bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs
Authors: Touihri Leila , Ahmed Sami Belhaj , Chtourou Yacine , Daoud Rahma , Bahloul Chokri 
Published: December 2012

Abstract

Background
During the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV) or distemper virus (CDV) after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage.

Methods
We have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV) 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an “Internal Ribosome Entry Site” (IRES) domain.

Results
The monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The FMDV 2A was also efficient in the design of multivalent plasmids.

Conclusions
In a single shot, the design of efficient multivalent plasmids will be very beneficial for DNA-based vaccination against numerous diseases.
Hypofractionated radiotherapy for primary or secondary oligometastatic lung cancer using Tomotherapy
Authors: Chang Heng-Jui , Ko Hui-Ling , Lee Cheng-Yen , Wu Ren-Hong , Yeh Yu-Wung , Jiang Jiunn-Song , Kao Shang-Jyh , Chi Kwan-Hwa 
Published: December 2012

Abstract

Background
To retrospectively review the outcome of patients with primary or secondary oligometastatic lung cancer, treated with hypofractionated Tomotherapy.

Methods
Between April 2007 and June 2011, a total of 33 patients with oligometastatic intrapulmonary lesions underwent hypofractionated radiotherapy by Tomotherapy along with appropriate systemic therapy. There were 24 primary, and 9 secondary lung cancer cases. The radiation doses ranged from 4.5 to 7.0 Gy per fraction, multiplied by 8–16 fractions. The median dose per fraction was 4.5 Gy (range, 4.5-7.0 Gy), and the median total dose was 49.5 Gy (range, 45–72 Gy). The median estimated biological effective dose at 10 Gy (BED10) was 71.8 Gy (range, 65.3–119.0 Gy), and that at 3 Gy (BED3) was 123.8 Gy (range, 112.5–233.3 Gy). The mean lung dose (MLD) was constrained mainly under 1200 cGy. The median gross tumor volume (GTV) was 27.9 cm3 (range: 2.5–178.1 cm3).

Results
The median follow-up period was 25.8 months (range, 3.0–60.7 months). The median overall survival (OS) time was 32.1 months for the 24 primary lung cancer patients, and >40 months for the 9 metastatic lung patients. The median survival time of the patients with extra-pulmonary disease (EPD) was 11.2 months versus >50 months (not reached) in the patients without EPD (p < 0.001). Those patients with smaller GTV (≦27.9 cm3) had a better survival than those with larger GTV (>27.9 cm3): >40 months versus 12.85 months (p = 0.047). The patients with ≦2 lesions had a median survival >40 months, whereas those with ≧3 lesions had 26 months (p = 0.065). The 2-year local control (LC) rate was 94.7%. Only 2 patients (6.1%) developed ≧grade 3 radiation pneumonitis.

Conclusion
Using Tomotherapy in hypofractionation may be effective for selected primary or secondary lung oligometastatic diseases, without causing significant toxicities. Pulmonary oligometastasis patients without EPD had better survival outcomes than those with EPD. Moreover, GTV is more significant than lesion number in predicting survival.
Preclinical models in radiation oncology
Authors: Kahn Jenna , Tofilon Philip J , Camphausen Kevin 
Published: December 2012

Abstract
As the incidence of cancer continues to rise, the use of radiotherapy has emerged as a leading treatment modality. Preclinical models in radiation oncology are essential tools for cancer research and therapeutics. Various model systems have been used to test radiation therapy, including in vitro cell culture assays as well as in vivo ectopic and orthotopic xenograft models. This review aims to describe such models, their advantages and disadvantages, particularly as they have been employed in the discovery of molecular targets for tumor radiosensitization. Ultimately, any model system must be judged by its utility in developing more effective cancer therapies, which is in turn dependent on its ability to simulate the biology of tumors as they exist in situ. Although every model has its limitations, each has played a significant role in preclinical testing. Continued advances in preclinical models will allow for the identification and application of targets for radiation in the clinic.
Metabolic Flux-Based Modularity using Shortest Retroactive distances
Authors: Sridharan GauthamVivek , Yi Michael , Hassoun Soha , Lee Kyongbum 
Published: December 2012

Abstract

Background
Graph-based modularity analysis has emerged as an important tool to study the functional organization of biological networks. However, few methods are available to study state-dependent changes in network modularity using biological activity data. We develop a weighting scheme, based on metabolic flux data, to adjust the interaction distances in a reaction-centric graph model of a metabolic network. The weighting scheme was combined with a hierarchical module assignment algorithm featuring the preservation of metabolic cycles to examine the effects of cellular differentiation and enzyme inhibitions on the functional organization of adipocyte metabolism.

