Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between absence of epidermal growth factor receptor immunoreactivity and poor prognosis in patients with atypical meningioma.

OBJECT The clinical behavior of meningiomas is variable. Because multiple growth factor receptors have been identified in these tumors, the authors sought to assess the capacity of the expression patterns of a subset of these receptors to stratify meningioma cases. METHODS Eighty-four meningiomas were analyzed, including 36 benign, 29 atypical, and 19 malignant lesions. Immunohistochemical staining was performed for epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR)-beta, basic fibroblast growth factor receptor (BFGFR), and MIB-1. Survival analyses were performed using follow-up data obtained in patients with newly diagnosed tumors. Immunoreactivity for EGFR was observed in 47% of benign, 48% of atypical, and 42% of malignant tumors. Staining for BFGFR was identified in 89% of benign, 97% of atypical, and 95% of malignant lesions. Immunostaining for PDGFR-beta was evident in all the lesions assessed. Mean MIB-I indices for benign, atypical, and malignant cases were 3.6 (range 0.5-15.3), 8.2 (range 1.5-23.1) and 18.3 (range 1.0-55.8), respectively. Overall mean follow-up duration was 9.0 years (range 5.1-18.8 years). Lack of EGFR immunoreactivity was identified as a strong predictor of shorter overall survival in patients with atypical meningioma (p = 0.003, log-rank test). This association was not evident in cases of benign or malignant meningiomas. CONCLUSIONS There is a significant association between EGFR immunoreactivity and prolonged survival in patients with atypical meningioma. Given the variable behavior of atypical meningiomas, EGFR assessment could improve existing strategies for patient stratification and treatment.
Combinatorial Domain Hunting: An effective approach for the identification of soluble protein domains adaptable to high‐throughput applications

Exploitation of potential new targets for drug and vaccine development has an absolute requirement for multimilligram quantities of soluble protein. While recombinant expression of full‐length proteins is frequently problematic, high‐yield soluble expression of functional subconstructs is an effective alternative, so long as appropriate termini can be identified. Bioinformatics localizes domains, but doesn't predict boundaries with sufficient accuracy, so that subconstructs are typically found by trial and error. Combinatorial Domain Hunting (CDH) is a technology for discovering soluble, highly expressed constructs of target proteins. CDH combines unbiased, finely sampled gene‐fragment libraries, with a screening protocol that provides “holistic” readout of solubility and yield for thousands of protein fragments. CDH is free of the “passenger solubilization” and out‐of‐frame translational start artifacts of fusion‐protein systems, and hits are ready for scale‐up expression. As a proof of principle, we applied CDH to p85α, successfully identifying soluble and highly expressed constructs encapsulating all the known globular domains, and immediately suitable for downstream applications.
Endotoxin‐induced bacterial translocation and mucosal permeability: Role of xanthine oxidase, complement activation, and macrophage products

Background and MethodsPreviously, we documented that nonlethal doses of endotoxin injure the intestinal mucosal barrier and promote bacterial translocation from the gut to systemic organs. The current study was performed to determine the role of cytokines and complement activation in the pathogenesis of endotoxin-induced mucosal injury and bacterial translocation, as well as to quantify the magnitude of endotoxin-induced intestinal mucosal permeability. ResultsThe frequency of endotoxin-induced bacterial translocation was similar between normal outbred (88%), complement deficient (67%), and macrophage-hyporesponsive (55%) mice, indicating that neither complement nor macrophage activation is necessary for endotoxin-induced bacterial translocation to occur. As early as 2 hrs after endotoxin challenge, there was evidence of a greater than two-fold increase in ileal (p = .008) but not jejunal (p = .11) permeability as measured by the clearance of 51Cr EDTA. Both the increase in endotoxin-induced ileal permeability and the occurrence of bacterial translocation were largely prevented by pretreatment with allopurinol, a competitive inhibitor of xanthine oxidase. ConclusionsThese results suggest that endotoxin-induced bacterial translocation, mucosal injury, and ileal permeability are mediated via activation of xanthine oxidase, and not through complement activation or the liberation of macrophage products.
Heat stress enhances arterial baroreflex control of muscle sympathetic nerve activity via increased sensitivity of burst gating, not burst area, in humans

