Miracle-dz/UniFAR-FTUs huggingface dataset:
Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells.

The mechanisms of cell death induced by ATP depletion were studied in primary cultures of mouse proximal tubular (MPT) cells. Graded ATP depletion, ranging in severity from ∼2 to 70% of control levels, was induced by incubating cells with either antimycin or 2-deoxyglucose, with varying concentrations of dextrose. We found that cells subjected to ATP depletion below ∼15% of control died uniformly of necrosis. In contrast, cells subjected to ATP depletion between ∼25 and 70% of control all died by apoptosis. The rapidity of cell death was proportional to the severity of reduction of cell ATP content and was independent of the mechanism of cell death. Renal growth factors, epidermal growth factor (EGF) and high-dose insulin, did not ameliorate apoptotic cell death induced by ATP depletion. We conclude that ATP depletion can cause either necrosis or apoptosis in MPT cells. Furthermore, we have identified a narrow range of ATP depletion (∼15 to 25% of control) representing a threshold that determines whether cells die by necrosis or apoptosis.
Association between implementation of a code stroke system and poststroke epilepsy

Objective We aimed to investigate the effect of a code stroke system on the development of poststroke epilepsy. Methods We retrospectively analyzed consecutive patients treated with IV thrombolysis under or outside the code stroke system between 2003 and 2012. Patients were followed up for at least 2 years or until death. Factors with p < 0.1 in univariate comparisons were selected for multivariable logistic and Cox regression. Results A total of 409 patients met the eligibility criteria. Their median age at stroke onset was 75 years (interquartile range 64–83 years); 220 (53.8%) were male. The median follow-up duration was 1,074 days (interquartile range 119–1,671 days). Thirty-two patients (7.8%) had poststroke seizures during follow-up, comprising 7 (1.7%) with acute symptomatic seizures and 25 (6.1%) with late-onset seizures. Twenty-six patients (6.4%) fulfilled the definition of poststroke epilepsy. Three hundred eighteen patients (77.8%) were treated with the code stroke system while 91 (22.2%) were not. After adjustment for age and stroke etiology, use of the code stroke system was associated with decreased odds of poststroke epilepsy (odds ratio = 0.36, 95% confidence interval 0.14–0.87, p = 0.024). Cox regression showed lower adjusted hazard rates for poststroke epilepsy within 5 years for patients managed under the code stroke system (hazard ratio = 0.60, 95% confidence interval 0.47–0.79, p < 0.001). Conclusion The code stroke system was associated with reduced odds and instantaneous risk of poststroke epilepsy. Further studies are required to identify the contribution of the individual components and mechanisms against epileptogenesis after stroke. Classification of evidence This study provides Class III evidence that for people with acute ischemic stroke, implementation of a code stroke system reduces the risk of poststroke epilepsy.
PGE2/EP3/SRC signaling induces EGFR nuclear translocation and growth through EGFR ligands release in lung adenocarcinoma cells

Prostaglandin E2 (PGE2) interacts with tyrosine kinases receptor signaling in both tumor and stromal cells supporting tumor progression. Here we demonstrate that in non-small cell lung carcinoma (NSCLC) cells, A549 and GLC82, PGE2 promotes nuclear translocation of epidermal growth factor receptor (nEGFR), affects gene expression and induces cell growth. Indeed, cyclin D1, COX-2, iNOS and c-Myc mRNA levels are upregulated following PGE2 treatment. The nuclear localization sequence (NLS) of EGFR as well as its tyrosine kinase activity are required for the effect of PGE2 on nEGFR and downstream signaling activities. PGE2 binds its bona fide receptor EP3 which by activating SRC family kinases, induces ADAMs activation which, in turn, releases EGFR-ligands from the cell membrane and promotes nEGFR. Amphiregulin (AREG) and Epiregulin (EREG) appear to be involved in nEGFR promoted by the PGE2/EP3-SRC axis. Pharmacological inhibition or silencing of the PGE2/EP3/SRC-ADAMs signaling axis or EGFR ligands i.e. AREG and EREG expression abolishes nEGFR induced by PGE2. In conclusion, PGE2 induces NSCLC cell proliferation by EP3 receptor, SRC-ADAMs activation, EGFR ligands shedding and finally, phosphorylation and nEGFR. Since nuclear EGFR is a hallmark of cancer aggressiveness, our findings reveal a novel mechanism for the contribution of PGE2 to tumor progression.
Loss of PTEN promotes formation of signaling-capable clathrin-coated pits

