Miracle-dz/UniFAR-FTUs huggingface dataset:
CD13/aminopeptidase N is a negative regulator of mast cell activation

Antigen‐induced mast cell (MC) activation via cross‐linking of IgE‐bound high‐affinity receptors for IgE (FcεRI) underlies type I allergy and anaphylactic shock. Comprehensive knowledge of FcεRI regulation is thus required. We have identified a functional interaction between FcεRI and CD13 in murine MCs. Antigen‐triggered activation of IgE‐loaded FcεRI results in cocapping and cointernalization of CD13 and equivalent internalization rates of up to 40%. Cointernalization is not unspecific, because ligand‐driven KIT internalization is not accompanied by CD13 internalization. Moreover, antibody‐mediated cross‐linking of CD13 causes IL‐6 production in an FcεRI‐dependent manner. These data are indicative of a functional interaction between FcεRI and CD13 on MCs. To determine the role of this interaction, CD13‐deficient bone marrow‐derived MCs (BMMCs) were analyzed. Intriguingly, antigen stimulation of CD13‐deficient BMMCs results in significantly increased degranulation and proinflammatory cytokine production compared to wild‐type cells. Furthermore, in a low‐dose model of passive systemic anaphylaxis, antigen‐dependent decrease in body temperature, reflecting the anaphylactic reaction, is substantially enhanced by the CD13 inhibitor bestatin (–5.9 ± 0.6°C) and by CD13 deficiency (–8.8 ± 0.6°C) in contrast to controls (–1.2 ± 1.97°C). Importantly, bestatin does not aggravate anaphylaxis in CD13‐deficient mice. Thus, we have identified CD13 as a novel negative regulator of MC activation in vitro and in vivo. —Zotz, J. S. , Wölbing, F. , Lassnig, C. , Kauffmann, M. , Schulte, U. , Kolb, A. , Whitelaw, B. , Müller, M. , Biedermann, T. , Huber, M. CD13/aminopeptidase N is a negative regulator of mast cell activation. FASEB J. 30, 2225–2235 (2016). www.fasebj. org
Cyclophosphamide for CLL: to be or not CYP2B activated?

In this issue of Blood , Johnson et al 1 report their findings of the hepatic cytochrome P450 (CYP) enzyme gene polymorphisms in patients with chronic lymphocytic leukemia (CLL) treated with fludarabine and cyclophosphamide (FC) within a clinical trial. Patients with at least one *6 allele had significantly lower rates of complete response and also less toxicity than patients with *1/*1 alleles, as well as a trend of shorter progression-free survival (PFS). Albeit indirect, this is the first indication in a controlled clinical trial of a significant impact of cyclophosphamide (CPA) bioactivation in CLL and a step toward tailored therapy of cancer.
Differences in Collagen Expression in Cumulus Cells after Exposure to Highly Purified Menotropin or Recombinant Follicle-Stimulating Hormone in a Mouse Follicle Culture Model1

Abstract Extracellular matrix (ECM) formation by cumulus cells is an important process that determines fertilization and embryo quality. Several collagen types are present in the ovarian follicular ECM and are related to proliferation, steroidogenesis, and luteinization. In vitro mouse follicles can optimally grow and provide developmentally competent oocytes with 10 IU/L recombinant follicle-stimulating hormone (rFSH). As a model for superovulation, experiments with 100 IU/L rFSH or 100 IU/L highly purified menotropin (HP-hMG) exposure during antral growth were undertaken. Col4a1, Col4a2, and Col6a2 expression levels were analyzed at three time points during antral growth and at a 4-h interval up to 16 h after ovulation induction using quantitative PCR. The presence and induction of the collagen mRNA and protein were confirmed in cumulus from in vivo- and in vitro-grown follicles, and TGFBs 1 and 2 were assayed as potential regulators. The study revealed that exposure to 100 IU/L FSH, as in both superovulation conditions, significantly influenced the follicle morphology and slowed down nuclear maturation and mucification (P < 0.05). This coincided with an increased expression of the three collagens in the cumulus-oocyte complex at the end of antral growth and in the first hours following the ovulatory dose of human chorionic gonadotropin (P < 0.05). The increased expression might reflect a differentiation but is most likely due to a precocious luteinization of the cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein levels, fewer COCs with an increased collagen expression and with a more synchronous nuclear maturation. This suggests that the presence of luteinizing hormone activity tempered the effect of the elevated FSH dose.
A Potential Biodegradable Mg-Y-Ag Implant with Strengthened Antimicrobial Properties in Orthopedic Applications

