Miracle-dz/UniFAR-FTUs huggingface dataset:
Living with disabling chronic pain: results from a face-to-face cross-sectional population-based study

Objectives To estimate the prevalence of disabling chronic pain (DCP) in Spanish adults, to analyse its characteristics, to determine its multimorbidity and to identify its associated factors. Settings 2011 Andalusian Health Survey, a cross-sectional population survey based on face-to-face home interviews. Participants 6507 people aged 16 years or older and living in Andalusia, Spain. Outcomes The response variable was disabling chronic pain. Multivariate multinomial logistic regression models were used to analyse the association of factors with disabling chronic pain. The sample design was considered throughout the statistical analysis. Results The prevalence of disabling chronic pain in the Spanish adult population was 11.36% (95% CI 11.23 to 11.49), while that of non-disabling chronic pain was 5.67% (95% CI 5.57 to 5.77). Disabling chronic pain was associated with high multimorbidity (especially in women (51%) and in the elderly (70%) with three or more additional chronic diseases), as well as with disadvantaged social status (such as female gender (OR=2.12), advanced age (OR10-year increase=1.28), unemployment (OR=1.33), manual work (OR=1.26), low income (OR=1.14) and reduced emotional social support (OR=1.04)). Other influential factors were tobacco consumption (OR=1.42), sleeping ≤7 hours (OR=1.2)], environmental or work conditions (OR=1.16) and quality of life (ORmental=1.21, ORphysical=2.37). Conclusions The population with disabling chronic pain was associated with multimorbidity, vulnerable social status and an impaired quality of life. In contrast, the population with non-disabling chronic pain showed almost no differences when compared with the population without chronic pain. The association between DCP and mental disorders highlights the need for psychosocial services in the management of chronic pain.
Graph Energies of Egocentric Networks and Their Correlation with Vertex Centrality Measures

Graph energy is the energy of the matrix representation of the graph, where the energy of a matrix is the sum of singular values of the matrix. Depending on the definition of a matrix, one can contemplate graph energy, Randić energy, Laplacian energy, distance energy, and many others. Although theoretical properties of various graph energies have been investigated in the past in the areas of mathematics, chemistry, physics, or graph theory, these explorations have been limited to relatively small graphs representing chemical compounds or theoretical graph classes with strictly defined properties. In this paper we investigate the usefulness of the concept of graph energy in the context of large, complex networks. We show that when graph energies are applied to local egocentric networks, the values of these energies correlate strongly with vertex centrality measures. In particular, for some generative network models graph energies tend to correlate strongly with the betweenness and the eigencentrality of vertices. As the exact computation of these centrality measures is expensive and requires global processing of a network, our research opens the possibility of devising efficient algorithms for the estimation of these centrality measures based only on local information.
Can routine inpatient mortality data improve HIV mortality estimates? Inpatient mortality at an urban hospital in South Africa.

BACKGROUND South Africa (SA) has one of the world's largest HIV treatment programmes, to which a dramatic increase in life expectancy has been attributed. However, there continue to be concerns regarding the reporting of HIV-related mortality in SA, which varies by source. As accurate HIV mortality estimates are key to measuring the success of the national programme as well as identifying areas for improvement, we propose a complementary approach to monitoring changes in HIV-related mortality using routine inpatient records to examine trends in causes of death and HIV status over time. OBJECTIVES To investigate the feasibility of this approach by calculating mortality due to natural causes in the medical ward of a hospital during 2010 by HIV status. METHODS We conducted a cross-sectional study of inpatient mortality at a regional hospital in Johannesburg, SA, analysing all deaths due to natural causes among adult medical ward inpatients. Cause of death was recorded from the mortuary register. HIV status was ascertained directly from the mortuary register or from laboratory tests specific for HIV diagnosis or monitoring. RESULTS Of 1 167 inpatients who died, the majority were HIV-positive (58%). HIV positivity among males (55%) was slightly lower than that among females (61%), and HIV-positive patients were younger (median 40 years) than those who were HIV-negative (56 years) and of unknown HIV status (68 years). 'Infections and parasites' was the most common cause of natural death (29%). On average, HIV-positive patients were admitted for slightly longer (mean 10.5 days) than HIV-negative patients (9.6 days) and those of unknown HIV status (8.9 days), yet HIV-positive inpatient deaths accounted for the majority (62%) of the total bed days. CONCLUSIONS Even with widespread access to antiretroviral therapy, the majority of inpatient natural deaths at a large public sector hospital in 2010 were of HIV-positive patients and were probably related to HIV. In view of the importance of accurate data on causes of death, both for the HIV programme and to track other diseases, large-scale expansion of this approach over a longer period should be considered.
Patients' Perspective: What has Changed in Deciding about Breast-Conserving Surgery for Early-Stage Breast Cancer in Turkey?

