Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of protease-activated receptor 1 (PAR1) on platelets and responsiveness to thrombin receptor activating peptide (TRAP) during systemic inflammation in humans

Summary Thrombin is a coagulation protease that activates platelets, endothelial cells, leukocytes and mesenchymal cells. Thrombin signaling is mediated at least in part by protease-activated receptors (PARs). As little is known about the in vivoregulation of PAR1, this study aimed to characterize the effects of systemic thrombin formation during human endotoxemia on the regulation of PAR1 and the associated responsiveness of human platelets to thrombin receptor activating peptide (TRAP). Endotoxin (2 ng/kg) was infused into 40 healthy men to study the regulation of PAR1 in systemic human inflammation. The SPAN12 antibody was used to determine the in vivoregulation of PAR1. To measure whether modulation of the PAR1 receptor may be associated with altered platelet reactivity, whole blood was stimulated with TRAP ex vivo. Thrombin generation was determined by prothrombin (F1+2) fragment. F1+2levels increased almost 9-fold from 0.5±0.1 nmol/L to 4.5±1.9 nmol/L at 4 h (p<0.001). PAR1 decreased by ~8% (p<0.001) within 2 h after endotoxin infusion and stayed at those levels until 6 h. Concomitantly, TRAP induced P-selectin expression maximally decreased by 18% (p<0.001) at 6 h. In conclusion, PAR1 expression is down-regulated on platelets during systemic thrombin formation induced by inflammation in humans which results in decreased responsiveness to subsequent stimulation of the PAR1 receptor.
Effect of varying the mitomycin-C treatment area in glaucoma filtration surgery in the rabbit.

PURPOSE To investigate the effect of varying the treatment area of subconjunctival mitomycin-C (MMC) using an adapted rabbit model of filtration surgery. METHODS Twenty-four New Zealand White rabbits underwent filtration surgery, with random allocation to one of three treatments: 5-minute subconjunctival applications of MMC (0.4 mg/ml) with either a large (8 x 10 mm) or small (4 x 2 mm) sponge or no treatment (control). Drainage was achieved by placing an intravenous cannula through a scleral tunnel into the anterior chamber. Rabbits were examined at set intervals for up to 30 days after surgery. Measurements of appearance, size, height, and vascularity of blebs and of intraocular pressure and anterior chamber depth were made by a masked observer. Histologic analysis of eyes was performed at 3, 14, and 30 days. RESULTS Statistical analysis showed a significant difference in bleb survival among all groups (log rank P = 0.0054, with 100% survival with large areas of MMC treatment). Comparison between large and small treatment area groups revealed significant differences in bleb survival (log rank P = 0.0388); bleb area (between-subject analysis, P = 0.009), and bleb height (between-subject analysis, P = 0.005). These differences were seen clinically, with large areas of MMC treatment producing diffuse and elevated blebs, small areas of treatment producing thin-walled and localized blebs with scarring at 21 days, and no treatment resulting in comparatively vascularized and scarred blebs before 14 days. Histologic analysis revealed clear differences among groups, with an increase in subconjunctival cellularity and scar tissue in eyes with failed blebs. CONCLUSIONS The size of the area of subconjunctival MMC treatment significantly affects surgical outcome. Histologic features mirror differences observed clinically. Alteration of the size of the MMC treatment area may provide an alternative and more controllable approach to modulating the wound-healing response after drainage surgery and, more important in the clinical context, to modifying bleb morphology.
Distal humerus cortical strains following total elbow arthroplasty

