Miracle-dz/UniFAR-FTUs huggingface dataset:
Antitumor Indolequinones Induced Apoptosis in Human Pancreatic Cancer Cells via Inhibition of Thioredoxin Reductase and Activation of Redox Signaling

Indolequinones (IQs) were developed as potential antitumor agents against human pancreatic cancer. IQs exhibited potent antitumor activity against the human pancreatic cancer cell line MIA PaCa-2 with growth inhibitory IC50 values in the low nanomolar range. IQs were found to induce time- and concentration-dependent apoptosis and to be potent inhibitors of thioredoxin reductase 1 (TR1) in MIA PaCa-2 cells at concentrations equivalent to those inducing growth-inhibitory effects. The mechanism of inhibition of TR1 by the IQs was studied in detail in cell-free systems using purified enzyme. The C-terminal selenocysteine of TR1 was characterized as the primary adduction site of the IQ-derived reactive iminium using liquid chromatography-tandem mass spectrometry analysis. Inhibition of TR1 by IQs in MIA PaCa-2 cells resulted in a shift of thioredoxin-1 redox state to the oxidized form and activation of the p38/c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathway. Oxidized thioredoxin is known to activate apoptosis signal-regulating kinase 1, an upstream activator of p38/JNK in the MAPK signaling cascade and this was confirmed in our study providing a potential mechanism for IQ-induced apoptosis. These data describe the redox and signaling events involved in the mechanism of growth inhibition induced by novel inhibitors of TR1 in human pancreatic cancer cells.
Western Medicine: Integrating Emergency Care with Population Health Routine Laboratory Testing to Evaluate for Medical Illness in Psychiatric Patients in the Department Is Largely Unrevealing

Objectives: This is a prospective study of psychiatric patients presenting to the emergency department (ED) to determine the value of routine laboratory studies used to attempt to exclude concomitant medical illness. Methods: Physical exams and laboratory tests were performed on 375 psychiatric patients presenting for “medical clearance” in the ED. Upon completion of these tests, the percentage and impact of abnormal physical exams and laboratory results were assessed. Results: Fifty-six of 375 patients (14.9%) had a non-substance-induced laboratory abnormality. Forty-two of these 56 patients (75.0%) also had abnormal history or physical exam findings indicating laboratory screening. Ten had normal history and physical exams with insignificant laboratory abnormalities. The four (1.1% [95% CI 0.3-2.7%]) remaining patients with normal history and physical exams had abnormal urinalyses which did not affect final disposition or contribute to altered behavior. Conclusion: Patients presenting to the ED with psychiatric chief complaints, benign histories and normal physical exams have a low likelihood of clinically significant laboratory findings.
Prophylactic mesh use during primary stoma formation to prevent parastomal hernia

INTRODUCTION Parastomal hernia (PSH) is a common problem following stoma formation. The optimal technique for stoma formation is unknown although recent studies have focused on whether placement of prophylactic mesh at stoma formation can reduce PSH rates. The aim of this study was to systematically review use of prophylactic mesh versus no mesh with regard to occurrence of PSH and peristomal complications. METHODS A systematic search was performed using PubMed, Embase™ and the Cochrane Library to identify randomised controlled trials that analysed placement of prophylactic mesh versus no mesh at time of initial surgery. Meta‐analysis was performed using random effects methods. RESULTS A total of 506 studies were identified by our search strategy. Of these, 8 studies were included, involving 430 patients (217 mesh vs 213 no mesh). Prophylactic mesh placement resulted in a significantly lower rate of PSH formation (42/217 [19.4%] vs 92/213 [43.2%]) with a combined risk ratio of 0.40 (95% confidence interval [CI]: 0.21‐0.75, p=0.004). Placement of prophylactic mesh did not result in increased peristomal complications (15/218 [6.9%] vs 16/227 [7.0%]) with a combined risk ratio of 1.0 (95% CI: 0.49‐2.01, p=0.990). CONCLUSIONS Prophylactic placement of mesh at primary stoma formation may reduce the incidence of PSH, without an increase in peristomal complications. However, the overall quality of the randomised controlled trials included in the meta‐analysis was poor, and should prompt caution regarding the applicability of the findings of the individual studies and the meta‐analysis to everyday practice.
Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline.

