Miracle-dz/UniFAR-FTUs huggingface dataset:
Sarcomas With CIC-rearrangements Are a Distinct Pathologic Entity With Aggressive Outcome: A Clinicopathologic and Molecular Study of 115 Cases

CIC-DUX4 gene fusion, resulting from either a t(4;19) or t(10;19) translocation, is the most common genetic abnormality detected in EWSR1-negative small blue round cell tumors. Following their discovery it was debated if these tumors should be classified as variants of Ewing sarcoma (ie, atypical Ewing sarcoma) or as a stand-alone pathologic entity. As such the WHO classification temporarily grouped the CIC-rearranged tumors under undifferentiated sarcomas with round cell phenotype, until further clinical evidence was available. However, most studies reported so far include small series with limited follow-up information, which preclude a more definitive assessment. The present work investigates the clinicopathologic features of a large cohort of sarcomas with CIC gene rearrangement, to define their clinical presentation, morphologic spectrum, and outcome. Our study further examines the overall survival of the CIC-positive cohort compared with a control group of EWSR1-rearranged Ewing sarcoma matched for age and stage. The study cohort included 115 patients, with a mean age of 32 years and a slight male predominance. Most tumors occurred in the soft tissue (86%), predominantly deep-seated and equally divided among trunk and extremity, followed by visceral locations (12%) and rarely in the bone (3%). Microscopically, most tumors showed round to ovoid cytomorphology but half of the cases showed also focal areas of spindling and epithelioid/rhabdoid phenotype, with frequent myxoid stromal changes. Variable CD99 reactivity was seen in 84% cases, with a diffuse pattern only in 23% of cases, whereas nuclear WT1 was seen in 92%. A CIC-DUX4 fusion was detected in 57% of cases, with either DUX4 on 4q35 (35%) or on 10q26 in 25 (22%) cases. No FOXO4 gene rearrangements were present in 39 cases tested. Clinical follow-up was available in 57 patients, with a 5-year survival of 43%, which was significantly lower than the 77% 5-year survival in the control Ewing sarcoma group (P=0.002). Our findings show that CIC-DUX4 sarcomas occur most commonly in young adults within the somatic soft tissues, having a wide spectrum of morphology including round, epithelioid and spindle cells, and associated with an aggressive clinical course, with an inferior overall survival compared with Ewing sarcoma. The results support the classification of CIC-rearranged tumors as an independent molecular and clinical subset of small blue round cell tumors distinct from Ewing sarcoma.
Variation in tomato host response to Bemisia tabaci (Hemiptera: Aleyrodidae) in relation to acyl sugar content and presence of the nematode and potato aphid resistance gene Mi

Two commercial cultivars of tomato, Alta and Peto 95, the accession line number LA716 of Lycopersicon pennellii and lines 94GH-006 and 94GH-033 (backcrosses between Peto 95 and LA716), with different leaf acyl sugar contents were screened for resistance to Bemisia argentifolii Bellows & Perring (corresponding to the Spanish B-biotype of Bemisia tabaci (Gennadius)), in greenhouse- and field-no-choice experiments. There was no oviposition on LA716 (with the highest acyl sugar content) while the greatest fecundity and fertility values were observed on the cultivar Alta (no acyl sugar content). However, no clear relationship was found between the low acyl sugar content in the other tomato cultivars tested and whitefly reproduction. Thus, resistance to B. tabaci did not appear to correlate with acyl sugar content below a threshold level of 37.8 μg cm-2leaf. In a greenhouse choice-assay, B. tabaci exhibited reduced host preference and reproduction on the commercial tomato cultivars Motelle, VFN8 and Ronita all of which carry the Mi gene resistance to Meloidogyne nematodes and the aphid Macrosiphum euphorbiae (Thomas), than on the Mi-lacking cultivars Moneymaker, Rio Fuego and Roma. When data of Mi-bearing plants were pooled, the mean values for daily infestation and pupal production of B. tabaci were significantly lower than those of Mi-lacking plants. This reflected a level of antixenosis- and antibiosis-based resistance in commercial tomato and indicated that Mi, or another closely linked gene, might be implicated in a partial resistance which was not associated either with the presence of glandular trichomes or their exudates. These findings support the general hypothesis for the existence of similarities among the resistance mechanisms to whiteflies, aphids and nematodes in commercial tomato plants.
Nuclear Import Mechanism for Myocardin Family Members and Their Correlation with Vascular Smooth Muscle Cell Phenotype*

