Miracle-dz/UniFAR-FTUs huggingface dataset:
High levels of glucocorticoid receptors in patients with active Crohn's disease may predict steroid resistance

Up to 20% of Crohn's disease (CD) patients respond poorly to glucocorticoids (GC). A product of an alternative splicing of the glucocorticoid receptor (GR) premRNA, GRβ, may play a role as a dominant inhibitor of the glucocorticoid response. Increasing evidence suggests that inflammatory cytokines such as interleukin (IL)‐18 alternate the splicing of the primary transcript between the two isoforms GRβ and GRα in hGR gene of CD patients. The aim of this study is to assess the expression of GRα and GRβ in patients with CD and to look for a possible correlation between these receptors and the response to glucocorticoid treatment. Forty‐two CD patients and 17 healthy volunteers were studied. Quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) was performed using real‐time PCR techniques. Serum IL‐18 protein levels were measured by enzyme‐linked immunosorbent assay (ELISA). The amount of hGRα‐mRNA in patients in remission was significantly lower than in controls (P < 0·05). The amount of hGRβ‐mRNA was significantly higher in GC‐resistant patients in the active stage of disease compared with all other groups (P < 0·05). Patients in the active stage of the disease had higher levels of IL‐18 than patients in remission and both had higher levels than controls (P < 0·05). The amounts of IL‐18 were directly correlated with the amount of hGRβ mRNA in GC‐resistant patients with an active disease. High levels of hGRβ might be connected to GC resistance. IL‐18 might participate in the alternative splicing of the hGR preliminary mRNA of CD patients. The results support the theory that augmented hGRβ mRNA expression level in PBMC is connected with GC‐resistance of CD patients.
NFATc1 Regulates PD-1 Expression upon T Cell Activation1

PD-1 is a transmembrane protein involved in the regulation of immunological tolerance. Multiple studies have reported an association between high levels of PD-1 expressed on T cell surfaces and exhaustion in lymphocyte populations when challenged by chronic viral infections, such as HIV. By using model systems consisting of murine EL4 cells, which constitutively express PD-1, and primary murine CD8 T cells that express PD-1 upon T cell stimulation, we have identified two tissue-specific hypersensitive sites at the 5′ CR of the PD-1 locus. Gene reporter assays in CD8 T cells have shown that one of these sites has robust transcriptional activity in response to cell stimulation. Cell treatment with the calcineurin inhibitor cyclosporine A or a NFAT-specific inhibitor led to a sharp reduction in PD-1 expression in the constitutive and inducible systems. Furthermore, analysis of this region by chromatin immunoprecipitation assay revealed NFATc1 binding associated with gene activation in EL4 and primary CD8 T cells. Mutation of the NFATc1 binding site in PD-1 reporter constructs resulted in a complete loss of promoter activity. Together, these results demonstrate that PD-1 gene regulation occurs in part via the recruitment of NFATc1 to a novel regulatory element at the pdcd1 locus and provides the molecular mechanism responsible for the induction of PD-1 in response to T cell stimulation.
Does swarming cause honey bees to update their solar ephemerides?

SUMMARY Spatial orientation in the social insects offers several examples of specialized learning mechanisms that underlie complex learning tasks. Here we study one of these systems: the processes by which honey bees update, or fail to update, their memories of the sun's daily pattern of movement (the solar ephemeris function) in relation to the landscape. Specifically, we ask whether bees that have initially learned the solar ephemeris function relative to a conspicuous treeline at their natal site can later realign the ephemeris to a differently oriented treeline. We first confirm and clarify an earlier finding that bees transplanted passively (by being carried) do not re-learn the solar ephemeris in relation to the new treeline. When they cannot detect the sun directly, as on overcast days, these transplanted bees use a solar ephemeris function appropriate for their natal site, despite days or weeks of experience at the new site. We then ask whether bees put through a swarming process as they are transplanted are induced to re-learn the solar ephemeris function at the new site, as swarming is a natural process wherein bees transplant themselves. Most of the swarmed bees failed to re-learn, even though they did extensive learning flights (in comparison with those of non-swarmed controls) as they first emerged from the hive at the new site. We hypothesize that the bees' representation of the solar ephemeris function is stored in an encapsulated cognitive module in which the ephemeris is inextricably linked to the reference landscape in which it was learned.
Tracheal mucus rheology in patients undergoing diagnostic bronchoscopy. Interrelations with smoking and cancer.