The aseptic loosening of total elbow replacements is a serious complication resulting in significant patient morbidity. It is thought to occur secondary to stress shielding of the distal humeral cortex by the stiff stem of the implant. Some total elbow prostheses incorporate an anterior flange intended to improve implant stability and peri-articular load transfer in an attempt to reduce this effect. However, few studies have directly assessed the changes in cortical strains following total elbow arthroplasty or the biomechanical advantage of the anterior flange design. A regular and a long flange Coonrad–Morrey total elbow prosthesis were implanted into six Sawbone synthetic humeri. The constructs were subjected to physiological loads in axial compression (500 N), antero-posterior bending (50 N) and antero-posterior compression with condylar supports (300 N). Digital image correlation was used to measure the distal antero-lateral cortical strains and the results compared with those of whole Sawbones that had been tested in the same way. Significant stress shielding was demonstrated over the distal humeral cortex following prosthesis implantation during axial compression. In contrast, cortical strains increased following prosthesis implantation during antero-posterior compression with condylar supports. The increase in cortical strains following total elbow arthroplasty may help to maintain the integrity of the anterior cortex offering additional stability for implants with an anterior flange. These results are important for the development of future total elbow prosthesis designs and indicate that simulating the action of the forearm muscles is essential when evaluating changes in strain about the distal humerus in vitro.
Body mass index and risk of malignant lymphoma in Scandinavian men and women.

BACKGROUND The incidence of non-Hodgkin lymphoma and prevalence of obesity are increasing globally. A suggested positive association between obesity and risk of non-Hodgkin lymphoma has prompted us to investigate the relationship between body mass index (BMI) and risk of malignant lymphoma subtypes in a population-based case-control study. METHODS Telephone interviews were conducted with 3055 case patients with non-Hodgkin lymphoma and 618 case patients with Hodgkin lymphoma diagnosed between October 1, 1999, and August 30, 2002, and 3187 population-based control subjects. The interviews assessed current height, normal adult weight, and other possible risk factors. Multivariable odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for risk of lymphoma were estimated by unconditional logistic regression. All statistical tests were two-sided. RESULTS BMI was not associated with risk of overall non-Hodgkin lymphoma or of Hodgkin lymphoma (for example, comparing the highly obese group [BMI > or =35.0 kg/m2] with the normal-weight group [BMI = 18.5-24.9 kg/m2], OR for risk of non-Hodgkin lymphoma = 0.9, 95% CI = 0.6 to 1.3; P(trend) across all categories of BMI = . 27). BMI was also not associated with risk of any non-Hodgkin lymphoma subtype evaluated, although there was some evidence of a positive association with risk of diffuse large B-cell lymphoma (for example, comparing the highly obese group with the normal-weight group, OR for diffuse large B-cell lymphoma = 1.5, 95% CI = 0.9 to 2.4; P(trend) =. 05). CONCLUSIONS Excess weight does not appear to be associated with an increased risk of malignant lymphoma in general, or with a risk of most major lymphoma subtypes. Hence, the growing incidence of obesity is unlikely to be an important contributor to the increasing incidence of non-Hodgkin lymphoma worldwide.
Stop-and-go approximation effects on COSMO-SkyMed spotlight SAR data

Spotlight SAR data processing is already an established topic; efficient and accurate solutions have been proposed over the last years. However, the assumptions of these algorithms start to be invalid when applied to high-resolution spotlight SAR data. In particular the motion of the satellite during the transmission and reception of the chirp signal deteriorate the impulse response function (IRF), if not properly considered (so called stop-and-go approximation). In this paper stop-and-go approximation effects on COSMO-SkyMed (CSK) civilian spotlight SAR data are showed, demonstrating that it plays a not negligible role on SAR images with a resolution in the meter regime. A new data processing chain including stop-and-go correction is proposed, for high precision image formation of CSK civilian spotlight SAR data. The proposed approach is validated using real data acquired by CSK satellites in the civilian spotlight mode.
Trust and Antitrust

Whether or not everything which matters to us is the sort of thing that can thrive or languish (I may care most about my stamp collection) or even whether all the possibly thriving things we care about need trust in order to thrive (does my rubber tree? ), there surely is something basically right about Bok's claim. Given that I cannot myself guard my stamp collection at all times, nor take my rubber tree with me on my travels, the custody of these things that matter to me must often be transferred to others, presumably to others I trust. Without trust, what matters to me would be unsafe, unless like the Stoic I attach myself only to what can thrive, or be safe from harm, however others act. The starry heavens above and the moral law within had better be about the only things that matter to me, if there is no one I can trust in any way. Even my own Stoic virtue will surely thrive better if it evokes some trust from others, inspires some trustworthiness in them, or is approved and imitated by them. To Bok's statement, however, we should add another, that not all the things that thrive when there is trust between people, and which matter, are things that should be encouraged to thrive. Exploitation and
Epithelial thickness profile as a method to evaluate the effectiveness of collagen cross-linking treatment after corneal ectasia.