The relationship between muscle sympathetic nerve activity (MSNA) and diastolic blood pressure has been used to describe two sites for arterial baroreflex control of MSNA. By determining both the likelihood of occurrence for sympathetic bursts and the area of each burst for a given diastolic blood pressure, both a ‘gating’ and an ‘area’ control site has been described in normothermic humans. Assessing the effect of heat stress on these mechanisms will improve the understanding of baroreflex control of arterial blood pressure under this thermal condition. Therefore, the purpose of this study was to test the hypothesis that heat stress enhances arterial baroreflex control of burst gating and area. In 10 normotensive subjects (age, 32 ± 2 years; mean ±s.e.m.), MSNA (peroneal) was assessed using standard microneurographic techniques. Five minute periods of data were examined during normothermic and whole‐body heating conditions. The burst incidence (i.e. number of sympathetic bursts per 100 cardiac cycles) and the area of each burst were determined for each cardiac cycle and were placed into 3 mmHg intervals of diastolic blood pressure. During normotheric conditions, there was a moderate, negative relationship between burst incidence and diastolic blood pressure (slope =−2.49 ± 0.38; r2= 0.73 ± 0.06; mean ±s.e.m.), while area per burst relative to diastolic blood pressure exhibited a less strong relationship (slope =–1.13 ± 0.46; r2= 0.45 ± 0.09). During whole‐body heating there was an increase in the slope of the relationship between burst incidence and diastolic blood pressure (slope =–4.69 ± 0.44; r2= 0.84 ± 0.03) compared to normothermia (P < 0.05), while the relationship between area per burst and diastolic blood pressure was unchanged (slope =–0.92 ± 0.29; r2= 0.41 ± 0.08) (P= 0.50). The primary finding of this investigation is that, at rest, whole‐body heating enhanced arterial baroreflex control of MSNA through increased sensitivity of a ‘gating’ mechanism, as indicated by an increase in the slope of the relationship between burst incidence and diastolic blood pressure. This occurrence is likely to afford protection against potential decreases in arterial blood pressure in an effort to preserve orthostatic tolerance during heat stress.
How Important is Marital Fairness over the Lifespan?

Do marital relationships become more equitable over time? Is a sense of fairness or equity in marriage equally important at different points across the lifespan? To answer these and related equity/intimacy questions, a sample of middle-aged and older married women was asked to describe the level of equity in their marriages at eight points across their lifespan and their feelings about the equity/inequity at each point. The aggregated results suggested women begin a marriage with a sense of overbenefit, move into a period of underbenefit during their middle years, and finally feel fairly treated in late middle age. The disaggregated data revealed three distinct patterns of equity/inequity over the lifespan. Women's reactions to the level of equity at each stage followed the predicted curvilinear pattern.
Proteomic Comparison of Amnion and Chorion and Evaluation of the Effects of Processing on Placental Membranes.

OBJECTIVE The purpose of this study is to compare the growth factor and cytokine content found within the amnion and chorion layers and to determine the effects of dehydration on them. MATERIALS AND METHODS Placentas were collected from 5 to 6 consented donors following elective cesarean section, and 1-cm2 sections of either amnion or chorion were immediately stored at -80°C or dehydrated prior to -80°C storage until proteomic analysis. Signaling molecules from tissue samples were evaluated using quantitative multiplex proteomics microarrays, and data were analyzed based on a per cm2 basis and also on pg/mg of extracted protein for potency. RESULTS Fresh chorion contained more of some signaling molecules per cm2 compared with amnion. Specifically, the chorion contained significantly higher levels of adiponectin, APN, ANG-2, bFGF, EG-VEGF, HGF, IGF-1, PDGF-AA, PDGF-BB, TIMP-2, and TIMP-4. When samples were dehydrated, a significant drop in total growth factor and cytokine content was observed in both amnion and chorion samples with a loss of 51.1% ± 20.2% and 55.5% ± 37.3%, respectively. When evaluating the potency of fresh amnion and fresh chorion, there were similar levels of signaling molecules found with some exceptions. Amnion had significantly higher GAL-7, TGF-β1, and IL-1F5, and chorion had significantly more EG-VEGF, PDGF-BB, and TIMP-2. CONCLUSION The processing of placental membranes can have a dramatic effect on the total growth factor and cytokine load found within these tissues.
Spatial and cortical influences exerted on cuneothalamic and thalamocortical neurons of the cat

