Miracle-dz/UniFAR-FTUs huggingface dataset:
Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas.

Clinical and molecular findings suggest that the four major histological subtypes of ovarian carcinoma (serous, clear cell, mucinous, and endometrioid) likely represent distinct disease entities. Prior studies have shown that ovarian endometrioid adenocarcinomas (OEAs) often carry mutations in the CTNNB1 gene, which encodes beta-catenin, a critical component of the Wnt signaling pathway. However, the nature of other defects in the Wnt signaling pathway in ovarian carcinomas remains largely unknown. Thus, in 45 primary OEAs and two OEA-derived cell lines, we sought to comprehensively address the prevalence of and mechanisms underlying beta-catenin and Wnt pathway deregulation. CTNNB1 missense mutations were detected in 14 primary tumors. All mutations affected the NH(2)-terminal regulatory domain of beta-catenin, presumably rendering the mutant proteins resistant to degradation. Immunohistochemical studies revealed nuclear accumulation of beta-catenin in all but two tumors with CTNNB1 mutations. Two primary tumors lacking CTNNBI mutations showed strong nuclear immunoreactivity for beta-catenin. In one of the two tumors, biallelic inactivation of the APC gene was found. In the remaining 29 primary OEAs, unequivocal nuclear beta-catenin immunoreactivity was not observed, though a nonsense mutation in AXIN1 was observed in one tumor and a truncating frameshift mutation in AXIN2 was seen in another case. Both OEA-derived cell lines studied (TOV-112D and MDAH-2774) had elevated constitutive T-cell factor/lymphoid enhancer factor transcriptional activity. TOV-112D cells were shown to harbor mutant beta-catenin, whereas a missense AXIN1 sequence alteration was identified in MDAH-2774 cells. Collectively, our findings demonstrate frequent defects of the Wnt signaling pathway in a particular subtype of ovarian carcinomas, i.e., OEAs. Although mutations in the CTNNB1 gene are the most common mechanism of beta-catenin deregulation in OEAs, beta-catenin deregulation may also result from mutations in the APC, AXIN1, and AXIN2 genes.
Efficacy and safety of biphasic insulin aspart 70/30 versus exenatide in subjects with type 2 diabetes failing to achieve glycemic control with metformin and a sulfonylurea

ABSTRACT Objective: To compare safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 30) with exenatide in subjects with type 2 diabetes mellitus (T2DM) not achieving glycemic targets with metformin and sulfonylurea in a randomized, open-label, 24-week trial. Research design and methods: Subjects (N = 372, T2DM > 6 months, age ≥ 18 and ≤ 80 years, HbA1c ≥ 8%, insulin naive not achieving glycaemic targets, receiving metformin and sulfonylurea) were randomized 1: 1: 1 to receive either BIAsp 30 QD (12 U before supper); BIAsp 30 BID (12 U divided equally between pre-breakfast and pre-supper); or exenatide (5 µg BID for 4 weeks and 10 µg BID thereafter). Efficacy (HbA1c, fasting plasma glucose [FPG]) and safety (adverse events and hypoglycemic episodes) were assessed. Results: Glycemic control achieved with both BIAsp 30 BID and BIAsp 30 QD was superior to that with exenatide (BIAsp 30 BID-exenatide: HbA1c difference −0.91% [95% CI: −1.23 to −0.59%] and BIAsp 30 QD-exenatide: difference: −0.67% [95% CI: −0.99 to −0.34%]). At the end of the study, more subjects achieved HbA1c < 7% and ≤ 6.5% in the BIAsp 30 BID group than in the exenatide group (HbA1c < 7%: 37% vs. 20%, p = 0.0060; HbA1c ≤ 6.5%: 25% vs. 8%, p = 0.0004, respectively). Combined hypoglycemic episodes (major, minor, symptoms only) were reported by 56%, 61%, and 29% of the subjects in the BIAsp 30 QD, BIAsp 30 BID, and exenatide groups, respectively. Weight gain was observed in the BIAsp 30 group (BIAsp 30 QD: 2.85 kg, BIAsp 30 BID: 4.08 kg) and weight loss was observed in the exenatide group (−1.96 kg). Nausea or vomiting was responsible for discontinuation of seven subjects in the exenatide group and one subject in the BIAsp 30 BID group. Conclusions: Significantly more T2DM patients (poorly controlled with combination metformin/sulfonylurea) achieved glycemic goals when treated with BIAsp 30 than with exenatide. The high baseline HbA1c values (∼10.2%) and the long duration of diabetes (∼9 years) suggests that some subjects may have been in an advanced stage of their diabetes and may not have had sufficient β-cell function for a GLP-1 mimetic to be effective. The insulin-treated groups had more minor hypoglycemic events and weight gain but less gastrointestinal side-effects. In summary, BIAsp 30 was more efficacious in helping patients with high baseline HbA1c achieve glycemic goals. Clinical trial registration: www.clinicaltrials. gov, NCT00097877
Serum dehydroepiandrosterone sulfate levels and pubarche in short children born small for gestational age before and during growth hormone treatment.

