bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN)
Authors: Palumbo Antonio , Bringhen Sara , Ludwig Heinz , Dimopoulos Meletios A. , Bladé Joan , Mateos Maria V. , Rosiñol Laura , Boccadoro Mario , Cavo Michele , Lokhorst Henk , Zweegman Sonja , Terpos Evangelos , Davies Faith , Driessen Christoph , Gimsing Peter , Gramatzki Martin , Hàjek Roman , Johnsen Hans E. , Leal Da Costa Fernando , Sezer Orhan , Spencer Andrew , Beksac Meral , Morgan Gareth , Einsele Hermann , San Miguel Jesus F. , Sonneveld Pieter 
Published: August 2011

Abstract
Most patients with newly diagnosed multiple myeloma (MM) are aged > 65 years with 30% aged > 75 years. Many elderly patients are also vulnerable because of comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time because of an aging population. Most elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more susceptible to side effects and are often unable to tolerate full drug doses. For these patients, lower-dose-intensity regimens improve the safety profile and thus optimize treatment outcome. Further research into the best treatment strategies for vulnerable elderly patients is urgently needed. Appropriate screening for vulnerability and an assessment of cardiac, pulmonary, renal, hepatic, and neurologic functions, as well as age > 75 years, at the start of therapy allows treatment strategies to be individualized and drug doses to be tailored to improve tolerability and optimize efficacy. Similarly, occurrence of serious nonhematologic adverse events during treatment should be carefully taken into account to adjust doses and optimize outcomes.
Involvement of mTOR signaling in sphingosylphosphorylcholine-induced hypopigmentation effects
Authors: Jeong Hyo-Soon , Lee Seung Hoon , Yun Hye-Young , Baek Kwang Jin , Kwon Nyoun Soo , Park Kyoung-Chan , Kim Dong-Seok 
Published: August 2011

AbstractBackgroundSphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types. In the present study, we investigated the effects of SPC on melanogenesis and SPC-modulated signaling pathways related to melanin synthesis.MethodsMelanin production was measured in Mel-Ab cells. A luciferase assay was used to detect transcriptional activity of the MITF promoter. Western blot analysis was performed to examine SPC-induced signaling pathways.ResultsSPC produced significant hypopigmentation effects in a dose-dependent manner. It was found that SPC induced not only activation of Akt but also stimulation of mTOR, a downstream mediator of the Akt signaling pathway. Moreover, SPC decreased the levels of LC3 II, which is known to be regulated by mTOR. Treatment with the mTOR inhibitor rapamycin eliminated decreases in melanin and LC3 II levels by SPC. Furthermore, we found that the Akt inhibitor LY294002 restored SPC-mediated downregulation of LC3 II and inhibited the activation of mTOR by SPC.ConclusionsOur data suggest that the mTOR signaling pathway is involved in SPC-modulated melanin synthesis.
Neighborhood disparities in stroke and myocardial infarction mortality: a GIS and spatial scan statistics approach
Authors: Pedigo Ashley , Aldrich Tim , Odoi Agricola 
Published: August 2011

Abstract

Background
Stroke and myocardial infarction (MI) are serious public health burdens in the US. These burdens vary by geographic location with the highest mortality risks reported in the southeastern US. While these disparities have been investigated at state and county levels, little is known regarding disparities in risk at lower levels of geography, such as neighborhoods. Therefore, the objective of this study was to investigate spatial patterns of stroke and MI mortality risks in the East Tennessee Appalachian Region so as to identify neighborhoods with the highest risks.

Methods
Stroke and MI mortality data for the period 1999-2007, obtained free of charge upon request from the Tennessee Department of Health, were aggregated to the census tract (neighborhood) level. Mortality risks were age-standardized by the direct method. To adjust for spatial autocorrelation, population heterogeneity, and variance instability, standardized risks were smoothed using Spatial Empirical Bayesian technique. Spatial clusters of high risks were identified using spatial scan statistics, with a discrete Poisson model adjusted for age and using a 5% scanning window. Significance testing was performed using 999 Monte Carlo permutations. Logistic models were used to investigate neighborhood level socioeconomic and demographic predictors of the identified spatial clusters.

Results
There were 3,824 stroke deaths and 5,018 MI deaths. Neighborhoods with significantly high mortality risks were identified. Annual stroke mortality risks ranged from 0 to 182 per 100,000 population (median: 55.6), while annual MI mortality risks ranged from 0 to 243 per 100,000 population (median: 65.5). Stroke and MI mortality risks exceeded the state risks of 67.5 and 85.5 in 28% and 32% of the neighborhoods, respectively. Six and ten significant (p < 0.001) spatial clusters of high risk of stroke and MI mortality were identified, respectively. Neighborhoods belonging to high risk clusters of stroke and MI mortality tended to have high proportions of the population with low education attainment.