ABSTRACT Defective endocytosis and vesicular trafficking of signaling receptors has recently emerged as a multifaceted hallmark of malignant cells. Clathrin-coated pits (CCPs) display highly heterogeneous dynamics on the plasma membrane where they can take from 20 s to over 1 min to form cytosolic coated vesicles. Despite the large number of cargo molecules that traffic through CCPs, it is not well understood whether signaling receptors activated in cancer, such as epidermal growth factor receptor (EGFR), are regulated through a specific subset of CCPs. The signaling lipid phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3], which is dephosphorylated by phosphatase and tensin homolog (PTEN), is a potent tumorigenic signaling lipid. By using total internal reflection fluorescence microscopy and automated tracking and detection of CCPs, we found that EGF-bound EGFR and PTEN are enriched in a distinct subset of short-lived CCPs that correspond with clathrin-dependent EGF-induced signaling. We demonstrated that PTEN plays a role in the regulation of CCP dynamics. Furthermore, increased PI(3,4,5)P3 resulted in higher proportion of short-lived CCPs, an effect that recapitulates PTEN deletion. Altogether, our findings provide evidence for the existence of short-lived ‘signaling-capable’ CCPs. Highlighted Article: EGFR and PTEN localize to short-lived clathrin-coated pits (CCPs), and PTEN regulates CCP dynamics and signaling, suggesting compartmentalized signaling is crucial for proper signaling transduction.
Development of Saudi e-health literacy scale for chronic diseases in Saudi Arabia: using integrated health literacy dimensions

Abstract Objective Health literacy has become a global issue, and it is important that patients and individuals are able to use information technology to access health information and educational services. The research objective is to develop a Saudi e-health literacy scale (SeHL) for measuring e-health literacy among Saudis suffering from non-communicable diseases (NCD). Methods Overall, 14 relevant papers in related interdisciplinary fields were reviewed to select the most useful literacy dimensions. From these articles, we extracted the most common dimensions used to measure e-health literacy across the disciplines. Multiple workshops with multidisciplinary team members reviewed and evaluated items for SeHL. Results Four key aspects of e-health literacy—use of technology/media, information-seeking, usefulness and confidence—were identified and integrated as e-health literacy dimensions. These will be used to measure e-health literacy among Saudi patients with NCDs. A translation from Arabic to English was performed in order to ensure that translation process was accurate. A SeHL scale was developed to measure e-health literacy among Saudi patients. By understanding e-health literacy levels, we will be able to create a patient-education system to be used by patients in Saudi Arabia. Conclusions As information technology is increasingly used by people of all ages all over the world, e-health literacy has been identified as a key factor in determining health outcomes. To date, no comprehensive scale exists to assess e-health literacy levels among speakers of Arabic, particularly among people with NCD such as diabetes, cardiovascular diseases and hypertension.
Polymeric Nanoparticles for Increasing Oral Bioavailability of Curcumin

Despite the promising biological and antioxidant properties of curcumin, its medical applications are limited due to poor solubility in water and low bioavailability. Polymeric nanoparticles (NPs) adapted to oral delivery may overcome these drawbacks. Properties such as particle size, zeta potential, morphology and encapsulation efficiency were assessed. Then, the possibility of storing these NPs in a solid-state form obtained by freeze-drying, in vitro curcumin dissolution and cytocompatibility towards intestinal cells were evaluated. Curcumin-loaded Eudragit® RLPO (ERL) NPs showed smaller particle diameters (245 ± 2 nm) and better redispersibility after freeze-drying than either poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL) NPs. The former NPs showed lower curcumin encapsulation efficiency (62%) than either PLGA or PCL NPs (90% and 99%, respectively). Nevertheless, ERL NPs showed rapid curcumin release with 91 ± 5% released over 1 h. The three curcumin-loaded NPs proposed in this work were also compatible with intestinal cells. Overall, ERL NPs are the most promising vehicles for increasing the oral bioavailability of curcumin.
Heart failure patients’ desires for spiritual care, perceived constraints, and unmet spiritual needs: relations with well-being and health-related quality of life