PURPOSE To illustrate the hypothesis that epithelial thickness profile maps could be a useful adjunct to topography in monitoring patients after corneal collagen cross-linking (CXL) treatment. METHODS Epithelial thickness profile in vivo was measured by Artemis very high-frequency (VHF) digital ultrasound scanning (ArcScan Inc) across the central 10-mm corneal diameter of a patient before collagen CXL for corneal ectasia after LASIK and at intervals up to 2 years later. Manifest refraction, corneal topography, and corneal front-surface aberrations were also monitored. Epithelial thickness changes were cross-correlated with corneal topography changes and corneal front-surface aberration changes. RESULTS Corneal collagen CXL appeared effective in halting the progression of corneal ectasia. Manifest refraction showed a reduction in spherical equivalent over time after CXL in both eyes. Corneal topography demonstrated stable central keratometry in both eyes. Corneal wavefront aberrations demonstrated a reduction of higher order root-mean-square coma and spherical aberration in both eyes. The epithelial thickness profile was altered, with a slight reduction of the area of epithelial thinning and decreased peripheral thickening. This resulted in minimizing the difference between the thinnest and thickest epithelium and might indicate an improvement of the condition. There were no significant changes in minimum stromal and minimum corneal thicknesses. CONCLUSIONS Epithelial thickness maps provide useful information for monitoring the progression of corneal ectasia after corneal collagen CXL, showing in this case, at least no further progression of the ectasia.
Enhanced suppression of pulmonary metastasis of malignant melanoma cells by combined administration of α‐galactosylceramide and interleukin‐18

α‐Galactosylceramide (α‐GalCer) shows antitumor effects by activating natural killer (NK) cells indirectly through stimulation of the secretion of cytokines by NKT cells, whereas interleukin (IL)‐18 shows antitumor effects by activating NK cells directly. In the present study, we examined the antitumor effect of the combined administration of α‐GalCer and IL‐18. An injection of NK cell‐sensitive mouse B16 melanoma cells into a mouse tail vein produced pulmonary metastasis. The daily administration of α‐GalCer or IL‐18 alone for 4 days starting 1 day after the injection of B16 melanoma cells markedly suppressed the number of pulmonary metastatic foci, and their combined administration enhanced the antitumor effect compared with single administration. The antitumor effect of their combined administration was completely abolished by treatment of mice with anti‐asialo GM1 serum, which depletes NK cells but not NKT cells. Combined administration of α‐GalCer and IL‐18 enhanced the cytotoxicity of NK cells and increased the number of NK cells in the lung. Analysis of NKT cell‐dependent and NK cell‐independent secretion of cytokines, to which NK cells can respond, showed that the administration of α‐GalCer increased the secretion of IL‐2, IL‐4, interferon‐γ, IL‐12, granulocyte‐macrophage colony‐stimulating factor, tumor necrosis factor‐α, and IL‐10, and the combined administration of α‐GalCer and IL‐18 enhanced the secretion of IL‐2, IL‐4, interferon‐γ, and granulocyte‐macrophage colony‐stimulating factor further but only slightly. These results show that IL‐18 in combination with α‐GalCer exerts an antitumor effect on NK cell‐sensitive tumors primarily by the direct stimulation of NK cells by IL‐18 and the indirect stimulation of NK cells by α‐GalCer through its activation of NKT cells. (Cancer Sci 2008; 99: 113–120)
'Liver let die': oxidative DNA damage and hepatotropic viruses.