Results
Our analysis found that the differences between various metabolic states primarily involved the assignment of two specific reactions in fatty acid synthesis and glycerogenesis. Our analysis also identified cyclical interactions between reactions that are robust with respect to metabolic state, suggesting possible co-regulation. Comparisons based on cyclical interaction distances between reaction pairs suggest that the modular organization of adipocyte metabolism is stable with respect to the inhibition of an enzyme, whereas a major physiological change such as cellular differentiation leads to a more substantial reorganization.

Conclusion
Taken together, our results support the notion that network modularity is influenced by both the connectivity of the network’s components as well as the relative engagements of the connections.
Mutation screen in the GWAS derived obesity gene SH2B1including functional analyses of detected variants
Authors: Volckmar Anna-Lena , Bolze Florian , Jarick Ivonne , Knoll Nadja , Scherag André , Reinehr Thomas , Illig Thomas , Grallert Harald , Wichmann Heinz-Erich , Wiegand Susanna , Biebermann Heike , Krude Heiko , Fischer-Posovszky Pamela , Rief Winfried , Wabitsch Martin , Klingenspor Martin , Hebebrand Johannes , Hinney Anke 
Published: December 2012

Abstract

Background
The SH2B1 gene (Src-homology 2B adaptor protein 1 gene) is a solid candidate gene for obesity. Large scale GWAS studies depicted markers in the vicinity of the gene; animal models suggest a potential relevance for human body weight regulation.

Methods
We performed a mutation screen for variants in the SH2B1 coding sequence in 95 extremely obese children and adolescents. Detected variants were genotyped in independent childhood and adult study groups (up to 11,406 obese or overweight individuals and 4,568 controls). Functional implications on STAT3 mediated leptin signalling of the detected variants were analyzed in vitro.

Results
We identified two new rare mutations and five known SNPs (rs147094247, rs7498665, rs60604881, rs62037368 and rs62037369) in SH2B1. Mutation g.9483C/T leads to a non-synonymous, non-conservative exchange in the beta (βThr656Ile) and gamma (γPro674Ser) splice variants of SH2B1. It was additionally detected in two of 11,206 (extremely) obese or overweight children, adolescents and adults, but not in 4,506 population-based normal-weight or lean controls. The non-coding mutation g.10182C/A at the 3’ end of SH2B1 was only detected in three obese individuals. For the non-synonymous SNP rs7498665 (Thr484Ala) we observed nominal over-transmission of the previously described risk allele in 705 obesity trios (nominal p = 0.009, OR = 1.23) and an increased frequency of the same allele in 359 cases compared to 429 controls (nominal p = 0.042, OR = 1.23). The obesity risk-alleles at Thr484Ala and βThr656Ile/γPro674Ser had no effect on STAT3 mediated leptin receptor signalling in splice variants β and γ.

Conclusion
The rare coding mutation βThr656Ile/γPro674Ser (g.9483C/T) in SH2B1 was exclusively detected in overweight or obese individuals. Functional analyzes did not reveal impairments in leptin signalling for the mutated SH2B1.
FGFR-1 amplification in metastatic lymph-nodal and haematogenous lobular breast carcinoma
Authors: Brunello Eleonora , Brunelli Matteo , Bogina Giuseppe , Caliò Anna , Manfrin Erminia , Nottegar Alessia , Vergine Marco , Molino Annamaria , Bria Emilio , Massari Francesco , Tortora Giampaolo , Cingarlini Sara , Pedron Serena , Chilosi Marco , Zamboni Giuseppe , Miller Keith , Martignoni Guido , Bonetti Franco 
Published: December 2012

Abstract

Background
Lobular breast carcinoma usually shows poor responsiveness to chemotherapies and often lacks targeted therapies. Since FGFR1 expression has been shown to play pivotal roles in primary breast cancer tumorigenesis, we sought to analyze the status of FGFR1 gene in a metastatic setting of lobular breast carcinoma, since promising FGFR1 inhibitors has been recently developed.