Abstract Little information is available about HF patients’ desires regarding having their healthcare providers address their spiritual concerns, feeling constrained in doing so, and the extent to which their spiritual needs go unmet. Nearly half of our sample reported high levels of unmet spiritual needs and reported moderately strong desires to have their doctor or other healthcare professional attend to their spiritual needs, and moderately strong feelings of constraint in doing so. Spiritual constraint and unmet spiritual needs were associated with poorer spiritual, psychological and physical well-being, but these effects varied, depending on patients’ desire to discuss spiritual needs. These findings have important implications for clinical management of HF patients.
CD39 and immune regulation in a chronic helminth infection: The puzzling case of Mansonella ozzardi

Background Chronic helminth infections typically induce an immunoregulatory environment, with markedly reduced immune responses to both parasite-specific and unrelated bystander antigens. Here we tested whether these changes are also observed in human infections with Mansonella ozzardi, a neglected filarial nematode widely distributed across Latin America. Methods CD4+ T cell populations from microfilaremic (Fil+) and uninfected (Fil-) inhabitants in M. ozzardi-endemic riverine communities in Brazil were characterized by flow cytometry analysis. Plasma concentrations of a wide range of cytokines and chemokines were measured. We examined whether M. ozzardi infection is associated with suppressed in vitro lymphoproliferative and inflammatory cytokine responses upon stimulation with filarial antigen, unrelated antigens or mitogens. Principal findings/Conclusions Fil+ subjects had lower plasma levels of selected inflammatory cytokines, such as TNF-α, IL-8, and IL-6, than their Fil- counterparts. However, we found no evidence for attenuated T-cell responses to filarial antigens or co-endemic pathogens, such as malaria parasites and Toxoplasma gondii. CD4+ T cells expressing CD39, an ectonucleosidase involved in the generation of the anti-inflammatory molecule adenosine, were increased in frequency in Fil+ subjects, compared to uninfected controls. Significantly, such an expansion was directly proportional to microfilarial loads. Surprisingly, CD39 blocking with a neutralizing antibody suppressed antigen-driven lymphoproliferation in vitro, while decreasing inflammatory cytokine responses, in Fil+ and Fil- individuals. These findings suggest that circulating CD4+ CD39+ T cells comprise subsets with both regulatory and stimulatory roles that contribute to the immune homeostasis in chronic M. ozzardi infection.
POC-NLW Template for Chinese Word Segmentation

,Q this paper, a language tagging tem-plate named POC-NLW (position of a character within an n-length word) is pre-sented. Based on this template, a WZR-stage statistical model for Chinese word segmentation is constructed. In this method, the basic word segmentation is based on n-gram language model, DQG a Hidden Markov tagger based on the POC-NLW template is used to imple-ment the out-of-vocabulary (OOV) word identification. The system participated in the MSRA_Close and UPUC_Close word segmentation tracks at SIGHAN Bakeoff 2006. Results returned by this bakeoff are reported here.
Obesity, sarcopenia, sarcopenic obesity and reduced mobility in Brazilian older people aged 80 years and over

ABSTRACT Objective To analyze which abnormalities in body composition (obesity, sarcopenia or sarcopenic obesity) are related to reduced mobility in older people aged 80 years and older. Methods The sample included 116 subjects aged 80 years and older. The body composition was measured using dual-energy X-ray absorptiometry (DXA) and mobility was assessed by motor tests. The χ2 test was used to analyze the proportion of older people with sarcopenia, obesity and sarcopenic obesity based on sex as well as to indicate an association between obesity, sarcopenia, sarcopenic obesity and mobility. Binary logistic regression, adjusted for the variables (sex and osteoarticular diseases), was used to express the magnitude of these associations. One-way analysis of variance was used to compare the mobility of four groups (Normal, Obesity, Sarcopenia and Sarcopenic Obesity). Results The Sarcopenia Group had lower performance in the lower limbs strength test and in sum of two tests compared with Obesity and Normal Groups. Older people with sarcopenia had higher chance of reduced mobility (OR: 3.44; 95%CI: 1.12-10.52). Conclusion Older people aged 80 years and older with sarcopenia have more chance for reduction in mobility.
Crystallization Controlled by Silicate Surfaces in Nylon 6‐Clay Nanocomposites

