic acid alters the cellular morphology of slice‐cultured serotonergic neurons in the rat

Retinoids influence cellular processes such as differentiation, proliferation and apoptosis via retinoic acid receptor (RAR) and retinoid X receptor (RXR), and have therapeutic applications in several cancers and dermatologic diseases. Recent reports indicate that depression occasionally occurs in patients using the acne drug Accutane, the active component of which is 13‐cis‐retinoic acid (13‐cis‐RA). Although impairment of serotonin (5‐HT)‐expressing neurons, including morphologic changes, is thought to be associated with depressive symptoms, the effects of 13‐cis‐RA on 5‐HT neurons have not been examined. The present study demonstrated that 13‐cis‐RA alters the morphology of 5‐HT neurons in cultured rat midbrain slices. The 13‐cis‐RA‐induced changes were partially blocked by RXR and RAR antagonists. Furthermore, cotreatment with RAR and RXR agonists altered the morphology of 5‐HT neurons to a greater extent than the individual application of each agonist. The morphologic changes were completely blocked by RXR antagonist, whereas RAR antagonist partially blocked the effects. These results suggest that 13‐cis‐RA exerts its action on slice‐cultured 5‐HT neurons, at least in part, through specific retinoid receptors. Moreover, RXR has a greater influence on the morphology of 5‐HT neurons than RAR. The receptor‐mediated actions of 13‐cis‐RA presented here may provide a clue for further research on depression associated with the use of 13‐cis‐RA.
Molecular and expression analysis of a family of the Amblyomma americanum tick Lospins

SUMMARY Serine proteinase inhibitors (serpins) are a family of structurally similar but functionally diverse proteins that regulate several important proteolytic cascades in most branches of life. We have characterized 17 Amblyomma americanum serpin cDNAs here named as `Lospins' (L; an acronym for Lone Star tick serpin) that possess three β-sheets, eight α-helices and a reactive center loop consistent with the consensus serpin superfamily secondary structures. Visual inspection of deduced amino acid sequences revealed two patterns of basic residues: (i) 86DKSRVLKAYKRL97 in L5 and L13–16 and (ii) 158VRDKTRGKI166 in all Lospins, which are similar to consensus glycosaminoglycan (GAG) binding sites (XBnXmBX, where X and B are non-basic and basic residues, n=1 or 2 and m=1, 2 or 3). On three-dimensional models, the two putative GAG binding sites mapped onto α-helices D and F, respectively, with calculation of electrostatic surface potentials revealing basic patches on L5 and L13–16 models that are comparable to the heparin-binding site on antithrombin. RT-PCR expression analysis of 15 selected genes showed that the majority (11/15) of the Lospins were ubiquitously expressed in the midgut, ovary and salivary glands. On a neighbor-joining phylogeny guide tree, 15 serpins from other ticks and 17 Lospins from this study, a total of 32 tick serpin sequences, segregated into five groups with Lospins in groups A and D being conserved across tick species. The discovery of Lospins in this study sets the framework for future studies to understand the role of serpins in tick physiology.
Inhibition of rat mammary tumorigenesis by voluntary exercise.

In this study, the anti-promoting effect of voluntary (wheel) exercise on 7, 12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumorigenesis was investigated. All rats were fed high fat diets (23% of calories as fat) to mimice the typical western diet. Two doses of DMBA were used to determine if the antipromoting effects of exercise were dependent on the strength of the initiating agent. In addition, tumor estrogen receptors were assayed to determined whether exercise, through an estrogen-suppressing mechanism, selects for estrogen receptor-negative tumors. Female Sprague-Dawley rats were fed a semi-purified 23% fat (corn oil) diet (AIN-76A) and, on day 50 of age administered DMBA by gavage at 5 or 10 mg/rat. Rats were then randomized into 4 groups (n = 30) as follows: 1) low DMBA/sedentary; 2) low DMBA/exercise; 3) high DMBA/-sedentary; and 4) high DMBA/exercise. Active rats were placed in wheel-cage units, which allowed voluntary access to an activity wheel for 133 (low DMBA) and 77 (high DMBA) days, respectively, Sedentary rats were placed in conventional cages. Both active groups exhibited significantly lower total tumor numbers than their sedentary controls: 75 vs 102 (low DMBA) (p < 0.05) and 90 vs 160 (high DMBA) (p < 0.001). Compared to sedentary controls, latency was significantly lengthened in the low but not the high DMBA active groups; multiplicity, in contrast, was significantly decreased in the high, but not the low DMBA exercised group. Exercise had no effect on overall tumor incidence. When segregated into exercise tertiles, total tumor active compared to the least active tertile, particularly in the high DMBA group. (ABSTRACT TRUNCATED AT 250 WORDS)
Differences between NSA 94-106 and IEEE 299 LF magnetic shielding measurements