Background: This study aims to describe patients' perception of early breast cancer, factors influencing the choice of operation, patients' sources of information about the disease and the seriousness with which this information is considered, and to address what surgeons can do to enlighten their patients prior to decision-making. Methods: Patients were asked to complete a questionnaire consisting of 3 sections: The first section addressed influential factors during the decision-making process; the second pertained to the role of surgeons or health facilities in the process; and the third asked patients to revisit their initial choice of surgery. Results: 237 patients were included in the study. Statistical analyzes regarding demographic features showed that nulliparous, younger than 50 years, never or <5 years married, highly educated, business-owning, employed, and stage I breast cancer patients preferred breast-conserving surgery (BCS) to mastectomy. Conclusion: Although the rate of BCS is a technical quality indicator for breast cancer centers, providing sufficient patient counseling, involving the patient in the decision-making process, and offering every possible surgical option are key to improving quality of life. Systematic counseling should be provided to breast cancer patients who have primary tumors that are eligible for BCS.
CD147 promotes progression of head and neck squamous cell carcinoma via NF‐kappa B signaling

CD147/basigin (BSG) is highly upregulated in many types of cancer, our previous study has found that CD147/BSG is highly expressed in head and neck squamous cell carcinoma (HNSCC) stem cells, but its role in HNSCC and the underlying mechanism is still unknown. In this study, we investigated the role of CD147 in the progression of HNSCC. Real‐time PCR, western blot and immunohistochemistry were used to detect the expression of CD147 in total 189 HNSCC tissues in compared with normal tissues. In addition, we used proliferation, colony formation, cell cycle and apoptosis, migration and invasion as well as wound‐healing assay to determine the biological roles of CD147 in HNSCC. Then, a xenograft model was performed to evaluate tumor‐promoting and metastasis‐promoting role of CD147 in HNSCC. The results showed that upregulated CD147 expression was associated with aggressive clinicopathologic features in HNSCC. In addition, CD147 promoted proliferation, migration and reduced the apoptosis phenotype of HNSCC cells in vitro as well as tumor initiation and progression in vivo. Furthermore, we demonstrated that CD147 promoted HNSCC progression through nuclear factor kappa B signaling. Therefore, we concluded that CD147 promoted tumor progression in HNSCC and might be a potential prognostic and treatment biomarker for HNSCC.
Experimental Evidence for Resecretion of PGE2 across Rat Alveolar Epithelium by OATP2A1/SLCO2A1-Mediated Transcellular Transport

