Miracle-dz/UniFAR-FTUs huggingface dataset:
Proliferation of IL‐6‐independent multiple myeloma does not require the activity of extracellular signal‐regulated kinases (ERK1/2)

The evolutionarily conserved Ras/Raf/MEK/ERK pathway is thought to be essential for proliferation of eukaryotic cells. The human multiple myeloma (MM) cell line 8226 encodes an activated K‐ras allele and proliferates without requirement for the main MM growth and survival factor IL‐6. Surprisingly, the addition of the MEK1/2 inhibitors PD98059 or U0126 to 8226 cultures at doses that block virtually all ERK1/2 activity had minimal effects on the rapid proliferation of this cell line. In contrast, proliferation of the IL‐6‐dependent MM cell line, ANBL‐6 was blocked by PD98059. Levels of activated forms of the other classical MAP kinases (JNK and p38) were very low during MM cell proliferation and, therefore, do not substitute for the mitogenic activities normally regulated by ERK kinases. These data demonstrate that proliferation of 8226 cells does not require ERK1/2 activity, and suggest that IL‐6‐independent growth of MM may correlate with independence from a requirement for ERK activity. Other signal transduction pathways that appear to regulate cell cycle progression in these cells were examined. J. Cell. Physiol. 193: 42–54, 2002. © 2002 Wiley‐Liss, Inc.
RISK FACTORS FOR CENTRAL SEROUS CHORIORETINOPATHY: A Systematic Review and Meta-Analysis

Purpose: Central serous chorioretinopathy (CSC) is a common retina disease and has a relative high recurrence rate, etiology, and pathogenesis of which remains ambiguous. The systematic review and meta-analysis aimed to measure risk factors for CSC in a quantitative method, providing some precautions and interventions on this disease and preventing further recurrences. Methods: A comprehensive literature review relating to risk factors for CSC through PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and VIP databases was conducted before March 2015. Odds ratio (OR) with 95% confidence interval (CI) was calculated after data combination to assess the associations between risk factors and CSC. Results: A total of 9839 patients in 17 studies were included and risk factors with significant differences found between CSC and control groups were listed as follows: hypertension (OR = 1.7; 95% CI: 1.28–2.25), Helicobacter pylori (H. pylori) infection (OR = 3.12; 95% CI: 1.81–5.40), steroid usage (OR = 4.29; 95% CI: 2.01–9.15), sleeping disturbance (OR = 1.90; 95% CI: 1.28–1.83), autoimmune disease (OR=3.44; 95% CI: 1.90–6.26), psychopharmacologic medication use (OR = 2.69; 95% CI: 1.63–4.45), and Type-A behavior (OR = 2.53; 95% CI: 1.08–5.96). Conclusion: The authors concluded that hypertension, H. pylori infection, steroid usage, sleeping disturbance, autoimmune disease, psychopharmacologic medication use, and Type-A behavior were possible risk factors relating to the occurrence of CSC.
Prevalence of carotid canal dehiscence in the human middle ear: A report of 1000 temporal bones

A total of 1000 human temporal bones were used to study the prevalence of carotid canal dehiscence, microdehiscence, and thin bony coverage. Additionally, this study compares the prevalence according to sex and temporal bone age. A carotid canal dehiscence was detected in 77 (7.7%) bones. It was present bilaterally in 23.2% of the paired temporal bones. The prevalence of carotid canal dehiscence decreases with increasing temporal bone age. It was found in 10 (15.9%) bones in the younger than 2 age group, as opposed to 43 (6.3%) bones from the 40 and older group.
The Mechanism of Binding and Secretion of Alkaline Phosphatase Across the Cell Membranes of Pseudomonas aeruginosa.

