Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis.

BACKGROUND Genome-wide association studies have implicated single nucleotide polymorphisms (SNPs) in 7 genes as glioma risk factors, including 2 (TERT, RTEL1) involved in telomerase structure/function. We examined associations of these 7 established glioma risk loci with age at diagnosis among patients with glioma. METHODS SNP genotype data were available for 2286 Caucasian glioma patients from the University of California, San Francisco (n = 1434) and the Mayo Clinic (n = 852). Regression analyses were performed to test for associations between "number of risk alleles" and "age at diagnosis," adjusted for sex and study site and stratified by tumor grade/histology where appropriate. RESULTS Four SNPs were significantly associated with age at diagnosis. Carrying a greater number of risk alleles at rs55705857 (CCDC26) and at rs498872 (PHLDB1) was associated with younger age at diagnosis (P = 1.4 × 10(-22) and P = 9.5 × 10(-7), respectively). These SNPs are stronger risk factors for oligodendroglial tumors, which tend to occur in younger patients, and their association with age at diagnosis varied across tumor subtypes. In contrast, carrying more risk alleles at rs2736100 (TERT) and at rs6010620 (RTEL1) was associated with older age at diagnosis (P = 6.2 × 10(-4) and P = 2.5 × 10(-4), respectively). These SNPs are risk factors for all glioma grades/histologies, and their association with age at diagnosis was consistent across tumor subgroups. CONCLUSIONS Carrying a greater number of risk alleles might be expected to decrease age at diagnosis. However, glioma susceptibility conferred by variation in telomerase-related genes did not follow this pattern. This supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life than those utilizing telomerase-independent mechanisms (ie, alternative lengthening of telomeres).
Daily Currency Interventions in Emerging Markets: Incorporating Reserve Accumulation to the Reaction Function

Abstract Understanding the intervention policy of central banks on currency markets is important for both practitioners and researchers. Existing models for central bank interventions exclusively focus on exchange rate targeting in level or volatility. However, central banks in emerging economies use international reserves as an insurance against sudden capital outflows and use interventions to manage them. Omitting the reserve component in the reaction function may therefore lead to a bias and wrong conclusions. We therefore extend the reaction function by incorporating a reserve component and illustrate its benefit by applying it to the case of Turkey. We find that the intervention policy of the Turkish Central Bank indeed incorporated interventions to manage their reserves and is therefore better described by our extended model. Furthermore it provides a more accurate description of changes in the central bank’s policy. Our results strongly suggest to incorporate reserve variables in intervention functions for emerging countries.
Effects of health beliefs about mammography and breast cancer and telephone reminders on re-screening in Turkey.

OBJECTIVE To assess the effect of telephone reminders on repeat screening mammogram completion among women who have already had one or more mammograms. METHODS Seven hundred and forty women whose turn came for further mammography and who could be reached by telephone out of 1,372 women registered at a Cancer Screening and Education Center (CSEC) were studied in Erzurum, Turkey, from January to June 2008. RESULTS Before reminders with the telephone, of the 740 women, while only 29 (3.9%) had mammograms, after telephone reminders, approximately half of the women (46.4%) received mammograms by coming to the CSEC. Level of awareness of risk of breast cancer, intention, marital status, perceived mammography barriers were factors impacting on behavior. CONCLUSION It was found that reminding women registered at the mammography center of their appointments was effective in reinforcing behavior. Health professionals can, through reminder and guidance, reduce the level of perceived barriers related to having a mammography and secure continuity in mammography check-ups.
Managing radical innovations in established companies

Established companies need to take several aspects into account when considering the management of radical innovations and must simultaneously ensure the profitability and functioning of the existing business. The main contribution of this study lies in exploring how radical and incremental innovations are separated and managed. The paper intends to clarify how companies can evaluate ideas, organise decision-making, utilise external parties optimally, and organise innovation activities while ensuring adequate linkages to existing business processes. This study analyses the practical implementation of innovation activities in a leading telecom company with advanced practices for managing innovations. The case company has established a separate innovation unit and defined a process for radical innovations. Linkages to other existing development processes are strengthened by including key personnel from these processes in the company's innovation process. These arrangements aid in acknowledging numerous aspects presented in the literature in conjunction with radical innovations.
A New Scoring System for Prognostic Stratification of Patients With Alcoholic Hepatitis