Prostaglandin transporter Oatp2a1/Slco2a1 is expressed at the apical (AP) membranes of type-1 alveolar epithelial (AT1) cells. To investigate the role of OATP2A1 in prostaglandin E2 (PGE2) handling by alveolar epithelium, we studied PGE2 transport across and secretion from monolayers of rat AT1-like (AT1-L) cells obtained by trans-differentiation of type-2 alveolar epithelial cells isolated from male Wistar rats. Rat AT1-L cells expressed Oatp2a1/Slco2a1, together with smaller amounts of Mrp4/Abcc4 and Oct1/Slc22a1. PGE2 uptake was saturable with Km 43.9 ± 21.9 nM. Transcellular transport of PGE2 across AT1-L cells grown on permeable filters in the AP-to-basolateral (BL) direction was 5-fold greater than that in the reverse direction and was saturable with Km 118 ± 26.8 nM; it was significantly inhibited by OATP inhibitors bromosulfophthalein (BSP) and suramin, and an MRP4 inhibitor, Ceefourin 1. We simultaneously monitored the effects of BSP on the distribution of PGE2 produced by bradykinin-treated AT1-L cells and PGE2-d4 externally added on the AP side of the cells. In the presence of BSP, PGE2 increased more rapidly on the AP side, whereas PGE2-d4 decreased more slowly on the AP side. The decrease in PGE2-d4 from the AP side corresponded well to the increase on the BL side, indicating that intracellular metabolism did not occur. These results suggest that Oatp2a1 and Mrp4 mediate transepithelial transport of PGE2 in the AP-to-BL direction. Therefore, OATP2A1 may be an important regulator of PGE2 in alveolar epithelium by reducing secretion of PGE2 and facilitating “resecretion” of PGE2 present in the alveolar lumen to the interstitial space or blood.
On the intersection of tame subgroups in groups acting on trees

Let $G$ be a group acting on a tree $T$ with finite edge stabilizers of bounded order. We provide, in some very interesting cases, upper bounds for the complexity of the intersection $H\cap K$ of two tame subgroups $H$ and $K$ of $G$ in terms of the complexities of $H$ and $K$. In particular, we obtain bounds for the Kurosh rank $Kr(H\cap K)$ of the intersection in terms of Kurosh ranks $Kr(H)$ and $Kr(K)$, in the case where $H$ and $K$ act freely on the edges of $T$.
Subspecialization within default mode nodes characterized in 10,000 UK Biobank participants

Significance The default mode network (DMN) encompasses supramodal association areas involved in higher-order cognition. One speculation is that this neural system is important for brain-wide information flow. We tested this account by exploring whether DMN patterns are informative about functional coupling or structural associations in the rest of the brain. Our multimodal pattern analysis findings highlight how the DMN nodes are fractionated: In specific subnodes, gray-matter morphology was linked to fiber tracts from the hippocampus in the medial temporal limbic system. In adjacent subnodes, fluctuations in neural activity were linked to between-network connectivity shifts. Such a mosaic architecture may be a prerequisite for many of the roles the DMN may play in advanced cognitive processes. The human default mode network (DMN) is implicated in several unique mental capacities. In this study, we tested whether brain-wide interregional communication in the DMN can be derived from population variability in intrinsic activity fluctuations, gray-matter morphology, and fiber tract anatomy. In a sample of 10,000 UK Biobank participants, pattern-learning algorithms revealed functional coupling states in the DMN that are linked to connectivity profiles between other macroscopical brain networks. In addition, DMN gray matter volume was covaried with white matter microstructure of the fornix. Collectively, functional and structural patterns unmasked a possible division of labor within major DMN nodes: Subregions most critical for cortical network interplay were adjacent to subregions most predictive of fornix fibers from the hippocampus that processes memories and places.
Immunotoxicity of titanium dioxide nanoparticles via simultaneous induction of apoptosis and multiple toll-like receptors signaling through ROS-dependent SAPK/JNK and p38 MAPK activation