Chronic infections by the hepatotropic viruses hepatitis B virus (HBV) and hepatitis C virus (HCV) are major risk factors for the development of hepatocellular carcinoma (HCC). It is estimated that more than 700,000 individuals per year die from HCC, and around 80 % of HCC is attributable to HBV or HCV infection. Despite the clear clinical importance of virus-associated HCC, the underlying molecular mechanisms remain largely elusive. Oxidative stress, in particular DNA lesions associated with oxidative damage, play a major contributory role in carcinogenesis, and are strongly linked to the development of many cancers, including HCC. A large body of evidence demonstrates that both HBV and HCV induce hepatic oxidative stress, with increased oxidative DNA damage being observed both in infected individuals and in murine models of infection. Here, we review the impact of HBV and HCV on the incidence and repair of oxidative DNA damage. We begin by giving a brief overview of oxidative stress and the repair of DNA lesions induced by oxidative stress. We then review in detail the evidence surrounding the mechanisms by which both viruses stimulate oxidative stress, before focusing on how the viral proteins themselves may perturb the cellular response to oxidative DNA damage, impacting upon genome stability and thus hepatocarcinogenesis.
Cognitive Dysfunctions in Bipolar Disorder: Evidence of Neuropsychological Disturbances

Although cognitive dysfunctions in psychosis have classically been associated with schizophrenia, there is clinical evidence that some bipolar patients show cognitive disturbances either during acute phases or in remission periods. The authors critically review the data on cognitive impairment in bipolar disorder. The main computerized databases (Medline, Psychological Abstracts, Current Contents) have been consulted crossing the terms ‘cognitive deficits’, ‘neuropsychology’, ‘intellectual impairment’, ‘mania’, ‘depression’ and ‘bipolar disorder’. Changes in the fluency of thought and speech, learning and memory impairment, and disturbances in associational patterns and attentional processes are as fundamental to depression and mania as are changes in mood and behavior. Moreover, a significant number of bipolar patients show persistent cognitive deficits during remission from affective symptoms. However, there are several methodological pitfalls in most studies such as unclear remission criteria, diagnostic heterogeneity, small sample sizes, absence of longitudinal assessment, practice effect and poor control of the influence of pharmacological treatment. Most studies point at the presence of diffuse cognitive dysfunction during the acute phases of bipolar illness. Most of these deficits seem to remit during periods of euthymia, but some of them may persist in approximately one third of bipolar patients. Methodological limitations warrant further research in order to clear up the relationship between neuropsychological functioning and clinical, demographic and treatment variables in bipolar disorder.
Microbial Ecophysiology of Whey Biomethanation: Characterization of Bacterial Trophic Populations and Prevalent Species in Continuous Culture

The organization and species composition of bacterial trophic groups associated with lactose biomethanation were investigated in a whey-processing chemostat by enumeration, isolation, and general characterization studies. The bacteria were spatially organized as free-living forms and as self-immobilized forms appearing in flocs. Three dominant bacterial trophic group populations were present (in most probable number per milliliter) whose species numbers varied with the substrate consumed: hydrolytic, 1010; acetogenic, 107 to 1010; and methanogenic, 106 to 109. The three prevalent species utilizing lactose were identified as Leuconostoc mesenteroides, Klebsiella oxytoca, and Clostridium butyricum. Clostridium propionicum and Desulfovibrio vulgaris were the dominant lactate-consuming, hydrogen-producing acetogenic bacteria, while D. vulgaris was the only significant ethanol-degrading species. Methanosarcina barkeri and Methanothrix soehngenii were identified as the dominant acetate-utilizing methanogens, and Methanobacterium formicicum was the prevalent hydrogen-utilizing methanogen. A microbial food chain is proposed for lactose biomethanation that comprises multiple species in three different groups, with the major hydrogen-producing acetogen being a sulfate-reducing species, D. vulgaris, which functioned in the absence of significant levels of environmental sulfate.
Establishment of a reference interval for urinary neutrophil gelatinase-associated lipocalin