For the characterisation of the LF magnetic shielding of conductive materials two setups are available. Although for both methods, loop antennas are used, two different configurations are defined. The one referenced in NSA 94-106 (formerly NSA 65-6) is called the parallel setup. The one referenced in IEEE 299 (formerly MIL STD 285) is called the coplanar setup. When performing measurements under similar conditions, different values for the resulting shielding effectiveness (SE) are obtained. This paper will discuss the background why differences are occurring.
Contrast cine left ventriculography: comparison of two pigtail catheter shapes and analysis of factors determining the final quality.

Ventricular arrhythmias or inadequate opacification of the ventricular cavity during contrast-cine left ventriculography frequently interfere with evaluation of regional wall motion, ejection fraction or mitral regurgitation. In this prospective, randomized study traditional (straight) pigtail catheter was compared with a new, large loop pigtail catheter (both 6 French, large lumen) in terms of the quality of the cine left ventriculograms. Straight (Group I) and curved pigtail (Group II) groups were further subdivided randomly into a preset (13 cc per second for 3 seconds with a pressure rise time of 0.5 seconds) injection rate (Group IA, n = 46, and Group IIA, n = 48) or operator definded injection rate (Group IB, n = 49, and Group IIB, n = 45) subgroups. The ventricular tachycardia and couplets occurred at similar frequency among the groups. The curved pigtail subgroups showed significantly more frequent catheter induced mitral regurgitation. However, the opacification and overall quality of the left ventriculograms were distributed similarly between the groups. Because the catheter type and injection protocol did not affect the left ventriculogram quality in our study, variables determining opacification and overall quality rating are analyzed in the overall group of 190 patients. Left ventricular opacification was excellent in 72, acceptable in 108 and marginal in 10 patients. The patients with marginal opacification were significantly heavier (P = .004) with larger left ventricular enddiastolic volumes (P = .019), and smaller amount of contrast volume per enddiastolic volume (P = .005) and kilogram body weight (P = .003). The overall quality of left ventriculograms were excellent in 38, acceptable in 133, and marginal in 19 patients. The patients with excellent left ventriculograms were significantly younger (P = .019) and slightly less heavy (P = 0.09). Significantly more female patients were also in this group (P = .036). Ventricular tachycardia was the most common cause of unsatisfactory left ventriculograms. In the RAO view, deeper (more apical) placement of the catheter was associated with higher incidence of ventricular tachycardia (53%). The most "silent" area was the posterobasal area. In conclusion, the perfect left ventriculogram remains to be an elusive goal in routine clinical practice. When using 6F highflow pigtail catheters and nonionic contrast agents, more basal catheter position and higher contrast volume increase the quality of the left ventriculograms.
Mechanism of extracellular ATP‐induced increase of cytosolic Ca2+ concentration in isolated rat ventricular myocytes.