OBJECTIVES: Prognostic stratification of patients with alcoholic hepatitis (AH) may improve the clinical management and facilitate clinical trials. We aimed at developing a scoring system capable of providing prognostic stratification of patients with AH.METHODS: Patients with biopsy-proven AH were prospectively included between 2000 and 2006. The biochemical, clinical, portal hemodynamic and histological parameters were evaluated. A Cox regression model was used for univariate and multivariate analyses. A predictive score was built using variables obtained at admission identified in the multivariate analysis. The resulting score was validated in an independent prospective cohort.RESULTS: In total, 103 patients with biopsy-proven AH were included in the study cohort. Age, serum bilirubin, serum creatinine, and international normalized ratio (INR) independently predicted 90-day mortality. We generated the Age, serum Bilirubin, INR, and serum Creatinine (ABIC) score: (age × 0.1) + (serum bilirubin × 0.08) + (serum creatinine × 0.3) + (INR × 0.8). The area under the curve (AUC) was 0.82. Using the Kaplan-Meier analysis with the cutoff values of 6.71 and 9.0, we identified patients with low, intermediate, and high risk of death at 90 days (100%, 70%, and 25% of survival rate, respectively). Using the same cutoff values, the ABIC score also stratified patients according to their risk of death at 1 yr. These results were validated by a confirmatory cohort (N = 80). CONCLUSIONS: The ABIC score is a new tool that allows the stratification of risk of death in patients with AH at 90 days and 1 yr. This score can help improve the management of these patients and also help to perform clinical trials.
Routine bone marrow examination in the initial evaluation of paediatric Hodgkin lymphoma: the Canadian perspective

Bone marrow examination (BME) in paediatric Hodgkin lymphoma (HL) was evaluated, as evidence from adult HL suggests it may be unnecessary. An internet‐based survey was used to examine the practice of Canadian paediatric oncologists regarding BME in children and the impact of routine BME was evaluated in patients with HL treated at our institution. Sixteen of 17 paediatric oncology centres were represented. Forty‐three percent of eligible doctors completed the survey. Routine BME for stages III and IV disease was consistent nationally. By contrast, 54% and 70% of respondents reported performing routine BME for stages I and II HL respectively. Respondents were more likely to report performing routine BME in low‐stage HL if trained outside Canada (P = 0·04, stage I; P = 0·07, stage II) or practicing at smaller centres (P = 0·05, stage I; P = 0·03, stage II). At our institution, 62 patients were eligible for analysis. Only four patients (6·5%) had a positive BME. Anaemia was the only significant risk factor (P = 0·006). No patient with otherwise low stage was found to have marrow involvement. Comparison of staging with and without BME demonstrated no significant difference to final risk classification. BME in paediatric patients with low‐stage HL has extremely low yield and may be unnecessary.
Temporal dynamics of neural activity in motor execution and inhibition processing

Although many neuroimaging studies using functional magnetic resonance imaging have shown the neuronal networks for motor execution and inhibition processing, the precise activation timing of each brain region is not yet well understood. In the present study, we investigated the temporal dynamics of neural activities in multiple brain regions using magnetoencephalography (MEG) and electroencephalography (EEG) simultaneously during somatosensory Go/No‐go paradigms. The results of MEG showed that neural activities in the bilateral premotor area at approximately 150 ms and in the primary motor cortex at approximately 250 ms were only detected in Go trials, while brain responses in the bilateral prefrontal cortex at approximately 170 ms were only observed in No‐go trials. In addition, the amplitudes of the N140 and P300 components in EEG was significantly larger in No‐go trials than in Go trials, and the latencies of N140 and P300 were significantly later in No‐go trials than in Go trials. Our results indicated the time courses of neural processing in response execution and inhibition processing, and revealed differences in their underlying neural mechanisms.
Merging county administrations – cross-national evidence of fiscal and political effects