This work aimed to study the responses of cuneothalamic and thalamocortical cells to electrical stimulation of the body surface in α‐chloralose‐anaesthetized cats. It was found that both classes of cells had a central excitatory receptive field, an edge overlapping the field centre whose stimulation elicited inhibitory–excitatory (cuneothalamic cells) and excitatory–inhibitory (thalamocortical cells) sequences, and a surrounding or peripheral area usually being inhibitory. Manipulating the descending corticofugal activity by removing the fronto‐parietal cortex, electrical stimulation, or by placing picrotoxin or muscimol over the sensorimotor cortex demonstrated that the cortical feedback potentiated effects driven from the field centre and the surround. In particular this potentiated centre‐driven excitation and surround‐driven inhibition, but some of the data points to more complex patterns. The inhibition elicited in cuneothalamic cells from the edge and the surround of the field was faster than the excitation induced from the field centre. Effects at the edge of the field centre included late excitatory responses relayed via the cerebral cortex. There were also direct corticofugal excitatory inputs to the field centre. Excitatory surrounds were occasionally observed, the assumption being that in most cases these were suppressed by the enhanced inhibition driven from the cortex. The data indicate that the cortico‐subcortical feedback contributes not only to enhance the surround antagonism of a centre response but also to increase the time resolution of thalamic and cuneate relay somesthetic neurons.
Different granule cell populations innervate superficial and deep regions of the external plexiform layer in rat olfactory bulb

Studies on the morphological organization of the main olfactory bulb have indicated that there are subpopulations of granule cells with different dendritic patterns in the external plexiform layer (EPL). Small, extracellular injections of horseradish peroxidase (HRP) were made iontophoretically into superficial and deep parts of the EPL and the granule cell layer (GCL) in adult rats. Superficial EPL injections principally labeled superficial granule cell somata, whereas deep EPL injections labeled both superficial and deep granule cell somata. Injections in the superficial GCL labeled granule cell dendritic processes extending across the entire EPL. However, deep GCL injections labeled few granule cell dendrites in the superficial EPL, but labeled many such processes in the deep EPL. These results were the same in material processed with the Hanker‐Yates procedure, where the morphology of individual neurons could be studied, and in the more sensitive tetramethyl benzidineprocedure.
Risk factors and incidence of thromboembolic events (TEEs) in older men and women with breast cancer.

BACKGROUND The purpose of this study is to evaluate the risk factors and the prevalence of thromboembolic events (TEEs) in breast cancer patients. PATIENTS AND METHODS This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare database. Breast cancer patients diagnosed from 1992 to 2005 ≥66 years old were identified. International Classification of Diseases, Ninth Revision, and Healthcare Common Procedure Coding System codes were used to identify TEEs within 1 year of the breast cancer diagnosis. Analyses were conducted using descriptive statistics and logistic regression. RESULTS A total of 89 841 patients were included, of them 2658 (2.96%) developed a TEE. In the multivariable analysis, males had higher risk of a TEE than women [odd ratio (OR) = 1.57; confidence interval (CI) 1.10-2.25] and blacks had higher risk than whites (OR = 1.20; CI 1.04-1.40). Compared with stage I patients, patients with stage II, III and IV had 22%, 39% and 98% increase, respectively, in risk. Placement of central catheters (OR = 2.71; CI 2.43-3.02), chemotherapy treatment (OR = 1.66; CI 1.48-1.86) or treatment with erythropoiesis-stimulating agents (ESAs) (OR = 1.33; CI 1.33-1.52) increase the risk. Other significant predictors included comorbidities, age, receptor status, marital status and year of diagnosis. Similar estimates were seen for pulmonary embolism, deep vein thromboembolism and other TEEs. CONCLUSIONS In total, 2.96% of patients in this cohort developed a TEE within 1 year from breast cancer diagnosis. Stage, gender, race, use of chemotherapy and ESAs, comorbidities, receptor status and catheter placement were associated with the development of TEEs.
ALK Expression in Rhabdomyosarcomas: Correlation with Histologic Subtype and Fusion Status