Background Titanium dioxide nanoparticles (TiO2 NPs) represent a scientific breakthrough in the areas of biological and medicinal applications. Interaction of TiO2 NPs with components of innate immune system remains elusive. Aim This study explored in vitro immunotoxicity of murine macrophage RAW 264.7 to TiO2 NPs (20 nm, negative charge) and its underlying molecular mechanism by way of immunoredox profiling. Materials and methods In this study, chemically synthesized BSA-functionalized TiO2 NPs (20 nm, negative charge) were characterized and immunotoxicity was investigated on RAW 264.7 cells. Results We found that reactive oxygen species levels significantly increased with increasing nitric oxide production, whereas depleting endogenous antioxidant super oxide dismutase as well as nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels. Furthermore, NPs exposure increased the expression of apoptotic factors such as BAX, BIM, and PUMA with disruption of mitochondrial membrane potential (Δψm) that lead to decrease in immunocytes. Molecular immune profiling revealed the activation of multiple toll-like receptors (TLRs) 4/9/12/13 simultaneously with the phosphorylation of p-p38MAPK and p-SAPK/c-Jun N-terminal kinase (JNK) compared to untreated control. Conclusion Collectively, this study shows that the molecular nature of TiO2SA20(−) NP-induced immunotoxicity in RAW 264.7 macrophage is simultaneous induction of immunocyte apoptosis and multiple TLRs signaling through oxidative stress-dependent SAPK/JNK and p38 mitogen-associated protein kinase activation. This is the first study to address newer molecular mechanism of TiO2SA20(−) NP-induced immunotoxicity.
The Definition of Bioregions in Palaeontological Studies of Diversity and Biogeography Affects Interpretations: Palaeozoic Tetrapods as a Case Study

Studies of diversity, whether of species richness within regions (alpha diversity) or faunal turnover between regions (beta diversity), will depend heavily on the “bioregions” into which a study area is divided. However, such studies in the palaeontological literature have often been extremely arbitrary in their definition of bioregions and have employed a wide variety of spatial scales, from individual localities to formations/basins to entire continents. Such bioregions will not necessarily be separated by biologically meaningful boundaries, and results obtained at different spatial scales will not be directly comparable. In many neontological studies, however, bioregions are defined more rigorously, usually as areas of endemicity. Here a procedure is proposed whereby this principal may be applied to palaeontological datasets. In each time bin/assemblage localities are subjected to two hierarchical cluster analyses, the first grouping the localities by geographic distance, the second by taxonomic distance. Clusters shared between the two will represent continuous geographic areas of endemicity and so may be used as bioregions. When calculating alpha or beta diversity through time, the spatial scale at which the bioregions are defined needs to be standardised between each time bin. This is done by grouping clusters of localities below a predefined geographic cluster node height. This approach is used to assess changes in beta diversity of Palaeozoic tetrapods and resolve disagreements regarding changes in faunal provinciality across the Carboniferous/Permian boundary. When the bioregions are defined at a smaller spatial scale, splitting the globe into many small regions, beta diversity decreases substantially during the earliest Permian. However, when the bioregions are defined at larger spatial scales, representing areas roughly the size of continents, beta diversity remains high. This result indicates that local environmental barriers to dispersal were decreasing in importance, rejecting previous suggestions that the rainforest collapse caused an “island biogeography” effect. Instead, dispersal at this time is restricted by continental-scale barriers, with the increased orogenic uplift as a possible control.
Association of Secondary Preventive Cardiovascular Treatment After Myocardial Infarction With Mortality Among Patients With Schizophrenia