We examined the differences in tracheal mucus rheology between nonsmokers and smokers, and between smokers with and without lung cancer. Mucus was collected from patients undergoing diagnostic bronchoscopy without atropine by holding a cytology brush in contact with the tracheal mucosa for 10 to 15 s. Samples were obtained from 43 patients 24 to 79 yr of age: nine nonsmokers, 18 current smokers, and 16 exsmokers (greater than 6 months); 12 patients (nine smokers, three exsmokers) had lung cancer. Pulmonary function testing showed that the nonsmoker patients had significant restrictive lung disease, and the patients with cancer had significant irreversible airway obstruction. The viscoelastic properties of the mucus samples were determined by magnetic microrheometry. Two parameters are reported: G* (modulus of rigidity) and tan delta (loss tangent), each measured at 1 and 100 rad/s. G* is an index of overall deformability (elastic and viscous), and tan delta is the ratio of viscous to elastic deformability. For nonsmoker patients, the viscoelastic parameters were virtually identical to those found previously for normal volunteers. For smokers without cancer, the mucus had a lower value of tan delta 1 rad/s and therefore was predicted to be more easily transportable by ciliary action; for exsmokers without cancer, ciliary transportability as calculated from viscoelasticity was even higher because of both low tan delta and low G*. Mucus from patients with cancer was not significantly different from that of nonsmokers; however, the mucus was predicted to be less easily clearable by ciliary action than was that from smokers and exsmokers without cancer, mainly because of a higher tan delta at 1 rad/s. (ABSTRACT TRUNCATED AT 250 WORDS)
Coracoid Impingement

Subacromial impingement syndrome, or rotator cuff disease, is a common cause of shoulder pain. A less frequently recognized cause is coracoid or subcoracoid impingement. There have been only a few reports of this condition in the literature, and although there are definitely cases that go unrecognized, coracoid impingement is probably a relatively uncommon cause of shoulder pain. Patients with this disorder usually have localized pain anteriorly, especially with forward elevation, internal rotation, and cross arm adduction. Symptoms are presumed to be the result of impingement of the subscapularis tendon between the coracoid process and the lesser tuberosity. Initial treatment is nonoperative and based on activity modification and physical therapy, but operative decompression may be required if conservative measures fail. The following is a case report of coracoid impingement treated by operative decompression.
Functional Gene Diversity and Metabolic Potential of the Microbial Community in an Estuary-Shelf Environment

Microbes play crucial roles in various biogeochemical processes in the ocean, including carbon (C), nitrogen (N), and phosphorus (P) cycling. Functional gene diversity and the structure of the microbial community determines its metabolic potential and therefore its ecological function in the marine ecosystem. However, little is known about the functional gene composition and metabolic potential of bacterioplankton in estuary areas. The East China Sea (ECS) is a dynamic marginal ecosystem in the western Pacific Ocean that is mainly affected by input from the Changjiang River and the Kuroshio Current. Here, using a high-throughput functional gene microarray (GeoChip), we analyzed the functional gene diversity, composition, structure, and metabolic potential of microbial assemblages in different ECS water masses. Four water masses determined by temperature and salinity relationship showed different patterns of functional gene diversity and composition. Generally, functional gene diversity [Shannon–Weaner’s H and reciprocal of Simpson’s 1/(1-D)] in the surface water masses was higher than that in the bottom water masses. The different presence and proportion of functional genes involved in C, N, and P cycling among the bacteria of the different water masses showed different metabolic preferences of the microbial populations in the ECS. Genes involved in starch metabolism (amyA and nplT) showed higher proportion in microbial communities of the surface water masses than of the bottom water masses. In contrast, a higher proportion of genes involved in chitin degradation was observed in microorganisms of the bottom water masses. Moreover, we found a higher proportion of nitrogen fixation (nifH), transformation of hydroxylamine to nitrite (hao) and ammonification (gdh) genes in the microbial communities of the bottom water masses compared with those of the surface water masses. The spatial variation of microbial functional genes was significantly correlated with salinity, temperature, and chlorophyll based on canonical correspondence analysis, suggesting a significant influence of hydrologic conditions on water microbial communities. Our data provide new insights into better understanding of the functional potential of microbial communities in the complex estuarine-coastal environmental gradient of the ECS.
Molecular Background of miRNA Role in Asthma and COPD: An Updated Insight

