Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of auricular lymph node cell lymphocyte proliferation and cytokine production as non-radioactive endpoints during murine contact allergy

The murine local lymph node assay (LLNA) has been developed as a test method to assess allergic contact dermatitis. In spite of the validity of the LLNA, attention was drawn to the two disadvantages: use of radioactivity for in vivo measurement of lymph node cell proliferation ([3H]-thymidine labeling) and the possibility of false positive results caused by non-specific cell activation as a result of inflammatory processes in the skin (irritation). We aimed to investigate the following non-radioactive endpoints of LLNA: 5-bromo-2′-deoxyuridine (BrdU) incorporation ex vivo and in vivo, in vivo and ex vivo cytokine production with or without phytohemagglutinin (PHA) stimulation. Here, 8-12-week-old female BALB/c mice were treated topically with the strong sensitizer 2,4-dinitrochlorobenzene (DNCB) in acetone:olive oil (AOO, 4:1 [v/v]) at levels of 0.025, 0.05, 0.01, or 0.25% (w/v). Ear thickness was also measured to determine the differentiation index (DI) indicating the proportion of non-specific activation due to irritating properties of test compound. At the concentration of 0.05%, stimulation index (SI) value was found to be 3 for DNCB based on in vivo and ex vivo BrdU incorporation. The results of the in vivo and ex vivo non-radioactive LLNA assays were compatible both with each other and with previous radioactive LLNA data. Our results indicate that non-radioactive endpoints may be used as an alternative to the [3H]-thymidine LLNA. The levels of TH1 cytokines (IL-2 and IFNγ) and TH2 cytokines (IL-4 and IL-5) in lymph node cell cultures were significantly (P < 0.01) increased when DNCB was applied at the concentrations of 0.05 and 0.1%, respectively. As the DI was > 1, the applied concentrations of DNCB caused only allergic effect but not any irritant effect. This study reports that the use of these non-radioactive endpoints can assess allergic contact dermatitis caused by chemicals.
Speed and Expertise in Stock Picking: Older, Slower, and Wiser?

Abstract There are significant differences among sell-side analysts in how frequently they revise recommendations. We show that much of this variation is an analyst-individual trait. Analysts who change recommendations more slowly make recommendations that are more influential and generate better portfolio returns. Slower-revising analysts tend to change recommendations following corporate news that are harder to interpret by nonstock experts, and our evidence suggests that their investment value derives from their ability to better interpret hard-to-assess information. On average, analysts change recommendations less frequently as their career progresses; however, recommendation speed-style is the dominant predictor of their recommendation value.
Nutritional status of COPD patients with acute exacerbation.

The prevalence and features of nutritional status in patients with chronic obstructive pulmonary disease (COPD) have been studied extensively in stable conditions, but are poorly defined in the presence of an acute exacerbation. The aim of this study is to evaluate the nutritional status of COPD patients with acute exacerbation and possible relationship between nutritional parameters and pulmonary functions. The study group consisted of 53 COPD patients acutely admitted to the hospital for standardized medical treatment. The nutritional status of patients was assessed by anthropometric measurements, biochemical analysis, and immunologic testing. The patients were divided into two groups as having severe (FEV1 < 50%) and mild to moderate (FEV1 ? 50%) COPD and weight loss greater than 5% for the comparison of the study parameters. Ideal body weight (IBW%) was found as 104.42 +/- 4.30 in severe COPD, where as it was 115.31 +/- 7.28 in mild to moderate COPD group (p= 0.07). There was no relationship demonstrated between IBW% and FEV1. IBW% was correlated with DLCO for the total study population (r= 0.353, p= 0.035). Weight loss greater than 5% of body weight (BW) was observed in 54% of patients. Comparison of the patient's actual weight to their usual weight revealed statistically significant weight loss (p< 0.01). Mean values of serum albumin, transferrin were found in normal range. Delayed type hypersensitivity skin test revealed normal immune status. When the study parameters were compared, no any statistically significant differences in parameters related to nutritional status were detected, between severe and mild to moderate COPD groups. As a statistically significant weight loss was found between the actual and usual weights of the patients, monitoring of nutritional parameters and eventual dietetic treatment should also be included in the goals of the medical treatment of patients with COPD in acute exacerbation.
Pannexin 3 is required for late stage bone growth but not for initiation of ossification in avian embryos