1. Changes in the cytosolic Ca2+ concentration ([Ca2+]i) of isolated rat ventricular myocytes in suspension were measured in response to extracellular ATP using the fluorescent Ca2+ indicators Quin‐2 and Fura‐2. 2. ATP produced a concentration‐, time‐ and Mg(2+)‐dependent, biphasic increase of [Ca2+]i whereas slowly hydrolysable ATP analogues produced a slow, monophasic increase of [Ca2+]i and the non‐hydrolysable ATP analogues were without effect. 3. Extracellular Ca2+ was required for the ATP‐induced increase of [Ca2+]i and pre‐treatment of the cells with caffeine, ryanodine, verapamil or nimodipine partially inhibited the [Ca2+]i increase. 4. Whole‐cell patch‐clamp experiments revealed that ATP activated an ionic current that had a linear current‐voltage relationship with a reversal potential near O mV. Quinidine, a putative P2 purinergic receptor blocker, abolished the ATP‐activated current. The ATP‐activated current was Mg2+ dependent. 5. Associated with the ATP‐activated current was cellular depolarization. In a physiological solution, ATP depolarized cells to the threshold for the firing of action potentials. In the presence of the voltage‐activated ion channel blockers tetrodotoxin, 4‐aminopyridine, caesium and nitrendipine, ATP depolarized cells to ‐44 +/‐ 6 mV from a resting potential of ‐66 +/‐ 4 mV (n = 11). 6. Sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis and autoradiography demonstrated that extracellular ATP stimulated the phosphorylation of several extracellular membrane‐bound proteins. The phosphorylation of these proteins was concentration, time and Mg2+ dependent. Pre‐treatment of cells with the slowly hydrolysable ATP analogues inhibited the ATP‐induced phosphorylation. Adenosine 5'‐O‐3‐thiotriphosphate (ATP gamma S) thiophosphorylated proteins with the same apparent molecular weight as the proteins phosphorylated by ATP. 7. These results suggest that the ATP‐induced increase of [Ca2+]i is a result of the activation, possibly by protein phosphorylation, of a novel ion channel carrying inward current. The ATP‐activated channel may be permeable to Na+ and Ca2+ and causes [Ca2+]i to rise. More importantly, this inward current depolarizes the cell to the threshold of inducing spontaneous firing of action potentials. The firing of action potentials results in the influx of Ca2+ through L‐type Ca2+ channels which would trigger Ca2+ release from the sarcoplasmic reticulum and lead to the increase in [Ca2+]i.
Development and validation of a prognostic model for recurrent glioblastoma patients treated with bevacizumab and irinotecan

Abstract Background Predictive markers and prognostic models are required in order to individualize treatment of recurrent glioblastoma (GBM) patients. Here, we sought to identify clinical factors able to predict response and survival in recurrent GBM patients treated with bevacizumab (BEV) and irinotecan. Material and methods A total of 219 recurrent GBM patients treated with BEV plus irinotecan according to a previously published treatment protocol were included in the initial population. Prognostic models were generated by means of multivariate logistic and Cox regression analysis. Results In multivariate analysis, corticosteroid use had a negative predictive impact on response at first evaluation (OR 0.45; 95% CI 0.22–0.93; p = 0.03) and at best response (OR 0.51; 95% CI 0.26–1.02; p = 0.056). Three significant (p < 0.05) prognostic factors associated with reduced progression-free survival and overall survival (OS) were identified. These factors were included in the final model for OS, namely corticosteroid use (HR 1.70; 95% CI 1.18–2.45; p = 0.004), neurocognitive deficit (HR 1.40; 95% CI 1.04–1.89; p = 0.03) and multifocal disease (HR 1.56; 95% CI 1.15–2.11; p < 0.0001). Based on these results a prognostic index able to calculate the probability for OS at 6 and 12 months for the individual patient was established. The predictive value of the model for OS was validated in a separate patient cohort of 85 patients. Discussion and conclusion A prognostic model for OS was established and validated. This model can be used by physicians to risk stratify the individual patient and together with the patient decide whether to initiate BEV relapse treatment.
Using a neural network model to forecast flood events on the Big Thompson River