The crystallization behavior of pure nylon 6 (N6) and its nanocomposite with montmorillonite has been studied in detail. The crystallization rate of N6 is faster in the presence of clay compared to pure N6, as revealed by light scattering experiments. Nylon 6 crystallizes exclusively in the γ-form in the nanocomposite because of the epitaxial crystallization, which is also revealed from the transmission electron microscopic images (sandwiched structure) of the crystallized sample. The storage modulus of the nanocomposite is always higher than the pure nylon 6, irrespective of crystallization temperatures. Much higher increment of storage modulus for pure nylon 6 with increasing crystallization temperature is explained by the higher amount of the thermally stable α-form at higher temperature. A unique mechanism has been proposed to illustrate the crystallization behavior of nylon 6 in the presence of the clay particles.
Developing 3D Scaffolds in the Field of Tissue Engineering to Treat Complex Bone Defects

Abstract Polymers have been extensively used to develop 3D scaffolds in the field of tissue engineering and consist of certain design requirements such as biocompatibility, structural properties, and varying porosity inside of complex geometries, all with the ultimate goal of incorporating living cells within the scaffold structure. In this work, we present the synthesis and material characterization of hybrid spools using polycaprolactone (PCL) as the base polymer. We demonstrate that a commercial 3D Fused Deposition Modeling printer such as MakerBot can be used to print 3D scaffolds using three types of polymer spools: PCL, PCL-poly lactic acid, and PCL-hydroxyapatite. Data derived from computer tomography can be used to develop hollow porous cages using PCL. Finally, we demonstrate that log-pile scaffolds are capable of being infused with a mixture of living cells and gelatin hydrogel and that high cellular viability is maintained throughout the printed structure. This work could be potentially useful .
Impact of orthodontic treatment on self-esteem and quality of life of adult patients requiring oral rehabilitation.

OBJECTIVE To evaluate whether orthodontic treatment in adults requiring oral rehabilitation is effective for increasing patients' self-esteem and quality of life (QoL). MATERIALS AND METHODS The sample consisted of 102 adult patients (77 women and 25 men) aged between 18 and 66 years (mean, 35.1 years) requiring oral rehabilitation and orthodontic treatment simultaneously. Rosenberg's Self-Esteem (RSE) Scale and a questionnaire about QoL based on the Oral Health Impact Profile (OHIP-14) were used to determine self-esteem and QoL scores retrospectively. Questionnaires were carried out in two stages, T1 (start of treatment) and T2 (6 months after). To compare score changes between T1 and T2, the data obtained from the RSE Scale were evaluated with paired t tests, and data from the quality-of-life questionnaire were assessed by applying descriptive statistics. RESULTS The results showed a statistically significant increase in self-esteem (P < .001) and a great improvement on patients' QoL. CONCLUSIONS Orthodontic treatment causes a significant increase in self-esteem and QoL, providing psychological benefits for adult patients in need of oral rehabilitation.
Nanostructured WO3 – Synthesis and Properties

Porous tungsten oxide (WO3) nanofibers were synthesized by electrospinning aqueous solutions of polyvinylpyrrolidone (PVP) and ammonium metatungstate (AMT). The as-spun fibers and their annealing were studied by scanning electron microscope (SEM). SEM results showed that the WO3 fibers have a large amount of pores with diameters ranging from 50 nm to 100 nm, and pure monoclinic WO3 nanoscaled fibers formed between 500 and 600 °C. When a higher temperature (700 °C) was used, the tungsten oxide nanofibers totally disintegrated. When heated at 600 °C, the fibers broken into nanorods by the mechanical pressure. However, when the annealing treatment was low (500 °C), the fiber-like crystalline structure that can be seen. When the optimal temperature was used, the structure of the obtained WO3 nanofibers with novel morphology and crystallinity were captured.
Effect of dispersion on graphite nanosheet composites

