Miracle-dz/UniFAR-FTUs huggingface dataset:
Biocompatibility and functionality of a tissue-engineered living corneal stroma transplanted in the feline eye.

PURPOSE Corneal tissue shortage has become a major concern worldwide, which has motivated the search for alternative solutions to eye bank human eyes for corneal transplantation. Minimally invasive lamellar transplantation and tissue engineering may offer new opportunities for the rehabilitation of diseased corneas. The aim of this study was to evaluate the biocompatibility and functionality of stromal lamellar grafts tissue-engineered (TE) in vitro and transplanted in vivo in the cornea of a feline model. METHODS The corneal stromas were engineered in culture from corneal stromal cells using the self-assembly approach, without the addition of exogenous material or scaffold. Eight healthy animals underwent two intrastromal grafts in one eye and the contralateral eye was used as a control. Animals were followed with slit-lamp ophthalmic examination, corneal esthesiometry and optical coherent tomography. Confocal microscopy, immunofluorescence, histology, and transmission electron microscopy (TEM) were performed at 4 months. RESULTS Four months after transplantation, the TE-stromal grafts were transparent, functional, and well tolerated by the eye. All grafts remained avascular, with no signs of immune rejection, despite a short course of low-dose topical steroids. Corneal sensitivity returned to preoperative level and reinnervation of the grafts was confirmed by confocal microscopy and immunofluorescence. Histology and TEM of the TE-grafts showed a lamellar stromal structure with regular collagen fibril arrangement. CONCLUSIONS These results open the way to an entirely new therapeutic modality. Intracorneal filling using a biocompatible, transparent, and malleable TE-stroma could be the basis for multiple types of novel therapeutic options in corneal interventional surgery.
Genetic and Proteomic Features Associated with Survival after Treatment with Erlotinib in First-Line Therapy of Non-small Cell Lung Cancer in Eastern Cooperative Oncology Group 3503

Introduction: Serum proteomics and mutations in the epidermal growth factor receptor (EGFR) and KRAS have been associated with benefit after therapy with EGFR-targeted therapies in non-small cell lung cancer, but all three have not been evaluated in any one study. Hypothesis: Pretreatment serum proteomics predicts survival in Western advanced non-small cell lung cancer patients with wild-type EGFR and independent of KRAS mutation status. Methods: We analyzed available biospecimens from Eastern Cooperative Oncology Group 3503, a single-arm phase II study of erlotinib in first-line advanced lung cancer, for proteomics signatures in the previously described serum matrix-assisted laser desorption ionization proteomic classifier (VeriStrat) as well as for KRAS and EGFR mutations. Results: Out of 137 enrolled patients, analyzable biologic samples were available on 102. Nine of 41 (22%) demonstrated KRAS mutations and 3 of 41 (7%) harbored EGFR mutations. VeriStrat classification identified 64 of 88 (73%) as predicted to have “good” and 24 of 88 (27%) predicted to have “poor” outcomes. A statistically significant correlation of VeriStrat status (p < 0.001) was found with survival. EGFR mutations, but not KRAS mutations, also correlated with survival. Conclusions: The previously defined matrix-assisted laser desorption ionization predictor remains a potent and highly clinically significant predictor of survival after first-line treatment with erlotinib in patients with wild-type EGFR and independent of mutations in KRAS.
The importance of transformational leadership style for the well-being of employees working with older people.

AIM This paper is a report of a study to explore the relationships between transformational leadership, followers' perceived working conditions and employee well-being and job satisfaction. BACKGROUND There is some evidence that transformational leadership style is linked to employee job satisfaction and well-being. However, it is not clear whether this is due to (i) a direct relationship between leadership and job satisfaction and well-being outcomes or (ii) whether followers' perceived working conditions mediate this relationship. METHODS A cross-sectional design was applied to data from a questionnaire study of 447 staff caring for older people in Denmark. Data were collected in 2005. A theory-driven model of the relationships between leadership, working conditions, job satisfaction and well-being was tested using structural equation modelling. RESULTS The transformational leadership style was closely associated with followers' working conditions, namely involvement, influence and meaningfulness. Involvement was associated with job satisfaction and meaningfulness was associated with well-being. However, working conditions were closely correlated with each other, and thus the mediating mechanisms may operate through several different working conditions. A direct path between leadership behaviour and employee well-being was also found. CONCLUSION Considering working conditions in the absence of studying leadership behaviour (or vice versa) may reveal an incomplete picture of the impact of work and work relationships on well-being. Work re-design interventions focused on influence may benefit from the consideration of training managers to exert transformational leadership behaviours.
Uptake of Lipoprotein‐Associated α‐Tocopherol by Primary Porcine Brain Capillary Endothelial Cells