Abstract : During growth, pH of the medium decreases resulting in the inactivation of cell-free and surface-bound alkaline phosphatase, whereas periplasm-located alkaline phosphatase is not affected. The decreased pH of the medium induced permeability changes in the outer cell wall which resulted in the complete release of alkaline phosphatase after sucrose extraction. The permeability change of the outer cell wall is pH dependent and reversible. The periplasm-located alkaline phosphatase remains constant during growth of Pseudomonas aeruginosa. A hypothetical model of the mechanism for the release of periplasm-located proteins into the growth medium during growth is presented. (Author)
Transmission of human immunodeficiency virus to sexual partners of hemophiliacs

To examine the variables associated with heterosexual transmission of human immuno‐deficiency virus (HIV), we studied 32 couples in our hemophilia center who had steady sexual relationships for periods more than 1 year. Of the 32 sexual partners of the hemophiliacs, five (15.6%) were HIV seropositive. All five hemophiliacs with HIV transmission to their sexual partners had measurable immunologic deficiencies, as shown by their lower median T‐helper (CD‐4 +) lymphocyte count of 172 cells/mm3. The hemophiliacs without transmission had a slightly higher median CD‐4 + count of 297 cells/mm3 (P = 26). To determine if factors other than the degree of immunologic deficiency in the hemophiliac might contribute to HIV transmission, 18 of the 32 couples were studied more intensively by confidential, coded questionnaires. Regular condom use was reported by nine couples (50%). Two of nine women (22%) without condom usage acquired HIV. One of nine women (11%) using condoms was seropositive; she also reported eight needlestick injuries while assisting her spouse with clotting factor treatments. Intravenous drug abuse was reported in two of the five couples with HIV transmission. Thus, hemophiliacs are at risk for transmitting HIV parenterally as well as venereally. Despite various risk behaviors associated with HIV transmission, the prevalence of infection in our cohort of hemophiliacs' sexual partners is low and within the range (6.8–22%) reported by others. This study underscores the need for comprehensive education and counseling in what previously appeared to be a homogeneous clinic population at risk for transmitting HIV to others.
Childhood adversity and herpesvirus latency in breast cancer survivors.

OBJECTIVE Childhood adversity has been linked to greater emotional and physiological sensitivity to stress. Stress has well-documented effects on cellular immunity, including enhanced herpesvirus reactivation. This study assessed whether childhood adversity was associated with the expression of two latent herpesviruses, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) in adults, and whether this association could be detected beyond the psychological distress women experienced in the aftermath of a breast cancer diagnosis and its treatment. METHODS One hundred and eight breast cancer survivors completed questionnaires and provided blood samples to assess EBV virus capsid antigen (VCA) IgG antibody titers and CMV IgG antibody titers. RESULTS Breast cancer survivors who experienced more childhood adversities had higher EBV and CMV antibody titers than those with fewer childhood adversities. Those who experienced more childhood adversities also had more depressive symptoms, less education, and poorer sleep quality than those with fewer childhood adversities. Depressive symptoms, education, sleep quality, age, BMI, cancer stage, comorbidities, and weekly alcohol consumption were not related to EBV or CMV antibody titers. Time since last treatment was negatively associated with EBV and CMV antibody titers. Elevated antibody titers to latent herpesviruses represent poorer cellular immune system control over viral latency; these data suggest that those with more childhood adversities have poorer cellular immune function. CONCLUSIONS These findings add to the emerging literature suggesting that adverse early experiences may make people more vulnerable to immune dysregulation in adulthood. The consequences of early adversity appear to persist across the life span.
Social Networks, Interpersonal Social Support, and Health Outcomes: A Health Communication Perspective

This manuscript discusses the development, impact, and several major research findings of studies in the area of social network support and health outcomes. The review focuses largely on the development of online social support networks and the ways in which they may interact with face-to-face support networks to influence physical and psychological health outcomes. The manuscript discusses this area and it presents a research agenda for future work in this area from an Associate Editor's perspective.
Testicular oxidative stress. Effects of experimental varicocele in adolescent rats.

