Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Expression of Vasoactive Intestinal Polypeptide Receptor 1 and 2 mRNA in Murine Intestinal T Lymphocyte Subtypes

Neuropeptides may exert a variety of effects on the immune cells at both systemic and mucosal immune sites. The immunoregulatory properties refer to the ability of physiological signals and pathways to influence various immune functions. Vasoactive intestinal polypeptide (VIP), a neuropeptide present in high concentration in gut, was studied for its production and receptor expression in intraepithelial and lamina propria T lymphocytes of mouse intestine. Using reverse transcription‐polymerase chain reaction (RT‐PCR) analysis, it was demonstrated that VIP receptor 1 (VIPR1) was constantly expressed in intraepithelial and lamina propria T lymphocytes from both small and large intestine. In contrast, VIPR2 was identified only in T cells from small intestine. Further studies on purified subpopulations of T lymphocytes indicated the existence of VIPR2 in CD8+ T cells, but not CD4+ and CD4CD8 double negative T cells, although all these three subpopulations displayed VIPR1. In addition, VIPR1 mRNA was detected in splenic T lymphocytes, but no signal was obtained for VIPR2 mRNA, even after stimulation of the cells with anti‐CD3ε‐chain mAb, phorbol 12‐myristate 13‐acetate (PMA) and/or VIP. The presence of VIP receptor(s) on intestinal T lymphocytes was supported by the detection of VIP on the cell surface using dual colour immunoflowcytometry. In‐vitro treatment with VIP resulted in a tendency towards an increased size of the VIP immunoreactive T cell population and significantly enhanced the average immunofluorescence intensity of the surface labelling. This indicates that the receptors are partially occupied by locally produced VIP in vivo and that more peptide molecules can be bound on the lymphocytes when needed, released and accumulated in higher concentration at the action sites. We failed to detect the expression of VIP mRNA in T lymphocytes, from either intestine or spleen. These observations support that VIP may be an important immune modulator in gut acting through specific receptors on T lymphocytes. The differential mRNA expression of VIP receptor subtypes in cells with different phenotypes and in different immune compartments may suggest diverse regulatory roles of the neuropeptide in immune responses.
Just How Useful Are Health Rankings?

Ranking health of the counties and states is popular. Such rankings often make the news in local papers, radio, and television news broadcasts. County Health Rankings & Roadmaps (University of Wisconsin Population Health Institute 2014) rankings are done on two components, Health Outcomes and Health Factors. Health Outcomes refer to rates of such things as premature deaths, poor health days, and low birthweight. Health Factors include smoking, obesity, and teen births, as well as other social and economic factors. According to the 2014 County Health Rankings & Roadmaps (University of Wisconsin Population Health Institute 2014), the county where I live in Iowa ( Johnson) has an overall Health Outcomes ranking of 13 out of 99 counties and a Health Factors ranking of 2. However, if I lived a little southeast in Muscatine County, approximately 32 miles by car, things would appear to be quite a bit different. Muscatine County has a Health Outcomes rank of 62 out of 99 and a Health Factors rank of 82. What are we to do with this information? These ranks can “mobilize” communities to action aimed at addressing the deficiencies. At another level, decision makers might divert programming and funding to shore up the problem areas. The implication is that a low rank suggests there may be a problem with the community’s health that could be made better. Just how meaningful are these ranks and the differences in the ranks? Previous work has investigated the reliability of rankings in a number of venues (Goldstein and Spiegelhalter 1996; Marshall et al. 1998; Parry et al. 1998; Adab et al. 2002; van Dishoeck et al. 2011; Zhang et al. 2014) and health rankings in particular (Arndt et al. 2011, 2013). Reliability here refers to the degree of instability of the ranks due to random noise. These are just a ©Health Research and Educational Trust DOI: 10.1111/1475-6773.12350 EDITORIAL
The Akaike information criterion in DCE-MRI: Does it improve the haemodynamic parameter estimates?