By intercalating and exfoliating natural graphite flakes, expanded graphite was obtained and used as the additive for making composites. The expanded graphite was composed of partly connected graphite nanosheets. Three types of composites were made, representing three levels of dispersing the graphite nanosheets. The first was the impregnation of epoxy resin to the expanded graphite by resin transfer molding. No dispersion was applied, and the expanded graphite can retain its original shape. The second was the use of a high-power sonication to break apart the expanded graphite. The thickness of the sonicated expanded graphite was reduced to about 100 times. The third method was to use a high-shear strain rate to separate the graphite nanosheets from the expanded graphite and to disperse them into the resin. The thickness range of the graphite nanosheets was 20–50 nm, about 100 times thinner than the sonicated ones. Compression and impact tests were conducted. The influence of dispersion on the material behavior was studied. Some fracture modes associated with the layered microstructures of the graphite nanosheets were observed. A simple model was used to study the stress transfer and frictional energy consumption of the pullout of the nanosheet. POLYM. COMPOS. , 2010. © 2009 Society of Plastics Engineers
Screen for reactivation of MeCP2 on the inactive X chromosome identifies the BMP/TGF-β superfamily as a regulator of XIST expression

Significance Rett syndrome is a neurodevelopmental disorder in girls who are heterozygous for a mutation in the X-linked gene MeCP2. Because cells in these individuals will be missing MeCP2 function only when the wild-type copy of the gene is on the inactive X, reactivation of the silenced copy of MeCP2 presents a potential therapeutic strategy. To identify genes that silence MeCP2 on the inactive X and that could therefore prove valuable as therapeutic targets, we carried out a screen for genes whose down-regulation reactivated a MeCP2 reporter on the inactive X. The 30 genes we have identified reveal a genetic circuitry required for maintenance of X-chromosome inactivation in differentiated cells and a large number of targets suitable for pharmacologic intervention. Rett syndrome (RS) is a debilitating neurological disorder affecting mostly girls with heterozygous mutations in the gene encoding the methyl-CpG–binding protein MeCP2 on the X chromosome. Because restoration of MeCP2 expression in a mouse model reverses neurologic deficits in adult animals, reactivation of the wild-type copy of MeCP2 on the inactive X chromosome (Xi) presents a therapeutic opportunity in RS. To identify genes involved in MeCP2 silencing, we screened a library of 60,000 shRNAs using a cell line with a MeCP2 reporter on the Xi and found 30 genes clustered in seven functional groups. More than half encoded proteins with known enzymatic activity, and six were members of the bone morphogenetic protein (BMP)/TGF-β pathway. shRNAs directed against each of these six genes down-regulated X-inactive specific transcript (XIST), a key player in X-chromosome inactivation that encodes an RNA that coats the silent X chromosome, and modulation of regulators of this pathway both in cell culture and in mice demonstrated robust regulation of XIST. Moreover, we show that Rnf12, an X-encoded ubiquitin ligase important for initiation of X-chromosome inactivation and XIST transcription in ES cells, also plays a role in maintenance of the inactive state through regulation of BMP/TGF-β signaling. Our results identify pharmacologically suitable targets for reactivation of MeCP2 on the Xi and a genetic circuitry that maintains XIST expression and X-chromosome inactivation in differentiated cells.
Detection of circulating tumor cells by reverse transcription-quantitative polymerase chain reaction and magnetic activated cell sorting in the peripheral blood of patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. Circulating tumor cells (CTCs) are considered a major cause of recurrence and metastasis in cancer; however, the detection of CTCs is challenging owing to their very low numbers in peripheral blood (around 10 CTCs per 1,000,000 erythrocytes). Cancer-testis antigens (CTAs) are specific tumor markers for CTCs. The present study aimed to evaluate the sensitivity and specificity of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for the detection of nine CTAs as well as placenta-specific antigen 1 (PLAC1) in peripheral blood mononuclear cell (PBMC) samples collected from 51 patients with HCC. The effectiveness of magnetic-activated cell sorting (MACS) for tumor-cell enrichment, through the depletion of CD45+ leukocytes in PBMC samples, was also assessed. Immunocytochemistry along with hematoxylin and eosin staining demonstrated that RT-qPCR achieved an overall positive detection rate for CTAs and PLAC1 of 70.6%; the highest rates were observed for melanoma-associated antigen A3 (MAGEA3), synovial sarcoma X breakpoint 1, MAGEA1, NY-ESO-1, L antigen 1 and PLAC1. MACS-detected intact CTCs in PBMCs were confirmed by H&E staining and morphological assessment; 12 out of 19 (63.2%) patients were identified as positive for CTAs. Screening for these five CTAs and PLAC1 by RT-qPCR may offer a potentially valuable prognostic tool with good sensitivity and specificity in patients with HCC that may be enhanced by MACS.