Inflammatory airway diseases are a significant health problems requiring new approaches to the existing therapies and addressing fundamental issues. Difficulties in developing effective therapeutic strategies might be caused by lack of understanding of their exact molecular mechanism. MicroRNAs (miRNAs) are a class of regulators that already revolutionized the view of gene expression regulation. A cumulating number of investigations show a pivotal role of miRNAs in the pathogenesis of asthma, chronic obstructive pulmonary disease (COPD), or airway remodeling through the regulation of many pathways involved in their pathogenesis. Expression changes of several miRNAs have also been found to play a role in the development and/or improvement in asthma or COPD. Still, relatively little is known about the role of miRNAs in inflammatory disorders. The microRNA profiles may differ depending on the cell type or antigen-presenting cell. Based on the newest literature, this review discusses the current knowledge concerning miRNA contribution and influence on lung inflammation and chosen inflammatory airway diseases: asthma and COPD.
Reduced daily risk of glycemic variability: comparison of exenatide with insulin glargine.

BACKGROUND Conventional methods describing daily glycemic variability (i.e., standard deviation and coefficient of variation) do not express risk. Low and High Blood Glucose Indices (LBGI and HBGI, respectively) and Average Daily Risk Range (ADRR) are parameters derived from self-monitored blood glucose (SMBG) data that quantify risk of glycemic excursions and temporal aspects of variability. In the present study, variability parameters were used to assess effects of exenatide and insulin glargine on risk of acute blood glucose extremes. METHODS New (LBGI, HBGI, and ADRR) and conventional variability analyses were applied retrospectively to SMBG data from patients with type 2 diabetes suboptimally controlled with metformin and a sulfonylurea plus exenatide or insulin glargine as a next therapeutic step. Exenatide- (n = 282) and insulin glargine-treated (n = 267) patients were well matched. RESULTS Exenatide treatment reduced ADRR overall (exenatide, mean +/- SEM, 16.33 +/- 0.45; insulin glargine, 18.54 +/- 0.49; P = 0.001). Seventy-seven percent of exenatide-treated patients were at low risk for glucose variability compared with 62% of glargine-treated patients (P = 0.00023). LBGI for exenatide remained minimal for all categories and significantly lower than glargine for all comparisons, and HBGI for exenatide remained low or moderate for all categories and significantly lower than glargine after the morning and evening meals. Reduced variability in exenatide-treated patients was shown by conventional methods but provided no indications of risk. CONCLUSIONS Average glycemic control was similar for both treatment groups. However, exenatide treatment minimized risk for glycemic variability and extremes to a greater degree than insulin glargine treatment.
Factors Related to Silent Myocardial Damage in Hemodialysis Patients