OBJECTIVE To examine the extent to which persons with mild cognitive impairment (MCI) have an increased risk of Alzheimer disease (AD) and a more rapid rate of decline in cognitive function compared to similar persons without cognitive impairment. METHOD Participants were 786 community-based persons (221 with MCI and 565 without cognitive impairment) from the Rush Memory and Aging Project, an ongoing longitudinal clinical-pathologic study of common chronic conditions of old age. All participants underwent detailed annual clinical and neuropsychological evaluations. The authors examined the risk of incident AD and rate of change in global cognitive function among persons with MCI and those without cognitive impairment; all statistical models controlled for age, sex, and education. RESULTS Over an average of 2.5 years of follow-up, 57 persons with MCI (25.8%) developed AD, a rate 6.7 times higher than those without cognitive impairment. In addition, persons with MCI declined considerably more rapidly each year on a measure of global cognitive function than those without cognitive impairment. CONCLUSIONS Mild cognitive impairment is associated with a greatly increased risk of incident Alzheimer disease and a more rapid rate of decline in cognitive function.
Deposition of size-selected metal clusters generated by magnetron sputtering and gas condensation: a progress review

This paper presents a topical review of the production and deposition of size–selected metal clusters generated by magnetron sputtering and gas condensation. Clusters with up to 75,000 atoms can be obtained by controlling the gas pressure in the sputtering source, prior to size selection with a novel (time–of–flight) mass filter. The clusters are deposited on the model graphite substrate to study the cluster–surface interaction. Two regimes for cluster deposition have been identified at elevated impact energies: (i) ‘pinning’ (ca. 10 eV per atom) and (ii) implantation (ca. 100 eV per atom). Of particular importance is the pinning regime, since this allows the fabrication of monodispersed cluster arrays, which are stable against diffusion at room temperature (and above). The deposition of size–selected metal clusters represents a novel method of preparing surface nanostructures, with potential applications including model catalyst studies and the immobilization of biological molecules.
Heterogeneity of outcomes in schizophrenia

Background Care for people with schizophrenia should address a wide range of outcomes, including professional and consumer perspectives. Aims To measure changes in psychopathology functioning, needs for care and quality of life; to develop predictive models for each outcome domain; and to assess the frequency of ‘good'and ‘poor’ outcomes, as defined in a series of different definitions that use combinations of the four domains measured. Method Three-year follow-up of a 1-year-treated prevalence cohort of 107 patients with an ICD–10 diagnosis of schizophrenia attending the South Verona community-based mental health service. Results Mean symptom severity and some types of needs for care worsen, but quality of life shows no change. Functioning shows a non-significant trend to deteriorate. Between 32% and 42% of the variance in the four key outcomes was explained by our model. Different definitions of good'and ‘poor’ outcome included 0–31% of patients, depending on the definition used. Conclusions The 3-year outcome for schizophrenia depends on the domain of outcome used, whether staff or patient ratings are used and the stringency of the definitions used for good and poor outcome.
Absence of Hyper-Responsiveness to Methacholine after Specific Bronchial Provocation Tests in a Worker With Hydroxyapatite-Induced Occupational Asthma