Background: Pannexin 3 (PANX3) is a channel‐forming protein capable of stimulating osteogenesis in vitro. Here, we studied the in vivo roles of PANX3 in the chicken embryo using the RCAS retroviral system to over‐express and knockdown expression during endochondral bone formation. Results: In the limbs, PANX3 RNA was first detected in the cartilage condensations and became restricted to the prehypertrophic cartilage of the epiphyses, diaphysis, and perichondrium. The increase in PANX3 was not sufficient to alter osteogenesis; however, knockdown with a virus containing an interference RNA construct caused a 20% reduction in bone volume. The control virus containing an shEGFP cassette did not affect development. Interestingly, the phenotype was restricted to later stages rather than to proliferation of the skeletogenic mesenchyme, formation of the cartilage condensation, or creation of the hypertrophic zones. In addition, there was also no change in readouts of Hedgehog, WNT, fibroblast growth factor, or bone morphogenetic protein signaling using either quantitative real‐time polymerase chain reaction or radioactive in situ hybridization. Conclusions: Based on the normal expression domains of PANX3 and the relatively late manifestation of the phenotype, it is possible that PANX3 hemichannels may be required to facilitate the transition of hypertrophic chondrocytes to osteoblasts, thereby achieving final bone size. Developmental Dynamics 245:913–924, 2016. © 2016 Wiley Periodicals, Inc.
Benign nevus cells in the capsule of lymph nodes

Six cases are reported in which the capsule of a lymph node contained clusters of benign‐appearing nevus cells. The marginal sinus and the parenchyma of the lymph node did not contain similar cells. Four of the six cases had known malignant tumors, but no malignant cells or cells that resembled the original tumor were seen in the lymph nodes. Because of their histologic appearance, the cells are interpreted as benign nevus cells. Possible explanations for the unusual location include a previously overlooked variation of “normal” anatomy, an aberration of embryogenesis, or “benign metastasis” of nevus cells.
The Farnesyltransferase Inhibitor L‐744,832 Inhibits the Growth of Astrocytomas through a Combination of Antiproliferative, Antiangiogenic, and Proapoptotic Activities

The 21-kD cellular protein Ras is known to play a critical role in a wide range of cellular events, including proliferation, cytoskeletal rearrangement, development, and apoptosis. Activated Ras is bound to GTP, whereas Ras•GDP represents the inactive protein. Up to 30% of human malignancies express a mutant form of this protein in which Ras is constitutively present in its activated GTP-bound form. Such oncogenic mutations have not been identified in glioblastoma multiforme (GBM). We have however demonstrated that Ras activation is critical in the proliferation of these tumors1 as well as important in the secretion of the angiogenic factor vascular endothelial growth factor (VEGF2), with Ras activation occurring secondary to overexpression of the receptor tyrosine kinases platelet derived growth factor receptor (PDGF-R) and epidermal growth factor receptor (EGF-R). 1 As farnesyltransferase inhibitors (FTIs) inhibit the posttranslational modification of Ras, preventing the association of Ras with its upstream activators at the cell surface, we hypothesized that astrocytoma cells would be growth inhibited by such agents. The FTI L-744,832 was provided by Allen Oliff (Merck Research Laboratories, West Point, Pennsylvania). Six astrocytoma cell lines were evaluated, including five established lines (U87, U118, U138, U343, and U373). In addition, U118:EGFRvIII cells were evaluated, which express the constitutively activated truncated receptor EGFRvIII, expressed in a large subset of GBMs. We previously showed that U118:EGFRvIII cells constitutively express higher levels of activated Ras•GTP. Cells were treated with L-744,832 at doses ranging from 10 nM to 100 μM, and the concentration of vehicle was kept constant in all wells (0.1% methanol). Cells were grown in 96-well plates, and proliferation was measured using the tetrazolium compound MTS, which is bioreduced by viable cells into a colored formazan product. Dose-response curves (Hill plots) were constructed by modeling a log normal doseresponse relationship. Logistic regression (probit analysis) was used to estimate the LD50 for each cell line as the dose at which proliferation was reduced to 50% of control wells. All astrocytoma cell lines were growth inhibited by L-744,832, with IC50 ranging from 5.3 to 17.4 μM. Cells expressing EGFRvIII were more sensitive to L-
The Effect of Ephedrine on the Onset Time of Rocuronium

