bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8+T cell epitope at two distinct regions of the genome
Authors: Nogueira Raquel T , Nogueira Alanderson R , Pereira Mirian CS , Rodrigues Maurício M , Galler Ricardo , Bonaldo Myrna C 
Published: March 2011

AbstractBackgroundThe attenuated Yellow fever (YF) 17D vaccine virus is one of the safest and most effective viral vaccines administered to humans, in which it elicits a polyvalent immune response. Herein, we used the YF 17D backbone to express aTrypanosoma cruziCD8+T cell epitope from the Amastigote Surface Protein 2 (ASP-2) to provide further evidence for the potential of this virus to express foreign epitopes. The TEWETGQI CD8+T cell epitope was cloned and expressed based on two different genomic insertion sites: in thefgloop of the viral Envelope protein and the protease cleavage site between the NS2B and NS3. We investigated whether the site of expression had any influence on immunogenicity of this model epitope.ResultsRecombinant viruses replicated similarly to vaccine virus YF 17D in cell culture and remained genetically stable after several serial passages in Vero cells. Immunogenicity studies revealed that both recombinant viruses elicited neutralizing antibodies to the YF virus as well as generated an antigen-specific gamma interferon mediated T-cell response in immunized mice. The recombinant viruses displayed a more attenuated phenotype than the YF 17DD vaccine counterpart in mice. Vaccination of a mouse lineage highly susceptible to infection byT. cruziwith a homologous prime-boost regimen of recombinant YF viruses elicited TEWETGQI specific CD8+T cells which might be correlated with a delay in mouse mortality after a challenge with a lethal dose ofT. cruzi.ConclusionsWe conclude that the YF 17D platform is useful to expressT. cruzi(Protozoan) antigens at different functional regions of its genome with minimal reduction of vector fitness. In addition, the modelT. cruziepitope expressed at different regions of the YF 17D genome elicited a similar T cell-based immune response, suggesting that both expression sites are useful. However, the epitope as such is not protective and it remains to be seen whether expression of larger domains of ASP-2, which include the TEWETGQI epitope, will elicit better T-CD8+ responses to the latter. It is likely that additional antigens and recombinant virus formulations will be necessary to generate a protective response.
The transcription factor Foxg1 regulates telencephalic progenitor proliferation cell autonomously, in part by controlling Pax6 expression levels
Authors: Manuel Martine N , Martynoga Ben , Molinek Mike D , Quinn Jane C , Kroemmer Corinne , Mason John O , Price David J 
Published: March 2011

Abstract

Background
The transcription factor Foxg1 is an important regulator of telencephalic cell cycles. Its inactivation causes premature lengthening of telencephalic progenitor cell cycles and increased neurogenic divisions, leading to severe hypoplasia of the telencephalon. These proliferation defects could be a secondary consequence of the loss of Foxg1 caused by the abnormal expression of several morphogens (Fibroblast growth factor 8, bone morphogenetic proteins) in the telencephalon of Foxg1 null mutants. Here we investigated whether Foxg1 has a cell autonomous role in the regulation of telencephalic progenitor proliferation. We analysed Foxg1

+/+
↔Foxg1

-/-
chimeras, in which mutant telencephalic cells have the potential to interact with, and to have any cell non-autonomous defects rescued by, normal wild-type cells.

Results
Our analysis showed that the Foxg1

-/-
cells are under-represented in the chimeric telencephalon and the proportion of them in S-phase is significantly smaller than that of their wild-type neighbours, indicating that their under-representation is caused by a cell autonomous reduction in their proliferation. We then analysed the expression of the cell-cycle regulator Pax6 and found that it is cell-autonomously downregulated in Foxg1

-/-
dorsal telencephalic cells. We went on to show that the introduction into Foxg1

-/-
embryos of a transgene designed to reverse Pax6 expression defects resulted in a partial rescue of the telencephalic progenitor proliferation defects.