The Akaike information criterion and the associated Akaike weights (AW) rank pharmacokinetic models on the basis of goodness-of-fit and number of parameters. The usefulness of this information for improving the haemodynamic parameter estimates from DCE-MRI was investigated through two examples. In each of these, the estimates from the two-compartment exchange model (2CXM) were combined on the basis of the AW with those of a simplified model (either the uptake model or the extended Tofts model). Data were simulated using the 2CXM for a range of experimental and tissue conditions. Two multimodel approaches exploiting the AW were investigated: the ‘best model’ approach which selects the parameter estimates from the model with highest AW and the ‘weighted model’ approach in which AW-weighted averages of the estimates from the competing models are calculated. Although these approaches were shown to be beneficial in some cases, they were found to frequently lead to unexpected increases in the bias and/or uncertainty of the resulting parameter estimates. Within the limited scope of this simulation study, the use of the Akaike criterion showed no systematic benefit over a fitting strategy involving only the more complex model.
Test-Retest Variability in Structural and Functional Parameters of Glaucoma Damage in the Glaucoma Imaging Longitudinal Study

PurposeTo determine the test-retest variability in perimetric, optic disc, and macular thickness parameters in a cohort of treated patients with established glaucoma. Patients and MethodsIn this cohort study, the authors analyzed the imaging studies and visual field tests at the baseline and 6-month visits of 162 eyes of 162 participant in the Glaucoma Imaging Longitudinal Study (GILS). They assessed the difference, expressed as the standard error of measurement, of Humphrey field analyzer II (HFA) Swedish Interactive Threshold Algorithm fast, Heidelberg retinal tomograph (HRT) II, and retinal thickness analyzer (RTA) parameters between the two visits and assumed that this difference was due to measurement variability, not pathologic change. A statistically significant change was defined as twice the standard error of measurement. ResultsIn this cohort of treated glaucoma patients, it was found that statistically significant changes were 3.2 dB for mean deviation (MD), 2.2 for pattern standard deviation (PSD), 0.12 for cup shape measure, 0.26 mm2 for rim area, and 32.8 μm and 31.8 μm for superior and inferior macular thickness, respectively. On the basis of these values, it was estimated that the number of potential progression events detectable in this cohort by the parameters of MD, PSD, cup shape measure, rim area, superior macular thickness, and inferior macular thickness was 7.5, 6.0, 2.3, 5.7, 3.1, and 3.4, respectively. ConclusionsThe variability of the measurements of MD, PSD, and rim area, relative to the range of possible values, is less than the variability of cup shape measure or macular thickness measurements. Therefore, the former measurements may be more useful global measurements for assessing progressive glaucoma damage.
Binding of SH2-B Family Members within a Potential Negative Regulatory Region Maintains JAK2 in an Active State

ABSTRACT The tyrosine kinase Janus kinase 2 (JAK2) transduces signaling for the majority of known cytokine receptor family members and is constitutively activated in some cancers. Here we examine the mechanisms by which the adapter proteins SH2-Bβ and APS regulate the activity of JAK2. We show that like SH2-Bβ, APS binds JAK2 at multiple sites and that binding to phosphotyrosine 813 is essential for APS to increase active JAK2 and to be phosphorylated by JAK2. Binding of APS to a phosphotyrosine 813-independent site inhibits JAK2. Both APS and SH2-Bβ increase JAK2 activity independent of their N-terminal dimerization domains. SH2-Bβ-induced increases in JAK2 dimerization require only the SH2 domain and only one SH2-Bβ to be bound to a JAK2 dimer. JAK2 mutations and truncations revealed that amino acids 809 to 811 in JAK2 are a critical component of a larger regulatory region within JAK2, most likely including amino acids within the JAK homology 1 (JH1) and JH2 domains and possibly the FERM domain. Together, our data suggest that SH2-Bβ and APS do not activate JAK2 as a consequence of their own dimerization, recruitment of an activator of JAK2, or direct competition with a JAK2 inhibitor for binding to JAK2. Rather, they most likely induce or stabilize an active conformation of JAK2.
Evidence-based diagnosis and management of tubal factor infertility

