Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of ionizing radiation on gene expression in cultured rat heart cells

Purpose : To determine the in vitro effect of ionizing radiation on TGF- β 1, FGF-2, IL-1 β, atrial natriuretic peptide (ANP) and procollagen types I and III gene expression in three different cell types of rat heart. Materials and methods : Primary cell cultures of myocytes and fibroblasts and cultures of a rat heart endothelial cell line (RHEC) were irradiated with single doses of 2.0, 8.5 or 15 Gy. At different time-points after irradiation (4-336 h), gene expression was analysed using a competitive PCR technique. Results : Irradiation of cultured rat heart cells may lead to temporary changes in expression of the genes studied. Analysis of the radiation response of cultured myocytes, cardiac fibroblasts and rat heart endothelial cells reveals different responses with regard to (1) the dose necessary to evoke changes in mRNA expression, (2) the level of and (3) the duration of the 'induced' response. The changes observed were small and between parallel experiments the onset and time-course of the induced gene expression varied between 4 and 48 h. The average expression of TGF- β 1 mRNA between 4 and 48 h was significantly elevated in endothelial cells after a dose of 2.0 Gy, in fibroblasts after a dose of 8.5 Gy and in myocytes after a dose of 15 Gy. Down-regulation of TGF- β 1 mRNA in myocytes was observed after a dose of 8.5 Gy. FGF-2 and procollagen type-I mRNAs were significantly elevated in fibroblasts after a dose of 2.0 Gy. For all three cell types, no effect of dose on the timing or size of the gene expression was observed. Conclusions : Although irradiation of cultured heart cells influences expression of genes involved in tissue remodelling, the observed differences were too small and too restricted in time and dose to explain the exact role of these cell types in processes leading to radiation-induced cardiac fibrosis.
Choir versus Solo Singing: Effects on Mood, and Salivary Oxytocin and Cortisol Concentrations

The quantification of salivary oxytocin (OXT) concentrations emerges as a helpful tool to assess peripheral OXT secretion at baseline and after various challenges in healthy and clinical populations. Both positive social interactions and stress are known to induce OXT secretion, but the relative influence of either of these triggers is not well delineated. Choir singing is an activity known to improve mood and to induce feelings of social closeness, and may therefore be used to investigate the effects of positive social experiences on OXT system activity. We quantified mood and salivary OXT and cortisol (CORT) concentrations before, during, and after both choir and solo singing performed in a randomized order in the same participants (repeated measures). Happiness was increased, and worry and sadness as well as salivary CORT concentrations were reduced, after both choir and solo singing. Surprisingly, salivary OXT concentrations were significantly reduced after choir singing, but did not change in response to solo singing. Salivary OXT concentrations showed high intra-individual stability, whereas salivary CORT concentrations fluctuated between days within participants. The present data indicate that the social experience of choir singing does not induce peripheral OXT secretion, as indicated by unchanged salivary OXT levels. Rather, the reduction of stress/arousal experienced during choir singing may lead to an inhibition of peripheral OXT secretion. These data are important for the interpretation of future reports on salivary OXT concentrations, and emphasize the need to strictly control for stress/arousal when designing similar experiments.
Follicle-stimulating hormone (FSH) during the secondary surge in gilts as influenced by administration of porcine follicular fluid (pFF).

The effect of volume and frequency of administration of porcine follicular fluid (pFF) on FSH concentration was determined in mature gilts during the period of the secondary FSH surge (d 0 to 5; d 0 = onset of estrus) and following withdrawal of pFF (d 5.5 to 9). Crossbred gilts (n = 14) were randomized in a 3 x 2 factorial treatment design involving three doses of pFF (0, 5, or 10 ml) and once- vs twice-daily pFF administration. Porcine FF was aspirated from medium and large follicles and treated with 5 mg of activated charcoal per milliliter of pFF to remove steroids. Once-daily administration of pFF, regardless of dose, failed to suppress mean concentrations of FSH during the secondary FSH surge. Treatment of gilts twice daily with 10 ml of pFF suppressed (P less than .05) area under the FSH curve during the secondary FSH surge compared with gilts given saline. Gilts treated twice daily with 5 ml pFF showed comparable suppression of plasma FSH from d 0 to 3 but began to overcome FSH inhibition after d 3. As a result, FSH release only tended to be lower than controls for the entire treatment period (P less than .1). Mean FSH concentrations were increased (P less than .05) during the post-treatment period (d 5.5 to 9) by treatment with intermediate (5 ml pFF, two times daily and 10 ml pFF, one time daily) and high (10 ml pFF, two times daily) doses of pFF. Neither ovulation rate nor interestrous interval was affected by pFF administration. (ABSTRACT TRUNCATED AT 250 WORDS)
Plasma nitrite/nitrate and endothelin‐1 concentrations in neonatal sepsis

