Miracle-dz/UniFAR-FTUs huggingface dataset:
Nuclear inclusion bodies of mutant and wild‐type p53 in cancer: a hallmark of p53 inactivation and proteostasis remodelling by p53 aggregation

Although p53 protein aggregates have been observed in cancer cell lines and tumour tissue, their impact in cancer remains largely unknown. Here, we extensively screened for p53 aggregation phenotypes in tumour biopsies, and identified nuclear inclusion bodies (nIBs) of transcriptionally inactive mutant or wild‐type p53 as the most frequent aggregation‐like phenotype across six different cancer types. p53‐positive nIBs co‐stained with nuclear aggregation markers, and shared molecular hallmarks of nIBs commonly found in neurodegenerative disorders. In cell culture, tumour‐associated stress was a strong inducer of p53 aggregation and nIB formation. This was most prominent for mutant p53, but could also be observed in wild‐type p53 cell lines, for which nIB formation correlated with the loss of p53's transcriptional activity. Importantly, protein aggregation also fuelled the dysregulation of the proteostasis network in the tumour cell by inducing a hyperactivated, oncogenic heat‐shock response, to which tumours are commonly addicted, and by overloading the proteasomal degradation system, an observation that was most pronounced for structurally destabilized mutant p53. Patients showing tumours with p53‐positive nIBs suffered from a poor clinical outcome, similar to those with loss of p53 expression, and tumour biopsies showed a differential proteostatic expression profile associated with p53‐positive nIBs. p53‐positive nIBs therefore highlight a malignant state of the tumour that results from the interplay between (1) the functional inactivation of p53 through mutation and/or aggregation, and (2) microenvironmental stress, a combination that catalyses proteostatic dysregulation. This study highlights several unexpected clinical, biological and therapeutically unexplored parallels between cancer and neurodegeneration. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Microbial Transformation of Nitroaromatics in Surface Soils and Aquifer Materials

Microorganisms indigenous to surface soils and aquifer materials collected at a munitions-contaminated site transformed 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), and 2,6-dinitrotoluene (2,6-DNT) to amino-nitro intermediates within 20 to 70 days. Carbon mineralization studies with both unlabeled (TNT, 2,4-DNT, and 2,6-DNT) and radiolabeled ([14C]TNT) substrates indicated that a significant fraction of these source compounds was degraded to CO2.
[Early education for children with Prader-Willi syndrome].

MATERIAL AND METHOD A cohort of 21 children (under 42 months of age) with Prader-Willi syndrome were followed in a longitudinal way by the referral center team with evaluation of language and cognitive function (every six months). RESULTS Disorders seen between birth and the second year are primarily related to hypotonia with oropharyngeal dysphagia and impact on the pre-lingual phase of communication. After 2 years the psychomotor delay and the disorders of language acquisition effect development. When compared to patients who had treatment after 4 years and with data published in the literature, those patients with an early diagnosis and early treatment using kinesitherapy and logopedy showed faster linguistic acquisition. However articulation disorders still remain. CONCLUSION AND RECOMMENDATIONS This work highlights the importance of early readaptation associating kinesitherapy, logopedy and psychomotoricity which can improve the cognitive phenotype of these children.
Systematic Reviews andMeta-and Pooled Analyses Transmission of Mycobacterium tuberculosis in Households and the Community : A Systematic Review andMeta-Analysis

The individualand population-level impact of household tuberculosis exposure on transmission is unclear but may have implications for the effectiveness and implementation of control interventions. We systematically searched for and included studies in which latent tuberculosis infection was assessed in 2 groups: children exposed and unexposed to a household member with tuberculosis. We also extracted data on the smear and culture status of index cases, the age and bacillus Calmette-Guérin vaccination status of contacts, and study design characteristics. Of 6,176 citations identified from our search strategy, 26 studies (13,999 children with household exposure to tuberculosis and 174,097 children without) from 1929–2015 met inclusion criteria. Exposed children were 3.79 (95% confidence interval (CI): 3.01, 4.78) times more likely to be infected than were their community counterparts. Metaregression demonstrated higher infection among children aged 0–4 years of age compared with children aged 10–14 years (ratio of odds ratios = 2.24, 95% CI: 1.43, 3.51) and among smear-positive versus smear-negative index cases (ratio of odds ratios = 5.45, 95% CI: 3.43, 8.64). At the population level, we estimated that a small proportion (<20%) of transmission was attributable to household exposure. Our results suggest that targeting tuberculosis prevention efforts to household contacts is highly effective. However, a large proportion of transmission at the population level may occur outside the household.
Factions in Nondemocracies: Theory and Evidence from the Chinese Communist Party