Background. Both traditional and non-traditional risk factors play a role for the development of cardiovascular disease in hemodialysis patients. However, a specific relationship between these risk factors and silent myocardial damage is unknown. Methods. Demographic, anthropometric, clinical, and laboratory data were collected. Silent myocardial damage was defined by elevated cardiac troponin I values above cutoff values. Results. In total, 113 hemodialysis patients were included. Cardiac troponin I concentrations were below cutoff value (<2.3 ng/mL) in 103 (91.2%) patients (Group 1), whereas 10 (8.8%) patients had elevated concentrations (Group 2). Group 1 patients had higher levels of hemoglobin (p = 0.002) and high-density lipoprotein cholesterol (p = 0.002) and lower C-reactive protein (p = 0.003) and tumor necrosis factor-α (p = 0.005) levels, as well as less incidence of left ventricular hypertrophy (p = 0.045), when compared to Group 2 patients. Diabetes mellitus (Beta = +0.160, p = 0.021), left ventricular hypertrophy (Beta = +0.247, p < 0.0001), uncontrolled blood pressure (Beta = +0.170, p = 0.016), normalized protein equivalent of total nitrogen appearance (Beta = −0.230, p = 0.001), hemoglobin (Beta = −0.302, p < 0.0001), and tumor necrosis factor-α (Beta = +0.506, p < 0.0001) were found to be independently associated with cardiac troponin I levels in multiple linear regression analysis. Conclusions. Both traditional and non-traditional risk factors are related with silent myocardial damage, which is considered to an antecedent of major cardiovascular events. Hemodialysis patients, even when asymptomatic, must be closely followed up for the presence of these risk factors.
Higher Order Factors of Personality: Do They Exist?

Scales that measure the Big Five personality factors are often substantially intercorrelated. These correlations are sometimes interpreted as implying the existence of two higher order factors of personality. The authors show that correlations between measures of broad personality factors do not necessarily imply the existence of higher order factors and might instead be due to variables that represent same-signed blends of orthogonal factors. Therefore, the hypotheses of higher order factors and blended variables can only be tested with data on lower level personality variables that define the personality factors. The authors compared the higher order factor model and the blended variable model in three participant samples using the Big Five Aspect Scales, and found better fit for the latter model. In other analyses using the HEXACO Personality Inventory, they identified mutually uncorrelated markers of six personality factors. The authors conclude that correlations between personality factor scales can be explained without postulating any higher order dimensions of personality.
Radiographic features of the dorsal condylar sagittal ridge of the third metacarpal and metatarsal bones in young Warmblood stallions

Summary Objectives: To describe the radiographic appearance of the dorsoproximal aspect of the sagittal ridge of the third metacarpal/metatarsal bone in Warmblood horses. Methods: The lateromedial radiographic projections of the metacarpo-/metatarsophalangeal joints performed on horses as a part of stallion selection were used. The dorsal aspect of the distal third metacarpal/metatarsal bone was divided in two areas. The appearance of the bone surface in area I was classified as normal, irregular, notch, indentation and lucency. For area II, the categories were normal, irregular, depression or lucency and flattening of the sagittal ridge. Other abnormalities at the dorsal aspect were also noted. Results: In area I, 51.5% of the ridges appeared normal, 19.3% were irregular, 8.9% had a notch, 8.1% had a lucency, and 12.2% had an indentation. In 1.2% of the horses a fragment was present, and in 1.7% a fragment was suspected. In area II, 90.6% of the metacarpo-/metatarsophalangeal joints were normal, 6.2% were irregular, 2.9% showed a depression or lucency, and the sagittal ridge in 0.2% was flattened. A fragment was present in 0.3%, and suspected in 0.4%. Clinical significance: Morphological variation is present at the dorsal aspect of the metacarpo-/metatarsophalangeal joint in young Warmblood stallions. These various aspects should be recognised and described in horses presented for prepurchase examination. However, their clinical relevance in the individual horse is unclear and needs further investigation. Funding: Stijn Hauspie is a research fellow of the “Special Research Fund”, Ghent University (Belgium).
Thaw depth determines reaction and transport of inorganic nitrogen in valley bottom permafrost soils