Aim: To determine the changes in plasma nitrite/nitrate (NOx) and endothelin‐1 (ET‐1) concentrations during neonatal sepsis. Methods: In a prospective study, 60 consecutive newborns meeting the criteria for sepsis and without receiving exogenous nitric oxide (25 haemoculture‐positive [HC+] and 35 haemoculture‐negative [HC–]) were compared with 68 healthy newborns (46 full‐term and 22 preterm). NOx and ET‐1 concentrations were measured in each newborn within 48 h of diagnosis of sepsis and then every third day up to three determinations. SNAP‐II and SNAPPE‐II severity scores were performed at the moment of highest clinical severity. Results: At the beginning of the sepsis period, controls and septicaemic newborns had similar NOx and ET‐1 levels, with the exception of infants with severe HC+ sepsis. Throughout the sepsis period, NOx increased in moderate HC+ sepsis and decreased in HC– sepsis, reaching a significant difference at the end of the study period (59.9 ± 72.7 vs 33.9 ± 15.3 μmol/L; p= 0.036). Meanwhile, ET‐1 in newborns with severe HC+ sepsis remained higher than that in the moderate HC+ sepsis group and HC– group, reaching significant differences in all the periods. The highest ET‐1 value was positively correlated with SNAP‐II and SNAPPE‐II scores.
The GALAD scoring algorithm based on AFP, AFP-L3, and DCP significantly improves detection of BCLC early stage hepatocellular carcinoma

Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of death in cirrhotic patients worldwide. The detection rate for early stage HCC remains low despite screening programs. Thus, the majority of HCC cases are detected at advanced tumor stages with limited treatment options. To facilitate earlier diagnosis, this study aims to validate the added benefit of the combination of AFP, the novel biomarkers AFP-L3, DCP, and an associated novel diagnostic algorithm called GALAD. Material and methods: Between 2007 and 2008 and from 2010 to 2012, 285 patients newly diagnosed with HCC and 402 control patients suffering from chronic liver disease were enrolled. AFP, AFP-L3, and DCP were measured using the µTASWako i30 automated immunoanalyzer. The diagnostic performance of biomarkers was measured as single parameters and in a logistic regression model. Furthermore, a diagnostic algorithm (GALAD) based on gender, age, and the biomarkers mentioned above was validated. Results: AFP, AFP-L3, and DCP showed comparable sensitivities and specifities for HCC detection. The combination of all biomarkers had the highest sensitivity with decreased specificity. In contrast, utilization of the biomarker-based GALAD score resulted in a superior specificity of 93.3 % and sensitivity of 85.6 %. In the scenario of BCLC 0/A stage HCC, the GALAD algorithm provided the highest overall AUROC with 0.9242, which was superior to any other marker combination. Conclusions: We could demonstrate in our cohort the superior detection of early stage HCC with the combined use of the respective biomarkers and in particular GALAD even in AFP-negative tumors.
Recent trends in the treatment of prolonged grief

Purpose of review Treatment for prolonged grief has been controversial. However, recent studies have clarified several key issues, offering important guidance to clinicians. This review summarizes the most recent evidence on the efficacy of grief treatments, moderators of treatment response, and new treatment approaches. Recent findings Recent research findings highlight that grief therapy is efficacious when targeted to adult and child grievers with persistent and elevated levels of distress. However, when grief therapy is applied as a universal intervention, it has minimal to no benefits, either for adults or for children. Earlier intervention for children is associated with greater efficacy. In recent studies, therapies employing cognitive–behavioral techniques, such as cognitive restructuring and exposure, have shown particularly robust effects in ameliorating grief symptoms. Other intervention approaches, including pharmacotherapy, internet-based, family-based, and preventive, have shown initial promise, but insufficient data exist to validate their efficacy to date. Summary Prolonged grief, a pattern of persistent and elevated distress following a loss, is increasingly recognized as an independent form of psychopathology that is responsive to treatment. Therapies that employ cognitive–behavioral techniques are efficacious in ameliorating the symptoms of prolonged grief and should be more widely used. However, grief therapy should not be deployed as a blanket intervention for all grievers. Antidepressant medication may serve a useful adjunctive role in grief therapy completion and in reducing bereavement-related depression.
Identification and Characterization of a Novel Biotin Biosynthesis Gene in Saccharomyces cerevisiae