The time from loss of consciousness to tracheal intubation is a period during which the patient is at risk of hypoxia and pulmonary aspiration. The length of this period is usually determined by the establishment of neuromuscular blockade, so it is usually desirable to use a muscle relaxant with a short onset time. The onset time is partly determined by the speed with which these drugs reach the neuromuscular junction, a factor that appears to be proportional to cardiac output and muscle blood flow (1). Since ephedrine can increase these variables (2,3), our hypothesis was that it could reduce the onset time of muscle relaxants. The aim of this study was to evaluate the effects of a single dose of ephedrine, given at the moment of induction, on the onset time of rocuronium and on blood pressure and heart rate evolution during the induction sequence.
Plasma follistatin is elevated in patients with type 2 diabetes: relationship to hyperglycemia, hyperinsulinemia, and systemic low‐grade inflammation

Plasma follistatin is elevated in patients with low‐grade inflammation and insulin resistance as observed with polycystic ovary syndrome. In the present study, we evaluated plasma follistatin in patients with type 2 diabetes characterised by low‐grade inflammation and assessed the acute effects of hyperglycemia, hyperinsulinemia and LPS on plasma follistatin.
Setting our bibliographic references free: towards open citation data

Purpose – Citation data needs to be recognised as a part of the Commons – those works that are freely and legally available for sharing – and placed in an open repository. The paper aims to discuss this issue. Design/methodology/approach – The Open Citation Corpus is a new open repository of scholarly citation data, made available under a Creative Commons CC0 1.0 public domain dedication and encoded as Open Linked Data using the SPAR Ontologies. Findings – The Open Citation Corpus presently provides open access (OA) to reference lists from 204,637 articles from the OA Subset of PubMed Central, containing 6,325,178 individual references to 3,373,961 unique papers. Originality/value – Scholars, publishers and institutions may freely build upon, enhance and reuse the open citation data for any purpose, without restriction under copyright or database law.
Ridge alterations following immediate implant placement in the dog: flap versus flapless surgery.

OBJECTIVE To assess the healing process after flap or flapless surgery in immediate implant placement. MATERIAL AND METHODS This study was carried out on five Beagle dogs. Four implants were placed in the lower jaw in each dog immediately after tooth extraction. Flap surgery was performed before the extraction on one side (control), and flapless on the contrary (test). After 3 months of healing, the dogs were sacrificed and prepared for histological analysis. RESULTS Ten implants were placed in each group. Two failed (one of each group). The percentage of bone-implant contact was very similar in both groups: 64.8% and 65.1% for the flap and the flapless group, respectively. The difference between the mean distance from the peri-implant mucosa margin to the first bone-implant contact at the buccal aspect was statistically significant between both groups (3.02 mm. flapless and 3.69 mm. flap group). The mean first bone-implant contact at the buccal aspect was located in relation to the sand-blasted and acid-etched level at 0.82 mm for the flapless group and 1.33 mm for the flap group. This difference was not statistically significant. CONCLUSION Flapless immediate implant surgery produces a significant reduction in the vestibular biologic width and a minor reduction in buccal bone plate resorption.
Angiotensin receptor blockers: Therapeutic targets and cardiovascular protection