OBJECTIVE This present study was undertaken to determine the levels of malondialdehyde (MDA), nitric oxide (NO) and total antioxidant status (TAS) in testes of adolescent rats with experimental bilateral varicocele and to determine the effects of oxidative stress on testis produced by varicocele. METHODS 6-week-old, male Wistar rats, weighing 146-334 g (228.37 +/- 41.34 g), were randomly allocated into two groups. The first group underwent selective and bilateral partial ligation of the spermatic vein (n = 28), and the second group underwent a sham operation and served as the controls (n = 15). Animals were sacrificed 12 weeks after surgery and dilatation of the spermatic veins was observed in the first study group. Bilateral orchiectomy was performed in all rats, and MDA, NO and TAS levels were measured. RESULTS In the study group, the mean MDA (SEM) level was 15.58 +/- 6.07 micromol/g protein, and in the control group, it was 11.59 +/- 3.86 micromol/g protein, respectively; this difference was statistically significant (p < 0.05). The mean NO level was 82.73 +/- 77.84 nmol/g protein in the study group, whereas 28.65 +/- 20.18 nmol/g protein in the control group, this difference was also statistically significant (p < 0.005). The mean TAS levels of the study and control groups were 0.91 +/- 0.32 and 1.78 +/- 0.46 nmol/g tissue, respectively, and this difference was also statistically significant (p < 0.001). But there was no correlation between these three parameters (MDA<-->TAS: r = -0.103, p > 0.05; MDA<-->NO: r = -0.104, p > 0.05; NO<-->TAS: r = -0.123, p > 0.05). CONCLUSION These findings suggest that varicocele may change the testicular oxidative status and may play a role in testicular dysfunction that causes infertility.
Revision: Is Visual Perception a Requisite for Visual Imagery?

Vision is the most highly developed sense in man and represents the doorway through which most of our knowledge of the external world arises. Visual imagery can be defined as the representation of perceptual information in the absence of visual input. Visual imagery has been shown to complement vision in this acquisition of knowledge—it is used in memory retrieval, problem solving, and the recognition of properties of objects. The processes underlying visual imagery have been assimilated to those of the visual system and are believed to share a neural substrate. However, results from studies in congenitally and cortically blind subjects have opposed this hypothesis. Here I review the currently available evidence.
Comparing performances of logistic regression and neural networks for predicting melatonin excretion patterns in the rat exposed to ELF magnetic fields

Various studies have been reported on the bioeffects of magnetic field exposure; however, no consensus or guideline is available for experimental designs relating to exposure conditions as yet. In this study, logistic regression (LR) and artificial neural networks (ANNs) were used in order to analyze and predict the melatonin excretion patterns in the rat exposed to extremely low frequency magnetic fields (ELF‐MF). Subsequently, on a database containing 33 experiments, performances of LR and ANNs were compared through resubstitution and jackknife tests. Predictor variables were more effective parameters and included frequency, polarization, exposure duration, and strength of magnetic fields. Also, five performance measures including accuracy, sensitivity, specificity, Matthew's Correlation Coefficient (MCC) and normalized percentage, better than random (S) were used to evaluate the performance of models. The LR as a conventional model obtained poor prediction performance. Nonetheless, LR distinguished the duration of magnetic fields as a statistically significant parameter. Also, horizontal polarization of magnetic fields with the highest logit coefficient (or parameter estimate) with negative sign was found to be the strongest indicator for experimental designs relating to exposure conditions. This means that each experiment with horizontal polarization of magnetic fields has a higher probability to result in “not changed melatonin level” pattern. On the other hand, ANNs, a more powerful model which has not been introduced in predicting melatonin excretion patterns in the rat exposed to ELF‐MF, showed high performance measure values and higher reliability, especially obtaining 0.55 value of MCC through jackknife tests. Obtained results showed that such predictor models are promising and may play a useful role in defining guidelines for experimental designs relating to exposure conditions. In conclusion, analysis of the bioelectromagnetic data could result in finding a relationship between electromagnetic fields and different biological processes. Bioelectromagnetics 31:164–171, 2010. © 2009 Wiley‐Liss, Inc.
Material Implication and General Indicative Conditionals

This paper falls into two parts. In the first part, I argue that consideration of general indicative conditionals, e.g., sentences like If a donkey brays it is beaten, provides a powerful argument that a pure material implication analysis of indicative if p, q is correct. In the second part I argue, opposing writers like Jackson, that a Gricean style theory of pragmatics can explain the manifest assertability conditions of if p, q in terms of its conventional content – assumed to be merely (p⊃q) – and the conversational implicature contents which utterance of if p, q may gain in certain contexts. I also defend the pragmatic approach against a recent objection by Edgington that appeal to pragmatics cannot explain what we are inclined to say about the believability conditions, as opposed to the assertability conditions, of indicative if p, q.
Risk Measures for Autocorrelated Hedge Fund Returns

Standard risk metrics tend to underestimate the true risks of hedge funds because of serial correlation in the reported returns. Getmansky, Lo, and Makarov (2004) derive mean, variance, Sharpe ratio, and beta formulae adjusted for serial correlation. Following their lead, we derive adjusted downside and global measures of individual and systemic risks. We distinguish between normally and fat-tailed distributed returns and show that adjustment is particularly relevant for downside risk measures in the case of fat tails. An empirical analysis reveals that unadjusted risk measures can considerably underestimate the true extent of individual and systemic risks for hedge funds.
Personalised prescribing for asthma ‐ is pharmacogenetics the answer?