Importance Cardioprotective medication use is an important secondary preventive treatment after cardiovascular events. Patients with schizophrenia have excess cardiovascular morbidity and mortality, but no studies have investigated whether taking recommended cardioprotective medication can reduce this excess mortality. Objective To assess the association of exposure to secondary cardiovascular treatment with all-cause mortality after myocardial infarction among patients with schizophrenia compared with the general population. Design, Setting, and Participants This nationwide cohort study included individuals admitted with first-time myocardial infarction in Denmark from January 1, 1995, to December 31, 2015. The cohort was dichotomously divided by a diagnosis of schizophrenia. Data on the prescription of guideline-recommended cardioprotective medication, including antithrombotics, &bgr;-blockers, vitamin K antagonist, angiotensin-converting enzyme inhibitors, and statins, were obtained from the nationwide registries. Exposures Time exposed to cardioprotective medication. Main Outcomes and Measure Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% CIs for the association between treatment exposure and all-cause mortality after myocardial infarction between patients with and without schizophrenia. Results The cohort included 105 018 patients with myocardial infarction, including 684 patients with schizophrenia (0.7%; 483 male [70.6%]; mean [SD] age at diagnosis, 57.3 [10.6] years) and 104 334 general population patients (99.3%; 73 454 male [70.4%]; mean [SD] age at diagnosis, 61.0 [10.6] years), with a total follow-up of 796 435 person-years and 28 059 deaths. Patients diagnosed with schizophrenia who did not receive cardioprotective treatment had the highest mortality rate (HR, 8.78; 95% CI, 4.37-17.64) compared with the general population treated, with treated patients diagnosed with schizophrenia having an increased HR of 1.97 (95% CI, 1.25-3.10). The analyses of the associations of different cardiac therapy strategies with mortality rates revealed that patients with schizophrenia who were treated with any combination of triple therapy had mortality rates similar to those observed in the general population (HR, 1.05; 95% CI, 0.43-2.52) in the multivariable analysis. Conclusions and Relevance Cardioprotective medication after myocardial infarction should be carefully managed to improve prognosis. The study results suggest that some of the increased cardiac mortality among patients with schizophrenia can be reduced if these patients are efficiently administered combinations of secondary preventive treatments after cardiac events.
Targeting Purinergic Receptor P2Y2 Prevents the Growth of Pancreatic Ductal Adenocarcinoma by Inhibiting Cancer Cell Glycolysis

Purpose: Extensive research has reported that the tumor microenvironment components play crucial roles in tumor progression. Thus, blocking the supports of tumor microenvironment is a promising approach to prevent cancer progression. We aimed to determine whether blocking extracellular ATP–P2RY2 axis could be a potential therapeutic approach for PDAC treatment. Experimental Design: Expression of P2RY2 was determined in 264 human PDAC samples and correlated to patient survival. P2RY2 was inhibited in human PDAC cell lines by antagonist and shRNA, respectively, and cell viability, clonogenicity, and glycolysis were determined. RNA sequencing of PDAC cell line was applied to reveal underlying molecular mechanisms. Multiple PDAC mouse models were used to assess the effects of the P2RY2 inhibition on PDAC progression. Results: P2RY2 was upregulated and associated with poor prognosis in PDAC. Activated P2RY2 by increased extracellular ATP in tumor microenvironment promoted PDAC growth and glycolysis. Further studies showed that the agonist-activated P2RY2 triggered PI3K/AKT–mTOR signaling by crosstalk with PDGFR mediated by Yes1, resulting in elevated expression of c-Myc and HIF1α, which subsequently enhanced cancer cell glycolysis. Genetic and pharmacologic inhibition of P2RY2 impaired tumor cell growth in subcutaneous and orthotopic xenograft model, as well as delayed tumor progression in inflammation-driven PDAC model. In addition, synergy was observed when AR-C118925XX, the selective antagonist of P2RY2 receptor, and gemcitabine were combined, resulting in prolonged survival of xenografted PDAC mice. Conclusions: These findings reveal the roles of the P2RY2 in PDAC metabolic reprogramming, suggesting that P2RY2 might be a potential metabolic therapeutic target for PDAC.
Impact of Knowledge Management on Innovation: Evidence from a South Asian Country

Ever growing need for innovation has become a big challenge for organisations. Consequently, Knowledge management (KM) is gaining importance in the business world as one of the critical enablers for innovation. This study answers the question whether KM philosophy helps organisations develop capabilities to induce innovation, especially in the context of developing economies. Based on the empirical evidence from the service sector of Pakistan, we show that knowledge acquisition, knowledge dissemination, and responsiveness to knowledge significantly influence an organisation’s capabilities to produce innovative outputs. We also bring to the fore a mutual relationship of KM components with each other, thereby highlighting that knowledge acquisition is important for knowledge dissemination which in turn determines an organisation’s responsiveness to knowledge. We used structural equation modelling (SEM) to develop a model among three endogenous KM factors and one exogenous factor, innovation. Our findings show a significant relationship of all variables, though the strength of each varies, hence confirming the hypothesis that KM, if implemented effectively, improves organisation’s ability to innovate.