ABSTRACT Yeast Saccharomyces cerevisiae cells generally cannot synthesize biotin, a vitamin required for many carboxylation reactions. Although sake yeasts, which are used for Japanese sake brewing, are classified as S. cerevisiae, they do not require biotin for their growth. In this study, we identified a novel open reading frame (ORF) in the genome of one strain of sake yeast that we speculated to be involved in biotin synthesis. Homologs of this gene are widely distributed in the genomes of sake yeasts. However, they are not found in many laboratory strains and strains used for wine making and beer brewing. This ORF was named BIO6 because it has 52% identity with BIO3, a biotin biosynthesis gene of a laboratory strain. Further research showed that yeasts without the BIO6 gene are auxotrophic for biotin, whereas yeasts holding the BIO6 gene are prototrophic for biotin. The BIO6 gene was disrupted in strain A364A, which is a laboratory strain with one copy of the BIO6 gene. Although strain A364A is prototrophic for biotin, a BIO6 disrupted mutant was found to be auxotrophic for biotin. The BIO6 disruptant was able to grow in biotin-deficient medium supplemented with 7-keto-8-amino-pelargonic acid (KAPA), while the bio3 disruptant was not able to grow in this medium. These results suggest that Bio6p acts in an unknown step of biotin synthesis before KAPA synthesis. Furthermore, we demonstrated that expression of the BIO6 gene, like that of other biotin synthesis genes, was upregulated by depletion of biotin. We conclude that the BIO6 gene is a novel biotin biosynthesis gene of S. cerevisiae.
Immunocytochemical evidence for SNARE protein‐dependent transmitter release from guinea pig horizontal cells

Horizontal cells are lateral interneurons that participate in visual processing in the outer retina but the cellular mechanisms underlying transmitter release from these cells are not fully understood. In non‐mammalian horizontal cells, GABA release has been shown to occur by a non‐vesicular mechanism. However, recent evidence in mammalian horizontal cells favors a vesicular mechanism as they lack plasmalemmal GABA transporters and some soluble NSF attachment protein receptor (SNARE) core proteins have been identified in rodent horizontal cells. Moreover, immunoreactivity for GABA and the molecular machinery to synthesize GABA have been found in guinea pig horizontal cells, suggesting that if components of the SNARE complex are expressed they could contribute to the vesicular release of GABA. In this study we investigated whether these vesicular and synaptic proteins are expressed by guinea pig horizontal cells using immunohistochemistry with well‐characterized antibodies to evaluate their cellular distribution. Components of synaptic vesicles including vesicular GABA transporter, synapsin I and synaptic vesicle protein 2A were localized to horizontal cell processes and endings, along with the SNARE core complex proteins, syntaxin‐1a, syntaxin‐4 and synaptosomal‐associated protein 25 (SNAP‐25). Complexin I/II, a cytosolic protein that stabilizes the activated SNARE fusion core, strongly immunostained horizontal cell soma and processes. In addition, the vesicular Ca2+‐sensor, synaptotagmin‐2, which is essential for Ca2+‐mediated vesicular release, was also localized to horizontal cell processes and somata. These morphological findings from guinea pig horizontal cells suggest that mammalian horizontal cells have the capacity to utilize a regulated Ca2+‐dependent vesicular pathway to release neurotransmitter, and that this mechanism may be shared among many mammalian species.
The multidimensionality of schizotypy in nonpsychotic relatives of patients with schizophrenia and its applications in ordered subsets linkage analysis of schizophrenia