ABSTRACT While many central governments amalgamate municipalities, mergers of larger county administrations are rare and hardly explored. In this article, we assess both fiscal and political effects of county mergers in two different institutional settings: counties act autonomously as upper-level local governments (Germany), or counties being decentralised branches of the state government (Austria). We apply difference-in-differences estimations to county merger reforms in each country. In both cases, some counties were amalgamated while others remain untouched. Austrian counties (Bezirke) and German counties (Landkreise) widely differ in terms of autonomy and institutions, but our results are strikingly similar. In both cases, we neither find evidence for cost savings nor for staff reductions. Instead, voter turnout consistently decreases in merged counties, and right-wing populists seem to gain additional support. We conclude that political costs clearly outweigh fiscal null benefits of county merger reforms – independent of the underlying institutional setting.
Circadian Phase Variation in Bipolar I Disorder

Abnormalities in circadian rhythms are prominent features of bipolar I disorder (BD1). To investigate circadian variation in BD1, we evaluated morningness–eveningness (M/E), a stable trait reflecting circadian phase, using the composite scale (CS) among BD1 patients (DSM IV criteria; n=75), unscreened controls (n=349), and patients with schizophrenia (SZ) or schizoaffective disorder (SZA) (n=81). Our analyses showed that CS scores correlated significantly with age but did not differ by gender among the controls. BD1 patients differed significantly from controls and from SZ/SZA patients when age was considered. CS scores were distributed bi‐modally among BD1 cases. There are several possible reasons for the observed heterogeneity. Younger BD1 patients, and those with rapid mood swings, were significantly more likely to have lower CS scores (i.e., to score in the ‘evening’ range and to have later circadian phase). CS scores were also positively correlated with the age at onset and the duration of the most severe depressive episodes. These relationships were not observed among the SZ/SZA groups. Thus, distinct patterns of M/E were noted among BD1 patients and among BD1 subgroups. The impact of medication, mood state, and chronicity on CS scores needs to be considered.
Unexpected Roles for Ciliary Kinesins and Intraflagellar Transport Proteins

Transport of proteins in the ciliary shaft is driven by microtubule-dependent motors, kinesins. Prior studies suggested that the heterotrimeric ciliary kinesin may be dispensable for certain aspects of transport in specialized cilia of vertebrate photoreceptor cells. To test this possibility further, we analyzed the mutant phenotype of the zebrafish kif3a gene, which encodes the common motor subunit of heterotrimeric ciliary kinesins. Cilia are absent in all organs examined, leading to the conclusion that kif3a is indispensable for ciliogenesis in all cells, including photoreceptors. Unexpectedly, kif3a function precedes ciliogenesis as ciliary basal bodies are mispositioned in mutant photoreceptors. This phenotype is much less pronounced in intraflagellar transport (IFT) mutants and reveals that kif3a has a much broader role than previously assumed. Despite the severity of their basal body phenotype, kif3a mutant photoreceptors survive longer compared to those in IFT mutants, which display much weaker basal body mispositioning. This effect is absent in kif3a;IFT double mutants, indicating that IFT proteins have ciliary transport-independent roles, which add to the severity of their photoreceptor phenotype. kif3a is dispensable for basal body docking in otic vesicle sensory epithelia and, surprisingly, short cilia form in mechanosensory cristae even in the absence of kif3a. In contrast to Kif3a, the functions of the Kif3c-related protein, encoded by the kif3c-like (kif3cl) gene, and the homodimeric ciliary kinesin, kif17, are dispensable for photoreceptor morphogenesis. These studies demonstrate unexpected new roles for both ciliary heterotrimeric kinesins and IFT particle genes and clarify the function of kif17, the homodimeric ciliary kinesin gene.
Heterogeneity of insulin action in muscle: influence of blood flow.