Nitrate (NO3–) export coupled with high inorganic nitrogen (N) concentrations in Alaskan streams suggests that N cycles of permafrost‐influenced ecosystems are more open than expected for N‐limited ecosystems. We tested the hypothesis that soil thaw depth governs inorganic N retention and removal in soils due to vertical patterns in the dominant N transformation pathways. Using an in situ, push–pull method, we estimated rates of inorganic N uptake and denitrification during snow melt, summer, and autumn, as depth of soil–stream flowpaths increased in the valley bottom of an arctic and a boreal catchment. Net NO3– uptake declined sharply from snow melt to summer and decreased as a nonlinear function of thaw depth. Peak denitrification rate occurred during snow melt at the arctic site, in summer at the boreal site, and declined as a nonlinear function of thaw depth across both sites. Seasonal patterns in ammonium (NH4+) uptake were not significant, but low rates during the peak growing season suggest uptake that is balanced by mineralization. Despite rapid rates of hydrologic transport during snow melt runoff, rates of uptake and removal of inorganic N tended to exceed water residence time during snow melt, indicating potential for retention of N in valley bottom soils when flowpaths are shallow. Decreased reaction rates relative to water residence time in subsequent seasons suggest greater export of inorganic N as the soil–stream flowpath deepens due to thawing soils. Using seasonal thaw as a proxy for longer term deepening of the thaw layer caused by climate warming and permafrost degradation, these results suggest increasing potential for export of inorganic N from permafrost‐influenced soils to streams.
Empirical Substantiation of Sport Trademark Dilution: Quasi-Experimental Examination of Dilutive Effects

Trademark dilution law provides mark owners with another federal claim against unauthorized users in addition to the traditional claim for infringement. While dilution law has become a major vehicle of trademark enforcement for many branding companies, its rationale has been criticized by scholars, particularly, in terms of the ambiguous concept of the harm allegedly cause by dilution. Given the issue, this study examined whether dilutive use of famous sport trademarks has substantially harmful effects on the distinctive psychological value of the senior marks. It first attempted to develop an ad hoc measurement solution based on Keller’s (1993) brand equity theory. A follow-up quasi-experimental study examined the impact of given dilutive information. The result shows that a majority of the senior marks revealed substantially increased brand equity scores rather than decreased value. The result suggests that the harm argued in light of dilution theory is questionable, which calls for more empirical proofs.
A Novel Fully Human Anti-CD40 Monoclonal Antibody, 4D11, for Kidney Transplantation in Cynomolgus Monkeys

Background. CD40-CD154 pathway blockade by anti-CD154 monoclonal antibodies (mAbs) significantly prolongs allograft survival in nonhuman primates. However, thromboembolic complications have prevented clinical application. Thus, blockade of the counter molecule by a novel fully human anti-CD40 mAb, 4D11, is an attractive alternative. Methods. Kidney transplantations were performed between outbred cynomolgus monkeys (stimulation index >3 in a mixed lymphocyte reaction). The animals were divided into five groups: nontreatment control (Group 1, n=3), 10-week treatment with either 10 mg/kg (Group 2, n=3), 20 mg/kg (Group 3, n=3), or 40 mg/kg (Group 4, n=1), and 4-week treatment (Group 5, n=1 each) with 10 mg/kg, 20 mg/kg, or 40 mg/kg followed by monthly administration. Graft survival, biochemistry, complete blood counts, lymphocyte phenotypes, blood drug levels, antidonor and antidrug antibodies, and renal histology were examined. Results. Survival (days) was as follows: Group 1 (5, 6, 7), Group 2 (150, 108, 108), Group 3 (84, 108, 379), Group 4 (147), and Group 5 (147, 102, 112). Two animals in Group 3 with normal graft function were killed upon development of hydronephrosis and cerebral infarction. B lymphocytes fell to one-third of the preoperative value at 4 weeks after transplantation in all animals. Antidonor antibodies developed in most of the animals after stopping drug treatment or at the time of death. No animals except for one formed anti-4D11 antibody. Conclusion. 4D11 appears to be a promising agent for antirejection treatment in clinical organ transplantation.