Hydroxyapatite is commonly used as a filler to replace amputated bone or as a coating to promote bone ingrowth into prosthetic implants. Many modern implants, such as hip replacements and dental implants, are coated with hydroxyapatite. We report a patient with occupational asthma due to hydroxyapatite, proven by a specific inhalation challenge, who experienced an early asthmatic reaction after exposure to hydroxyapatite, without increased airway responsiveness to methacholine despite an increased eosinophil count in the peripheral blood. A 38-year-old male dental implant worker visited our allergy department for the evaluation of occupational asthma. He had treated dental implant titanium surfaces with hydroxyapatite for 1.5 years. One year after starting his employment, he noticed symptoms of rhinorrhea, paroxysmal cough, and chest tightness. His symptoms were aggravated during and shortly after work and subsided several hours after work. When he stopped working for 2 months because of his chest symptoms, he became asymptomatic. After restarting his work, his symptoms reappeared and were aggravated. A methacholine bronchial challenge test had a negative response. The following day, a specific bronchial provocation test with wheat powder was negative. On the third day, a specific bronchial provocation test with hydroxyapatite powder produced an early asthmatic response. On the fourth day, a methacholine bronchial challenge test was negative. Further studies are needed to evaluate the exact pathogenetic mechanism of hydroxyapatite-induced occupational asthma.
Exploration of the gene expression correlates of chronic unexplained fatigue using factor analysis.

OBJECTIVE To identify biomarkers of chronic fatigue syndrome (CFS) and related disorders through analysis of microarray data, pathology test results and self-report symptom profiles. METHOD To empirically derive the symptom domains of the illnesses, factor analysis was performed on responses to self-report questionnaires (multidimensional fatigue inventory, Centers for Disease Control and Prevention (CDC) symptom inventory and Zung depression scale) before validation with independent datasets. Gene expression patterns that distinguished subjects across each factor dimension were then sought. RESULTS A four-factor solution was favored, featuring 'fatigue' and 'mood disturbance' factors. Scores on these factors correlated with measures of disability on the Short Form (SF)-36. A total of 57 genes that distinguished subjects along each factor dimension were identified, although the separation was significant only for subjects beyond the extreme (15th and 85th) percentiles of severity. Clustering of laboratory parameters with expression of these genes revealed associations with serum measurements of pH, electrolytes, glucose, urea, creatinine, and liver enzymes (aspartate amino transferase [AST] and alanine amino transferase [AST]); as well as hematocrit and white cell count. CONCLUSION CFS is a complex syndrome that cannot simply be associated with changes in individual laboratory tests or expression levels of individual genes. No clear association with gene expression and individual symptom domains was found. However, analysis of such multifacetted datasets is likely to be an important means to elucidate the pathogenesis of CFS.
CONDITION, GENOTYPE‐BY‐ENVIRONMENT INTERACTION, AND CORRELATIONAL SELECTION IN LIZARD LIFE‐HISTORY MORPHS

Abstract We compared reproductive allocation and variation in condition and survivorship of two heritable female throat color morphs (orange and yellow) in a free‐living population of side‐blotched lizards (Uta stansburiana). Using path analysis and structural equation modeling, we investigated how variation in the social environment affected clutch size and egg mass and two condition traits (postlaying mass, immunological condition) and how these traits in turn affected female field survival. In the presence of many neighbors, both morphs increased their clutch sizes, although these effects were only significant in yellow females. In addition, yellow females increased their egg mass in the presence of many orange neighbors. Orange females surrounded by many orange neighbors showed sign of stress in the form of immunosuppression, whereas this effect was less pronounced in yellow females. The morphs also differed in the impact of variation in clutch size and egg mass on both condition traits. Finally, female morphotype and immune responsiveness affected fitness interactively, and hence these two traits showed signs of fitness epistasis: Selection gradients on this trait were opposite in sign in the two morphs. The correlational selection gradient (γthroatxantibody response) between female throat color and antibody responsiveness was ‐0.365. Our data thus reveal important interactive effects such as genotype‐by‐environment interaction toward the social environment and morph‐specific trade‐offs as well as the occurrence of correlational selection. We discuss the use of naturally occurring and conspicuous genetic polymorphisms in field studies of selection and life‐history allocation.
Serum lipid peroxidation markers are correlated with those in brain samples in different stress models

