Miracle-dz/UniFAR-FTUs huggingface dataset:
Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse

Infection with cagA-positive Helicobacter pylori is associated with gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma of B cell origin. The cagA-encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system and, upon tyrosine phosphorylation by Src family kinases, specifically binds to and aberrantly activates SHP-2 tyrosine phosphatase, a bona fide oncoprotein in human malignancies. CagA also elicits junctional and polarity defects in epithelial cells by interacting with and inhibiting partitioning-defective 1 (PAR1)/microtubule affinity-regulating kinase (MARK) independently of CagA tyrosine phosphorylation. Despite these CagA activities that contribute to neoplastic transformation, a causal link between CagA and in vivo oncogenesis remains unknown. Here, we generated transgenic mice expressing wild-type or phosphorylation-resistant CagA throughout the body or predominantly in the stomach. Wild-type CagA transgenic mice showed gastric epithelial hyperplasia and some of the mice developed gastric polyps and adenocarcinomas of the stomach and small intestine. Systemic expression of wild-type CagA further induced leukocytosis with IL-3/GM-CSF hypersensitivity and some mice developed myeloid leukemias and B cell lymphomas, the hematological malignancies also caused by gain-of-function SHP-2 mutations. Such pathological abnormalities were not observed in transgenic mice expressing phosphorylation-resistant CagA. These results provide first direct evidence for the role of CagA as a bacterium-derived oncoprotein (bacterial oncoprotein) that acts in mammals and further indicate the importance of CagA tyrosine phosphorylation, which enables CagA to deregulate SHP-2, in the development of H. pylori-associated neoplasms.
Does stereotype threat affect test performance of minorities and women? A meta-analysis of experimental evidence.

A meta-analysis of stereotype threat effects was conducted and an overall mean effect size of |. 26| was found, but true moderator effects existed. A series of hierarchical moderator analyses evidenced differential effects of race- versus gender-based stereotypes. Women experienced smaller performance decrements than did minorities when tests were difficult: mean ds = |. 36| and |. 43|, respectively. For women, subtle threat-activating cues produced the largest effect, followed by blatant and moderately explicit cues: ds = |. 24|, |. 18|, and |. 17|, respectively; explicit threat-removal strategies were more effective in reducing stereotype threat effects than subtle ones: ds = |. 14| and |. 33|, respectively. For minorities, moderately explicit stereotype threat-activating cues produced the largest effect, followed by blatant and subtle cues: ds = |. 64|, |. 41|, and |. 22|, respectively; explicit removal strategies enhanced stereotype threat effects compared with subtle strategies: ds = |. 80| and |. 34|, respectively. In addition, stereotype threat affected moderately math-identified women more severely than highly math-identified women: ds = |. 52| and |. 29|, respectively; low math-identified women suffered the least from stereotype threat: d= |. 11|. Theoretical and practical implications of these findings are discussed.
Home haemodialysis-international trends and variation.

BACKGROUND Home haemodialysis (HD) has the best patient outcomes and is the most cost-effective of any dialysis modality, but its use has been declining in many countries. METHODS Point prevalence rates of different dialysis modalities and transplantation were obtained from national and regional registries for the most recent available year (2001-03) for 21 high-income and 12 middle-income countries. Relationships with median age and prevalence of diabetic nephropathy, healthcare expenditure and population density were assessed. Long-term trends in the use of home HD during the last two to four decades were obtained for seven countries. RESULTS The prevalence of home HD varies from 0 to 58.4 per million population, and varies between countries, more than any other renal replacement therapy (RRT) modality. There is a positive association between the use of peritoneal dialysis and home HD (Spearman's rho = 0.531, P = 0.013), but no correlation with transplantation prevalence. There is a negative correlation with median age of the renal replacement population (rho = -0.552, P = 0.018). There is no association with prevalence of diabetic nephropathy, healthcare expenditure or population density. Temporal trends in home HD prevalence are dramatically different in different countries, with several countries expanding its use in the last few years. CONCLUSION The use of home HD varies dramatically between and within countries. The variation cannot be explained by the variation in the use of other RRT modalities, nor by prevalence of diabetic nephropathy, national wealth or population density. The inverse correlation with median age is difficult to explain. Significant expansion of home HD is likely to be possible in most countries, and will be increasingly important as the impressive results of more frequent HD gain credence.
Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma.