In order to design a potential biodegradable implant, which combines with fine mechanical and antimicrobial properties, Mg-4Y-1Ag (mass fraction, %) alloys were produced by permanent mold casting and then hot extrusion. The microstructure, mechanical behavior, anti-corrosion behavior, and antimicrobial properties of the experimental alloys were comprehensively investigated. The results showed that α-Mg, Mg24Y5 (ε), and AgMg4 phases existed in the Mg-4Y-1Ag. The grain size of Mg-4Y-1Ag was greatly refined through hot-extrusion. The as-extruded Mg-4Y-1Ag alloy exhibit an ultimate tensile strength of 202.7 MPa with a good elongation of 33.6%. The compressive strength of as-extruded Mg-4Y-1Ag was 385 MPa, and the strength remained 183 MPa after immersing in PBS solution for four weeks. The as-extruded alloy had better corrosion resistance than as-cast alloy and as-extruded pure magnesium in PBS solution, for the reason of refined grain and the formation of Y2O3 film on the surface of Mg-4Y-1Ag alloy. Furthermore, the as-extruded Mg-4Y-1Ag alloys were superior to Ti6Al4V (TC4) and as-extruded pure magnesium in antimicrobial property for released Ag+ ion. Obvious inhibition halo was observed in the LB agar plate adding with as-extruded Mg-4Y-1Ag alloys. Also as-extruded Mg-4Y-1Ag alloys showed no cytotoxicity by co-culturing with L929 using the MTT method.
Insulin resistance in patients with post‐adolescent acne

Post‐adolescent acne has been defined as acne in a patient aged >25 years. Acne vulgaris first develops at the onset of puberty as a result of hormonal changes. During puberty, there is a transient decline in insulin sensitivity. We hypothesized that insulin resistance might persist after puberty in patients with post‐adolescent acne.
The Effect of Enalapril and Telmisartan on Clinical and Biochemical Indices of Sympathetic Activity in Hypertensive Patients

Objective. To compare the effect of ARB and ACE inhibitor on sympathetic activity in 32 hypertensives. Design and Methods. After a four-week wash-out period, patients were randomized to four weeks of therapy with enalapril or telmisrtan, with crossover to another drug for another four weeks. Blood pressure (BP), NPY, and catecholamine levels and HRV (frequency analysis) were measured during wash-out, in basal condition, and after postural stimulation test (PST). Results. Both drugs significantly reduced BP and NPY as compared to initial values, while no differences in BP and NPY between drugs were observed. Increase in NPY during PST was significantly higher in the enalapril than in the telmisartan group and during the wash-out period. No differences between enalapril and telmisartan in plasma catecholamines were observed. Telmisartan decreased low frequency/high frequency ratio as compared to initial values and enalapril values. Conclusions. Despite similar BP control, telmisartan attenuated autonomic balance more effectively than enalapril.
Genome‐wide DNA methylation profiles in urothelial carcinomas and urothelia at the precancerous stage

To clarify genome‐wide DNA methylation profiles during multistage urothelial carcinogenesis, bacterial artificial chromosome (BAC) array‐based methylated CpG island amplification (BAMCA) was performed in 18 normal urothelia obtained from patients without urothelial carcinomas (UCs) (C), 17 noncancerous urothelia obtained from patients with UCs (N), and 40 UCs. DNA hypo‐ and hypermethylation on multiple BAC clones was observed even in N compared to C. Principal component analysis revealed progressive DNA methylation alterations from C to N, and to UCs. DNA methylation profiles in N obtained from patients with invasive UCs were inherited by the invasive UCs themselves, that is DNA methylation alterations in N were correlated with the development of more malignant UCs. The combination of DNA methylation status on 83 BAC clones selected by Wilcoxon test was able to completely discriminate N from C, and diagnose N as having a high risk of carcinogenesis, with 100% sensitivity and specificity. The combination of DNA methylation status on 20 BAC clones selected by Wilcoxon test was able to completely discriminate patients who suffered from recurrence after surgery from patients who did not. The combination of DNA methylation status for 11 BAC clones selected by Wilcoxon test was able to completely discriminate patients with UCs of the renal pelvis or ureter who suffered from intravesical metachronous UC development from patients who did not. Genome‐wide alterations of DNA methylation may participate in urothelial carcinogenesis from the precancerous stage to UC, and DNA methylation profiling may provide optimal indicators for carcinogenetic risk estimation and prognostication. (Cancer Sci 2009)
Mathematical model for decarburization of ultra-low carbon steel during RH treatment