It has been suggested that the programming of the endocrine axes occurs during critical phases of fetal development and will be affected by intrauterine growth retardation. As a result, children born small for gestational age (SGA) might have several hormonal disturbances. In later life, one of the questions that might arise is: Do short children born SGA have higher serum dehydroepiandrosterone sulfate (DHEAS) levels than their peers? Therefore, we compared serum DHEAS levels of 181 short prepubertal children aged 3-9 yr born SGA [birth length (SD score) below -2 for gestational age] with a control group of 170 prepubertal age-matched, normal-statured children born appropriate for gestational age (birth length between -2 and +2 SD score). Because relatively high serum DHEAS levels at a young age might result in a premature pubarche, we investigated the incidence of premature pubarche. We also investigated the association between serum DHEAS levels and bone maturation. In addition, we analyzed whether 1 yr of GH treatment with 1 and 2 mg/m(2). d ( approximately 0.035 and 0.070 mg/kg.d, respectively) had an effect on serum DHEAS levels of prepubertal short SGA children. Serum DHEAS levels of the SGA group were comparable with those of age-matched appropriate for gestational age controls. The incidence of premature pubarche was comparable with that of the normal population. There was a weak negative correlation between serum DHEAS levels and bone maturation after the age of 7 yr. After 1 yr of GH treatment, the increase of serum DHEAS levels was the same for both GH dosage groups and the untreated group. In conclusion, this study shows that small size at birth, which might be a feature of fetal growth restriction, has no effect on serum DHEAS levels before the age of 9 yr. The incidence of premature pubarche is comparable with the normal population. Finally, 1 yr of GH treatment has no effect on serum DHEAS levels.
Effects of substance P on excitability and ionic currents of normal and axotomized rat dorsal root ganglion neurons

Substance P (SP) may act within dorsal root ganglia (DRG) to modulate the transmission of nociceptive information. Because peripheral nerve injury (axotomy) alters the peptide content of sensory neurons, we used whole‐cell recording to examine the effects of sciatic nerve section on the sensitivity of rat lumbar DRG neurons to SP (0.3–1 µm). At 1 µm, SP increased the excitability of ‘small’, putative nociceptive neurons but had little effect on the excitability of ‘large’ neurons. Two‐four weeks after sciatic nerve section, however, the effect of SP on ‘large’ axotomized neurons was increased and its effect on ‘small’ neurons was decreased. SP did not affect Ca2+ channel currents in control or axotomized neurons. The effects of SP on the current‐voltage (I–V) relationship of 77% of neurons involved increased inward current at potentials below −30 mV and suppressed outward current at potentials above −20 mV. The effects of SP on the I–V relationship were similar in control and in axotomized neurons and the altered sensitivity of ‘small’ and ‘large’ cells could not be attributed to axotomy‐induced changes in input resistance or membrane potential. The possible relevance of alterations in sensitivity, of ‘large’ DRG neurons to SP, to the generation of neuropathic pain is discussed.
Managing Critical Pathway Variances

As the use of critical pathways expands at an increasing rate, we are faced with the issue of how to manage variances from the pathway. Variance management is not clearly defined in the literature, and many institutions search for the best approach. We have implemented a number of different techniques for variance management at Fletcher Allen Health Care. Our success benefits both patients and providers.
Stray Losses in Induction Machines: Part I, Definition, Origin and Measurement