PURPOSE To study the clinical significance of transformation to diffuse large B-cell lymphoma (DLBCL) in patients with follicular lymphoma (FL). PATIENTS AND METHODS From 1972 to 1999, 325 patients were diagnosed with FL at St Bartholomew's Hospital (London, United Kingdom). With a median follow-up of 15 years, progression occurred in 186 patients and biopsy-proven transformation in 88 of the 325. The overall repeat biopsy rate was 70%. RESULTS The risk of histologic transformation (HT) by 10 years was 28%, HT not yet having been observed after 16.2 years. The risk was higher in patients with advanced stage (P = .02), high-risk Follicular Lymphoma International Prognostic Index (FLIPI; P = .01), and International Prognostic Index (IPI; P = .04) scores at diagnosis. Expectant management (as opposed to treatment being initiated at diagnosis) also predicted for a higher risk of HT (P = .008). Older age (P = .005), low hemoglobin level (P = .03), high lactate dehydrogenase (P < .0001), and high-risk FLIPI (P = .01) or IPI (P = .003) score at the time of first recurrence were associated with the diagnosis of HT in a biopsy performed at that time. The median survival from transformation was 1.2 years. Patients with HT had a shorter overall survival (P < .0001) and a shorter survival from progression (P < .0001) than did those in whom it was not diagnosed. CONCLUSION Advanced stage and high-risk FLIPI and IPI scores at diagnosis correlate with an increased risk of HT. This event strongly influences the outcome of patients with FL by shortening their survival. There may be a subgroup of patients in whom HT does not occur.
Inherent dynamics within the Crimean‐Congo Hemorrhagic fever virus protease are localized to the same region as substrate interactions

Crimean‐Congo Hemorrhagic fever virus (CCHFV) is one of several lethal viruses that encodes for a viral ovarian tumor domain (vOTU), which serves to cleave and remove ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) from numerous proteins involved in cellular signaling. Such manipulation of the host cell machinery serves to downregulate the host response and, therefore, complete characterization of these proteases is important. While several structures of the CCHFV vOTU protease have been solved, both free and bound to Ub and ISG15, few structural differences have been found and little insight has been gained as to the structural plasticity of this protease. Therefore, we have used NMR relaxation experiments to probe the dynamics of CCHFV vOTU, both alone and in complex with Ub, discovering a highly dynamic protease that exhibits conformational exchange within the same regions found to engage its Ub substrate. These experiments reveal a structural plasticity around the N‐terminal regions of CCHFV vOTU, which are unique to vOTUs, and provide a rationale for engaging multiple substrates with the same binding site.
Linkage Analysis with Dense SNP Maps in Isolated Populations

Objective: SNP maps are becoming the gold standard for genetic markers, even for linkage analyses. However, because of the density of SNPs on most high throughput platforms, the resulting significant linkage disequilibrium (LD) can bias classical nonparametric multipoint linkage analyses. This problem may be even stronger in population isolates where LD can extend over larger distances and with a more stochastic pattern. We investigate the issue of linkage analysis with SNPs from the Affymetrix 500K GeneChip array in extended families from the isolated Hutterite population. Methods: We minimized LD between SNPs by two methods based on a LD block pattern (Merlin and SNPLINK) and by MASEL, a new algorithm that we proposed to select SNP subsets with minimum LD and with no prior hypothesis about the LD pattern. Results: Simulations, performed using the real LD pattern observed in the Hutterite population, show that sizeable inflation of linkage statistics persist when LD between SNPs is minimized by Merlin and SNPLINK. Inflation of linkage statistics is better controlled with MASEL. Conclusion: In this population, it may be difficult to extract from standard GeneChip arrays a SNP map without LD-driven bias that is more informative than a dense microsatellite map.
Measurement of sedentary behaviour in population health surveys: a review and recommendations