Methods
Fifteen tissue metastases from lobular breast carcinomas with matched primary infiltrative lobular breast carcinoma were recruited. Eleven cases showed loco-regional lymph-nodal and four haematogenous metastases.
FGFR-1 gene (8p12) amplification was evaluated by chromogenic in situ hybridization (CISH) analysis. Her-2/neu and topoisomerase-IIα gene status was assessed. E-cadherin and Hercept Test were also performed. We distinguished amplification (>6 or cluster of signals) versus gains (3–6 signals) of the locus specific FGFR-1 gene.

Results
Three (20%) primary lobular breast carcinomas showed >6 or cluster of FGFR1 signals (amplification), six cases (40%) had a mean of three (range 3–6) chromogenic signals (gains) whereas in 6 (40%) was not observed any abnormality. Three of 15 metastasis (20%) were amplified, 2/15 (13,4%) did not. The ten remaining cases (66,6%) showed three chromogenic signals.
The three cases with FGFR-1 amplification matched with those primary breast carcinomas showing FGFR-1 amplification. The six cases showing FGFR-1 gains in the primary tumour again showed FGFR-1 gains in the metastases. Four cases showed gains of FGFR-1 gene signals in the metastases and not in the primary tumours. Her-2/neu gene amplification was not observed in all cases but one (6%) case. Topoisomerase-IIα was not amplified in all cases.

Conclusions
1) a subset of metastatic lobular breast carcinoma harbors FGFR-1 gene amplification or gains of chromogenic signals; 2) a minor heterogeneity has been observed after matching primary and metastatic carcinomas; 3) in the era of tailored therapies, patients affected by the lobular subtype of breast carcinoma with FGFR1 amplification could be approached to the new target biological therapy such as emerging FGFR-1 inhibitors.
Delirium in the ICU: an overview
Authors: Cavallazzi Rodrigo , Saad Mohamed , Marik Paul E 
Published: December 2012

Abstract
Delirium is characterized by a disturbance of consciousness with accompanying change in cognition. Delirium typically manifests as a constellation of symptoms with an acute onset and a fluctuating course. Delirium is extremely common in the intensive care unit (ICU) especially amongst mechanically ventilated patients. Three subtypes have been recognized: hyperactive, hypoactive, and mixed. Delirium is frequently undiagnosed unless specific diagnostic instruments are used. The CAM-ICU is the most widely studied and validated diagnostic instrument. However, the accuracy of this tool may be less than ideal without adequate training of the providers applying it. The presence of delirium has important prognostic implications; in mechanically ventilated patients it is associated with a 2.5-fold increase in short-term mortality and a 3.2-fold increase in 6-month mortality. Nonpharmacological approaches, such as physical and occupational therapy, decrease the duration of delirium and should be encouraged. Pharmacological treatment for delirium traditionally includes haloperidol; however, more data for haloperidol are needed given the paucity of placebo-controlled trials testing its efficacy to treat delirium in the ICU. Second-generation antipsychotics have emerged as an alternative for the treatment of delirium, and they may have a better safety profile. Dexmedetomidine may prove to be a valuable adjunctive agent for patients with delirium in the ICU.
How quickly does structural reform pay off? An empirical analysis of the short-term effects of unemployment benefit reform
Authors: Bouis Romain , Causa Orsetta , Demmou Lilas , Duval Romain 
Published: December 2012

Abstract
While there is a fairly broad consensus regarding the potential adverse effects of generous unemployment benefit insurance on steady-state employment, the short-term effects of benefit reforms are not well-established. This paper contributes to fill this gap by estimating impulse responses to benefit reform “shocks” identified for a panel of OECD countries. Findings indicate that although it takes time for unemployment benefit reforms to pay off, such reforms do not appear to entail any negative short-run effects. There is however some suggestive evidence that reducing unemployment benefits could have negative short-run effects in “bad times”.