Conclusions
We conclude that Foxg1 exerts control over telencephalic progenitor proliferation by cell autonomous mechanisms that include the regulation of Pax6, which itself is known to regulate proliferation cell autonomously in a regional manner.
Gene amplification in human cells knocked down for RAD54
Authors: Ruiz-Herrera Aurora , Smirnova Alexandra , Khouriauli Lela , Nergadze Solomon G , Mondello Chiara , Giulotto Elena 
Published: March 2011

Background
In mammalian cells gene amplification is a common manifestation of genome instability promoted by DNA double-strand breaks (DSBs). The repair of DSBs mainly occurs through two mechanisms: non-homologous end-joining (NHEJ) and homologous recombination (HR). We previously showed that defects in the repair of DSBs via NHEJ could increase the frequency of gene amplification. In this paper we explored whether a single or a combined defect in DSBs repair pathways can affect gene amplification.

Results
We constructed human cell lines in which the expression of RAD54 and/or DNA-PKcs was constitutively knocked-down by RNA interference. We analyzed their radiosensitivity and their capacity to generate amplified DNA. Our results showed that both RAD54 and DNA-PKcs deficient cells are hypersensitive to γ-irradiation and generate methotrexate resistant colonies at a higher frequency compared to the proficient cell lines. In addition, the analysis of the cytogenetic organization of the amplicons revealed that isochromosome formation is a prevalent mechanism responsible for copy number increase in RAD54 defective cells.

Conclusions
Defects in the DSBs repair mechanisms can influence the organization of amplified DNA. The high frequency of isochromosome formation in cells deficient for RAD54 suggests that homologous recombination proteins might play a role in preventing rearrangements at the centromeres.
An investigation on the influence of glycerin on sclerosant foam stability
Authors: Peterson J D , Goldman M P 
Published: March 2011

Background Foam sclerotherapy is an increasingly popular modality in the treatment of varicose veins. Foam stability varies according to foam composition, volume and injection technique. Materials and methods A disposable plastic connector was used to create foam from 0.50% sodium tetradecyl sulphate (STS) mixed with varying volumes of glycerin. As a measure of foam stability, the half liquid time was defined as the time required for half of the original volume of sclerosing solution to settle. Three recordings were determined for each of the three mixtures of sclerosant foam. Results The time for sclerosing solution to settle to half of its initial volume was found to be 89 seconds for 0.50% STS alone, 117.7 seconds with the addition of 0.1 mL of 72% glycerin, and 114.7 seconds with the addition of 0.2 mL of 72% glycerin. Conclusion The small volumes of glycerin added to STS prolonged the half liquid time of STS foam up to 35%. As glycerin alone is unable to be foamed with the double-syringe system technique there may be a point at which further addition of glycerin has a negative effect on the half-life of foam.
Early Breast Cancer in the Older Woman
Authors: Gandhi Sonal , Verma Sunil 
Published: March 2011

Abstract

Background.
Women aged ≥65 are generally underrepresented in early breast cancer studies. Therefore, the optimal management of this group of women remains less certain.

Methods.
A literature review of recently published trials, reviews, and practice guidelines outlining the surgical and adjuvant management of early breast cancer in older women was performed.

Results.
Surgery remains as the cornerstone treatment for early breast cancer in the elderly. Adjuvant radiation is generally considered if the projected lifespan is &gt;5 years. Hormone receptor–positive disease is best treated with adjuvant endocrine treatment; aromatase inhibitors and tamoxifen are both options. Evidence for the use of adjuvant chemotherapy and trastuzumab for high-risk disease in the elderly is more limited. Polychemotherapy is still preferred in fit older women. Certain toxicities from systemic treatments can be more pronounced and should be carefully managed. Treatment with systemic agents should be individualized, with consideration of patient preference, performance status, comorbidities, and projected lifespan. Molecular tumor signatures may help better select patients for treatment in the future.