This paper theoretically and empirically investigates factional arrangements within the Chinese Communist Party (CCP), the governing political party of the People's Republic of China. Using detailed biographical information of political elites in the Central Committee and provincial governments, we present a set of new empirical regularities within the CCP, including systematic patterns of cross‐factional balancing at different levels of the political hierarchy and substantial faction premia in promotions. We propose and estimate an organizational economic model to characterize factional politics within single‐party nondemocratic regimes and its economic implications.
Credit Frictions and &Apos;Sudden Stops&Apos; in Small Open Economies: An Equilibrium Business Cycle Framework for Emerging Markets Crises

Financial frictions are a central element of most of the models that the literature on emerging markets crises has proposed for explaining the Sudden Stop phenomenon. To date, few studies have aimed to examine the quantitative implications of these models and to integrate them with an equilibrium business cycle framework for emerging economies. This paper surveys these studies, viewing them as ability-to-pay and willingness-to-pay variations of a framework that adds occasionally binding borrowing constraints to the small open economy real-business-cycle model. A common feature of the different models is that agents factor in the risk of future Sudden Stops in their optimal plans, so that equilibrium allocations and prices are distorted even when credit constraints do not bind. Sudden Stops are a property of the unique, flexible-price competitive equilibrium of these models that occurs in a particular region of the state space in which negative shocks make borrowing constraints binding. The resulting nonlinear effects imply that solving the models requires non-linear numerical methods, which are described in the survey. The results show that the models can yield relatively infrequent Sudden Stops with large current account reversals and deep recessions nested within smoother business cycles. Still, research in this area is at an early stage, and this survey aims to stimulate further work.
Reconstructing angina: cardiac symptoms are the same in women and men.

clude potassium content on the NFP. One might expect items with high levels of potassium to more often be labeled; however, categories where potassium information was most available had a wide range of potassium content, while some categories with expected high levels of potassium, such as canned whole tomatoes and canned beans, had low potassium information availability. The lack of potassium information on the NFP presents a problem for patients and consumers trying to make informed decisions when purchasing foods, particularly those motivated to minimize their risk of cardiovascular disease and those for whom potassium intake must be restricted. Lack of potassium information is also a problem for researchers and policy makers interested in understanding the overall and potassium-specific nutritional content of the packaged food supply. The New York City Department of Health and Mental Hygiene, along with 35 health authorities and health organizations, has called for a publicly accessible, productspecific nutrition database of packaged food products. The creation of such a database would allow for analyzing nutritional trends, which would inform recommendations to improve nutritional intake. While such a database is valuable with existing NFP information, its public health value would be enhanced if potassium information was consistently available. A limitation of this study is that the NSRI database was originally created to assess changes in sodium concentration; therefore, it includes a wide range of products, but only in food categories with significant potential for sodium reduction (eg, some desserts and beverages are not included). Also, only the top 80% of products sold within each category are represented in the analyses. The FDA is planning to revise the NFP, and potential improvements to its content and format are under consideration. The addition of potassium content and percent daily value to required NFP information could remedy the described deficit in publicly available nutrition information. Providing this important information to consumers, patients, and researchers would allow a more detailed understanding of the food supply, which would complement existing strategies to improve population nutritional intake.
Antineutrophil cytoplasmic autoantibodies in systemic lupus erythematosus

Although antineutrophil cytoplasmic antibodies (ANCA) were first associated with the primary vasculitides, it is now clear that 15-20% of patients with lupus have detectable ANCA. In this short review we confirm that the major link is with perinuclear ANCA (pANCA) but not cytoplasmic ANCA (cANCA). ANCA to myeloperoxidaseare associatedwith drug-inducedlupus.There may be a link between pANCA levels and disease activity in some patients although the links to specific organ involvement are not proven. ANCA in lupus must be interpreted cautiously with particular attention paid to laboratorytechnique, the size, age and genetic backgroundof the populationsstudied.
A new technique for measuring the cell growth and metabolism of endothelial cells seeded on vascular prostheses.