Conclusions
These methods for identifying disparities in mortality risks across neighborhoods are useful for identifying high risk communities and for guiding population health programs aimed at addressing health disparities and improving population health.
Concurrent image-guided intensity modulated radiotherapy and chemotherapy following neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma
Authors: Shueng Pei-Wei , Shen Bing-Jie , Wu Le-Jung , Liao Li-Jen , Hsiao Chi-Huang , Lin Yu-Chin , Cheng Po-Wen , Lo Wu-Chia , Jen Yee-Min , Hsieh Chen-Hsi 
Published: August 2011

Abstract

Background
To evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC).

Methods
Between August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction.

Results
After completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively.

Conclusion
HT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings.
Feedback, Self-Esteem, and Performance in Organizations
Authors: Kuhnen Camelia M. , Tymula Agnieszka 
Published: August 2011

We examine whether private feedback about relative performance can mitigate moral hazard in competitive environments by modifying the agents' self-esteem. In our experimental setting, people work harder and expect to rank better when told that they may learn their ranking, relative to cases when feedback will not be provided. Individuals who ranked better than expected decrease output but expect a better rank in the future, whereas those who ranked worse than expected increase output but lower their future rank expectations. Feedback helps create a ratcheting effect in productivity, mainly because of the fight for dominance at the top of the rank hierarchy. Our findings suggest that organizations can improve employee productivity by changing the likelihood of feedback, the reference group used to calculate relative performance, and the informativeness of the feedback message.This paper was accepted by Brad Barber, Teck Ho, and Terrance Odean, special issue editors.
The Party's Over: The Role of Earnings Guidance in Resolving Sentiment-Driven Overvaluation
Authors: Seybert Nicholas , Yang Holly I. 
Published: August 2011

This paper shows that an important link between investor sentiment and firm overvaluation is optimistic earnings expectations, and that management earnings guidance helps resolve sentiment-driven overvaluation. Using previously identified firm characteristics, we find that most of the negative returns to uncertain firms in months following high-sentiment periods fall within the three-day window around the issuance of management earnings guidance. Comparisons of guidance months to nonguidance months show that guidance issuance affects the magnitude and not just the daily distribution of negative returns. There is also some evidence of negative returns around earnings announcements for firms that previously issued guidance, suggesting that guidance does not entirely correct optimistic earnings expectations. To provide additional insight into the strength of the guidance effect, we show that the market reacts more strongly to surprises, particularly negative surprises, following high-sentiment periods. Finally, firms with higher transient institutional ownership are less likely to guide, and their guidance is less likely to contain bad news following high-sentiment periods, indicating that managers with a short-term focus are hesitant to correct optimistic market expectations.This paper was accepted by Brad Barber, Teck Ho, and Terrance Odean, special issue editors.
Skill, Luck, and the Multiproduct Firm: Evidence from Hedge Funds
Authors: de Figueiredo Rui J. P. , Rawley Evan 
Published: August 2011

We formalize the idea that when managers require external investment to expand, higher-skilled firms will be more likely to diversify in equilibrium, even though managers can exploit asymmetric information about their ability to raise capital from investors. We exploit the timing of new fund launches in the hedge fund industry to distinguish between agency and capability effects in firm product diversification decisions, using a large survivor-bias-free panel data set on the hedge fund industry from 1994 to 2006. Empirically we show that diversifying firms' excess returns are high relative to those of other firms prior to diversification and fall within firm following diversification, but are six basis points higher per month per unit of risk ex post compared to a matched sample of focused firms. The evidence suggests that managers exploit asymmetric information about their own ability to time diversification decisions; yet, the discipline of markets ensures that better firms diversify, on average. The results provide large-sample empirical evidence that agency effects and firm capabilities jointly influence diversification decisions. This paper was accepted by Bruno Cassiman, business strategy.
Option Pricing Under a Mixed-Exponential Jump Diffusion Model
Authors: Cai Ning , Kou S. G. 
Published: August 2011

This paper aims to extend the analytical tractability of the Black–Scholes model to alternative models with arbitrary jump size distributions. More precisely, we propose a jump diffusion model for asset prices whose jump sizes have a mixed-exponential distribution, which is a weighted average of exponential distributions but with possibly negative weights. The new model extends existing models, such as hyperexponential and double-exponential jump diffusion models, because the mixed-exponential distribution can approximate any distribution as closely as possible, including the normal distribution and various heavy-tailed distributions. The mixed-exponential jump diffusion model can lead to analytical solutions for Laplace transforms of prices and sensitivity parameters for path-dependent options such as lookback and barrier options. The Laplace transforms can be inverted via the Euler inversion algorithm. Numerical experiments indicate that the formulae are easy to implement and accurate. The analytical solutions are made possible mainly because we solve a high-order integro-differential equation explicitly. A calibration example for SPY options shows that the model can provide a reasonable fit even for options with very short maturity, such as one day. This paper was accepted by Michael Fu, stochastic models and simulation.
Fragile X family members have important and non-overlapping functions
Authors: Winograd Claudia , Ceman Stephanie 
Published: August 2011