An individual's response to anti‐asthma medication is likely to arise from a complex interaction between social, environmental and inherited factors. Studies indicate that genetic factors may account for 60–80% of the heterogeneity in treatment responsiveness in asthmatics. Identifying the genetic variants responsible may potentially lead to the development of novel treatments, improved effectiveness in the use of existing treatments and better prediction of efficacy in phase II and III trials. This article will briefly outline the current methods of identifying relevant treatment‐responsive genes and their genetic variants. The pharmacogenetics of the main asthma treatment groups will then be reviewed in detail. Finally, the impact of pharmacogenetics on the pharmaceutical industry, and clinical practice in the future will be discussed.
Screening for gestational diabetes mellitus

Gestational diabetes mellitus is associated with increased risk of complications for mother and child. Along with the growing epidemic of obesity and type 2 diabetes, the prevalence of gestational diabetes is expected to rise. With adequate and timely treatment, the risk of complications is reduced. Detection of gestational diabetes however is complicated, since often there are no symptoms. Currently no uniform strategy for detection of gestational diabetes exists. This thesis aims to evaluate costs and effects of various screening strategies in order to obtain a uniform (cost-)effective strategy for detection of gestational diabetes.
Up-Regulation of the μ-Opioid Receptor Gene Is Mediated through Chromatin Remodeling and Transcriptional Factors in Differentiated Neuronal Cells

The effects of morphine are mediated mainly through the μ opioid receptor (MOR). Expression of the MOR is up-regulated during neuronal differentiation in P19 embryonal carcinoma cells and epigenetic changes play an important role in MOR up-regulation. This study investigates the basis for differentiation-dependent alterations of MOR chromatin by studying the recruitment or dissociation of several factors to the remodeled chromatin locus. Chromatin immunoprecipitation assays were used to demonstrate the recruitment of the transcriptional activator Sp1 and the chromatin remodeling factors Brg1 and BAF155 to this promoter, as well as the dissociation of repressors [histone deacetylases, mSin3A, Brm, and methyl-CpG-binding protein 2 (MeCP2)]. Histone modifications (acetylation, induction of histone H3-lys4 methylation, and reduction of H3-lys9 methylation) were consistently detected on this promoter. Overexpression of Sp1 strongly enhanced MOR promoter activity, and the histone deacetylase inhibitor trichostatin A also increased promoter activity. In vitro DNA CpG-methylation of the promoter partially blocked binding of the Sp1 factor but induced MeCP2 binding. Coimmunoprecipitation studies also found novel evidence of an endogenous MeCP2 interaction with Sp3 but a weaker interaction with Sp1. Overall, the results suggest that during neuronal differentiation, MeCP2 and DNA methylation mediate remodeling of the MOR promoter by chromatin remodeling factors (Brg1 and BAF155) from a compacted state to a conformation allowing access for transcriptional factors. Subsequent recruitment of the activating transcription factor Sp1 to the remodeled promoter results in MOR up-regulation.
Perceived social support as a moderator of the relationship between caregiver well-being indicators and psychological symptoms

The present study examined the moderating role of perceived social support in caregiver well-being indicators — psychological symptoms relationship. The data obtained from 100 caregivers of children with leukaemia revealed that the caregivers who were more able to satisfy their basic needs, and perform their daily activities, reported lower levels of psychological symptoms if they perceived higher levels of social support. However, perceived social support did not alleviate the level of psychological symptoms of the caregivers who reported lower levels of satisfaction of basic needs and performance on daily activities. The findings were discussed in the light of the literature.
Successful outcome of liver transplantation in a patient with hepatitis C and common variable immune deficiency

Abstract. A 43-year-old man with common variable immune deficiency underwent liver transplantation for cirrhosis caused by hepatitis C virus (HCV). HCV had been acquired from a contaminated batch of immunoglobulin. He developed cirrhosis within 3 years of infection with the virus, then liver failure requiring liver transplantation. The immediate post-transplant course was uncomplicated. Five months after transplantation he developed liver failure, and the histological appearances were those of severe cholestatic hepatitis. Withdrawal of immunosuppression resulted in recovery from liver failure. Clearance of the HCV from serum was also observed and has been sustained during follow-up (despite the subsequent reintroduction of low-dose immunosuppression). The patient is alive and well more than 5 years after transplantation. His post-transplant course has been remarkable for the aggressive recurrence then clearance of the HCV.
Prevalence of anti rubella antibodies in pregnant and prepubertal females--a preliminary study.