Purpose of review The investigation for potential tubal disease is an essential step in the work-up of infertility. This review article provides an evidence-based overview of the diagnosis and management of tubal factor infertility. Recent findings While laparoscopic chromopertubation remains the gold standard in the diagnosis of tubal disease and hysterosalpingography is still widely used, newer modalities offer some advantages. Sonohysterography with the use of contrast medium is superior to hysterosalpingography and comparable to laparoscopic chromotubation in diagnosing tubal blockage. Chlamydia serology is the most cost-effective and least invasive diagnostic test for tubal disease, and it is comparable to, if not better than, hysterosalpingography. Depending on the nature and degree of tubal dysfunction as well as the age and ovarian reserve of the patient, various treatments for tubal infertility are available. For proximal tubal obstruction, transcervical tubal cannulation with tubal flushing is a reasonable first approach. Surgical techniques for tubal repair, such as salpingostomy or fimbrioplasty for distal tubal obstruction, can provide good results. Still, tubal factor remains a major indication for in-vitro fertilization and embryo transfer, which bypasses the tubal problem altogether. In certain situations, such as the presence of hydrosalpinx, prophylactic surgery can be used in conjunction with in-vitro fertilization and embryo transfer. Summary As with infertility in general, the diagnosis and management of tubal infertility should be tailored to the individual patient. Future studies should help to further clarify the role of the various diagnostic tests and therapeutic approaches for tubal infertility.
Halothane anaesthesia does not modify the cardiovascular response to phenylephrine in man.

Conflicting results exist regarding the ability of halothane to alter the vascular response to alpha 1 adrenergic agonists in animals. Because data from humans are lacking, we studied the haemodynamic response to phenylephrine (PHE) in eight patients about to undergo coronary artery bypass surgery before and during halothane anaesthesia. After obtaining baseline measurements in patients while awake, the responses to PHE infusion at 30, 40, and 50 micrograms.min-1 were determined. New baseline measurements were made following stabilisation during anaesthesia with halothane, one per cent inspired in oxygen, prior to surgical incision. Then the responses to identical PHE doses were measured again. Halothane did not influence the cardiovascular response to PHE: there was no dose-response shift for any cardiovascular variable. No arrhythmias or signs of ischaemia were observed. We conclude that one per cent halothane anaesthesia does not attenuate PHE-induced vasoconstriction in man.
Fatal Myocardial Infarction Potentially Induced by Paclitaxel

OBJECTIVE: To report a case of a fatal myocardial infarction (MI) possibly induced by paclitaxel in a patient with metastatic breast cancer. CASE SUMMARY: A 67-year-old African-American woman with metastatic breast cancer was treated with a paclitaxel infusion. Fifteen hours into the 24-hour continuous infusion, the patient developed tachypnea, respiratory distress, and chest pain. Paciltaxel infusion was discontinued. Electrocardiogram findings revealed ST elevation in leads 2, 3, and aVF acutely. The cardiac enzymes were abnormal and the echocardiogram changes showed severe global left ventricular dysfunction consistent with acute MI. The patient died 13 hours after stopping the paclitaxel infusion. DISCUSSION: Cardiac adverse effects of paclitaxel have been described in preliminary studies. Paclitaxel-induced cardiac abnormalities are usually described as asymptomatic and transient. MI secondary to paclitaxel infusion has rarely been reported. The mechanism by which paclitaxel causes cardiac abnormalities, especially myocardial damage, is not well understood. CONCLUSIONS: Myocardial damage secondary to paclitaxel infusion is a serious and life-threatening adverse effect. Caution should be exercised in all patients treated with paclitaxel until more information regarding risk factors is available.
Assessment of Ki-67 antigen immunostaining in squamous intraepithelial lesions of the uterine cervix. Correlation with the histologic grade and human papillomavirus type.

A formalin-fixation and paraffin-processing resistant epitope of Ki-67 cell proliferation-associated antigen was immunohistochemically detected by the MIB-1 monoclonal antibody (Immunotech, Marseille, France) in 25 routinely processed cervical biopsies showing normal squamous epithelium or squamous metaplasia and in 65 cervical intraepithelial lesions (SILs) (44 low grade and 21 high grade SILs) with human papillomavirus (HPV) infection. Expression of Ki-67 antigen was exclusively confined to the parabasal and basal layers of normal and metaplastic epithelium. There was no significant difference of Ki-67 antigen immunostaining between normal cervical biopsies and cases of squamous metaplasia. In SIL specimens, the staining was markedly increased in the parabasal and basal layers and Ki-67-positive cells were also distributed in the intermediate (low grade SIL) or all layers of epithelium (high grade SIL). Statistically significant differences for the density of Ki-67 antigen-labeled cells, which were assessed with an image analysis system, were found in comparisons between normal or metaplastic epithelium and SILs (P < .001) and between low grade SILs and high grade SILs (P < .001). In our series of SILs, HPV 16/18 and 31/33/35/novel types, which were found in both low grade and high grade SILs, were significantly associated with higher densities of Ki-67 antigen-positive cells than HPV 6/11 types that were found exclusively in low grade SILs. There was no significant difference found between the densities of Ki-67 antigen-labeled cells in HPV 16/18-positive and HPV 31/33/35/novel types-positive tissues in our series of SILs taken as a whole or when segregating SILs into low grade and high grade.
Predictors of dental care utilization among working poor Canadians.