For the improvement of vascular graft patency, an endothelial cell (EC) lining is desirable. It is essential that the EC remains viable after being seeded onto the prosthetic graft. The aim of this study was to adapt an Alamar redox assay (ABRA) as a technique to monitor the viability of ECs seeded on prosthetic grafts. To test the graft types, we seeded human umbilical vein ECs on compliant polyurethane (CPU), expanded polytetrafluoroethylene, and Dacron at a density of 2 x 10(5) cell/cm(2). After 24 h of incubation, ABRA was added, and the absorbance was measured at 4, 8, and 24 h. To assess seeded cell concentrations on grafts, we seeded CPU at densities ranging from 1 x 10(5) to 8 x 10(5) cell/cm(2). The validity of the test was assessed with sodium azide and mitomycin C, known physiological perturbators. ABRA reduction demonstrated that ECs were viable and functional postseeding on the prosthetic grafts. A significant correlation was observed with ABRA reduction and cell concentrations (p < 0.001). The acid phosphatase assay demonstrated enzyme activity in the cells, but they were not maintained under normal physiological conditions. The ABRA bioreduced product was soluble, stable, and noncytotoxic over 24 h. The assay is independent of the geometry or physiochemistry of the graft type. The technique allows the continuous assessment of the metabolism and viability of seeded cells, is simple to perform, and does not destroy the cells or graft materials.
Moving them on and in: The Process of Searching for and Selecting an Aged Care Facility

This exploratory, descriptive study examined the search and selection process for an aged care facility following discharge of a family member from an acute setting. Few studies have examined this process and its effects on families. Individuals from 25 families where a family member had been recently admitted to an aged care facility following discharge from an acute setting were interviewed. This article reports participants’ perceptions of the search and selection process and its effect on the family. Five major themes emerged from the data: good fortune, wear and tear on the sponsor, dealing with the system, urgency, and adjusting. The results can be used to inform and assist families and health professionals working with families in this situation.
Patients with syncope in a German emergency department: description of patients and processes.

BACKGROUND We studied the characteristics and resource utilization of patients with syncope in a German emergency department (ED). METHODS We carried out a single-center retrospective analysis of patients with syncope who presented to the ED of the Klinikum Nürnberg (a municipal hospital in Nuremberg, Germany). RESULTS Among the 28 477 patients who presented to the ED from 15 May 2009 to 30 September 2009, 440 (1.5%) presented with syncope. Their mean age was 62 years (standard deviation, 20 years); 50.4% were women, 43.4% were over age 70, 11.8% had cardiogenic and 4.8% neurological syncope, and 18.2% had more than two comorbid conditions. 20.7% were discharged after evaluation in the ED, 14.1% were brielfly hospitalized in the ED's clinical observation unit, and 56.6% were admitted to one of the hospital's specialty wards. 8.6% left the ED against medical advice. All of the syncope patients were evaluated by history-taking, physical examination, and 12-lead electrocardiogragraphy (ECG); ECG revealed abnormal findings in 36.4% of patients. Nearly all patients also underwent laboratory testing, which revealed hyponatremia (a serum sodium concentration under 130 mmol/L) in 5.9% and a serum creatinine level above 2 mg/dL in 5.3%. Many underwent technology-intensive tests such as cranial computed tomography (129 patients), but these tests only rarely yielded abnormal findings (3.1%). 27% of the syncope patients underwent Doppler ultrasonography of the vessels supplying the brain, with abnormal findings in 6.7% of cases. (Orthostatic testing was performed in 14.5% of the patients and was positive in 26.6%.) CONCLUSION Many patients presenting with syncope to a German ED are elderly, and multiple comorbidities are common. Technology-intensive testing in patients with syncope has a low diagnostic yield and consumes resources. The introduction of standards for the evaluation of syncope in the ED would be helpful.
Expression of survivin, PTEN and p27 in normal, hyperplastic, and carcinomatous endometrium