The state of the art of stray load losses in induction machines is discussed with respect to definition, origin and effects, and measurement techniques. The historical search for a definitive evaluation technique for these losses is discussed together with the recognized criticisms of each approach. It is noted that although this subject has been the object of intensive investigations for more than seventy years there is still very little agreement on either the origin or evaluation of stray load loss. This paper discusses the major works in the area with the objective of delimiting the problem so that a rational approach for future work may be promulgated.
Immertion : Immersion and Emotion in Digital Games

Immersion and the study of the emotion are key elements to the creation of a digital game. The elements that change their influence on the player are also important to give the user a better experience on the game. The goal of this project is connecting this two concepts, based on theoretical studies on the influence of both items, inside and outside the primordial concepts of creating a virtual environment systems. To accomplish this, it was created an application that is divided into three parts: the first one, an expert system, collects data on the degree of immersion in digital games of the Action Adventure style. The second part, a system based on fuzzy logic, analyzes the data collected in the first part to relate the emotion with immersion of that games. Finally, the third part groups the games studied according to degree of emotion they have. Ninety-six players of digital games in this survey answered the expert system, resulting in one hundred thirty-three completed questionnaires, with six hundred seventy-two variables defined and immersive three thousand four hundred and six statements defined. With this, it was concluded that the games of the studied style are more likely to give the player emotions such as Love, Hate, Pride and Shame.
Epidemiology of hepatocellular carcinoma in USA

Hepatocellular carcinoma (HCC) is increasing in frequency the USA. Age‐adjusted incidence, hospitalization, and mortality rates have doubled over the past two decades. There are striking differences in the incidence of HCC related to age, gender, race, and geographic region. Although it remains an affliction of the elderly (mean age 65), there has been a considerable shift toward younger cases. There is a birth cohort effect with those born after 1945. Men are affected three times more frequently than women, Asians two times more than African American and Hispanic people, who are affected two times more often than Caucasians. However, the recent increase has disproportionately affected Caucasian (and Hispanic) men between ages 45 and 65. Hepatitis C virus (HCV) infection acquired 2–4 decades ago explains at least half of the observed increase in HCC; HCV‐related HCC is likely tocontinue to increase for the next decade. A variable but significant proportion of cases (15–50%) do not have evidence for the risk factors of either viral hepatitis or heavy alcohol consumption. Insulin resistance syndrome manifesting as obesity and diabetes is emerging as a risk factor for HCC in the USA and may operate through the formation of non‐alcoholic fatty liver disease (NAFLD); however, its effect on the current trend in HCC remains unclear. While there has been a small recent improvement in survival, it remains generally dismal (median 8 months). Population‐based data in the USA indicate low application rate of HCC potentially curative therapy and marked regional differences.
[Volar plate fixation of distal radius fractures].

BACKGROUND We aimed to evaluate the results of volar locking and unlocking plate fixation of adult distal radius fractures. METHODS Thirty-four patients (14 female, 20 male, mean age: 48.5 +/- 17.9 years) who were treated for distal radius fractures were investigated retrospectively. The fractures were distributed as follows: 17.6% AO type B3, 11.8% AO type C2 and 70.6% AO type C3. The patients were evaluated clinically (Gartland and Werley score, visual analog scale (VAS), Disabilities of the Arm, Shoulder and Hand (DASH) score) and radiographically (Stewart score). RESULTS The mean follow-up of patients was 24 +/- 16.3 months. According to the Gartland-Werley score, the results were excellent in 24.9%, good in 55.9%, moderate in 11.8% and poor in 2.9% of the patients. The mean VAS score was 0.5 +/- 1.1, and the mean DASH score was 26.1. According to the Stewart criteria, 44.1% of the patients were rated as excellent, 52.9% as good and 2.9% as moderate. Two patients had complex regional pain syndrome, one patient carpal tunnel syndrome and one patient tenosynovitis. CONCLUSION Volar plate fixation is a good and effective treatment for distal radius fractures. The plate should be inserted properly and physiotherapy should not be ignored.
The Ras homolog Rhes affects dopamine D1 and D2 receptor-mediated behavior in mice