OBJECTIVE This study used the Gelberg-Andersen Behavioral Model for Vulnerable Populations to identify predictors of dental care utilization by working poor Canadians. METHODS A cross-sectional stratified sampling study design and telephone survey methodology was used to collect data from a nationally representative sample of 1049 working poor individuals aged 18 to 64 years. Working poor persons worked > or = 20 h a week, were not full-time students and had annual family incomes <$34,300. A pretested questionnaire included sociodemographic items, self-reported oral health measures and two dental care utilization outcomes: time since their last dental visit and the usual reason for dental visits. RESULTS Hierarchical stepwise logistic analyses identified independent predictors associated with visiting the dentist >1 year ago: male gender (OR = 1.63; P = 0.005), aged 25-34 years (OR = 2.05; P = 0.02), paying for dental care with cash or credit (OR = 2.31; P < 0.001), past welfare recipients (OR = 1.65; P = 0.03), <21 teeth (OR = 4.23; P < 0.001) and having a perceived need for dental treatment (OR=2.78; P < 0.001). Sacrificing goods or services to pay for dental treatment was associated with visiting the dentist within the past year. The predictors of visiting the dentist only when in pain/trouble were lone parent status (OR = 4.04; P < 0.001), immigrant status (OR = 1.72; P = 0.006), paying for dental care with cash or credit (OR = 2.71; P < 0.001), a history of an inability to afford dental care (OR = 1.62; P = 0.01), a satisfactory/poor/very poor self-rated oral health (OR = 2.10; P < 0.001), number of teeth <21 (OR = 2.58; P < 0.001) and having a perceived need for dental treatment (OR = 2.99; P < 0.001). CONCLUSIONS This study identified predisposing and enabling vulnerabilities that jeopardize the dental care-seeking practices of working poor persons. Dental care utilization was associated with relinquishing spending on other goods and services, which suggests that dental care utilization is a competing financial demand for economically constrained adults.
RAZOR: A Phase II Open Randomized Trial of Screening Plus Goserelin and Raloxifene Versus Screening Alone in Premenopausal Women at Increased Risk of Breast Cancer

Background: Ovarian suppression in premenopausal women is known to reduce breast cancer risk. This study aimed to assess uptake and compliance with ovarian suppression using the luteinizing hormone releasing hormone (LHRH) analogue, goserelin, with add-back raloxifene, as a potential regimen for breast cancer prevention. Methods: Women at ≥30% lifetime risk breast cancer were approached and randomized to mammographic screening alone (C-Control) or screening in addition to monthly subcutaneous injections of 3.6 mg goserelin and continuous 60 mg raloxifene daily orally (T-Treated) for 2 years. The primary endpoint was therapy adherence. Secondary endpoints were toxicity/quality of life, change in bone density, and mammographic density. Results: A total of 75/950 (7.9%) women approached agreed to randomization. In the T-arm, 20 of 38 (52%) of women completed the 2-year period of study compared with the C-arm (27/37, 73.0%). Dropouts were related to toxicity but also the wish to have established risk-reducing procedures and proven chemoprevention. As relatively few women completed the study, data are limited, but those in the T-arm reported significant increases in toxicity and sexual problems, no change in anxiety, and less cancer worry. Lumbar spine bone density declined by 7.0% and visually assessed mammographic density by 4.7% over the 2-year treatment period. Conclusions: Uptake is somewhat lower than comparable studies with tamoxifen for prevention with higher dropout rates. Raloxifene may preserve bone density, but reduction in mammographic density reversed after treatment was completed. Impact: This study indicates that breast cancer risk reduction may be possible using LHRH agonists, but reducing toxicity and preventing bone changes would make this a more attractive option. Cancer Epidemiol Biomarkers Prev; 27(1); 58–66. ©2017 AACR.
AN EMPIRICAL TEST OF PREDICTIONS OF TWO COMPETING MODELS FOR THE MAINTENANCE AND FATE OF HYBRID ZONES: BOTH MODELS ARE SUPPORTED IN A HARD‐CLAM HYBRID ZONE