In the prevention and treatment of cardiovascular disease, pharmacological treatment strategies should have several aims: (i) in individuals without overt cardiovascular disease, but with risk factors such as hypertension and/or diabetes, pharmacotherapy should prevent or delay disease development; (ii) in patients who have already progressed to cardiovascular disease, pharmacotherapy should help either to prevent or regress target organ damage (TOD); and (iii) in patients with TOD, pharmacotherapy should prevent events. Any medication intended for long‐term therapy also should be well tolerated. Inhibiting the renin–angiotensin system has proven a successful therapeutic strategy in cardiovascular and renal medicine. Angiotensin‐converting enzyme (ACE) inhibitors have demonstrated important advantages over conventional agents such as beta‐blockers and thiazide diuretics, and have become a relevant part of treatment for heart failure post‐myocardial infarction, left ventricular dysfunction and renal disease. Tolerability concerns may prevent their use in some patients, however. Angiotensin AT1 receptor blockers (ARBs) provide a different form of blockade of the renin–angiotensin system and a growing body of evidence suggests that this alternative approach may confer additional cardiovascular protection for some patient subgroups. In addition, ARBs generally are better tolerated than ACE inhibitors, enhancing patient compliance and persistence with long‐term therapy. Furthermore, evidence in favour of combining an ACE inhibitor and an ARB in certain circumstances is continuously growing.
Screening for Spousal or Partner Abuse in a Community Health Setting

&NA; The most frequent victims of domestic violence are women. Although estimates of spousal or partner abuse vary from 3.8% to 44%, this type of abuse is unrecognized and underreported. A screening study for abuse occurred in a community health setting. Some 2,410 women were screened. The results indicated an incidence rate of 8.4%. Health care providers have an obligation to identify, treat, and provide appropriate resources for victims of spousal abuse. Screening for spousal or partner abuse should take place in primary care settings.
Intraoperative dorsal language network mapping by using single‐pulse electrical stimulation

The preservation of language function during brain surgery still poses a challenge. No intraoperative methods have been established to monitor the language network reliably. We aimed to establish intraoperative language network monitoring by means of cortico‐cortical evoked potentials (CCEPs). Subjects were six patients with tumors located close to the arcuate fasciculus (AF) in the language‐dominant left hemisphere. Under general anesthesia, the anterior perisylvian language area (AL) was first defined by the CCEP connectivity patterns between the ventrolateral frontal and temporoparietal area, and also by presurgical neuroimaging findings. We then monitored the integrity of the language network by stimulating AL and by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. High‐frequency electrical stimulation (ES) performed during awake craniotomy confirmed language function at AL in all six patients. Despite an amplitude decline (≤32%) in two patients, CCEP monitoring successfully prevented persistent language impairment. After tumor removal, single‐pulse ES was applied to the white matter tract beneath the floor of the removal cavity in five patients, in order to trace its connections into the language cortices. In three patients in whom high‐frequency ES of the white matter produced naming impairment, this “eloquent” subcortical site directly connected AL and PL, judging from the latencies and distributions of cortico‐ and subcortico‐cortical evoked potentials. In conclusion, this study provided the direct evidence that AL, PL, and AF constitute the dorsal language network. Intraoperative CCEP monitoring is clinically useful for evaluating the integrity of the language network. Hum Brain Mapp 35:4345–4361, 2014. © 2014 Wiley Periodicals, Inc.
Role of CD4+ and CD8+ T cells in murine resistance to street rabies virus

Mice of the SJL/J and BALB/cByJ inbred strains are naturally resistant to street rabies virus (SRV) injected via the intraperitoneal route. To determine the cellular mechanism of resistance, monoclonal antibodies specific for CD4+ or CD8+ subsets of T cells were used to deplete the respective cell population in SRV-infected animals. Elimination of CD4+ T-helper cells abrogated the production of immunoglobulin G (IgG) neutralizing antibodies in response to rabies virus infection and reversed the resistant status of SJL/J and BALB/cByJ mice. In contrast, in vivo depletion of CD8+ cytotoxic T cells had no measurable effect on host resistance to SRV. These results indicate that serum neutralizing antibodies of the IgG class are a primary immunological mechanism of defense against rabies virus infection in this murine model of disease. CD8+ cytotoxic T lymphocytes, which have been shown to transfer protection in other rabies virus systems, appear to have no role in protecting mice against intraperitoneally injected SRV.
Cardiovascular and non-cardiovascular hospital admissions associated with atrial fibrillation: a Danish nationwide, retrospective cohort study