This study aimed to examine the multidimensionality of schizotypy and validate the structure using ordered subset linkage analyses on information from both relatives' schizotypy and probands' schizophrenia symptoms. A total of 203 and 1,310 nonpsychotic first‐degree relatives from simplex and multiplex schizophrenia families, respectively, were interviewed with the Diagnostic Interview for Genetic Studies, which contains a modified Structured Interview for Schizotypy. Using Mplus program with categorical factor indicators, a four‐factor model (Negative Schizotypy, Positive Schizotypy, Interpersonal Sensitivity, and Social Isolation/Introversion) was extracted by exploratory factor analysis from relatives of simplex families and was confirmed in relatives of multiplex families. The validity of each factor was supported by distinct linkage findings resulting from ordered subset analysis based on different combinations of schizophrenia–schizotypy factors. Six chromosomal regions with significant increase in nonparametric linkage z score (NPL‐Z) were found as follows: 15q21.1 (NPL‐Z = 3.60) for Negative Schizophrenia–Negative Schizotypy, 10q22.3 (NPL‐Z = 3.83) and 15q21.3 (NPL‐Z = 3.36) for Negative Schizophrenia–Social Isolation/Introversion, 5q14.2 (NPL‐Z = 3.20) and 11q23.3 (NPL‐Z = 3.31) for Positive Schizophrenia–Positive Schizotypy, and 4q32.1 (NPL‐Z = 3.31) for Positive Schizophrenia–Interpersonal Sensitivity. The greatest NPL‐Z of 3.83 on 10q22.3 in the subset was significantly higher than the greatest one of 2.88 in the whole sample (empirical P‐value = 0.04). We concluded that a consistent four‐factor model of schizotypy could be derived in nonpsychotic relatives across families of patients with different genetic loadings in schizophrenia. Their differential relations to linkage signals have etiological implications and provide further evidence for their validity. © 2009 Wiley‐Liss, Inc.
Ro 44-9883, a New Non-Peptidic GPIIb-GPIIIa Antagonist Prevents Platelet Loss in a Guinea Pig Model of Extracorporeal Circulation

Summary Extensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the present study was to test the efficacy of Ro 44-9883, a potent and selective peptidomimetic GPIIb-IIIa antagonist, in preventing platelet loss in guinea pigs undergoing extracorporeal circulation (ECC) with bubble oxygenation. In 15 guinea pigs, an arterio-arterial shunt was created and perfused for 1 h from the aortic arch to the descending aorta. The guinea pigs were divided into three groups: A control group receiving only heparin as an i.v. bolus, a low dose-treated group and a high dose-treated group receiving in addition to heparin and before starting ECC, 1 or 7 mg/kg Ro 449883 as an i.v. bolus, respectively. In the control group, the platelet count at 30 and 60 min of ECC was dramatically decreased (35 ± 4% and 25 ± 3% of initial value). In the low dose-treated group, Ro 44-9883 partially prevented the drop in platelet count (69 ± 8% and 54 ± 9%; p <0.05) whereas in the high dose-treated group, the platelet count was normal at 30 min (97 ± 8%) and only slightly decreased at 60 min (80 ± 7%). Mean arterial pressure and hematocrit were not significantly different between groups during the experiment. We conclude that i) ECC in guinea pigs provides an interesting in-vivo model for studying platelet loss by contact activation and ii) Ro 44-9883 prevents platelet loss during ECC in a dose dependent manner.
Gender, Race/Ethnicity, and National Institutes of Health R01 Research Awards: Is There Evidence of a Double Bind for Women of Color?

Purpose To analyze the relationship between gender, race/ethnicity, and the probability of being awarded an R01 grant from the National Institutes of Health (NIH). Method The authors used data from the NIH Information for Management, Planning, Analysis, and Coordination grants management database for the years 2000–2006 to examine gender differences and race/ethnicity-specific gender differences in the probability of receiving an R01 Type 1 award. The authors used descriptive statistics and probit models to determine the relationship between gender, race/ethnicity, degree, investigator experience, and R01 award probability, controlling for a large set of observable characteristics. Results White women PhDs and MDs were as likely as white men to receive an R01 award. Compared with white women, Asian and black women PhDs and black women MDs were significantly less likely to receive funding. Women submitted fewer grant applications, and blacks and women who were new investigators were more likely to submit only one application between 2000 and 2006. Conclusions Differences by race/ethnicity explain the NIH funding gap for women of color, as white women have a slight advantage over men in receiving Type 1 awards. Findings of a lower submission rate for women and an increased likelihood that they will submit only one proposal are consistent with research showing that women avoid competition. Policies designed to address the racial and ethnic diversity of the biomedical workforce have the potential to improve funding outcomes for women of color.
Mechanisms of a coniferous woodland persistence under drought and heat