The influence of blood flow (BF) and basal neuromotor tone on in vivo insulin-stimulated glucose uptake (Rg') in muscle was examined using the euglycemic clamp plus deoxyglucose/glucose tracer (insulin action) and labeled microsphere (BF) techniques. Anesthesia was used to produce perturbations in BF and/or activity compared with conscious rats. An index of muscle glycolytic flux (Gf) was estimated from Rg' in excess of glycogen synthesis. Gf and glycogen synthesis were significantly increased in soleus and red gastrocnemius (RG) during insulin infusion (150 mU/l) in conscious rats. Rg' was related to muscle BF in conscious rats (r = 0.92). In anesthetized rats, Rg' and BF were reduced in soleus, RG, red quadriceps, and plantaris (e.g., soleus 69%, P less than 0.001, and 80%, P less than 0.001, respectively). However, it is unlikely that Rg' and BF are causally related because fractional extraction of glucose by muscle was low (approximately 9%); fractional extraction increased during anesthesia (17%, P less than 0.01); BF but not Rg' was reduced by anesthesia in extensor digitorum longus, white gastrocnemius, and white quadriceps; and reduced Rg' during anesthesia in soleus and RG was mainly due to reduced GF. In conclusion, BF is not a major contributor to the heterogeneity in insulin-stimulated glucose uptake among individual muscles under basal conditions. These data suggest that neuromotor tone may indirectly influence the magnitude of muscle glucose uptake during insulin elevation via a substrate switching effect. This may give rise to a significant increase in glycolytic flux of glucose in those muscles that exhibit elevated activity even at rest (e.g., soleus). (ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of the oxygen uptake kinetics of club and olympic champion rowers.

PURPOSE To test the hypothesis that elite rowers would possess a faster, more economic oxygen uptake response than club standard rowers. METHODS Eight Olympic champion (ELITE) rowers were compared with a cohort of eight club standard (CLUB) rowers. Participants completed a progressive exercise test to exhaustion, repeated 6-min moderate and heavy square-wave transitions, and a maximal 2000-m ergometer time trial. RESULTS The time constant (tau) of the primary component (PC) was faster for the ELITE group compared with CLUB for moderate-intensity (13.9 vs 19.4 s, P = 0.02) and heavy-intensity (18.7 vs 22.4 s, P = 0.005) exercise. ELITE rowers consumed less oxygen for moderate (14.2 vs 15.6 mL x min(-1) x W(-1); P = 0.009) and heavy (12.1 vs 13.7 mL x min(-1) x W(-1); P = 0.01) exercise. A greater absolute slow component was observed in the ELITE group (P = 0.009), but no differences were noted when the slow component was expressed relative to work rate performed (P = 0.14). Intergroup correlation with time trial performance speed was significant for tauPC during heavy-intensity exercise (r = -0.59, P = 0.02). CONCLUSIONS Compared with CLUB rowers, the shorter time constant response and greater economy observed in ELITE rowers may suggest advantageous adjustment of oxidative processes from rest to work. Training status or performance level do not seem to be associated with a smaller slow component when comparing CLUB and ELITE oarsmen.
Relationships among cold hardiness, root growth potential and bud dormancy in three conifers.

Greenhouse-cultured, container-grown ponderosa pine (Pinus ponderosa var. scopulorum Engelm.), interior Douglas-fir (Pseudotsuga menziesii var. glauca (Beissn.) Franco) and Engelmann spruce (Picea engelmannii (Parry) Engelm. ) were cold acclimated and deacclimated in growth chambers over 19 weeks. Stem cold hardiness, total new root length at 14 days and days to bud break were measured weekly. Relationships among cold hardiness, root growth potential (RGP) and bud dormancy suggest that cold hardiness, which can be measured quickly, could provide a useful basis for estimating the two other parameters. During cold acclimation, there was a lag period in which stem cold hardiness remained at -15 degrees C and RGP was at a minimum, in all three species. Douglas-fir and Engelmann spruce buds remained fully dormant during this lag period. Ponderosa pine buds had no chilling requirement for the loss of dormancy, and reached quiescence during the lag period. Immediately following the lag period, as stem cold hardiness progressed to -22 degrees C, RGP increased to a high plateau in all three species, and Douglas-fir and Engelmann spruce buds approached quiescence. Cold deacclimation and bud development began immediately on exposure to warm, long days, but RGP remained high until stem cold hardiness returned to approximately -15 degrees C. At bud break, cold hardiness and RGP were at the minimum.
EGF mediates protection against Fas‐induced apoptosis by depleting and oxidizing intracellular GSH stocks