AbstractThe fragile X family of genes encodes a small family of RNA binding proteins including FMRP, FXR1P and FXR2P that were identified in the 1990s. All three members are encoded by 17 exons and show alternative splicing at the 3′ ends of their respective transcripts. They share significant homology in the protein functional domains, including the Tudor domains, the nuclear localization sequence, a protein-protein interaction domain, the KH1 and KH2 domains and the nuclear export sequence. Fragile X family members are found throughout the animal kingdom, although all three members are not consistently present in species outside of mammals: only two family members are present in the avian species examined, Gallus gallus and Taeniopygia guttata, and in the frog Xenopus tropicalis. Although present in many tissues, the functions of the fragile X family members differ, which are particularly evident in knockout studies performed in animals. The fragile X family members play roles in normal neuronal function and in the case of FXR1, in muscle function.
On the cutting edge of proprotein convertase pharmacology: from molecular concepts to clinical applications
Authors: Couture Frédéric , D'Anjou François , Day Robert 
Published: August 2011

AbstractThere is increasing interest in the therapeutic targeting of proteases for the treatment of important diseases. Additionally new protein-based therapeutic strategies have the potential to widen the available treatments against these pathologies. In the last decade, accumulated evidence has confirmed that the family of proteases known as proprotein convertases (PCs) are potential targets for viral infections, osteoarthritis, cancer and cardiovascular disease, among others. Nevertheless, there are still many unanswered questions about the relevance of targeting PCs in a therapeutic context, especially regarding the anticipated secondary effects of treatment, considering the observed embryonic lethality of some PC knockout mice. In this review, the benefits of PCs as pharmacological targets will be discussed, with focus on concepts and strategies, as well as on the state of advancement of actual and future inhibitors.
Graft copolymerization of granular starch maleate with acrylamide for enhancing grafting efficiency
Authors: Zhu Zhifeng , Zhang Longqiu , Li Manli 
Published: August 2011

Abstract
Graft copolymerization of granular starch maleate with acrylamide using Fenton’s initiator in aqueous dispersion was investigated for increasing grafting efficiency of the copoly­merization. The graft copolymerization was characterized in terms of grafting efficiency, grafting ratio, and conversion of monomer to polymer. Effects of maleate modification of starch on the efficiency, ratio, and conversion were explored. Influences of reaction variables such as pH value, molar ratio of H2O2 to Fe2+, initiator concentration, monomer concentration, polymerization temperature, and time on the copolymerization were investigated. It was observed that the modification of starch markedly increased grafting efficiency and ratio. The graft copolymerization should be carried out under the protection of nitrogen gas at 30°C–45°C for 3 h using H2O2/Fe(NH4)2(SO4)2 as initiator. Preferred molar ratio of H2O2/Fe(NH4)2(SO4)2/anhydroglucose was 20:1:1000 and optimal value of pH was in a range of 3–4. The condition could make grafting efficiency and conversion of monomer to polymer higher than 65% and 95%, respectively.
Genetic Analysis of Desiccation Tolerance inSaccharomyces cerevisiae
Authors: Calahan Dean , Dunham Maitreya , DeSevo Chris , Koshland Douglas E 
Published: August 2011

AbstractDesiccation tolerance, the ability to survive nearly total dehydration, is a rare strategy for survival and reproduction observed in all taxa. However, the mechanism and regulation of this phenomenon are poorly understood. Correlations between desiccation tolerance and potential effectors have been reported in many species, but their physiological significance has not been established in vivo. Although the budding yeast Saccharomyces cerevisiae exhibits extreme desiccation tolerance, its usefulness has been hampered by an inability to reduce tolerance more than a few fold by physiological or genetic perturbations. Here we report that fewer than one in a million yeast cells from low-density logarithmic cultures survive desiccation, while 20–40% of cells from saturated cultures survive. Using this greatly expanded metric, we show that mutants defective in trehalose biosynthesis, hydrophilins, responses to hyperosmolarity, and hypersalinity, reactive oxygen species (ROS) scavenging and DNA damage repair nevertheless retain wild-type levels of desiccation tolerance, suggesting that this trait involves a unique constellation of stress factors. A genome-wide screen for mutants that render stationary cells as sensitive as log phase cells identifies only mutations that block respiration. Respiration as a prerequisite for acquiring desiccation tolerance is corroborated by respiration inhibition and by growth on nonfermentable carbon sources. Suppressors bypassing the respiration requirement for desiccation tolerance reveal at least two pathways, one of which, involving the Mediator transcription complex, is associated with the shift from fermentative to respiratory metabolism. Further study of these regulators and their targets should provide important clues to the sensors and effectors of desiccation tolerance.
Cellular Morphogenesis Under Stress Is Influenced by the Sphingolipid Pathway Gene ISC1 and DNA Integrity Checkpoint Genes in Saccharomyces cerevisiae
Authors: Tripathi Kaushlendra , Matmati Nabil , Zheng W Jim , Hannun Yusuf A , Mohanty Bidyut K 
Published: August 2011