Immunohistochemical staining for anaplastic lymphoma kinase (ALK) has been described in rhabdomyosarcomas (RMS), especially the alveolar subtype. Previous studies have yielded conflicting results regarding the pattern of staining (nuclear versus cytoplasmic), and there has been no correlation with PAX3–7/FKHR fusion status. This study was undertaken to evaluate ALK receptor protein expression in a large series of RMS; to correlate these results with fusion status; and to investigate the possibility of 2p23 amplification or translocation using fluorescence in situ hybridization (FISH). Sixty-nine cases of RMS were examined and classified as alveolar RMS (ARMS), embryonal RMS (ERMS), or unclassifiable RMS (URMS) subtypes. Anaplastic lymphoma kinase immunohistochemistry was performed using anti-human CD246 antibody; cases were considered positive when more than 50% of cells had moderate or intense cytoplasmic and/or nuclear staining. There were 30 ARMS, 37 ERMS, and 2 URMS subtypes. Reverse transcription–polymerase chain reaction for PAX3/PAX7-FKHR fusion analysis had been done in all cases of ARMS, in 27 of 37 cases of ERMS, and in both URMS cases. Anaplastic lymphoma kinase staining was positive in 16 of 30 ARMS (53%) and 9 of 39 nonalveolar RMS (23%) cases (P < 0.05). Of the 21 ARMS cases with PAX3-FKHR fusion, 10 of 21 (48%) were positive for ALK staining; of the 6 ARMS cases with PAX7-FKHR fusion, 3 of 6 (50%) were positive for ALK staining; and 3 of 3 (100%) of the fusion-negative ARMS were positive with ALK staining. When comparing each of the ARMS subtypes, statistical significance was not reached. All positive cases showed dot-like cytoplasmic staining; nuclear staining was not seen. Of a subset of 6 ALK-positive ARMS submitted for break-apart FISH for the ALK locus, there was no evidence of a translocation; 1 case had ALK amplification and 2 had low-level gains of the ALK gene. We conclude that there is ALK overexpression in RMS, more commonly in ARMS than in ERMS, most likely independent of fusion status. Amplification or upregulation of ALK may underlie ALK protein overexpression.
Platelets release active matrix metalloproteinase‐2 in vivo in humans at a site of vascular injury: lack of inhibition by aspirin

When stimulated in vitro, human platelets release matrix metalloproteinase‐2 (MMP‐2) that, in turn, potentiates platelet activation. The present study investigated if MMP‐2 is released from activated platelets in vivo in humans and whether aspirin inhibits this release. MMP‐2 levels were measured by zymography, immunoblotting, flow‐cytometry and an activity assay system, in plasma prepared from blood emerging from a skin wound inflicted for the measurement of the bleeding time (shed blood) and simultaneously from venous blood in 27 healthy human volunteers. In a subgroup, the same measurements were carried out before and 1 h after aspirin intake. MMP‐2 was significantly higher in shed blood than in venous blood and increased progressively, consistent with ongoing platelet activation. A significant correlation was evident between platelet number and MMP‐2 in shed blood; platelet MMP‐2 content in shed blood was lower than that of platelets in venous blood. The level of active MMP‐2 released by activated platelets in vivo was within the range of concentrations that potentiate platelet activation. Aspirin did not reduce MMP‐2 release in vivo. In conclusion, MMP‐2 is released from platelets in vivo in humans at a localised site of vessel wall damage in amounts sufficient to potentiate platelet aggregation; aspirin does not reduce this release.
A Two-Step Heuristic Algorithm for Minimum-Crosstalk Routing Resource Assignment

This brief deals with the crosstalk minimization problem in an integrated routing resource assignment stage containing several operations between global routing and detailed routing. A two-step heuristic algorithm consisting of coarse assignment and detailed assignment is proposed. In coarse assignment, shield lines are planned based on the chromatic number of a light coarse coupling graph, and the assignment of segments that are longer than a predefined threshold is solved with semidefinite programming. In detailed assignment, a strategy based on a dynamic priority queue is introduced to mitigate common problems caused by sequential routing. Experimental results on a set of benchmarks show significant reduction in coupling length between sensitive segments compared to a prevalent bipartite-matching-based algorithm
Salt and Nitric Oxide Inhibition Induced Hypertension: The Role of Prostacycline and 8-Isoprostane