Background The purpose of this review was to determine the most valid and reliable questions for targeting key modes of sedentary behaviour (SB) in a broad range of national and international health surveillance surveys. This was done by reviewing the SB modules currently used in population health surveys, as well as examining SB questionnaires that have performed well in psychometric testing. Methods Health surveillance surveys were identified via scoping review and contact with experts in the field. Previous systematic reviews provided psychometric information on pediatric questionnaires. A comprehensive search of four bibliographic databases was used to identify studies reporting psychometric information for adult questionnaires. Only surveys/studies published/used in English or French were included. Results The review identified a total of 16 pediatric and 18 adult national/international surveys assessing SB, few of which have undergone psychometric testing. Fourteen pediatric and 35 adult questionnaires with psychometric information were included. While reliability was generally good to excellent for questions targeting key modes of SB, validity was poor to moderate, and reported much less frequently. The most valid and reliable questions targeting specific modes of SB were combined to create a single questionnaire targeting key modes of SB. Discussion Our results highlight the importance of including SB questions in survey modules that are adaptable, able to assess various modes of SB, and that exhibit adequate reliability and validity. Future research could investigate the psychometric properties of the module we have proposed in this paper, as well as other questionnaires currently used in national and international population health surveys.
Prevalence of Symptoms and Quality of Life Among Jordanian Cancer Patients

In Jordan, little is known about cancer-related symptoms prevalence, severity, and its impacts on patients’ quality of life. Therefore, this study was conducted to estimate cancer-related symptoms prevalence, severity, and predictors of quality of life of cancer patients in Jordan. A descriptive cross-sectional survey design was used. The sample consisted of 498 Jordanian cancer patients. There were slightly more males (51.6%) and a mean age of 44.3 (SD = 15.3) years. The mean of the number of symptoms reported by patients was 11 (SD = 3.3). The most prevalent symptoms were fatigue (92.5%), feeling drowsy (87.1%), lack of appetite (86.3%), being distressed (86.1%), and pain (85.5%). Furthermore, Jordanian cancer patients had low mean total scores for quality of life at a level of 18.5 (SD = 4.9). A comprehensive palliative care program is recommended, led by a representative from the Ministry of Health, to integrate palliative care within the current health care system in Jordan.
Tagged MRP 1 ( MRP 1 ) Activity Using Transient Expression of Fluorescently Analysis of Human Multidrug Resistance Protein 1 In Vivo

The multidrug resistance protein 1 (MRP1) contributes cellular resistance to a wide array of physiological toxins and chemotherapeutic agents. Its in vivo activity has been studied primarily in cells that have been continuously drug selected, culture conditions that might confound the effects of MRP1 expression with the effects of a cell’s detoxification machinery. Transient transfection with a MRP1-green fluorescent protein (EGFP) fusion protein allowed us to measure the activity of MRP1 in cells that had insufficient time to induce other chemoprotective proteins. Furthermore, separate transfections with MRP1-yellow fluorescent protein and a fluorescently tagged P-glycoprotein (MDR1-cyan fluorescent protein) permitted the drug-resistant properties of MRP1-expressing cells to be compared with those of MDR1-expressing cells. Our data showed that the expression of MRP1-EGFP results in significantly decreased cellular accumulation of tetramethylrhodamine ethyl ester (TMRE) and daunorubicin, mildly decreased cellular accumulation of mitoxantrone, and decreased nuclear accumulation of doxorubicin. Additionally, MRP1EGFP expression protected cells from the microtubule depolymerization caused by vincristine and colchicine, but not by vinblastine.
Network Coding over Time-Varying Networks by Means of Virtual Graphs

We present a method for network coding over time-varying networks with attractive tradeoffs between throughput and decoding-delay. We model the time-varying networks as a sequence of topology graphs. The method relies on designing a deterministic network code for a fixed virtual graph derived from the actual sequence of topologies, and on exploiting proper buffering in order to implement the code over the actual network. We show that, under certain conditions, this approach can achieve the maximum achievable throughput over the given time- varying network. We also present simulation results that validate the theoretical findings.
Taking the strain: quantifying the contributions of all cell behaviours to changes in epithelial shape