We aimed to investigate if expressions of survivin and p27 proteins are involved in the development of endometrioid carcinoma, along with whether there are any correlations between these proteins and loss of wild-type PTEN that is found in up to 80% of endometrial carcinomas. We also studied their correlations with classical prognostic factors and survival in endometrial carcinoma. To our knowledge, this is the first time survivin expression is investigated in endometrial hyperplasia along with endometrioid adenocarcinoma. For immunohistochemical analysis, 29 endometrioid adenocarcinoma, 38 endometrial hyperplasia, and 10 proliferative endometrium tissue samples were selected in the pathology archives. Staining of cells was scored as +2 if >50%, +1 if <50%, and negative if none were stained positive. Survivin expression increased from proliferative to hyperplasia to carcinoma cases. PTEN and p27 expressions decreased in hyperplasia and carcinoma cases with respect to proliferative endometrium. All these differences were statistically significant (P < 0.05). PTEN positively correlated to p27 (P < 0.05); however, neither was correlated with survivin. None of these genes were correlated with classical prognostic factors such as grade and myometrial invasion in endometrioid adenocarcinoma. However, mean survival was statistically significantly higher in PTEN-positive cases (46.6 vs 16.4 months) (P < 0.05). Survivin overexpression might be one of the important mechanisms in the development of endometrioid adenocarcinoma along with lost or decreased activity of PTEN and p27. However, survivin seems to exert its role in ways different from those of PTEN or p27 in the development of endometrioid adenocarcinoma. These findings on the role of survivin in endometrioid adenocarcinoma should be confirmed and the pathways through which survivin acts in endometrioid adenocarcinoma studied further with a larger sample size.
Face Recognition in Emotional Scenes: Observers Remember the Eye Shape but Forget the Nose

Face recognition is believed to be a highly specialized process that allows individuals to recognize faces faster and more accurately than ordinary objects. However, when faces are viewed in highly emotional contexts, the process becomes slower and less accurate. This suggests a change in recognition strategy compared to recognition in non-arousing contexts. Here we explore this finding by using a novel paradigm to determine which face dimensions are most important for recognizing faces that were initially encoded in highly emotional contexts. Participants were asked to recognize faces from a 3-alternative display after viewing a similar face that was embedded in either a neutral, positive, or negative emotional scene. Results showed that individuals rely on eye shape when recognizing faces that were encoded while embedded in either positive or negative emotional contexts, and ignore nose shape when recognizing faces that were encoded while embedded in negative emotional scenes. The findings suggest that, after encoding that face during heightened emotional arousal, individuals are more likely to commit errors when identifying a face on the basis of nose shape, and less likely to commit errors when identifying a face on the basis of eye shape.
High MMP‐9 activity levels in fragile X syndrome are lowered by minocycline

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by lack of the FMR1 protein, FMRP, a translational repressor. Its absence leads to up‐regulation of locally translated proteins involved in synaptic transmission and plasticity, including the matrix metalloproteinase‐9 (MMP‐9). In the Fmr1 knock‐out (KO), a mouse model of FXS, an abnormal elevated expression of MMP‐9 in the brain was pharmacologically down‐regulated after treatment with the tetracycline derivative minocycline. Moreover, the rescue of immature dendritic spine morphology and a significant improvement of abnormal behavior were associated with down‐regulation of MMP‐9. Here, we report on high plasma activity of MMP‐9 in individuals with FXS. In addition, we investigate MMP‐9 changes in patients with FXS who have gone through a minocycline controlled clinical trial and correlate MMP‐9 activity to clinical observations. The results of this study suggest that, in humans, activity levels of MMP‐9 are lowered by minocycline and that, in some cases, changes in MMP‐9 activity are positively associated with improvement based on clinical measures. © 2013 Wiley Periodicals, Inc.
Fate and metabolism of [15N]2,4,6‐trinitrotoluene in soil