A mathematical model was established to investigate the decarburization behaviour of ultra-low carbon steel during Ruhrstahl-Heraeus (RH) refining process. In this model, it was assumed that the decarburization reactions occur at four sites: Ar bubble surface, bath surface, bulk steel and splash droplet surface. The effect of Ar bubble behaviour and splash droplet behaviour on decarburization rate was taken into consideration specifically. The calculated results are basically consistent with the industrial experimental observations. Carbon concentration was mainly eliminated at bath surface at early stage of RH treatment, and was mostly removed in bulk steel at middle stage, and was removed at splash droplet surface in the final stage. The decarburization rate at different sites and its contribution to total decarburization value were evaluated in detail. The decarburization rate during RH treatment could be effectively improved by accelerating the drop of vacuum pressure at early stage. Appropriate increasing Ar gas flow rate was beneficial to deep decarburization by increasing the reaction area of droplet surface and bath surface.
Supplementation with pumpkin seed oil improves plasma lipid profile and cardiovascular outcomes of female non‐ovariectomized and ovariectomized Sprague‐Dawley rats

Pumpkin (Cucurbita species) seed oil (PSO) is a rich source of phytoestrogens and the aim of this study was to examine the effect of PSO supplementation on the total cholesterol (TC), low density lipoprotein cholesterol (LDL‐C), triglycerides, high density lipoprotein cholesterol (HDL‐C), systolic and diastolic blood pressure in non‐ovariectomized and ovariectomized Sprague‐Dawley rats. Female rats weighing 220–300 g were divided into non‐ovariectomized rats for supplementation with corn oil (control CO; n = 6) or PSO (control PSO; n = 5) and ovariectomized rats for supplementation with corn oil (OVX/CO; n = 6) or PSO (OVX/PSO; n = 5) for 5 days per week for 12 weeks (corn oil 40 mg/kg or PSO 40 mg/kg given orally). Systolic and diastolic blood pressures were measured weekly. Blood was collected at the end of the period for plasma lipid assays. Control PSO had lower TC, LDL–C, triglycerides and higher HDL‐C than the control CO. The OVX/CO had higher TC, LDL–C, triglycerides and lower HDL‐C than the control CO and these changes were prevented in the OVX/PSO rats. PSO supplementation also resulted in lower systolic and diastolic blood pressures in both non‐ovariectomized and ovariectomized rats. It is concluded that PSO supplementation can prevent changes in plasma lipids and blood pressure associated with inadequate oestrogen availability. Copyright © 2008 John Wiley & Sons, Ltd.
Antitumor Effects of Systemic DNAse I and Proteases in an In Vivo Model

Background. Cell-free DNA circulates in cancer patients and induces in vivo cell transformation and cancer progression in susceptible cells. Based on this, we hypothesized that depletion of circulating DNA with DNAse I and a protease mix could have antitumor effects. Study design. The study aimed to demonstrate that DNAse I and a protease mix can degrade in vitro DNA and proteins from the serum of healthy individuals and cancer patients, and in vivo in serum of Wistar rats,. Moreover, the antitumor effect of the systemically administered enzyme mix treatmentwas evaluated in nude mice subcutaneously grafted with the human colon cancer cell line SW480. Results. The serum DNA of cancer patients or healthy individuals was almost completely degraded in vitro by the enzymatic treatment, but no degradation was found with the enzymes given separately. The intravenous administration of the enzymes led to significant decreases in DNA and proteins from rat serum. No antitumor effect was observed in immunodeficient mice treated with the enzymes given separately. In contrast, the animals that received both enzymes exhibited a marked growth inhibition of tumors, 40% of them having pathological complete response. Conclusion. This study demonstrated that systemic treatment with DNAse I and a protease mix in rats decreases DNA and proteins from serum and that this treatment has antitumor effects. Our results support the hypothesis that circulating DNA could have a role in tumor progression, which can be offset by depleting it. Further studies are needed to prove this concept.
Cybersex Addiction in Heterosexual Female Users of Internet Pornography Can Be Explained by Gratification Hypothesis