Abstract: From the severe neurological syndromes resulting from vitamin E deficiency, it is evident that an adequate supply of the brain with α‐tocopherol (αTocH), the biologically most active member of the vitamin E family, is of utmost importance. However, uptake mechanisms of αTocH in cells constituting the blood‐brain barrier are obscure. Therefore, we studied the interaction of low (LDL) and high (HDL) density lipoproteins (the major carriers of αTocH in the circulation) with monolayers of primary porcine brain capillary endothelial cells (pBCECs) and compared the ability of these two lipoprotein classes to transfer lipoprotein‐associated αTocH to pBCECs. With regard to potential binding proteins, we could identify the presence of the LDL receptor and a putative HDL3 binding protein with an apparent molecular mass of 100 kDa. At 4°C, pBCECs bound LDL with high affinity (KD = 6 nM) and apolipoprotein E‐free HDL3 with low affinity (98 nM). The binding capacity was 20,000 (LDL) and 200,000 (HDL3) lipoprotein particles per cell. αTocH uptake was approximately threefold higher from HDL3 than from LDL when [14C]αTocH‐labeled lipoprotein preparations were used. The majority of HDL3‐associated αTocH was taken up in a lipoprotein particle‐independent manner, exceeding HDL3 holoparticle uptake 8‐ to 20‐fold. This uptake route is less important for LDL‐associated αTocH (αTocH uptake ∼1.5‐fold higher than holoparticle uptake). In line with tracer experiments, mass transfer studies with unlabeled lipoproteins revealed that αTocH uptake from HDL3 was almost fivefold more efficient than from LDL. Biodiscrimination studies indicated that uptake efficacy for the eight different stereoisomers of synthetic αTocH is nearly identical. Our findings indicate that HDL could play a major role in supplying the central nervous system with αTocH in vivo.
Predicting the clinical significance of red cell alloantibodies using a monocyte monolayer assay

Few data have been published that correlate in vitro monocyte monolayer assays (MMA) and red cell (RBC) survival in patients with alloantibodies of unknown significance. Over the past 6 years we gathered clinical correlations in 12 patients with the following antibodies: anti‐Lan (three patients), ‐Ge (three patients), ‐Yta (five patients), and ‐Ytb (one patient). RBC survival was estimated using 51Cr studies in seven patients and follow‐up of transfusion of incompatible blood in the other five. Six patients with no evidence of RBC destruction had negative MMA findings (anti‐Lan [one patient], ‐Ge [two patients], and ‐Yta [three patients]). Five patients with evidence of in vivo RBC destruction had significant MMA results. The two clinically significant anti‐Lans required fresh serum to give a meaningful MMA result. One patient (anti‐Ytb) had an MMA result of borderline significance‐normal 51Cr RBC survival at 1 hour‐but a reduced T50Cr. The MMA we used appeared to predict the clinical outcome of transfusion in every patient with antibodies to high‐frequency antigens whom we tested.
The Key Challenge for Canadian Public Policy: Generating Inclusive and Sustainable Economic Growth

Recent economic and fiscal projections produced by the Centre for the Study of Living Standards suggest that revenue growth over the next 23 years in most provinces and territories will be insufficient to maintain recent i ncreases in health expenditures while holding other spending constant on a real per capita basis. Motivated by these fiscal challenge s , we present a series of policy recommendations for Canada’s governments at all levels to foster greater economic growth. Higher GDP not only offers a means to raise government revenues, it also directly raises the well - being of Canadians. We consider options to boost economic growth in two broad ways. First, by boosting Canada’s productivity performance through policies pro moting private and public investment, education, technological innovation and diffusion, and trade. Second, by tapping into Canada’s underutilized labour supply, particularly by assisting women, older workers, persons with disabilities , Aboriginal people, and immigrants in successfully participating in the workforce. The recommendations in this report are guided by the Organization of Economic Co - operation and Development’ s green growth and inclusive growth frameworks and by the idea that government should take a more active role in supporting the economic activities of individuals and businesses.
Saliva and Serum Concentration of Lamotrigine in Patients With Epilepsy