JEL classification

E02, E24, E60, J38, J58, J68
Payments for ecological restoration and internal migration in China: the sloping land conversion program in Ningxia
Authors: Démurger Sylvie , Wan Haiyuan 
Published: December 2012

Abstract

Abstract
This paper analyzes the impact of the Sloping Land Conversion Program (SLCP) on rural labor migration in China. We use recent survey data from Ningxia Hui Autonomous Region and a difference-in-difference approach to assess the impact of the policy on labor migration decision. We find a significant effect of the policy: the migration probability increase due to the SLCP policy amounts to 17.5 percentage points in 2008. Furthermore, we highlight the role of policy duration in strengthening the impact of the program on migration. We also find that young, male and Hui nationality individuals are more likely to be impacted by the policy.

JEL codes
J22, J68, O13, Q23
Phase II Study of Lenalidomide and Rituximab As Salvage Therapy for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Authors: Badoux Xavier C. , Keating Michael J. , Wen Sijin , Wierda William G. , O'Brien Susan M. , Faderl Stefan , Sargent Rachel , Burger Jan A. , Ferrajoli Alessandra 
Published: December 2012

PurposeLenalidomide is an immunomodulatory drug active as salvage therapy for chronic lymphocytic leukemia (CLL). We combined lenalidomide with rituximab to improve response rates in patients with relapsed or refractory CLL.Patients and MethodsFifty-nine adult patients (age 42 to 82 years) with relapsed or refractory CLL were enrolled onto a phase II study of lenalidomide and rituximab. Patients had received prior fludarabine-based therapy or chemoimmunotherapy. Rituximab (375 mg/m2intravenously) was administered weekly during cycle one and on day 1 of cycles three to 12. Lenalidomide was started on day 9 of cycle one at 10 mg orally and administered daily continuously. Each cycle was 28 days. Rituximab was administered for 12 cycles; lenalidomide could continue indefinitely if patients benefitted clinically.ResultsThe overall response rate was 66%, including 12% complete responses and 12% nodular partial remissions. Time to treatment failure was 17.4 months. Median overall survival has not been reached; estimated survival at 36 months is 71%. The most common grade 3 or 4 toxicity was neutropenia (73% of patients). Fourteen patients (24%) experienced a grade 3 to 4 infection or febrile episode. There was one episode of grade 3 tumor lysis; one patient experienced renal failure during the first cycle of therapy, and one venous thromboembolic event occurred during the study.ConclusionThe combination of lenalidomide and rituximab is active in patients with recurrent CLL and warrants further investigation.
Radiofrequency Ablation With or Without Transcatheter Arterial Chemoembolization in the Treatment of Hepatocellular Carcinoma: A Prospective Randomized Trial
Authors: Peng Zhen-Wei , Zhang Yao-Jun , Chen Min-Shan , Xu Li , Liang Hui-Hong , Lin Xiao-Jun , Guo Rong-Ping , Zhang Ya-Qi , Lau Wan Yee 
Published: December 2012