Conclusions.
Age in itself should not be an absolute contraindication to any breast cancer therapy. Comprehensive, multidisciplinary assessment of elderly patients is imperative in evaluating eligibility for beneficial therapies.
Clinical Utility of Genetic Testing in Children and Adults with Steroid-Resistant Nephrotic Syndrome
Authors: Santín Sheila , Bullich Gemma , Tazón-Vega Bárbara , García-Maset Rafael , Giménez Isabel , Silva Irene , Ruíz Patricia , Ballarín José , Torra Roser , Ars Elisabet 
Published: March 2011

Summary

Background and objectives
The increasing number of podocyte-expressed genes implicated in steroid-resistant nephrotic syndrome (SRNS), the phenotypic variability, and the uncharacterized relative frequency of mutations in these genes in pediatric and adult patients with SRNS complicate their routine genetic analysis. Our aim was to compile the clinical and genetic data of eight podocyte genes analyzed in 110 cases (125 patients) with SRNS (ranging from congenital to adult onset) to provide a genetic testing approach.

Design, setting, participants, & measurements
Mutation analysis was performed by sequencing the NPHS1, NPHS2, TRPC6, CD2AP, PLCE1, INF2, WT1 (exons 8 and 9), and ACTN4 (exons 1 to 10) genes.

Results
We identified causing mutations in 34% (37/110) of SRNS patients, representing 67% (16/24) familial and 25% (21/86) sporadic cases. Mutations were detected in 100% of congenital-onset, 57% of infantile-onset, 24 and 36% of early and late childhood-onset, 25% of adolescent-onset, and 14% of adult-onset patients. The most frequently mutated gene was NPHS1 in congenital onset and NPHS2 in the other groups. A partial remission was observed in 7 of 26 mutation carriers treated with immunosuppressive agents and/or angiotensin-converting enzyme inhibitors. Patients with NPHS1 mutations showed a faster progression to ESRD than patients with NPHS2 mutations. None of these mutation carriers relapsed after kidney transplantation.

Conclusions
We propose a genetic testing algorithm for SRNS based on the age at onset and the familial/sporadic status. Mutation analysis of specific podocyte-genes has a clinical value in all age groups, especially in children.
Preliminary report: rapid prototyping models for Dysplastic hip surgery
Authors: Dhakshyani R. , Nukman Y. , Abu Osman N. , Vijay C. 
Published: March 2011

AbstractRapid prototyping (RP) is a technology used to produce physical models. The RP application is applied in the medical field to build anatomy models from high resolution multiplanar data such as Computed tomography (CT). CT of a female patient diagnosed with hip dysplasia was obtained prior to surgery. Specific software was used to prepare the physical model of the patient and was produced using fused deposition machine. Pre fused deposition models (FDM) were given to the orthopaedic surgeon to plan for the dysplastic hip dysplasia. The patient was scanned again using CT after surgery and a post model was produced. The outcome of the surgery was seen clearly by viewing the post model. Orthopaedic surgeon commented on his experience of using the models for the hip dysplasia surgery. These models were found to be very useful for pre surgery planning, determining procedure, implant sizes, positioning, bone grafting which also reduced surgery time by forty percent and increased surgeon confidence as rehearsal prior to actual surgery was made possible. This paper provides an understanding of the benefits of using RP models in hip dysplasia surgery as a good way to enhance both orthopaedic surgeon skill and knowledge.
Correlations between left ventricular mass index and cerebrovascular lesion
Authors: Kang Kyusik , Lee Seung-Hoon , Kim Beom , Lim Jae-Sung , Yoon Byung-Woo 
Published: March 2011