Computer-assisted tracking of the shapes of many cells over long periods of development has driven the exploration of novel ways to quantify the contributions of different cell behaviours to morphogenesis. A handful of similar methods have now been published that are used to calculate tissue deformations (strain rates) in epithelia. These methods are further used to quantify strain rates attributable to each of the cell behaviours in the tissue, such as cell shape change, cell rearrangement and cell division, that together sum to the tissue strain rates. In this review, aimed at developmental biologists, I will introduce the general approach, characterize differences in current approaches and highlight extensions of these methods that remain to be fully explored. The methods will make a major contribution to the emerging field of tissue mechanics. Precisely quantified strain rates are an essential first step towards exploring constitutive equations relating stress to strain via tissue mechanical properties. This article is part of the themed issue ‘Systems morphodynamics: understanding the development of tissue hardware’.
A game-theoretic approach to distributed scheduling of rigid demands on dynamical systems

A game-theoretic approach to load scheduling is explored within the context of constrained discrete-time linear time-invariant dynamical systems. Rigidity of individual load inputs dictates that it is only possible to translate the corresponding signals back-and-forth in time in order to form a feasible schedule. A game is devised to encode the trade-off between user sensitivities to shifts from the requested load and the need to respect constraints on the dynamic response of the system over a planning horizon. The optimal schedule is an equilibrium of the game for an appropriately selected pricing scheme. As such, learning algorithms can be used to devise distributed algorithms for recovering the optimal schedule.
Characterization of a Non‐UBA Domain Missense Mutation of Sequestosome 1 (SQSTM1) in Paget's Disease of Bone

Mutations affecting the ubiquitin‐associated (UBA) domain of sequestosome 1 (SQSTM1/p62) are commonly found in Paget's disease of bone (PDB) and impair SQSTM1's ability to bind ubiquitin, resulting in dysregulated NF‐κB signaling. In contrast, non‐UBA domain mutations are rarer, and little is known about how they manifest their effects. We present the first characterization at the molecular, cellular, and functional level of a non‐UBA domain missense mutation (A381V) of SQSTM1. Direct sequencing of exon 7 of the SQSTM1 gene in an Italian PDB patient detected a heterozygous C to T transversion at position 1182, resulting in an alanine to valine substitution at codon 381. Pull‐down assays showed the non‐UBA region of SQSTM1 that contains A381 is important in mediating ubiquitin‐binding affinity and that the A381V mutation exerts weak negative effects on ubiquitin binding. Structural and binding analyses of longer UBA constructs containing A381, using NMR spectroscopy and circular dichroism, showed this region of the protein to be largely unstructured and confirmed its contribution to increased ubiquitin‐binding affinity. Co‐transfections of U20S cells showed that the A381V mutant SQSTM1 co‐localized with ubiquitin with a cellular phenotype indistinguishable from wildtype. Finally, effects of the wildtype and mutant SQSTM1 on NF‐κB signaling were assessed in HEK293 cells co‐transfected with an NF‐κB luciferase reporter construct. A381V mutant SQSTM1 produced a level of activation of NF‐κB signaling greater than wildtype and similar to that of UBA domain mutants, indicating that non‐UBA and UBA domain mutations may exert their effects through a common mechanism involving dysregulated NF‐κB signaling.
Respiratory impedance and response to salbutamol in healthy Vietnamese children