For the entire period of recorded time, floods have been a major cause of loss of life and property. Methods of prediction and mitigation range from human observers to sophisticated surveys and statistical analysis of climatic data. In the last few years, researchers have applied computer programs called Neural Networks or Artificial Neural Networks to a variety of uses ranging from medical to financial. The purpose of the study was to demonstrate that Neural Networks can be successfully applied to flood forecasting. The river system chosen for the research was the Big Thompson River, located in North-central Colorado, United States of America. The Big Thompson River is a snow melt controlled river that runs through a steep, narrow canyon. In 1976, the canyon was the site of a devastating flood that killed 145 people and resulted in millions of dollars of damage. Using publicly available climatic and stream flow data and a Ward Systems Neural Network, the study resulted in prediction accuracy of greater than 97% in +/-100 cubic feet per minute range. The average error of the predictions was less than 16 cubic feet per minute. To further validate the model’s predictive capability, a multiple regression analysis was done on the same data. The Neural Network’s predictions exceeded those of the multiple regression analysis by significant margins in all measurement criteria.
Ensilaje como fuente de alimentación para el ganado

El ensilaje es la fermentacion anaerobia de carbohidratos solubles presentes en forrajes para producir acido lactico. El proceso permite almacenar alimento en tiempos de cosecha conservando calidad y palatabilidad, lo cual posibilita aumentar la carga animal por hectarea y sustituir o complementar concentrados. Su calidad es afectada por la composicion quimica de la materia a ensilar, el clima y los microorganismos empleados, entre otros. El ensilaje se almacena en silos que permiten mantener la condicion anaerobia, existen varios tipos y la escogencia del apropiado depende del tipo de explotacion ganadera, recursos econo- micos disponibles y topografia del terreno entre otros
Innovation Markets, Future Markets, or Potential Competition: How Should Competition Authorities Account for Innovation Competition in Merger Reviews?

The relevant competitors in regard to innovation might, but not necessarily do, correspond to the identified competitors on actual product markets. Hence, the conventional analysis of product markets, in order to assess the potential anticompetitive effects of mergers, is insufficient to capture innovation competition in its full extent. As a consequence, the aim of this article is to introduce and compare the existing alternative approaches that can, in principle, be used for the assessment of anticompetitive innovation effects in merger review. By focusing on the applied US Antitrust, it turns out that none of the existing approaches appears to be sufficient to fully account for innovation competition. However, the 'Innovation Market Analysis', the first framework especially designed for the assessment of innovation aspects, still might serve as a good starting point for the development of a revised assessment framework.
Nerve growth factor enhances cough and airway obstruction via TrkA receptor- and TRPV1-dependent mechanisms

Background: Nerve growth factor (NGF) is an important mediator of airway hyper-responsiveness and hyperalgesia but its role in cough is unknown. Objectives: In this study the effects of NGF on the cough reflex and airway calibre were investigated in guinea pigs. The involvement of the tropomyosin-related kinase A (TrkA) receptor and transient receptor potential vanilloid-1 (TRPV1), and the p38 mitogen-activated protein kinase (MAPK)-dependent pathway in any NGF-induced effects on cough and airway obstruction was also assessed. Methods: Guinea pigs were placed in a transparent whole-body plethysmograph box. Cough was assessed visually, acoustically and by analysis of the airflow signal. Airway obstruction was measured using enhanced pause (Penh) as an index. Results: Exposure of guinea pigs to NGF did not induce a cough response nor a significant airway obstruction. However, exposure of guinea pigs to NGF immediately before citric acid inhalation resulted in a significant increase in the citric acid-induced cough and airway obstruction compared with vehicle-treated animals. Pretreatment with the TrkA receptor antagonist, K252a, or the TRPV1 antagonist, iodoresiniferatoxin, significantly inhibited the NGF-enhanced cough and airway obstruction. Exposure to NGF also increased p38 MAPK phosphorylation, but pretreatment with the p38 MAPK inhibitor, SB203580, did not affect either the NGF-enhanced cough or airway obstruction despite preventing the NGF-induced elevation in p38 MAPK phosphorylation. Conclusions: The data show that NGF can enhance both cough and airway obstruction via a mechanism that involves the activation of the TrkA receptor and TRPV1 but not the p38 MAPK-dependent pathway.