Renal prostacycline (PGI2) and oxidative stress are known to be important factors that effect the natriurezis and diuresis. 8-iso prostaglandin F2α± (8-isoprostane), a member of F2-isoprostanes, is formed from the nonenzymatic reaction of arachidonic acid and oxygen radicals in vivo and in vitro, and also it is a marker of oxidative stress in vivo. The aim of this study is to determine the role of renal PGI2 and 8-isoprostane in a salt and nitric oxide (NO) inhibition-induced hypertension model. Rats were distributed equally among four groups (n = 6 per group). Control rats were given normal salt diet (0.32%); high-salt (HS) rats were given high salt diet (3.2%); NG-nitro-L-arginine (L-NNA) rats were given normal salt diet and 25 mg/kg L-NNA; HS+L-NNA rats were given high salt diet and 25 mg/kg L-NNA. Rats were placed in individual metabolic cages for 17 days. Systolic blood pressure (SBP) was measured at days initial, 7th and 14th . Urinary 8-isoprostane and PGI2 levels were analyzed. Salt- loading alone did not change SBP values. The average SBP in L-NNA and HS+L-NNA groups were shown to significantly enhance compared to initial and day 7th in the same groups, respectively. The levels of 8-isoprostane in the HS+L-NNA group was significantly enhanced compared to the other groups. L-NNA or HS diet alone did not change the levels of 8-isoprostane compared to the control group. L-NNA alone did not change PGI2 levels in urine compared to the control. PGI2 levels in the HS, and the HS+L-NNA group was significantly higher compared to the control group. This study concluded that NOS inhibition plus salt-loading induced oxidative stress and increased renal PGI2. Also, it is suggested that augmented oxidative stress may aggravate the hypertension. But the renal synthesis of PGI2 is increased in order to augment the diuresis and natriuresis without the effect of blood pressure (BP).
Absence of thyroid stunning after diagnostic whole-body scanning with 185 MBq 131I.

UNLABELLED There has been recent controversy regarding the optimal protocol for imaging and ablation of post-thyroidectomy patients. Several authors have suggested that a scanning dose of 185-370 MBq (5-10 mCi) (131)I may be capable of producing a stunning effect on thyroid tissue that may interfere with the uptake and efficacy of the subsequent ablation dose of radioiodine. The purpose of this study was to determine whether a 185-MBq (5 mCi) diagnostic dose of (131)I produces a visually apparent stunning effect 72 h before (131)I ablation therapy. METHODS One hundred twenty-two consecutive post-thyroidectomy patients for differentiated thyroid carcinoma received a 185-MBq (5 mCi) diagnostic dose of (131)I followed by a whole-body diagnostic scan at 72 h. On the same day the diagnostic scan was completed, the patient was admitted to the hospital and received an (131)I ablation therapy dose of 5550 MBq (150 mCi) in most cases. A postablation, whole-body scan was obtained at 72 h and compared with the previous diagnostic scan for any visual evidence of stunning. RESULTS No cases of visually apparent thyroid stunning were observed on any of the postablation scans with regard to the number of (131)I foci identified or the relative intensity of (131)I uptake seen. CONCLUSION Diagnostic whole-body scanning can be performed effectively with a 185-MBq (5 mCi) dose of (131)I 72 h before radioiodine ablation without concern for thyroid stunning.
Phosphorylation of STAT-3 in Response to Basic Fibroblast Growth Factor Occurs through a Mechanism Involving Platelet-activating Factor, JAK-2, and Src in Human Umbilical Vein Endothelial Cells

Platelet-activating factor (PAF) is a potent proinflammatory phospholipid with multiple pathological and physiological effects. We have shown that basic fibroblast growth factor (bFGF) supplementation induces rapid proliferation of human umbilical vein endothelial cells (HUVEC), which is reduced upon removal of bFGF or by bFGF immunoneutralization. The PAF receptor antagonist LAU-8080 inhibited bFGF-stimulated HUVEC proliferation, indicating the involvement of PAF in the bFGF-mediated signaling of HUVEC. Although FGF receptor phosphorylation was not affected by LAU-8080, the bFGF-mediated prolonged phosphorylation, and activation of Erk-1 and -2 were attenuated. Phosphorylation of STAT-3 was observed in the presence of PAF or bFGF, which was attenuated by PAFR antagonists. PAF-induced STAT-3 phosphorylation observed in HUVEC pretreated with either Src inhibitor PP1 or JAK-2 inhibitor AG-490 indicated (i) immediate (1 min) phosphorylation of STAT-3 is dependent on Src, (ii) JAK-2-dependent STAT-3 phosphorylation occurs after the delayed (30 min) PAF exposure, and (iii) prolonged (60 min) STAT-3 phosphorylation may be either through Src and/or JAK-2. Attenuation of the STAT-3 phosphorylation by the PAFR antagonists indicated signaling through the PAF receptor. Taken together, these findings suggest the production of PAF is important for bFGF-mediated signaling and that a dual kinase mechanism is involved in the PAF-mediated signal transduction cascade.