Objective To examine the excess risk of hospitalisation in patients with incident atrial fibrillation (AF). Design A nationwide, retrospective cohort study. Setting Denmark. Participants Data on all admissions in Denmark from 1997 to 2009 were collected from nationwide registries. After exclusion of subjects previously admitted for AF, data on 4 602 264 subjects and 10 779 945 hospital admissions contributed to the study. Primary and secondary outcome measures Age-stratified and sex-stratified admission rates were calculated for cardiovascular and non-cardiovascular admissions. Temporal patterns of readmission, relative risk and duration of frequent types of admission were calculated. Results Of 10 779 945 hospital admissions, 729 088(6.8%) were associated with AF. Admissions for cardiovascular reasons after 1, 3 and 6 months occurred for 6.0, 14.3 and 28.4% of AF patients versus 0.2, 0.6 and 1.8 of non-AF patients. Admissions for non-cardiovascular reasons after 1, 3 and 6 months comprised 6.8, 16.1 and 33.3% of AF patients and 1.2, 3.2 and 9.7% of non-AF patients. When stratified for age, AF was associated with similar cardiovascular admission rates across all age groups, while non-cardiovascular admission rates were higher in older patients. Within each age group and for both cardiovascular and non-cardiovascular admissions, AF was associated with higher rates of admission. When adjusted for age, sex and time period, patients with AF had a relative risk of 8.6 (95% CI 8.5 to 8.6) for admissions for cardiovascular reasons and 4.0 (95% CI 4.0 to 4.0) for admission for non-cardiovascular reasons. Conclusions This study confirms that the burden of AF is considerable and driven by both cardiovascular and non-cardiovascular admissions. These findings underscore the importance of using clinical and pharmacological means to reduce the hospital burden of AF in Western healthcare systems.
Structural Basis of BMP Signaling Inhibition by Noggin, a Novel Twelve-Membered Cystine Knot Protein

Background: The activity of bone morphogenetic proteins (BMPs) is regulated extracellularly by several families of secreted, negatively-acting factors. These BMP antagonists participate in the control of a diverse range of embryonic processes, such as establishment of the dorsal-ventral axis, neural induction, and formation of joints in the developing skeletal system. The ongoing process of neurogenesis in the adult brain also requires inhibition of BMP ligand activity. To date, the three-dimensional structures of these antagonists as well as the nature of their interaction with ligand have remained unknown. Toward that end, we have determined the crystal structure of the antagonist Noggin bound to BMP-7.Methods: The complex of the two homodimeric proteins was preformed, isolated by size exclusion chromatography, and crystallized at neutral pH. To probe the molecular interface of the complex and to quantitate the activity of a human mutant form, variant Noggin proteins were produced and their binding affinities were measured in vitro. The correlation between binding affinity and biological activity was examined with Noggin-soaked beads implanted in the developing chick limb bud.Results and Conclusions: The structure of the complex reveals that Noggin inhibits BMP signaling by blocking the binding sites of both types of receptors (Type I and Type II), mimicking their modes of binding. The affinity of Noggin variants for BMP-7 correlated well with the inhibition of BMP-induced chondrogenesis in the chick limb bud, confirming that Noggin acts by sequestering the ligand in an inactive state. Interestingly, the scaffold of Noggin was found to contain a cystine knot topology and protein fold similar to that of BMPs, indicating that ligand and antagonist may have evolved from a common ancestral gene.Clinical Relevance: Mutations in the human Noggin locus (NOG) are associated with three similar yet distinct skeletal dysplasias: proximal symphalangism (SYM1), multiple synostoses syndrome (SYNS1), and tarsal-carpal coalition syndrome (TCC). The crystal structure of the Noggin:BMP-7 complex provides a structural context for interpreting the effects of missense mutations with respect to Noggin protein folding, stability, or activity. The structure also provides the basis for engineering variants of Noggin that may have therapeutic applications in the treatment of fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder of connective tissue resulting from lymphocytic misexpression of BMPs.