Myocardin (Mycd), which is essential for the differentiation of the smooth muscle cell lineage, is constitutively located in the nucleus, although its family members, myocardin-related transcription factors A and B (MRTF-A/B), mostly reside in the cytoplasm and translocate to the nucleus in response to Rho signaling. The mechanism for their nuclear import is unclear. Here we investigated the mechanism for the nuclear import of Mycd family members and demonstrated any correlation between such mechanism and the phenotype of vascular smooth muscle cells (VSMCs). In cultured VSMCs, the knockdown of importin β1 inhibited the nuclear import of Mycd and MRTF-A/B. Their NH2-terminal basic domain was identified as a binding site for importin α/β1 by in vitro analyses. However, Mycd had a higher affinity for importin α/β1 than did MRTF-A/B, even in the absence of G-actin, and Mycd affinity for importin α1/β1 was stronger than for any other importin α/β1 heterodimers. The binding of Mycd to importin α/β1 was insensitive to G-actin, whereas that of MRTF-A/B was differently inhibited by G-actin. In dedifferentiated VSMCs, the levels of importins α1 and β1 were reduced concomitant with down-regulation of Mycd, serum response factor, and smooth muscle cell markers. By contrast, in differentiated VSMCs, their expressions were up-regulated. Thus, the nuclear import of Mycd family members in VSMCs depends on importin α/β1, and their relative affinities for importin α/β1 heterodimers determine Mycd nuclear import. The expression of Mycd nuclear import machineries is related to the expression levels of VSMC phenotype-dependent smooth muscle cell markers.
Sensitization to the conditioned rewarding effects of cocaine: pharmacological and temporal characteristics.

An unbiased place preference conditioning procedure was used to determine whether the repeated administration of cocaine results in sensitization to its conditioned rewarding effects. Rats received noncontingent injections of saline or cocaine (10 mg/kg i.p.) for 5 days. Place preference conditioning commenced 72 hr later. A minimum of three drug conditioning sessions was necessary for the establishment of cocaine-induced conditioned place preferences (CPP) in saline-pretreated rats. The minimum dose producing this effect was 10.0 mg/kg. In contrast, pre-exposure to cocaine resulted in significant place preferences occurring after only two drug conditioning sessions. Furthermore, CPP was observed in response to doses as low as 5.0 mg/kg. This shift in the cocaine dose-response curve was apparent when conditioning commenced either 3 or 7, but not 14, days after the cessation of cocaine pretreatment. An increased sensitivity to cocaine was also observed in rats which received only two cocaine (25.0 mg/kg) injections before conditioning and in those which had received either d-amphetamine (0.5 mg/kg) or morphine (5.0 mg/kg) for 5 days. Repeated administration of the D1 dopamine (DA) receptor antagonist, SCH-23390 (0.01-0.05 mg/kg), or the D2 antagonist, raclopride (0.1-1.0 mg/kg), for 5 days did not modify cocaine-induced place conditioning. Administration of SCH-23390 (0.05 mg/kg) in combination with cocaine, however, prevented the sensitized response to cocaine. In contrast, raclopride did not influence the sensitized response to cocaine. These data demonstrate that sensitization occurs to the conditioned rewarding effects of cocaine and suggest an involvement of D1 DA receptors in the development of this phenomenon.
Polarization Properties of Spun Single-Mode Fibers

Spun fibers are one of the most viable solutions to polarization mode dispersion. In this paper, their polarization properties are reviewed with special emphasis on randomly birefringent strongly spun fibers. The analysis is carried out by means of a new simplified model, which applies to a wide range of spin profiles that are either deterministic or random. It is shown that in general, a strongly spun fiber is characterized by an apparent random linear birefringence and an apparent deterministic circular birefringence. The latter term may originate unusual polarization properties; yet, in some cases of practical interest, it is equal to zero, and when this happens, the strongly spun fiber has the same statistical properties of an unspun one
Impact of Early Childhood Caries on the Oral Health-Related Quality of Life of Preschool Children and Their Parents