The authors examined the interindividual correlation between saliva and serum concentrations of lamotrigine (LTG) and the relationship between LTG concentration in saliva and the free LTG concentration in serum in 40 patients with epilepsy, aged 16 to 73 years, receiving stable doses of LTG and comedication. Saliva was collected before and after stimulation of salivary flow. The free LTG fraction was determined by equilibrium dialysis and ultrafiltration. Drug analysis was performed by high-performance liquid chromatography . The correlation between LTG daily dose and serum concentration was weak but significant (r = 0.47). There was high correlation between LTG concentration in serum and unstimulated (r = 0.85) or stimulated (r = 0.94) saliva, and between total LTG concentration in serum and the free LTG fraction as determined by ultrafiltration (r = 0.95) and equilibrium dialysis (r = 0.93). Lamotrigine concentration in stimulated saliva was significantly correlated to the free LTG fraction. Protein binding of LTG calculated from concentration in stimulated saliva, as determined by ultrafiltration and equilibrium dialysis, was 51.8% ± 13.03%, 68.05% ± 7.59%, and 58.72% ± 7.68% (mean ± standard deviation) respectively. The differences between the three methods were significant. The authors conclude that saliva sampling may be a useful alternative to blood tests for monitoring LTG treatment.
Endogenous histamine in the medial septum–diagonal band complex increases the release of acetylcholine from the hippocampus: a dual‐probe microdialysis study in the freely moving rat

The effects of histaminergic ligands on both ACh spontaneous release from the hippocampus and the expression of c‐fos in the medial septum–diagonal band (MSA‐DB) of freely moving rats were investigated. Because the majority of cholinergic innervation to the hippocampus is provided by MSA‐DB neurons, we used the dual‐probe microdialysis technique to apply drugs to the MSA‐DB and record the induced effects in the projection area. Perfusion of MSA‐DB with high‐KCl medium strongly stimulated hippocampal ACh release which, conversely, was significantly reduced by intra‐MSA‐DB administration of tetrodotoxin. Histamine or the H2 receptor agonist dimaprit, applied directly to the hippocampus, failed to alter ACh release. Conversely, perfusion of MSA‐DB with these two compounds increased ACh release from the hippocampus. Also, thioperamide and ciproxifan, two H3 receptor antagonists, administered into MSA‐DB, increased the release of hippocampal ACh, whereas R‐α‐methylhistamine, an H3 receptor agonist, produced the opposite effect. The blockade of MSA‐DB H2 receptors, caused by local perfusion with the H2 receptor antagonist cimetidine, moderated the spontaneous release of hippocampal ACh and antagonized the facilitation produced by H3 receptor antagonists. Triprolidine, an H1 receptor antagonist, was without effect. Moreover, cells expressing c‐fos immunoreactivity were significantly more numerous in ciproxifan‐ or thioperamide‐treated rats than in controls, although no colocalization of anti‐c‐fos and anti‐ChAT immunoreactivity was observed. These results indicate a role for endogenous histamine in modulating the cholinergic tone in the hippocampus.
Effect of a 3-year professional flossing program with chlorhexidine gel on approximal caries and cost of treatment in preschool children.

The aim was to evaluate the effect of chlorhexidine gel treatment on the incidence of approximal caries in preschool children. One hundred and seventeen 4-year-olds, divided into two groups, participated: (1) chlorhexidine gel group (n = 59), and (2) placebo gel group (n = 58). Group 1 was treated 4 times a year with a 1% chlorhexdine gel and group 2 with a placebo gel. Approximately 0.7 ml of gel was applied interdentally by means of a flat dental floss. A control group (group 3), which did not receive any flossing or gel treatment, was also included in the study (n = 116). After 3 years, i.e. when the children were 7 years old, the mean incidence of caries on approximal surfaces (defs), including both enamel and dentin lesions, was 2.59 in the chlorhexidine gel, 4.53 in the placebo gel and 4.20 in the control group (group 1 vs. 2 and group 1 vs. 3: p < 0.01). Mean number of approximal fillings at the end of the study, i.e. when the children were 7 years old, was 0.33 in the chlorhexidine gel, 1.04 in the placebo gel and 0.80 in the control group (group 1 vs. 2: p < 0.01; group 1 vs. 3: p < 0.05). The progression of approximal caries lesions, diagnosed on bitewing radiographs from the age of 5 to 7, was slower in the chlorhexidine than in the placebo gel group (the control group was not evaluated in this respect). A cost analysis, based on the total treatment time in minutes, showed a small gain for the flossing program. (ABSTRACT TRUNCATED AT 250 WORDS)
Risk Preferences Are Not Time Preferences: On the Elicitation of Time Preference under Conditions of Risk: Comment