Introduction Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a promising new biomarker for the early identification of acute kidney injury (AKI). We have determined a reference range in a large healthy population. In addition, as NGAL is a neutrophil-related protein, we investigated whether the presence of leukocyturia has the potential to significantly alter the specificity of NGAL in the diagnosis of AKI. Methods One hundred and seventy-four subjects (100 men, 74 women ranging from 19 to 88 y) were included in the reference population. Urinary NGAL was analysed on the Abbott ARCHITECT and results expressed in mass (μg/L) and also normalized to urinary creatinine (μg/mmol). Fifty-two leukocyturic urine samples were also analysed for NGAL. Results The 95th centile for NGAL was determined to be 107 μg/L (13 μg/mmol). There were significant gender-related differences for NGAL, with women having higher concentrations. There were significant age-related differences for NGAL between the 40–59 and 60–88 y age categories. There were significant age-related differences between the <40 and 60–88 y categories when NGAL was normalized to creatinine. In addition, we found significantly higher concentrations of NGAL in leukocyturia (P < 0.0001). Conclusions We have established a 95th centile cut-off for urinary NGAL in a reference population. We have demonstrated the important potential interference of leukocyturia in confounding the interpretation of NGAL in the diagnosis of AKI.
A predictive model for evaluating responsiveness to pemetrexed treatment in patients with advanced colorectal cancer.

PURPOSE To highlight the potential factors that could predict the response rate of patients with metastatic colorectal cancer (mCRC) treated with pemetrexed combined chemotherapy after first- or second-line chemotherapy using the FOLFOX regimen. MATERIALS AND METHODS Between January 2007 and July 2014, 54 patients diagnosed and pathologically-confirmed with advanced colorectal cancer in Jiangsu Cancer Hospital and Research Institute, were enrolled. They received pemetrexed at a dose of 500mg/m2 by 10 minute infusion on day 1, repeated every 3 weeks. Doses were modified depending on nadir counts of blood cells. Combined chemotherapeutic agents included irinotecan, lobaplatin, carboplatin, oxaliplatin, gemcitabine, cis-platinum or bevacizumab. Multiple variables (age, sex, hemoglobin, platinum drugs combined, metastasis sites, LDH, ALP, CEA>40 ug/ml) reported earlier were selected.We used logistic regression analysis to evaluate relationships between these and tumor response. RESULTS On multivariable analysis, we found that age was significant in predicting the responsiveness to pemetrexed (p<0.05) combined with oxaliplatin. We did not find any other factors which were significantly associated with the response rate to chemotherapy with pemetrexed and irinotecan. CONCLUSIONS By multivariate analysis, we found that age had significant impact on the responsiveness of pemetrexed when combined with oxaliplatin. Additional research based on genomic properties of host and tumors are needed to clarify markers for better selection of patients who could benefit from pemetrexed combined chemotherapy.
Mechanism of Sorting Proopiomelanocortin and Proenkephalin to the Regulated Secretory Pathway of Neuroendocrine Cells

Abstract: Proopiomelanocortin (POMC) and proenkephalin (PE) are synthesized at the endoplasmic reticulum and transported to the trans‐Golgi network (TGN) where they are sorted and packaged into dense‐core granules of the regulated secretory pathway (RSP). The mechanism of sorting POMC and PE to the RSP in neuroendocrine cells was investigated. Consensus sorting signals comprising two acidic residues and two hydrophobic residues exposed on the surface of N‐POMC1‐26 and N‐PE1‐32 were identified and shown to be sufficient and necessary for targeting POMC and PE to the RSP in PC12, Neuro2a, and AtT‐20 cells. The acidic residues of these sorting signals bind specifically to basic residues on the sorting receptor membrane, carboxypeptidase E (CPE), to effect sorting to the RSP. Analysis of POMC and PE sorting in Neuro2a cells depleted of CPE by CPE antisense RNA, and Cpefat/fat mouse pituitary cells lacking CPE showed missorting of both these molecules to the constitutive pathway in vivo. Thus, POMC and PE are sorted to the RSP at the TGN by a mechanism involving the interaction of a specific sorting signal on these molecules with the sorting receptor, CPE.