The aim of the present population study was to evaluate the impact of early childhood caries (ECC) on the oral health-related quality of life (OHRQoL) of preschool children and their parents/caregivers. A random sample of 638 children (aged 2–5 years) underwent a clinical oral examination to assess ECC, and their parents were invited to answer two questionnaires: one on the OHRQoL of the child, the Early Childhood Oral Health Impact Scale, and another on the characteristics and sociodemographic conditions of the child. Descriptive analysis, χ2 test, Mann-Whitney test, Kruskal-Wallis test, and hierarchically adjusted Poisson regression models were used. The prevalence of ECC was 52.2%. The number of teeth with decay ranged from 1 (n = 42; 6.6%) to 20 (n = 5; 0.8%), averaging 2.86 (SD = 4.04). There was a significant difference between the severity of ECC and OHRQoL in terms of the impact on both child and family (p < 0.001). An increase in the severity of ECC resulted in an increased negative impact on the quality of life of the child (rate ratio, RR = 5.32; 95% confidence interval, CI: 3.67–7.71). Greater age of the mother had a positive impact on the OHRQoL of preschool children (RR = 0.72; 95% CI: 0.54–0.97). Increased age resulted in an increased negative impact on the quality of life of the child (RR = 2.97; 95% CI: 1.61–5.47). ECC has a negative impact on the OHRQoL of children aged 2–5 years and their parents. Mothers aged 30 or older reported better OHRQoL, independent of the presence of ECC and the age of the child.
A nonameric core sequence is required upstream of the LYS genes of Saccharomyces cerevisiae for Lys14p‐mediated activation and apparent repression by lysine

The expression of the structural genes for lysine (LYS) biosynthesis is controlled by a pathway‐specific regulation mediated by the transcriptional activator Lys14 in the presence of α‐aminoadipate semialdehyde, an intermediate of the pathway acting as a co‐inducer. Owing to end product inhibition of the first step of the pathway, excess lysine reduces the production of the co‐inducer and causes apparent repression of the LYS genes. Analysis of LYS promoters and insertions within an heterologous reporter gene have allowed the characterization of an upstream activating element (UASLYS) able to confer Lys14‐ and α‐aminoadipate semialdehyde‐dependent activation as well as apparent repression by lysine to another yeast gene. This DNA motif is present as one or several copies in the promoters of at least six LYS genes. The consensus sequence derived from the comparison of the UASLYS showing the highest activation capacities comprises the nonameric core sequence TCCRNYGGA. The RNY sequence of the 3 bp spacer as well as the presence of flanking AT‐rich regions on both sides of the core sequence appear essential for optimal activation. Further evidence that this element is the target of Lys14p was provided by the demonstration that Lys14p binds to UASLYSin vitro. The binding is independent of the presence of the co‐inducer and is not affected by lysine. It depends on the integrity of the putative Zn(II)2Cys6 binuclear cluster contained in the Lys14p.
Left Atrial Remodelling in Competitive Adolescent Soccer Players

Abstract Left atrial (LA) enlargement and improved myocardial diastolic properties are a component of athlete’s heart. We performed a longitudinal study involving adolescent athletes to investigate the impact of training on LA remodelling and diastolic function. 21 competitive adolescent soccer players were enrolled and engaged in an 8-month training program. Echocardiographic analysis was performed at baseline, after 4 and 8 months. We assessed diastolic function by Doppler tissue imaging and we analyzed LA adaptations by 2D speckle-tracking echocardiography. After 4 months, LA mean volume index significantly increased (Δ=5.47±4.38 mL/m2, p≤0.0001). After 8 months, a further increase occurred (Δ=8.95±4.47 mL/m2, p≤0.0001). A higher E velocity (p=0.001; p=0.001), a greater E/A ratio (p=0.002; p=0.0009), a higher e’ peak (p= 0.005; p=0.001), and a greater e’/a’ ratio (p=0.01; p=0.0006) were observed at 4 and at 8 months, respectively. E/e’ ratio significantly decreased after 8 months (p≤0.005). Global peak atrial longitudinal strain and global peak atrial contraction strain values significantly decreased after 8 months (p=0.0004, p=0.01, respectively). An 8-month training program is associated with LA dimensional and functional training-specific adaptations in competitive adolescent soccer players. Myocardial diastolic properties can improve after training also in subjects already presenting with features of athlete’s heart.
Orofacial pain symptoms and associated disability and psychosocial impact in community-dwelling and institutionalized elderly in Hong Kong.