Several pieces of evidence have demonstrated the importance of reduction/oxidation (redox) signaling in biological processes, including sensitivity toward apoptosis. In parallel, it was recently reported that growth factors induce the generation of reactive oxygen species (ROS). Therefore, we tested the hypothesis that the anti‐apoptotic effect of epidermal growth factor (EGF) was mediated by changes in the redox state of hepatocytes through changes in GSH stocks. Isolated mouse hepatocytes were cultured and exposed to anti‐Fas stimulation in order to induce apoptosis. Cell death by apoptosis was assessed by Hoechst 33258 staining and by measuring caspase‐3 proteolysis activity. Cell treatment with EGF significantly decreased total (GSx) and reduced (GSH) glutathione levels in the presence and the absence of anti‐Fas. Furthermore, glutathione reductase activity was lower in EGF‐treated cultures (by 28%) as compared to untreated cultures which lead to a significant decline in GSH/GSx ratio. These effects were found to be EGF‐receptor tyrosine kinase activity dependent. Co‐stimulation of cells with anti‐Fas and EGF attenuated caspase‐3 activation and cell death by apoptosis by 70%. GSH monoethylester (GSHmee) significantly attenuated the effect of EGF on GSH and GSH/GSx ratio. It caused an increase in caspase‐3 activation and in the percentage of apoptotic cells in anti‐Fas + EGF‐treated cells, thus resulting in a 53% decline in the protective effect of EGF. In conclusion, EGF induces a significant and specific depletion and oxidization of intracellular GSH, paralleled by a protection against Fas‐induced apoptosis. GSH replenishment partly counteracted these effects suggesting that GSH depletion contributed to the protective effect of EGF against caspase‐3 activation and cell death by apoptosis. J. Cell. Physiol. 198: 62–72, 2004. © 2003 Wiley‐Liss, Inc.
Simulated driving performance following prolonged wakefulness and alcohol consumption: separate and combined contributions to impairment

The separate and combined effects of prolonged wakefulness and alcohol were compared on measures of subjective sleepiness, simulated driving performance and drivers’ ability to judge impairment. Twenty‐two males aged between 19 and 35 years were tested on four occasions. Subjects drove for 30 min on a simulated driving task under conditions determined by the factorial combination of 16 and 20 h of wakefulness and blood alcohol concentrations of 0.00 and 0.08%. The simulated driving session took place 30 min postingestion; subjects in the two alcohol conditions participated in a second 30‐min driving session 90‐min postingestion. Subjects made simultaneous ratings of their impairment while driving and retrospective ratings at the end of each test session. Subjective sleepiness measures were completed before and after each driving session. The combination of 20 h of prolonged wakefulness and alcohol produced significantly lower ratings of subjective sleepiness and driving performance that was worse, but not significantly so, than would be expected from the additive effects of each condition alone. Driving performance was always worse in the second driving session, during the elimination phase of alcohol metabolism, despite blood alcohol concentrations being lower than during the first driving session. There was a modest association between perceived and actual impairments in driving performance following prolonged wakefulness and alcohol. The findings suggest that the combination of prolonged wakefulness and alcohol consumption produced greater decrements in simulated driving performance than each condition alone and that drivers have only a modest ability to appreciate the magnitude of their impairment.
Do Risk Preferences Change? Evidence from the Great East Japan Earthquake

We investigate whether individuals' risk preferences change after experiencing a natural disaster, specifically, the 2011 Great East Japan Earthquake. Exploiting the panels of nationally representative surveys on risk preferences, we find that men who experienced greater intensity of the earthquake became more risk tolerant a year after the Earthquake. Interestingly, the effects on men's risk preferences are persistent even five years after the Earthquake at almost the same magnitude as those shortly after the Earthquake. Furthermore, these men gamble more, which is consistent with the direction of changes in risk preferences. We find no such pattern for women.