Andreoni and Sprenger (2012a, b) report evidence that distinct utility functions govern choices under certainty and risk. I investigate the robustness of this result to the experimental design. I find that the effect disappears completely when a multiple price list instrument is used instead of a convex time budget design. Alternatively, the effect is reduced by half when sooner and later payment risks are realized using a single lottery instead of two independent lotteries. The result is thus at least partially driven by intertemporal diversification, supporting an explanation in terms of concavity of the intertemporal, and not only atemporal, utility function. (JEL C91, D81, D91)
PFKFB3 modulates glycolytic metabolism and alleviates endoplasmic reticulum stress in human osteoarthritis cartilage

Glycolytic disorder has been demonstrated to be a major cause of osteoarthritis (OA) and chondrocyte dysfunction. The present work aimed to investigate the expression and role of the glycolytic regulator 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase 3 (PFKFB3) in OA cartilage. It was found that PFKFB3 expression was down‐regulated in human OA cartilage tissues and in tumour necrosis factor (TNF)‐α‐ or interleukin (IL)‐1β‐stimulated human chondrocytes. The glycolytic metabolism appeared as glucose utilization and adenosine triphosphate (ATP) generation, and lactate production was stunted in OA cartilage. However, the impaired glycolytic process in OA cartilage was improved by PFKFB3 overexpression, which was confirmed in TNF‐α‐ or IL‐1β‐treated chondrocytes. Furthermore, the expressions of endoplasmic reticulum (ER) stress‐associated genes including PERK, ATF3, IRE1, phosphorylated eIF2α (p‐eIF2α) and MMP13 were enhanced in OA cartilage explants, while they were decreased by AdPFKFB3 transfection. PFKFB3 also modulated the expressions of PERK, ATF3, IRE1, p‐eIF2α and MMP13 in tunicamycin‐exposed chondrocytes. Additionally, PFKFB3 improved the cell viability of OA cartilage explants and chondrocytes through the PI3K/Akt/C/EBP homologous protein (CHOP) signalling pathway. The transfection of AdPFKFB3 also significantly reduced caspase 3 activation and promoted aggrecan and type II collagen expressions in OA cartilage explants and chondrocytes. In all, this study characterizes a novel role of PFKFB3 in glycolytic metabolism and ER stress of OA cartilage explants and chondrocytes. The study might provide a potential target for OA prevention or therapy.
The proteome under translational control

A single eukaryotic gene can give rise to a variety of protein forms (proteoforms) as a result of genetic variation and multilevel regulation of gene expression. In addition to alternative splicing, an increasing line of evidence shows that alternative translation contributes to the overall complexity of proteomes. Identifying the repertoire of proteins and micropeptides expressed by alternative selection of (near‐)cognate translation initiation sites and different reading frames however remains challenging with contemporary proteomics. MS‐enabled identification of proteoforms is expected to benefit from transcriptome and translatome data by the creation of customized and sample‐specific protein sequence databases. Here, we focus on contemporary integrative omics approaches that complement proteomics with DNA‐ and/or RNA‐oriented technologies to elucidate the mechanisms of translational control. Together, these technologies enable to map the translation (initiation) landscape and more comprehensively define the inventory of proteoforms raised upon alternative translation, thus assisting in the (re‐)annotation of genomes.
Treatment of carpometacarpal osteoarthritis by arthrodesis in 12 horses.