The fates of the labels from [14C] and [15N] trinitrotoluene were analyzed in bioreactors under aerobic conditions in soil treated by a fungal bioremediation process with Stropharia rugosoannulata and in control soil. Up to 17.5% of the 15N label had a different fate than the 14C label. Three N‐mineralization processes were identified in detailed experiments with [15N]TNT. About 2% of the 15N label was found as NO3− and NH4−, showing simultaneous processes of direct TNT denitration (I) and reduction with cleavage of the amino groups (II). The enrichment of NO2−/NO3− (up to 7.5 atom% 15N abundance) indicates the formation of Meisenheimer complexes with a denitration of [15N]TNT. A 1.4% of the label was found distributed between N2O and N2. However, the 15N enrichment of the N2O (up to 38 atom%) demonstrated that both N atoms were generated from the labeled TNT and clearly indicates a novel formation process (III). We propose, as an explanation, the generation of N2O by cleavage from condensed azoxy metabolites. In addition, 1.7% of the 15N label was detected as biogenic amino acids in the wheat straw containing the fungus. Overall, 60 to 85% of the applied [15N]TNT was degraded and 52 to 64% was found as nonextractable residues in the soil matrix. Three percent was detected as 2‐amino‐4,6‐dinitrotoluene and 4‐amino‐2,6‐dinitrotoluene.
Kinetics of In Vitro Lysozyme Deposition on Silicone Hydrogel, PMMA, and FDA Groups I, II, and IV Contact Lens Materials

We sought to compare the kinetics of in vitro lysozyme deposition on silicone hydrogel (SH), polymethyl methacrylate (PMMA), and FDA groups I, II, and IV contact lenses. Lenses were incubated in 125I-labeled lysozyme for time periods ranging from 1 hr to 28 days, and radioactive counts were determined. SH lenses and PMMA deposited less lysozyme than conventional hydrogel lenses (p < 0.05). Lysozyme accumulation on group IV lenses reached a maximum on the seventh day and then plateaued, whereas on groups I, II, and SH lenses, deposition continued to increase across all time periods, reiterating that kinetics of lysozyme deposition is highly material dependent.
Evaluation of oligosaccharide addition to dog diets : in ̄ uences on nutrient digestion and microbial populations $

Seven adult mixed breed female dogs (17:4 2:9 kg) surgically ®tted with ileal T-cannulas were used in a 4 7 incomplete Latin square design experiment to evaluate oligosaccharide supplementation on dry matter (DM), nitrogen (N), ammonia, volatile fatty acid (VFA), bacteria, blood glucose concentrations, ileal pH, and fecal consistency. Fructooligosaccharide (FOS), mannanoligosaccharide (MOS), and xylooligosaccharide (XOS) were added at 5 g/kg of diet DM. There were no differences in DM digestibility, diet or fecal N, N digestibility, ileal or fecal ammonia, fecal consistency, ileal bacteria colony forming units, blood glucose, or ileal pH. Ileal butyrate proportion tended to be greater (P  0:07) in the control diet (0.076 of total VFA) compared with the oligosaccharide supplemented diets and lower (P  0:07) for the MOS diet compared with the FOS and XOS diets. Ileal propionate tended to be higher (P  0:09) in MOS (0.198 of total VFA) than FOS and XOS. Fecal bi®dobacteria numbers were unaffected by dietary treatment. Fecal Clostridium perfringens tended to be lower (P  0:09) in MOS when compared to FOS and XOS. Oligosaccharides had relatively minor effects on bacterial growth in the large intestine and VFA proportions in the small intestine of the canine. For oligosaccharide feeding to cause microbial changes in the canine greater amounts of oligosaccharide may be required, or it may require application in select dietary situations. # 2000 Elsevier Science B.V. All rights reserved.