In the context of Internet addiction, cybersex is considered to be an Internet application in which users are at risk for developing addictive usage behavior. Regarding males, experimental research has shown that indicators of sexual arousal and craving in response to Internet pornographic cues are related to severity of cybersex addiction in Internet pornography users (IPU). Since comparable investigations on females do not exist, the aim of this study is to investigate predictors of cybersex addiction in heterosexual women. We examined 51 female IPU and 51 female non-Internet pornography users (NIPU). Using questionnaires, we assessed the severity of cybersex addiction in general, as well as propensity for sexual excitation, general problematic sexual behavior, and severity of psychological symptoms. Additionally, an experimental paradigm, including a subjective arousal rating of 100 pornographic pictures, as well as indicators of craving, was conducted. Results indicated that IPU rated pornographic pictures as more arousing and reported greater craving due to pornographic picture presentation compared with NIPU. Moreover, craving, sexual arousal rating of pictures, sensitivity to sexual excitation, problematic sexual behavior, and severity of psychological symptoms predicted tendencies toward cybersex addiction in IPU. Being in a relationship, number of sexual contacts, satisfaction with sexual contacts, and use of interactive cybersex were not associated with cybersex addiction. These results are in line with those reported for heterosexual males in previous studies. Findings regarding the reinforcing nature of sexual arousal, the mechanisms of learning, and the role of cue reactivity and craving in the development of cybersex addiction in IPU need to be discussed.
In vivo cardiovascular effects of the new atypical neuroleptic sertindole.

INTRODUCTION The goal of this open clinical study was to perform a detailed investigation of the cardiovascular effects of the novel atypical neuroleptic sertindole. METHOD Thirty initially untreated schizophrenic inpatients (diagnosed according to DSM-III-R) underwent a total of 103 serial recordings of standardized autonomic tests during a sertindole dose titration programme (4-16 mg/d). The autonomic test battery included: (1) conventional ECGs with 12 channels, (2) computer-assisted analysis of the 5-min resting heart rate variability (HRV); (3) HRV during standard autonomic reflex tests (deep breathing test, 30:15 ratio); and (4) blood pressure measurement under resting conditions and during orthostatic stress (Schellong test). Reference values for the HRV study were obtained from healthy controls ( n =80). RESULTS The most important findings were: (1) sertindole significantly increased the resting heart rate; (2) sertindole induced a significant and probably dose-dependent prolongation of the frequency-corrected QT-times, while mean PQ-conduction times remained unchanged; (3) sertindole had no significant effects on autonomic parasympathetic tone, both in the resting study and following the autonomic reflex tests; and (4) sertindole at doses between 4 and 16 mg/d did not significantly influence blood pressure either under resting conditions or during orthostatic stress. CONCLUSION The implications of these findings for the cardiovascular safety and tolerance of sertindole are discussed comprehensively, while considering the pathophysiologically relevant mechanisms underlying the appearance of life-threatening cardiac arrhythmias and sudden cardiac death. ( Int J Psych Clin Pract 2001; 5:33-40).
The year in Cardiothoracic and Vascular Anesthesia: selected highlights from 2014.