OBJECTIVE The study investigated the experience of orofacial pain (OFP) symptoms and associated disability and psychosocial impact in community dwelling and institutionalized elderly people in Hong Kong. METHODS A community-based cross-sectional survey involving elders aged 60 years and above. Participants were recruited at social centres for the elderly and homes for the aged throughout Hong Kong. Elders who reported OFP symptoms in the previous four weeks took part. Standard questions were asked about OFP conditions in the previous month and the Manchester Orofacial Pain Disability Scale (MOPDS), the Oral Health Impact Profile (OHIP-14) and the General Health Questionnaire (GHQ-12) were administered. The MOPDS was translated and validated for use in Chinese elders. RESULTS 200 community dwelling and 200 institutionalized elders participated. Toothache was the most common symptom (62.0%) and burning sensation in the tongue was least common (0.5%). The distribution of pain symptoms, pain duration and severity and pain ratings were similar in both groups. The MOPDS (Chinese elders version) had good reliability and construct validity. The MOPDS and OHIP-14 summary scores was significantly higher in the institutionalized elderly (p < 0.001 and p < 0.013, respectively). Psychological distress (GHQ-12 score > or = 4) was more common among the institutionalized elderly (11%) than the community dwelling elderly (4.0%, p = 0.002). CONCLUSIONS Orofacial pain symptoms were associated with significant disability and had a detrimental impact on psychological distress level and quality of life, particularly in the institutionalized elderly. There is a need to improve access to professional care and health-related outreach services generally for elderly people in Hong Kong.
Whole-body hyperthermia in the scope of von Ardenne's systemic cancer multistep therapy (sCMT) combined with chemotherapy in patients with metastatic colorectal cancer: a phase I/II study

This phase I/II study evaluated the feasibility, toxicity and response rates of von Ardenne's systemic cancer multistep therapy (sCMT) when applied as an adjunct to cytostatic therapy in patients with metastatic colorectal cancer. sCMT consists of whole-body hyperthermia (WBH) at 41.8–42.1°C, hyperglycaemia and hyperoxaemia. All patients who entered the trial first received three monthly courses of chemotherapy (folinic acid, 50 mg, days 1–5; 5-fluorouracil, 425 mg/m2, days 1–5; mitomycin 8 mg/m2, day 1), followed by response evaluation according World Health Organization (WHO) criteria. Responders (partial/complete remission) were assigned to three further courses of chemotherapy, whereas non-responders (stable/progressive disease) were allocated to additional sCMT on day 1 of every subsequent chemotherapy course. The WBH procedure was administered under general anaesthesia employing the Iratherm-2000 radiant heat device. Of 28 patients enrolled, 19 received more than three treatment courses. Eight of these 19 patients had responded to chemotherapy (PR) and thus obtained three further courses of chemotherapy alone. In 10 of 19 patients who had not responded (SD, PD), three additional courses of chemotherapy were combined with sCMT (with 25 sCMT applications). One patient who did not respond to initial treatment declined sCMT and was continued with chemotherapy alone. It was found that sCMT was feasible, but associated with a specific spectrum of grade III/IV toxicity (skin 20%, pain 16%, peripheral nerves 8% of treatment courses). The fact that three patients who did not respond to initial chemotherapy achieved a PR after additional sCMT suggests that sCMT may enhance the effect of chemotherapy in patients with colorectal cancer.
Physical activity and all-cause mortality: what is the dose-response relation?

PURPOSE The purpose of this review is to assess the dose-response relation between physical activity and all-cause mortality. We examined these parameters of physical activity dose: volume, intensity, duration, and frequency. METHODS We used a computer-assisted literature search to identify papers on this topic. After excluding papers examining only two levels of physical activity or fitness, papers investigating specific causes of mortality, reviews, and those not written in English, 44 papers satisfying all criteria were included in this review. RESULTS There is clear evidence of an inverse linear dose-response relation between volume of physical activity and all-cause mortality rates in men and women, and in younger and older (> or = 60 yr) persons. Minimal adherence to current physical activity guidelines, which yield an energy expenditure of about 1000 kcal x wk(-1) (4200 kJ x wk(-1)), is associated with a significant 20--30% reduction in risk of all-cause mortality. Further reductions in risk are observed at higher volumes of energy expenditure. It is unclear whether a volume of <1000 kcal x wk(-1) also may be associated with lower risk; there are some data supporting this. Due to limited data, it is also unclear whether vigorous-intensity activity confers additional benefit beyond its contribution to volume of physical activity when compared with moderate-intensity activity. No data are available on duration and frequency of physical activity in relation to all-cause mortality rates after controlling for volume of physical activity. CONCLUSIONS All studies in this review are observational studies, so conclusions are based on Evidence Category C. There is an inverse linear dose-response relation between volume of physical activity and all-cause mortality. Further research is needed to clarify the contributions of its components--intensity, duration, and frequency--to decreased all-cause mortality rates.
The comprehension of metaphor by preschool children