Abstract
In Saccharomyces cerevisiae, replication stress induced by hydroxyurea (HU) and methyl methanesulfonate (MMS) activates DNA integrity checkpoints; in checkpoint-defective yeast strains, HU treatment also induces morphological aberrations. We find that the sphingolipid pathway gene ISC1, the product of which catalyzes the generation of bioactive ceramides from complex sphingolipids, plays a novel role in determining cellular morphology following HU/MMS treatment. HU-treated isc1Δ cells display morphological aberrations, cell-wall defects, and defects in actin depolymerization. Swe1, a morphogenesis checkpoint regulator, and the cell cycle regulator Cdk1 play key roles in these morphological defects of isc1Δ cells. A genetic approach reveals that ISC1 interacts with other checkpoint proteins to control cell morphology. That is, yeast carrying deletions of both ISC1 and a replication checkpoint mediator gene including MRC1, TOF1, or CSM3 display basal morphological defects, which increase following HU treatment. Interestingly, strains with deletions of both ISC1 and the DNA damage checkpoint mediator gene RAD9 display reduced morphological aberrations irrespective of HU treatment, suggesting a role for RAD9 in determining the morphology of isc1Δ cells. Mechanistically, the checkpoint regulator Rad53 partially influences isc1Δ cell morphology in a dosage-dependent manner.
Retroareolarisan elhelyezkedő emlőtumorok onkoplasztikai műtéte: centrális quadrantectomia és Grisotti-féle inferior dermoglandularis lebennyel való rekonstrukció
Authors: Bognár Gábor , Novák András , Barabás Loránd , Lóderer Zoltán , Ondrejka Pál 
Published: August 2011

Absztrakt
Az emlőrákos esetek 5–20%-át teszik ki a centrálisan elhelyezkedő emlőmalignomák, melyek kezelésében hosszú időn át nem volt elfogadott az emlőmegtartó műtét. E daganatoknál a hagyományos sebészi megoldás a mastectomia volt. A centrális emlődaganatoknál gyakori az emlőbimbó és bimbóudvar együttesének érintettsége, melynek sebészi kezelése szükségessé teszi annak teljes eltávolítását a tumor körüli megfelelő nagyságú biztonsági zónával, ami sok esetben megfelelő rekonstrukció nélkül kifogásolható kozmetikai eredményhez vezet. Az onkoplasztikai sebésztechnikák alkalmazásával ezekben az esetekben az onkológiai biztonság mellett jó kozmetikai eredménnyel végezhető el az emlőmegtartó műtét. Közleményünkben a centrális quadrantectomiát és az ezt követő inferior dermoglandularis Grisotti-lebennyel való emlőrekonstrukciót értékeljük.
A betegek kor és nem szerinti eloszlása a laparoscopos cholecystectomia szövődményei és a műtét utáni felépülés szempontjából
Authors: Siddiqui Muhammed RS , Barry JA , Lodha K , Parker M , Hasan F 
Published: August 2011

AbstractObjectives:Database review to analyse age and sex differences in complication and conversion rates and influence on return to normal daily activities and work after laparoscopic cholecystectomy (LC).Methods:658 patients had a laparoscopic cholecystectomy for proven gallstones between 9/4/2001 and 15/2/2006 under the care of one surgeon (F. H.) at Benenden hospital, Kent, UK.Results:We had a 65.5% response rate with 431 replies at a mean follow up of 22.4 months (2.3–52.8). There was a male to female ratio of 5:23 with a mean age of 54.2 years (22–83). Using linear regression we found no significant correlation with operative time and variables of age and sex (df= 2, 251,R2= 0.03,F= 0.574,p< 0.564). No significant correlation with number of complications and age or sex (df= 2, 334,R2= 0.004,F= 1.615,p< 0.200). Age (Exp(B) = 1.040,p< 0.51) and sex (Exp(B) = 0.863,p< 0.855) had no effect on conversion. No difference was found in relation to age and sex with return to normal daily activities (df= 2, 307,F= 0.904,p< 0.406). Age was a non-significant predictor of return to work (Beta = 0.040,p< 0.572) however men return to work significantly sooner (Beta = 0.191,p< 0.007).Conclusions:Operative time, number of complications, conversion to open and return to normal daily activities may not be affected by age or sex of patients. Hospital stay may be longer in older patients. Men appear to return to work sooner. Further analysis with validated questionnaires are required.