Objective Stress can stimulate increased production of oxygen radicals. We investigated the correlations between serum levels of lipid peroxidation markers and those in brain samples in different stress models. Methods Animals (n = 96) were divided equally into eight groups: a control group and groups treated with vitamin E (Vit E); exposed to immobilisation stress; exposed to immobilisation stress and treated with Vit E; exposed to cold stress; exposed to cold stress and treated with Vit E; exposed to both immobilisation and cold stress; and a final group exposed to both immobilisation and cold stress and treated with Vit E. Thiobarbituric acid-reactive substance (TBARS) in brain samples and levels of TBARS, corticosterone, conjugated dienes (CD), lipids, and paraoxonase-1 (PON1) activity in serum were analysed. Results Serum corticosterone (p < 0.001), CD (p < 0.05), lipid (p < 0.05) levels, and brain TBARS (p < 0.05) levels were significantly higher in all stress groups than in controls, and the elevated levels were reversed in the Vit E-treated stress groups (p < 0.05). Serum PON1 activity was not different among the groups (p > 0.05). Serum TBARS levels increased significantly in all stress groups (p < 0.05), but this elevation was only reversed in the group exposed to both immobilisation and cold stress and treated with Vit E (p < 0.001). Conclusion These results suggest that serum levels of lipid peroxidation markers can be determined readily and may be useful as indicators to evaluate the effects of oxidative stress in the brain.
Does egg-sharing compromise the chance of donors or recipients achieving a live birth?

BACKGROUND To evaluate the effect of egg-sharing and the outcome of assisted reproductive treatment (ART) in standard IVF/ICSI patients, egg-sharing donors and egg-sharing recipients. METHODS Descriptive cohort study to evaluate 276 egg-sharing cycles involving 192 egg-sharers, 274 recipient cycles receiving eggs from egg-sharers and 1098 non-egg-sharing standard IVF/ICSI cycles from January 1998 to December 2002. Patients were divided into three groups: group A, egg-sharers; group B, non-egg-sharers, age <36 years, FSH <10 IU/l, BMI <30 kg/m(2); and group C, egg-sharing recipients, all ages. Duration and amount of gonadotrophin required to achieve follicular maturity, number of eggs collected and donated, fertilization rate, pregnancy rates and live birth rates were compared between donor, recipient and standard IVF/ICSI patients. The chi(2 )test was used to test for statistical significance (P < 0.05). RESULTS There was no significant difference in pregnancy rate and live birth rate of egg-sharers, group A (42.0%, 33.0%), non-egg-sharers, group B (40.0%, 30.9%) and recipients, group C (41.4%, 28.6%). The number of oocytes collected, number of mature follicles and amount of gonadotrophin used was not significantly different between the two groups (A and B). The average number of embryos transferred and the mean number of eggs allocated between egg-sharers and recipients was not statistically different. CONCLUSION Egg-sharing does not compromise the chance of achieving a pregnancy or live birth for the egg-sharer or the recipient as compared to standard IVF/ICSI patients. The egg-sharers were not at a higher potential risk of ovarian stimulation syndrome and there was no imbalance of egg allocation.
Mast cells in the promotion and limitation of chronic inflammation

Summary: Observations of increased numbers of mast cells at sites of chronic inflammation have been reported for over a hundred years. Light and electron microscopic evidence of mast cell activation at such sites, taken together with the known functions of the diverse mediators, cytokines, and growth factors that can be secreted by appropriately activated mast cells, have suggested a wide range of possible functions for mast cells in promoting (or suppressing) many features of chronic inflammation. Similarly, these and other lines of evidence have implicated mast cells in a variety of adaptive or pathological responses that are associated with persistent inflammation at the affected sites. Definitively characterizing the importance of mast cells in chronic inflammation in humans is difficult. However, mice that genetically lack mast cells, especially those which can undergo engraftment with wildtype or genetically altered mast cells, provide a means to investigate the importance of mast cells and specific mast cell functions or products in diverse models of chronic inflammation. Such work has confirmed that mast cells can significantly influence multiple features of chronic inflammatory responses, through diverse effects that can either promote or, perhaps more surprisingly, suppress aspects of these responses.
MOLECULAR PHYLOGENY OF THE HAPLOSPORIDIA BASED ON TWO INDEPENDENT GENE SEQUENCES