AbstractLeft ventricular (LV) mass and LV geometry are well-established measures of hypertension chronicity and severity, have a prognostic value on cardiovascular morbidity and mortality, and are related to asymptomatic cerebral small-artery disease (SAD) and largeartery disease (LAD). The aim of the present study was to clarify the different effects of LV mass and LV geometry on underlying SAD compared with its effects on underlying LAD in ischemic stroke patients. Four hundred three ischemic stroke patients underwent echocardiography to determine LV mass index and relative wall thickness. Brain magnetic resonance imaging, angiography, and carotid magnetic resonance angiography were preformed to detect LAD (≥50% stenosis) and SAD (leukoaraiosis, microbleeds, and old lacunar infarction) in the brain. Multivariate analyses showed that the LV mass index was highly associated with underlying SAD but not with underlying LAD. Among the various subtypes of SAD, only cerebral microbleeds were closely related to the LV mass index. Concentric LV hypertrophy was not related to the presence of either SAD or LAD. Subgroup analyses revealed that, among the various subtypes of SAD, only cerebral microbleeds were associated with concentric LV hypertrophy. In conclusion, cerebral microbleeds may imply more advanced target organ damage than underlying LAD and ischemic subtypes of SAD.
Heart-rate changes in asphyxic preconditioning in rats depend on light-dark cycle
Authors: Svorc Pavol , Bacova Ivana , Benacka Roman , Svorc Pavol , Galanova Ruzena , Fulton Benjamin 
Published: March 2011

AbstractGenerally, it is assumed that heart-rhythm disorders during hypoxia result from the interplay between the autonomic nervous system (ANS) and the direct effect of hypoxia on cardiorespiratory structures of the central nervous system and on the myocardium. Circadian variability in the ANS may substantially influence the electrical stability of the myocardium, and thus it is associated with the preconditioning protective mechanism. We designed our study using anaesthetized Wistar rats (ketamine/xylazine 100 mg/15 mg/kg, i.m., open chest experiments) to evaluate the effect of preconditioning (PC) induced by 1 to 3 cycles (1 PC–3 PC) of asphyxia (5 min. of artificial hypoventilation, VT = 0.5 ml/100 g of b.w., 20 breaths/min.) and reoxygenation (5 min. of artificial ventilation, VT = 1 ml/100 g of b.w., 50 breaths/min.) on the heart rate (HR) during followed exposure 20 minutes of hypoventilation after adaptation to a light-dark (LD) cycle of 12 hours:12 hours. Hypoxic HR increases were only minimally prevented by 1 to 2 PC pre-treatment, particularly during the dark part of the day. A statistically significant HR increase required 3 PC and was seen only in the light part of the day. We concluded that possible ANS participation in asphyxic preconditioning depends not only on the number of preconditioned cycles but also on the LD cycle, when the ANS participation in preconditioning can be effective only in the light (nonactive) period.
Prospective evaluation of a clinical decision guideline to diagnose spinal epidural abscess in patients who present to the emergency department with spine pain
Authors: Davis Daniel P. , Salazar Anthony , Chan Theodore C. , Vilke Gary M. 
Published: March 2011

Object
A spinal epidural abscess (SEA) is rare but potentially devastating if not diagnosed early. Unfortunately, diagnostic delays and associated neurological deficits are common. The objectives of this analysis were to explore the use of a novel clinical decision guideline to screen patients who present to the emergency department (ED) with spine pain for SEA and to determine the diagnostic test characteristics of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level in patients at risk for SEA.

Methods
This was a prospective, cohort analysis comparing the incidence of diagnostic delays and presence of motor deficits at the time of diagnosis before and after implementation of a novel decision guideline using risk factor assessment followed by ESR and CRP testing prior to definitive imaging. A delay was defined as either multiple ED visits or admission to a nonsurgical service without a diagnosis of SEA. A 9-month substudy was performed in all patients who presented to the ED with spine pain so that the diagnostic test characteristics of the ESR and CRP level could be defined.

Results
A total of 55 patients with an SEA in the 9-year control period and 31 patients with an SEA in the 5-year study period were identified. Diagnostic delays were observed in 46 (83.6%) of 55 patients before guideline implementation versus 3 (9.7%) of 31 after guideline implementation (p < 0.001). Motor deficits were present at the time of diagnosis in 45 (81.8%) of 55 patients before guideline implementation versus 6 (19.4%) of 31 after guideline implementation (p < 0.001). The sensitivity and specificity of ESR in patients with an SEA risk factor were 100% and 67%, respectively. The receiver operating characteristic curve analysis revealed better test characteristics for ESR (area under curve 0.96) than for CRP (area under curve 0.81).