ABSTRACT Comprehension of metaphor in preschoolers was studied through an elicited repetition task. Subjects were 52 children aged 3;0 to 5;2. Repetition performance on metaphors was compared to repetitions of semantically well-formed literal sentences as well as semantically anomalous sentences, all matched for length, vocabulary and sentence structure. Accuracy on literal and metaphoric stimuli was comparable, and both were significantly better than performance on anomalous sentences. There were no effects for age or sex. It was shown that the metaphors were not semantically anomalous to the children and that they were processed on a par with literal language. The argument is advanced from a review of the literature that imitation implicates understanding of the material imitated. If metaphor is thus shown to emerge early in the child's linguistic repertory, figurative language, it may be argued, occupies a more central position in linguistic theory than it has been accorded.
The Future of Inflammatory Bowel Disease Therapy: Where Do We Go from Here?

There are six important trends that will impact the future of inflammatory bowel disease therapy. (1) Increased use of the biomarkers C-reactive protein (CRP) and fecal calprotectin, and increased imaging with colonoscopy and MRI enterography. (2) Increased use of pharmacokinetics to customize drug dosing for individual patients. Multiple factors impact the pharmacokinetics of monoclonal antibodies including the presence of antidrug antibodies, concomitant immunosuppression and low serum albumin and high CRP concentrations. (3) Evolution of treatment end points from symptoms to deep remission (a combination of both clinical remission and mucosal healing) to the prevention of bowel damage (in Crohn’s disease) and surgery in the short-to-intermediate term and prevention of disability in the longer term. (4) Evolving data demonstrate that azathioprine monotherapy is minimally effective as a disease modification agent in Crohn’s disease. Use of azathioprine as a monotherapy will decline. (5) Combination therapy with azathioprine and infliximab is superior to monotherapy with either agent. Use of combination therapy will increase. (6) There is a rich pipeline of novel therapeutic agents. Treatment strategies that appear particularly appealing include selective anti-integrin therapy with vedolizumab (anti-α4β7), etrolizumab (anti-β7 antibody) and PF-00547,659 (anti-MAdCAM-1 antibody), anti-interleukin 12/23p40 therapy with ustekinumab and Janus kinase 1, 2 and 3 inhibition with toafacitinib.
300 GHz radar for high resolution SAR and ISAR applications

In this paper we present the first high resolution SAR measurements performed in the lower terahertz region with the MIRANDA-300 system. The millimeter wave FMCW radar is operated at 300 GHz and provides a bandwidth of more than 40 GHz leading to a range resolution of a few millimeters. With an output power of around 5 mW over the complete bandwidth the system is mainly designed for short range applications up to several hundreds of meters. The capability of the radar has also been investigated in ISAR measurements. The presented results demonstrate the high image quality and the richness of details.
Service restoration of distribution systems based on NSGA-II

Distribution systems are becoming more flexible as a consequence of intelligent active network devices and smart metering. In addition load control is becoming an increasingly important tool for flexible distribution system operation and control. This paper presents a novel optimization approach to the service restoration problem that incorporates controllable load. Besides the traditional objectives, this paper adds a new objective - minimized reduction of controllable load, which may bring a new opportunity to make full use of load control. To solve the proposed optimization problem, the non-dominated sorting genetic algorithm-II (NSGA-II) is applied. Compared with the conventional genetic algorithm (GA), this algorithm does not need to convert multi-objectives to a single objective by weighting factors, and therefore retains the independence of the multi-objective formulation and aids the operator in selecting the most appropriate plan to restore service in the distribution system. A numerical example is presented to demonstrate and verify the feasibility and accuracy of the proposed optimization problem formulation and solution method.