A high incidence of childhood asthma has been reported in Ha Noi, Viet Nam, indicating a need to document lung function in these children. The degree of airway obstruction and reversibility may be evaluated from the forced oscillation assessment of respiratory resistance to reactance (Rrs, Xrs). Appropriate controls are necessary for a proper interpretation of patients. The aim of the study was to provide reference values on Rrs and Xrs and response to salbutamol in healthy Vietnamese children. One hundred seventy‐five children aged 6–11 year recruited from one public school in Ha Noi were studied. Measurements were obtained at baseline and after 200 µg inhaled salbutamol. Significant correlations were disclosed between Rrs or Xrs and standing height (P < 0.0001). Salbutamol significantly decreased Rrs (from 7.1 ± 1.9 hPa.sec/L to 6.2 ± 1.8 hPa.sec/L, P < 0.0001) and increased Xrs (from −1.22 ± 0.64 to −0.91 ± 0.61 hPa.sec/L, P < 0.0001). Rrs response to salbutamol lower limit of 95% confidence interval was −38% from baseline Rrs and, Xrs upper limit was +16% from baseline impedance. It is concluded that reference values for respiratory impedance (Zrs) and thresholds for clinically relevant response to bronchodilator are provided in primary school Vietnamese children. A smaller slope for the observed Rrs–body height relationship is suggested with reference to relevant studies in healthy Caucasians. Pediatr Pulmonol. 2008; 43:1013–1019. © 2008 Wiley‐Liss, Inc.
Meta-analysis of cancer microarray data reveals signaling pathway hotspots

Recent studies have shown that the identification of deregulated bio-molecular pathways in cancer may be more important than identification of individual genes through differential expression. Since the same pathway can be deregulated by a different subset of genes, it is critical to study pathways as a whole, rather than focus on individual genes. Most papers on meta-analysis of cancer datasets focus on the identification of a set of individual genes, and not on pathways, protein families and gene ontology terms. We have analyzed data from 87 microarray datasets consisting of 5,126 samples and spanning 25 different types of cancer. We have identified 212 KEGG pathways, 578 protein families and 1,717 gene ontology terms that are statistically significant (p < 0.01), and deregulated in cancer. Many of the top pathways and proteins from our meta-analysis, e.g., Jak-Stat pathway, Annexin proteins etc. are already known to play a pivotal role in carcinogenesis. To the best of our knowledge this is the largest meta analysis of cancer pathways, protein families and gene ontology terms to date.
Addressing psychosocial concerns for prostate cancer survivors: We've found a problem, now what?

The systematic review published in this issue of Psycho‐Oncology by Chambers et al provides the most recent compilation of the literature addressing psychosocial issues in prostate cancer. The analysis demonstrates a relative paucity of effective psychosocial and psychosexual interventions for men living with prostate cancer and their partners, with the available studies being relatively small with limited power to detect the intended outcomes. Several interventions in the review provide benefit to patients by reducing psychological distress and improving health‐related quality of life. Some of the most successful interventions are multimodal that combined educational approaches, peer support, and communication techniques to address patient needs from various angles. Evidence demonstrating the benefit of multimodal interventions suggests that providing an array of services in routine prostate cancer care may enable tailored support that more effectively addresses the individual needs of a diverse patient population. These services may include supportive counseling and psychological services, disease education support, opportunities for peer engagement, and financial and social services. As society strives to maximize the value of cancer care provided, including patient‐reported outcomes and patient satisfaction, as metrics of quality of care, will be imperative. Equally important is providing an appropriate array of services to optimize outcomes, effectively enhancing the value of care for prostate cancer survivors by directly affecting the numerator in the value equation (value = outcomes / cost). The health and well‐being of prostate cancer survivors cannot be considered in isolation from their relationships. It is striking that none of the couples‐based interventions assessed simultaneously improved outcomes for both prostate cancer survivors and their partners, with nearly half resulting in poorer outcomes for partners. In addition, interventions supporting the growing population of nontraditional patients and couples, including homosexual and transgender patients and partners, were not available. These findings identify an area ripe for the development of novel interventions, including those that maximally support each half of a couple individually to simultaneously improve
Estymacja struktury terminowej stóp procentowych w Polsce

Streszczenie W artykule podjeto temat estymacji struktury terminowej stop procentowych dla Polski. Przedstawiono w nim trzy metody stosowane przez banki centralne publikujące tego typu dane. Nastepnie rozwazono wyniki zastosowania tych metod dla Polski. Porownano jakośc estymacji, przy czym jako dwoma kryteriami. Pierwszym z nich bylo odchylenie kwadratowe teoretycznych cen obligacji od cen obserwowanych na rynku, a drugim – podobienstwo oszacowanej struktury zmienności do zmienności estymowanej na podstawie stop WIBOR.