The phylogenetic position of the Haplosporidia has confounded taxonomists for more than a century because of the unique morphology of these parasites. We collected DNA sequence data for small subunit (SSU) ribosomal RNA and actin genes from haplosporidians and other protists for conducting molecular phylogenetic analyses to help elucidate relationships of taxa within the group, as well as placement of this group among Eukaryota. Analyses were conducted using DNA sequence data from more than 100 eukaryotic taxa with various combinations of data sets including nucleotide sequence data for each gene separately and combined, as well as SSU ribosomal DNA data combined with translated actin amino acids. In almost all analyses, the Haplosporidia was sister to the Cercozoa with moderate bootstrap and jackknife support. Analysis with actin amino acid sequences alone grouped haplosporidians with the foraminiferans and cercozoans. The haplosporidians Minchinia and Urosporidium were found to be monophyletic, whereas Haplosporidium was paraphyletic. “Microcell” parasites, Bonamia spp. and Mikrocytos roughleyi, were sister to Minchinia, the most derived genus, with Haplosporidium falling between the “microcells” and the more basal Urosporidium. Two recently discovered parasites, one from abalone in New Zealand and another from spot prawns in British Columbia, fell at the base of the Haplosporidia with very strong support, indicating a taxonomic affinity to this group.
Biological, molecular, and structural analysis of a cytopathic variant from a molecularly cloned simian immunodeficiency virus

Some isolates of simian immunodeficiency virus (SIV) have been shown to infect Sup-T1 cells with slow kinetics and in the absence of cytopathic effects, including cell fusion or CD4 down-modulation (J. A. Hoxie, B. S. Haggarty, S. Bonser, J. Rackowski, H. Shan, and P. Kanki, J. Virol. 62:2557-2568, 1988). In the present study, we describe the isolation and characterization of a SIVmac variant, derived from the BK28 infectious molecular clone, that became highly cytopathic for Sup-T1 cells. This variant, termed CP-MAC, exhibited a number of differences from BK28, including (i) an altered tropism which largely restricted its host range to Sup-T1 cells, (ii) the ability to induce cell fusion and CD4 down-modulation, and (iii) a highly stable interaction of its external (SU) and transmembrane (TM) envelope glycoproteins. In addition, a marked increase in the level of surface envelope glycoproteins was observed both on CP-MAC-infected cells and on virions. The CP-MAC env gene was PCR amplified from infected cells, and sequence analysis identified five amino acid changes in SU and six in TM compared with BK28. The introduction of these changes into BK28 was shown to fully reconstitute the biological and morphological properties of CP-MAC. The limited number of mutations in CP-MAC should enable the molecular determinants to be more precisely defined and help to identify the underlying mechanisms responsible for the striking biological and structural alterations exhibited by this virus.
Transplantation of normal and DMD myoblasts expressing the telomerase gene in SCID mice.

The limited proliferative capacity of dystrophic human myoblasts severely limits their ability to be genetically modified and used for myoblast transplantation. The forced expression of the catalytic subunit of telomerase can prevent telomere erosion and can immortalize different cell types. We thus tested the ability of telomerase to immortalize myoblasts and analyzed the effect of telomerase expression on the success of myoblast transplantation. Telomerase expression did not significantly extend the human myoblast life span. The telomerase expressing myoblasts were nonetheless competent to participate in myofiber formation after infection with the retroviral vector. Although the new fibers obtained are less numerous than after the transplantation of normal myoblasts, these results demonstrate that the forced expression of telomerase does not block the ability of normal or dystrophic myoblasts to differentiate in vivo. It will be now necessary to determine the factors that prevent telomerase from extending the life span of human myoblasts before the potential of this intervention can be fully examined.