OBJECTIVE To evaluate arthrodesis as a treatment for carpometacarpal joint osteoarthritis (CMC-OA). STUDY DESIGN Case series. ANIMALS Horses (n=12) with CMC-OA. METHODS Arthrodesis was facilitated by insertion and fanning of a drill bit into the CMC joint at several (3-5) locations in 15 limbs. Follow-up radiographs were obtained for 7 horses (9 limbs). Outcome was determined by telephone survey of owners based on postoperative pain, return to use, appearance of the limb, and success of treatment. RESULTS Postoperative pain was slight or moderate in 10 of 12 (83%) horses during the first 30 days, and 11 of 12 (92%) horses were markedly improved by 6 months and capable of returning to work. Radiographically 6 CMC joints had a bony ankylosis at follow-up whereas 3 did not (mean 8.7 months). On long-term follow-up (mean 28.6 months) all horses had reduced severity of lameness, 10 of 12 (83%) were considered "sound," 8 (67%) returned to their original activity, and all owners considered arthrodesis highly successful as a treatment. CONCLUSION A drilling technique that produced CMC arthrodesis, allowed most horses to return to their original activity and was considered successful by all clients. CLINICAL RELEVANCE Arthrodesis of the CMC joint should be considered a treatment option for CMC-OA.
Resource-dependent livelihoods and the natural resource base

The natural resource base, terrestrial and marine, provides rural households in lower-income countries with income, food, shelter, and medicines, which are variously gathered and hunted in common lands and waters. These resources may be actively managed, either by the government or local community; or they may be de facto open access, with little effort by governments to prevent what may be de jure illegal extraction. This review appraises the literature that encompasses the direct value of wild resources to rural households, the extent to which these resources mitigate poverty and inequality, and the importance of the institutional context. More recent literature increasingly addresses competing demands on the resource base, which both supports nearby livelihoods and enhances ecosystem services such as biodiversity; and the extent to which initiatives such as community-based payments for ecosystem services change how people interact with the resource base.
Elevated Levels of Retinal Neurofilament mRNA Accompany Optic Nerve Regeneration

Abstract RNA isolated from goldfish retinas before and during optic nerve regeneration, when translated in vitro, directed the synthesis of neurofilament proteins that are normally found in high levels in the optic nerve. The major neurofilament proteins of the goldfish optic nerve comprise a group of four isoelectric variants of molecular weight 58,000 (58K) which we have identified previously as ON1‐ON4. The levels of ON1 and ON2 within the optic nerve had been shown to decrease shortly after optic nerve crush and then increase to precrush levels during the regeneration process. Employing two‐dimensional electrophoretic analysis of in vitro translation products and immunoprecipitations with antibodies specific for the ON proteins and an anti‐intermediate filament monoclonal antibody, we show that ON1 and ON2 are encoded by mRNA synthesized in the retinas. The synthesis of ON3 and ON4 by retina RNA was undetected. This confirms data from previous ex vivo experiments that indicated that ON1 and ON2 are of neuronal origin whereas ON3 and ON4 are nonneuronal. ON1 and ON2 synthesis increases dramatically during optic nerve regeneration to levels 10‐ and 30‐fold over precrush levels, respectively. In addition to ON, and ON2, the synthesis of a previously unidentified 52K protein is observed at relatively high levels 20 and 32 days after optic nerve crush, but is unobserved before regeneration. Thus, optic nerve regeneration can be correlated with specific changes in intermediate filament gene expression within the retina.
In vivo and in vitro effects of curcumin on head and neck carcinoma: a systematic review

BACKGROUND Head and neck squamous cell carcinoma (HNSCC) contributes globally to a great number of deaths and morbidity, in spite of new therapeutic strategies. There is a great need of new drugs that are significantly effective and less deleterious to the patients' general health. In this sense, phytotherapy is a tendency, with results pointing to its use as a chemo-preventive and adjuvant therapy. Therefore, the objective of this systematic review was to investigate the effects of curcumin on proliferation and survival of HNSCC. MATERIALS AND METHODS The search was conducted on six databases: Cochrane, LILACS, EMBASE, MEDLINE, PubMed, and Web of Science. In vitro and in vivo studies that evaluated the effects of curcumin on cell viability, tumor growth, cell cycle and/or cell death pattern in HNSCC cell lines or animal models were selected. RESULTS Of the 525 initially gathered studies, 30 met the inclusion criteria. These studies demonstrated that curcumin induces cytotoxicity, apoptosis (via intrinsic pathway), and cell cycle arrest in G2 /M phase in HSNCC cell lines. It also reduces tumor measurements in animal models. These events were mostly studied through MTT assay, flow cytometry, and cell cycle- and apoptosis-related proteins expression. CONCLUSION This systematic review demonstrated that curcumin is effective on HNSCC cell proliferation and survival, reinforcing the currently available evidence that curcumin could be an adjuvant drug in HNSCC treatment.