Prevalence of anti Rubella antibodies was determined using ELISA technique. Seventy seven percent pregnant and 51% pre-pubertal females showed evidence of immunity against rubella while 23% pregnant females were susceptible to rubella infection. There is a need to start rubella immunization programme for girls, to lower the incidence of congenital Rubella (JPMA 37: 6, 1987).
CD31‐triggered rearrangement of the actin cytoskeleton in human natural killer cells

In this report, we analyze whether CD31, also known as platelet‐endothelial cell adhesion molecule‐1 (PECAM‐1), can transduce an outside‐in signal in human natural killer (NK) lymphocytes in vitro. We show that CD31, but not HLA class‐I cross‐linking triggers an outside‐in transmembrane signal in NK lymphocytes, mediating cell spreading and cytoskeletal rearrangement. These phenomena are Mg2+, but not Ca2+ dependent, suggesting that signal transduction elicited by CD31 cross‐linking may involve an associated integrin. Two possible candidates would be αv and αL, whose function is known to depend on Mg2+. However, the CD31‐induced cytoskeletal rearrangement was not reduced by the use of αv‐ or αL‐specific F(ab′)2, suggesting that CD31 could transduce a signal by itself or by association with a still‐undefined integrin. Moreover, talin, but not vinculin or tubulin, appears to co‐localize with actin microfilaments in the membrane ruffles of NK cells that undergo cytoskeleton rearrangement following CD31 cross‐linking. Both spreading and cytoskeletal rearrangement appear to be regulated by intracellular cyclic‐3′,5′‐adenosine monophosphate (cAMP). Indeed, the activator of the adenylyl cyclase, forskolin, inhibited cell spreading and cytoskeletal rearrangement induced by CD31 cross‐linking. This phenomenon was also observed using the membrane‐permeants cAMP analog Sp adenosine‐3′,5′‐cyclic monophosphothioate (Sp‐cAMPS), but not its inactive isomer Rp‐cAMPS. Likewise, adhesion of NK lymphocytes to NIH/3T3 murine fibroblasts transfected with the cDNA encoding human CD31 was blocked by increasing intracellular cAMP levels. We suggest that intracellular cAMP may be involved in CD31‐mediated signal transduction, and may regulate NK‐endothelial cell adhesion and possibly, the tissue localization of NK cells.
Gastrin: levels and trophic action during advancing age.

Changes in antral and serum gastrin levels as well as gastrin (G) and somatostatin (D) cell density were examined in 4- to 16-mo-old Fischer-344 rats. In these rats, the responsiveness of the gastric mucosa to the trophic action of gastrin was also examined. It was observed that whereas serum gastrin levels declined steadily between 4 and 16 mo of age, antral gastrin levels rose sharply during this period. In the antrum of 16-mo-old rats, the density of G-cells, but not D-cells, was found to be lower than in their 4-mo-old counterparts. Thus, when D- to G-cell ratios were calculated, 16-mo-old rats revealed a 50% higher D- to G-cell ratio than the 4-mo-old animals. To assess the trophic action of gastrin, groups of 4-, 8-, and 16-mo-old rats were infused subcutaneously (osmotic minipump) with either saline or gastrin (G-17-I; 250 ng.kg-1.h-1) for 14 days. The gastric mucosa was assayed for thymidine kinase (an indicator of proliferative activity) and DNA and protein content. In the saline-infused rats, gastric mucosal thymidine kinase activity increased sharply between 4 and 16 mo of age without significantly affecting DNA or protein content (expressed as milligrams per 100 g of body weight), suggesting that the age-associated rise in proliferative activity is not accompanied by increased mucosal growth. (ABSTRACT TRUNCATED AT 250 WORDS)