Predictions of warmer droughts causing increasing forest mortality are becoming abundant, yet few studies have investigated the mechanisms of forest persistence. To examine the resistance of forests to warmer droughts, we used a five-year precipitation reduction (∼45% removal), heat (+4 °C above ambient) and combined drought and heat experiment in an isolated stand of mature Pinus edulis-Juniperus monosperma. Despite severe experimental drought and heating, no trees died, and we observed only minor evidence of hydraulic failure or carbon starvation. Two mechanisms promoting survival were supported. First, access to bedrock water, or ‘hydraulic refugia’ aided trees in their resistance to the experimental conditions. Second, the isolation of this stand amongst a landscape of dead trees precluded ingress by Ips confusus, frequently the ultimate biotic mortality agent of piñon. These combined abiotic and biotic landscape-scale processes can moderate the impacts of future droughts on tree mortality by enabling tree avoidance of hydraulic failure, carbon starvation, and exposure to attacking abiotic agents.
RECIPROCAL BEHAVIOUR ASSOCIATED WITH ALTERED HOMEOSTASIS AND PHOTOSENSITIVITY OF DROSOPHILA CLOCK MUTANTS

The circadian oscillators of genetically short–period and long–period Drosophila exhibit reciprocal behaviour in four distinct ways: (1) with respect to the dependence of period on temperature, (2) in the change of period during constant darkness after ten days of constant light, (3) in the change of period during the second ten days of darkness as compared with the period during the first ten days, and (4) in the period change resulting from exposure to low–intensity constant light. The homeostatic control of the dependence of period length on temperature is impaired in the mutants as compared with wild–type files. The normal Drosophila pacemaker may comprise two mutually coupled oscillators, whereas the mutants may represent a reduction in activity of one or the other constituent oscillator.
Intradiscal Electrothermal Treatment for Chronic Discogenic Low Back Pain: A Prospective Outcome Study With Minimum 1-Year Follow-Up

Study Design. Prospective case series. Objective. To determine the outcome of patients with chronic low back pain whose symptoms did not improve with aggressive nonoperative care and who chose (intradiscal electrothermal anuloplasty) IDET as an alternative to chronic pain management or interbody fusion surgery. Summary of Background Data. Patients with unremitting chronic discogenic low back pain are faced with the choice of long-term pain management or fusion surgery. Intradiscal electrothermal anuloplasty (IDET) was developed as an alternative minimally invasive treatment. Materials and Methods. Sixty-two patients from the author’s practice who had chronic low back pain unresponsive to nonoperative care, no evidence of compressive radiculopathy, and concordant pain reproduction at one or more disc levels on provocative discography were enrolled in the study. Visual analog scale (VAS) pain scores and Short Form (SF)-36 Health Status Questionnaire Physical Function subscale and SF-36 Bodily Pain subscale scores were assessed at baseline and at least 1 year later. Results. Mean follow-up was 16 months, and mean preoperative duration of symptoms was 60 months. Baseline and follow-up outcome measures demonstrated a mean change in VAS score of 3.0 (P < 0.001), mean change in SF-36 physical function of 20 (P < 0.001), and mean change in SF-36 bodily pain of 17 (P < 0.001). Symptoms improved in 44 (71%) of 62 of the study group on the SF-36 physical function subscale, in 46 (74%) of 62 on the SF-36 Bodily Pain subscale, and in 44 (71%) of 62 on the VAS scores. Twelve (19%) of 62 of the patients did not show improvement on any scale. Conclusion. A cohort of patients with chronic unremitting low back pain of discogenic origin whose symptoms had failed to improve with aggressive nonoperative care demonstrated a statistically significant and clinically meaningful improvement on the SF-36 and the VAS scores at a minimum follow-up of 1 year after IDET. The positive results should be validated with placebo-controlled randomized trials and studies that compare IDET with alternative treatments. —