Two models developed to discern the mode of selection in hybrid zones differ in some predictions. The tension‐zone model predicts that selection acts against hybrids and independently of the environment (endogenous selection) and that selection is invariant throughout the hybrid zone. The ecological selection‐gradient, or ecotone, model maintains that fitness of different genotypes varies in response to environmental variation (exogenous selection) and thus, that in a region of the zone, fitness of hybrids is at least equal to that of the parental species. Therefore, to assess the predominant mode of selection operating in a hybrid zone, it is fundamental to evaluate whether selection is acting specifically against hybrid individuals, that is, whether hybridity alone is the basis for deficiencies of hybrids, and to evaluate whether the relative fitness of hybrids versus that of pure species varies across the zone. In a hardclam (genus Mercenaria) hybrid zone located in a polyhaline lagoon in east‐central Florida, we used age‐specific and location‐specific analyses to determine that a hybrid deficit occurrs, that the deficit seems to be due to selection against hybrids, and that selection varies across the zone. Various measures of deviation from Hardy‐Weinberg equilibrium, linkage disequilibrium analyses, and shifts in allele frequencies at semidiagnostic loci support the idea that selection is strongest in the northern region of the lagoon, the zone of sympatry and hybridization. Southward, into the range of M. mercenaria (the numerically predominant species), the percentage of hybrids remains relatively high and selection against hybrids decreases. For some genetic linkage groups, selection for M. mercenaria alleles seems to be occurring, but selection seems to be acting principally against alleles characteristic of M. mercenaria and, to a lesser degree, for alleles characteristic of M. campechiensis (the rarer species). These findings and others from previous analyses we have done on this hybrid zone demonstrate that selection in the zone is complex, and that characteristics of both the tension‐zone and ecotone models are present. Supporting the tension‐zone model, selection against hybrids per se clearly occurs, but specific genotypes seem to be at a selective disadvantage, whereas others have a selective advantage, and selection operates differentially on the two parental species within the zone. Supporting the ecotone model, the strength of overall selection varies throughout the zone, and environmentally mediated selection in which each species and hybrids have an advantage in specific habitats occurs, but some selection against hybrids is invariant throughout the zone. Thus, the structure and genetic architecture of this hybrid zone appear to be products of a complicated interaction between both types of selective forces cited in the two competing models.
The Arabidopsis thaliana trp5 Mutant Has a Feedback-Resistant Anthranilate Synthase and Elevated Soluble Tryptophan

The first step of tryptophan biosynthesis is catalyzed by anthranilate synthase (AS), which is normally subject to feedback inhibition by tryptophan. Three independent trp5 mutants defective in the Arabidopsis thaliana AS [alpha] subunit structural gene ASA1 were identified by selection for resistance to the herbicidal compound 6-methylanthranilate. In all three mutants these biochemical changes are caused by a single amino acid substitution from aspartate to asparagine at residue position 341. Compared with the enzyme from wild-type plants, the tryptophan concentration causing 50% inhibition of AS activity in the trp5 mutant increased nearly 3-fold, the apparent Km for chorismate decreased by approximately 50%, and the apparent Vmax increased 60%. As a consequence of altered AS kinetic properties, the trp5 mutants accumulated 3-fold higher soluble tryptophan than wild-type plants. However, even though the soluble tryptophan levels were increased in trp5 plants, the concentrations of five tryptophan biosynthetic proteins remained unchanged. These data are consistent with the hypothesis that the reaction catalyzed by A. thaliana AS is rate limiting for the tryptophan pathway and that accumulation of tryptophan biosynthetic enzymes is not repressed by a 3-fold excess of end product.