Dopamine activates five different receptor subtypes and a complex array of intracellular signaling pathways. Rhes is a striatally expressed guanidine triphosphate-binding protein involved in dopamine signaling. Here we have used mutant mice to test whether Rhes (Ras homolog enriched in striatum) is involved in D1 and D2 dopamine receptor-mediated behaviors. Rhes was not necessary for the expression of normal D1/D2 receptor synergism, as measured by apomorphine-induced stereotypy. The stereotypic responses to D1/D2 costimulation and to D2 stimulation alone were significantly increased in mice lacking Rhes, but D1 receptor-mediated grooming was reduced in these mice. These results suggest that Rhes is normally inhibitory to behaviors induced by D1/D2 receptor costimulation and by D2 receptor stimulation alone. Rhes, however, seems to facilitate the D1-specific behavior of grooming.
Economic impact of dementia in developing countries: an evaluation of costs of Alzheimer-type dementia in Argentina

Background: There is no previous information about economic costs of Alzheimer's disease (AD) in South America. The objective of this study was to evaluate the costs of AD in Argentina. Methods: Eighty community-dwelling patients, 20 institutionalized AD patients and their respective primary caregivers, and 25 healthy elderly subjects participated in this study. The cognitive and neuropsychiatric impairments and severity of dementia were assessed with the Mini-mental State Examination, Neuropsychiatric Inventory and Clinical Dementia Rating, respectively. A structured interview about health and health-care resources used during the past 3 months was administered to family caregivers. The time devoted by carers to looking after the patients and the caregiver burden (Zarit's Burden Interview) were recorded. Results: The annual direct costs of the disease increased with cognitive deterioration from US$3420.40 in mild to US$9657.60 in severe AD, and with institutionalization (US$3189.20 outpatient vs. US$14 447.68 institutionalized). Most direct costs were paid for by the family. Conclusions: With the projected increase in the number of persons at risk for developing AD in emerging countries, the family cost of the disease will be significant. Dementia costs should be a matter of analysis when health policies are being designed in developing countries.
Strategic Behavior in Multi-unit Assignment Problems: Theory and Evidence from Course Allocations

This paper analyses the assignment problem when agents have multi-unit demand. Applications include task assignment in a team, course allocation, sport drafts and any other allocation problem where money does not play a role in balancing supply and demand. There is no known allocation mechanism that is ex-post efficient, strategyproof and minimally fair, and practical solutions must therefore trade off these different aspects. We study such a specific mechanism used at Harvard Business School to allocate courses to students. We argue that students in the HBS mechanism have an incentive to overreport their preferences for popular courses, that this incentive does not vanish with the size of the market and that it results in increased congestion. We confirm these predictions with detailed data on reported preferences and behavior in the HBS mechanism. We show that strategic behavior hurts students but that it might still be preferable to random serial dictatorship over course bundles, a strategyproof alternative.
Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection

Host immune response influences the clinical outcome of Helicobacter pylori infection leading to ulcer disease, gastric carcinoma and mucosa‐associated lymphoid tissue (MALT) lymphoma. A genetic risk profile for gastric cancer has been identified, but genetic susceptibility to develop MALT lymphoma is still unclear. We investigated the role of NOD1 and NOD2 as intracellular recognition molecules for pathogen‐associated molecules in H. pylori infection in vitro and analysed the influence of single nucleotide polymorphisms on susceptibility to ulcer disease and MALT lymphoma. Expression of NOD1 and NOD2 significantly sensitized HEK293 cells to H. pylori‐induced NF‐κB activation in a cag pathogenicity island (cagPAI)‐dependent manner. In cells carrying the Crohn‐associated NOD2 variant R702W the NF‐κB response was significantly diminished. NOD1/NOD2 expression levels were induced in the gastric epithelium in H. pylori‐positive patients. No mutations were found to be associated with gastritis or gastric ulcer development. However, the R702W mutation in the NOD2/CARD15 gene was significantly associated with gastric lymphoma. Carrier of the rare allele T had a more than doubled risk to develop lymphoma than controls [odds ratio (OR): 2.4, 95% confidence interval (CI): 1.2–4.6; P < 0.044]. H. pylori‐induced upregulation of NOD1 and NOD2 in vivo may play a critical role in the recognition of this common pathogen. A missense mutation in the leucine‐rich region of CARD15 is associated with gastric lymphoma.
A planar triplexer based on substrate integrated waveguide technology for TD-SCDMA applications