Purpose To compare radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). Patients and Methods A randomized controlled trial was conducted on 189 patients with HCC less than 7 cm at a single tertiary referral center between October 2006 and June 2009. Patients were randomly asssigned to receive TACE combined with RFA (TACE-RFA; n = 94) or RFA alone (n = 95). The primary end point was overall survival. The secondary end point was recurrence-free survival, and the tertiary end point was adverse effects. Results At a follow-up of 7 to 62 months, 34 patients in the TACE-RFA group and 48 patients in the RFA group had died. Thirty-three patients and 52 patients had developed recurrence in the TACE-RFA group and RFA group, respectively. The 1-, 3-, and 4-year overall survivals for the TACE-RFA group and the RFA group were 92.6%, 66.6%, and 61.8% and 85.3%, 59%, and 45.0%, respectively. The corresponding recurrence-free survivals were 79.4%, 60.6%, and 54.8% and 66.7%, 44.2%, and 38.9%, respectively. Patients in the TACE-RFA group had better overall survival and recurrence-free survival than patients in the RFA group (hazard ratio, 0.525; 95% CI, 0.335 to 0.822; P = .002; hazard ratio, 0.575; 95% CI, 0.374 to 0.897; P = .009, respectively). There were no treatment-related deaths. On logistic regression analyses, treatment allocation, tumor size, and tumor number were significant prognostic factors for overall survival, whereas treatment allocation and tumor number were significant prognostic factors for recurrence-free survival. Conclusion TACE-RFA was superior to RFA alone in improving survival for patients with HCC less than 7 cm.
Risk of Asynchronous Contralateral Breast Cancer in Noncarriers of BRCA1 and BRCA2 Mutations With a Family History of Breast Cancer: A Report From the Women's Environmental Cancer and Radiation Epidemiology Study
Authors: Reiner Anne S. , John Esther M. , Brooks Jennifer D. , Lynch Charles F. , Bernstein Leslie , Mellemkjær Lene , Malone Kathleen E. , Knight Julia A. , Capanu Marinela , Teraoka Sharon N. , Concannon Patrick , Liang Xiaolin , Figueiredo Jane C. , Smith Susan A. , Stovall Marilyn , Pike Malcolm C. , Haile Robert W. , Thomas Duncan C. , Begg Colin B. , Bernstein Jonine L. 
Published: December 2012

Purpose To fully characterize the risk of contralateral breast cancer (CBC) in patients with breast cancer with a family history who test negative for BRCA1 and BRCA2 mutations. Patients and Methods From our population-based case-control study comparing women with CBC to women with unilateral breast cancer (UBC), we selected women who tested negative for BRCA1 and BRCA2 mutations (594 patients with CBC/1,119 control patients with UBC). Rate ratios (RRs) and 95% CIs were estimated to examine the association between family history of breast cancer and risk of asynchronous CBC. Age- and family history–specific 10-year cumulative absolute risks of CBC were estimated. Results Family history of breast cancer was associated with increased CBC risk; risk was highest among young women (< 45 years) with first-degree relatives affected at young ages (< 45 years; RR, 2.5; 95% CI, 1.1 to 5.3) or women with first-degree relatives with bilateral disease (RR, 3.6; 95% CI, 2.0 to 6.4). Women diagnosed with UBC before age 55 years with a first-degree family history of CBC had a 10-year risk of CBC of 15.6%. Conclusion Young women with breast cancer who have a family history of breast cancer and who test negative for deleterious mutations in BRCA1 and BRCA2 are at significantly greater risk of CBC than other breast cancer survivors. This risk varies with diagnosis age, family history of CBC, and degree of relationship to an affected relative. Women with a first-degree family history of bilateral disease have risks of CBC similar to mutation carriers. This has important implications for the clinical management of patients with breast cancer with family history of the disease.
Medical Oncologists' Perceptions of Financial Incentives in Cancer Care
Authors: Malin Jennifer L. , Weeks Jane C. , Potosky Arnold L. , Hornbrook Mark C. , Keating Nancy L. 
Published: December 2012

Purpose The cost of cancer care continues to increase at an unprecedented rate. Concerns have been raised about financial incentives associated with the chemotherapy concession in oncology practices and their impact on treatment recommendations. Methods The objective of this study was to measure the physician-reported effects of prescribing chemotherapy or growth factors or making referrals to other cancer specialists, hospice, or hospital admissions on medical oncologists' income. US medical oncologists involved in the care of a population-based cohort of patients with lung or colorectal cancer from the Cancer Care Outcomes Research and Surveillance (CanCORS) study were surveyed regarding their perceptions of the impact of prescribing practices or referrals on their income. Results Although most oncologists reported that their incomes would be unaffected, compared with salaried oncologists, physicians in fee-for-service practice, and those paid a salary with productivity incentives were more likely to report that their income would increase from administering chemotherapy (odds ratios [ORs], 7.05 and 7.52, respectively; both P < .001) or administering growth factors (ORs, 5.60 and 6.03, respectively; both P < .001). Conclusion A substantial proportion of oncologists who are not paid a fixed salary report that their incomes increase when they administer chemotherapy and growth factors. Further research is needed to understand the impact of these financial incentives on both the quality and cost of care.