Jacob T. Gutsche, MD,* Prakash A. Patel, MD,* Frederick C. Cobey, MD, MPH,† Harish Ramakrishna, MD, FASE,‡ Emily K. Gordon, MD,* Hynek Riha, MD, DEAA, FCCP,§ Aris Sophocles, MD,* Kamrouz Ghadimi, MD,¶ Michael Fabbro, MD,* Lourdes Al-Ghofaily, MD,* Sy-Yeu S. Chern, MD,* Sophia Cisler, MD,* Gurmukh S. Sahota, MD,* Elizabeth Valentine, MD,* Stuart J. Weiss, MD, PhD,* Michael Andritsos, MD, George Silvay, MD, PhD,** and John G.T. Augoustides, MD, FASE, FAHA*
The relation between social network site usage and loneliness and mental health in community‐dwelling older adults

Loneliness is expected to become an even bigger social problem in the upcoming decades, because of the growing number of older adults. It has been argued that the use of social network sites can aid in decreasing loneliness and improving mental health. The purpose of this study was to examine whether and how social network sites usage is related to loneliness and mental health in community‐dwelling older adults.
Short-Term Local Adaptation of Historical Common Bean (Phaseolus vulgaris L.) Varieties and Implications for In Situ Management of Bean Diversity

Recognizing both the stakes of traditional European common bean diversity and the role farmers’ and gardeners’ networks play in maintaining this diversity, the present study examines the role that local adaptation plays for the management of common bean diversity in situ. To the purpose, four historical bean varieties and one modern control were multiplied on two organic farms for three growing seasons. The fifteen resulting populations, the initial ones and two populations of each variety obtained after the three years of multiplication, were then grown in a common garden. Twenty-two Simple Sequence Repeat (SSR) markers and 13 phenotypic traits were assessed. In total, 68.2% of tested markers were polymorphic and a total of 66 different alleles were identified. FST analysis showed that the genetic composition of two varieties multiplied in different environments changed. At the phenotypic level, differences were observed in flowering date and leaf length. Results indicate that three years of multiplication suffice for local adaptation to occur. The spatial dynamics of genetic and phenotypic bean diversity imply that the maintenance of diversity should be considered at the scale of the network, rather than individual farms and gardens. The microevolution of bean populations within networks of gardens and farms emerges as a research perspective.
Development of a Guideline for the Management of Ventilator-Associated Pneumonia Based on Local Microbiologic Findings and Impact of the Guideline on Antimicrobial Use Practices

Objective. To describe the development of a guideline for the management of ventilator-associated pneumonia (VAP) based on local microbiologic findings and to evaluate the impact of the guideline on antimicrobial use practices. Design. Retrospective comparison of antimicrobial use practices before and after implementation of the guideline. Setting. Intensive care units at Harborview Medical Center, Seattle, Washington, a university-affiliated urban teaching hospital. Patients. A total of 819 patients who received mechanical ventilation and who underwent quantitative bronchoscopy between July 1, 2003, and June 30, 2005, for suspected VAP. Interventions. Implementation of an evidence-based VAP guideline that focused on the use of quantitative bronchoscopy for diagnosis, administration of empirical antimicrobial therapy based on local microbiologic findings and resistance patterns, tailoring definitive antimicrobial therapy on the basis of culture results, and appropriate duration of therapy. Results. During the baseline period, 168 (46.7%) of 360 patients had quantitative cultures that met the diagnostic criteria for VAP, compared with 216 (47.1%) of 459 patients in the period after the guideline was implemented. The pathogens responsible for VAP remained similar between the 2 periods, except that the prevalence of VAP due to carbapenem-resistant Acinetobacter species increased from 1.8% to 15.3% (P < .001), particularly in late-onset VAP. Compared with the baseline period, there was an improvement in antimicrobial use practices after implementation of the guideline: antimicrobial therapy was more frequently tailored on the basis of quantitative culture results (103 [61.3%] of 168 vs 150 [69.4%] of 216 patients; P = .034), there was an increase in the use of appropriate definitive therapy (135 [80.4%] of 168 vs 193 [89.4%] of 216 patients; P = .001), and there wasadecrease in the mean duration oftherapy (12.0vs 10.7days; P = .0014). The all-cause mortality rate was similar in the periods before and after the guideline was implemented (38 [22.6%] of 168 vs 46 [21.3%] of 216 patients; P = .756). Conclusions. Implementation of a guideline for the management of VAP that incorporated the use of quantitative bronchoscopy, the use of empirical therapy based on local microbiologic findings, tailoring of therapy on the basis of culture results, and use of shortened durations of therapy led to significant improvements in antimicrobial use practices without adversely affecting the all-cause mortality rate.