In this paper, a planar triplexer based on the substrate integrated waveguide (SIW) technology for TD-SCDMA applications is proposed. The triplexer consists of three inductive window SIW bandpass filters, operated at bands of 1.88GHz–1.92GHz, 2.01GHz–2.025GHz and 2.3GHz–2.4GHz, respectively, and an optimized matching circuit. Moreover, by introducing a stepped-impedance microstrip lowpass filter, the spurious passbands can be effectively suppressed. The proposed triplexer is fabricated with standard printed circuit (PCB) process. The measured isolation is below −40dB in the designed bands, and moderate insert loss and good return loss are also obtained. All the performances presented in this paper demonstrate the proposed triplexer a promising candidate for TD-SCDMA applications.
18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography and positron emission tomography/computed tomography imaging of malignant pleural mesothelioma *

Malignant pleural mesothelioma (MPM) is the most common primary pleural tumor and its incidence is rising. Its diagnosis, staging and response assessment are challenging for imaging. Integrated positron emission tomography (PET)/CT increases the accuracy of overall staging in patients with mesothelioma and improves the selection of patients for curative surgical resection. It is particularly useful in identifying occult distant metastases. It may be used to predict prognosis and to assess the metabolic response to therapy.
Subramanian ’ s stable matching algorithm

Gale and Shapley introduced the well-known stable matching problem in 1962, giving an algorithm for the problem. Subramanian later showed that the problem can be solved by comparator circuits. Lê, Cook and Ye simplified his construction. We present an algorithm interpolating (in some sense) between the two. Our algorithm is a symmetrized “lazy” version of Gale-Shapley, while Subramanian’s algorithm in turn can be viewed as a lazy version of our algorithm. Subramanian’s algorithm employs three-valued logic, a device which arises more naturally in the setting of our algorithm. 1 Stable matching problem An instance of the stable matching problem consists of a set M of n men and a set W of n women. In addition, each person p ∈ M ∪ W has an order of preference over persons of the opposite sex: p : π1(p) π2(p) · · · πn(p). Person p prefers π1(p) the most, and πn(p) the least. If i > j then p prefers πi(p) over πj(p), in symbols πi(p) p πj(p). The person most preferred by p among a list P is denoted maxp P . The one least preferred is minp P . Beware that in terms of indices πi(p), maxp P is the person with lowest index! A matching S is a list of pairs (m,w) ∈ M × W such that each man is matched with exactly one woman. We will denote the match of a person p by S(p). A pair (m,w) / ∈ S is unstable if w m S(m) and m w S(w). In words, an unmatched pair (m,w) is unstable if both parties prefer the other person over their current partner. A matching is stable if there is no unstable pair. Gale and Shapley [1] have shown that a stable matching always exists, by giving an algorithm computing it. Their algorithm constructs a stable matching S with the additional property that for each man m, S(m) m T (m) for any stable matching T . In words, in S every man is matched with the best woman he could ever get in a stable matching. This matching is called the man-optimal stable matching. The same algorithm also shows the existence of the womanoptimal stable matching.
Linking intra‐ and interspecific assortative mating: Consequences for asymmetric sexual isolation

Assortative mating is of interest because of its role in speciation and the maintenance of species boundaries. However, we know little about how within‐species assortment is related to interspecific sexual isolation. Most previous studies of assortative mating have focused on a single trait in males and females, rather than utilizing multivariate trait information. Here, we investigate how intraspecific assortative mating relates to sexual isolation in two sympatric and congeneric damselfly species (genus Calopteryx). We connect intraspecific assortment to interspecific sexual isolation by combining field observations, mate preference experiments, and enforced copulation experiments. Using canonical correlation analysis, we demonstrate multivariate intraspecific assortment for body size and body shape. Males of the smaller species mate more frequently with heterospecific females than males of the larger species, which showed less attraction to small heterospecific females. Field experiments suggest that sexual isolation asymmetry is caused by male preferences for large heterospecific females, rather than by mechanical isolation due to interspecific size differences or female preferences for large males. Male preferences for large females and male–male competition for high quality females can therefore counteract sexual isolation. This sexual isolation asymmetry indicates that sexual selection currently opposes a species boundary.