Conclusions
A treatment guideline incorporating risk factor assessment followed by ESR and CRP testing was highly sensitive and moderately specific in identifying ED patients with SEA. A decrease in diagnostic delays and a lower incidence of motor deficits at the time of diagnosis was observed.
Attenuation of hematoma size and neurological injury with curcumin following intracerebral hemorrhage in mice
Authors: King Melanie D. , McCracken D. Jay , Wade F. Marlene , Meiler Steffen E. , Alleyne Cargill H. , Dhandapani Krishnan M. 
Published: March 2011

Object
Intracerebral hemorrhage (ICH) is associated with significant morbidity and mortality. Acute hematoma enlargement is an important predictor of neurological injury and poor clinical prognosis; but neurosurgical clot evacuation may not be feasible in all patients and treatment options remain largely supportive. Thus, novel therapeutic approaches to promote hematoma resolution are needed. In the present study, the authors investigated whether the curry spice curcumin limited neurovascular injury following ICH in mice.

Methods
Intracerebral hemorrhage was induced in adult male CD-1 mice by intracerebral administration of collagenase or autologous blood. Clinically relevant doses of curcumin (75–300 mg/kg) were administered up to 6 hours after ICH, and hematoma volume, inflammatory gene expression, blood-brain barrier permeability, and brain edema were assessed over the first 72 hours. Neurological assessments were performed to correlate neurovascular protection with functional outcomes.

Results
Curcumin increased hematoma resolution at 72 hours post-ICH. This effect was associated with a significant reduction in the expression of the proinflammatory mediators, tumor necrosis factor–α, interleukin-6, and interleukin-1β. Curcumin also reduced disruption of the blood-brain barrier and attenuated the formation of vasogenic edema following ICH. Consistent with the reduction in neuroinflammation and neurovascular injury, curcumin significantly improved neurological outcome scores after ICH.

Conclusions
Curcumin promoted hematoma resolution and limited neurological injury following ICH. These data may indicate clinical utility for curcumin as an adjunct therapy to reduce brain injury and improve patient outcome.
An extent of resection threshold for newly diagnosed glioblastomas
Authors: Sanai Nader , Polley Mei-Yin , McDermott Michael W. , Parsa Andrew T. , Berger Mitchel S. 
Published: March 2011

Object
The value of extent of resection (EOR) in improving survival in patients with glioblastoma multiforme (GBM) remains controversial. Specifically, it is unclear what proportion of contrast-enhancing tumor must be resected for a survival advantage and how much survival improves beyond this threshold. The authors attempt to define these values for the patient with newly diagnosed GBM in the modern neurosurgical era.

Methods
The authors identified 500 consecutive newly diagnosed patients with supratentorial GBM treated at the University of California, San Francisco between 1997 and 2009. Clinical, radiographic, and outcome parameters were measured for each case, including MR imaging–based volumetric tumor analysis.

Results
The patients had a median age of 60 years and presented with a median Karnofsky Performance Scale (KPS) score of 80. The mean clinical follow-up period was 15.3 months, and no patient was unaccounted for. All patients underwent resection followed by chemotherapy and radiation therapy. The median postoperative tumor volume was 2.3 cm3, equating to a 96% EOR. The median overall survival was 12.2 months. Using Cox proportional hazards analysis, age, KPS score, and EOR were predictive of survival (p < 0.0001). A significant survival advantage was seen with as little as 78% EOR, and stepwise improvement in survival was evident even in the 95%–100% EOR range. A recursive partitioning analysis validated these findings and provided additional risk stratification parameters related to age, EOR, and tumor burden.

Conclusions
For patients with newly diagnosed GBMs, aggressive EOR equates to improvement in overall survival, even at the highest levels of resection. Interestingly, subtotal resections as low as 78% also correspond to a survival benefit.