bluuebunny/crossref_metadata_2025_split huggingface dataset:
Finding a Panacea among Combination Cancer Therapies
Authors: Yamaguchi Ryuji , Perkins Guy 
Published: November 2011

Abstract
Because each cancer is a heterogeneous mix of cancer cells at different stages of development, we are faced with trying to treat many different diseased cells all at once. An authentic approach is to build a genomic and proteomic profile of a patient, identify the target oncogenes, and prescribe the combination of targeted drugs tailored for that patient. However, there are many practical problems with this personalized medicine approach: (i) cancers often generate treatment-resistant phenotypes, (ii) the treatment could be enormously expensive, and (iii) most of the targeted drugs have not been developed yet. We propose a different approach: therapies that combine 2-deoxyglucose (2DG) with Bcl-2 antagonist such as ABT-263/737 (ABT). Proapoptotic protein Bak is normally sequestered by Mcl-1 and Bcl-xL. Only when Bak is released from both Mcl-1 and Bcl-xL can it induce apoptosis. 2DG can prime highly glycolytic cells by dissociating Bak-Mcl-1 complex. Some brain cells and most cancer cells are primed by 2DG. ABT can bind to Bcl-xL, dissociating Bak-Bcl-xL complex, freeing Bak and inducing apoptosis. Because ABT cannot cross blood–brain barrier, the only cells exposed to both agents are highly glycolytic cancer cells located outside the brain. Because ABT directly triggers apoptosis at the step very near the terminal point of apoptosis, 2DG-ABT combination therapies are applicable to many types of cancer at all stages of development, with little side effect. Cancer Res; 72(1); 18–23. ©2011 AACR.
2-(3-{1-Carboxy-5-[(6-[18F]Fluoro-Pyridine-3-Carbonyl)-Amino]-Pentyl}-Ureido)-Pentanedioic Acid, [18F]DCFPyL, a PSMA-Based PET Imaging Agent for Prostate Cancer
Authors: Chen Ying , Pullambhatla Mrudula , Foss Catherine A. , Byun Youngjoo , Nimmagadda Sridhar , Senthamizhchelvan Srinivasan , Sgouros George , Mease Ronnie C. , Pomper Martin G. 
Published: November 2011

Abstract
Purpose: We have synthesized and evaluated in vivo 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, as a potential imaging agent for the prostate-specific membrane antigen (PSMA). PSMA is upregulated in prostate cancer epithelia and in the neovasculature of most solid tumors.
Experimental Design: [18F]DCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C(O)-glu urea precursor using 6-[18F]fluoronicotinic acid tetrafluorophenyl ester ([18F]F-Py-TFP) for introduction of 18F. Radiochemical synthesis was followed by biodistribution and imaging with PET in immunocompromised mice using isogenic PSMA PC3 PIP and PSMA- PC3 flu xenograft models. Human radiation dosimetry estimates were calculated using OLINDA/EXM 1.0.
Results: DCFPyL displays a Ki value of 1.1 ± 0.1 nmol/L for PSMA. [18F]DCFPyL was produced in radiochemical yields of 36%–53% (decay corrected) and specific radioactivities of 340–480 Ci/mmol (12.6–17.8 GBq/μmol, n = 3). In an immunocompromised mouse model [18F]DCFPyL clearly delineated PSMA+ PC3 PIP prostate tumor xenografts on imaging with PET. At 2 hours postinjection, 39.4 ± 5.4 percent injected dose per gram of tissue (%ID/g) was evident within the PSMA+ PC3 PIP tumor, with a ratio of 358:1 of uptake within PSMA+ PC3 PIP to PSMA− PC3 flu tumor placed in the opposite flank. At or after 1 hour postinjection, minimal nontarget tissue uptake of [18F]DCFPyL was observed. The bladder wall is the dose-limiting organ.
Conclusions: These data suggest [18F]DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues. Clin Cancer Res; 17(24); 7645–53. ©2011 AACR.
Determinants of Microvascular Network Topologies in Implanted Neovasculatures
Authors: Chang Carlos C. , Krishnan Laxminarayanan , Nunes Sara S. , Church Kenneth H. , Edgar Lowell T. , Boland Eugene D. , Weiss Jeffery A. , Williams Stuart K. , Hoying James B. 
Published: November 2011

Objective—
During neovascularization, the end result is a new functional microcirculation composed of a network of mature microvessels with specific topologies. Although much is known concerning the mechanisms underlying the initiation of angiogenesis, it remains unclear how the final architecture of microcirculatory beds is regulated. To begin to address this, we determined the impact of angiogenic neovessel prepatterning on the final microvascular network topology using a model of implant neovascularization.

Methods and Results—
We used 3D direct-write bioprinting or physical constraints in a manner permitting postangiogenesis vascular remodeling and adaptation to pattern angiogenic microvascular precursors (neovessels formed from isolated microvessel segments) in 3D collagen gels before implantation and subsequent network formation. Neovasculatures prepatterned into parallel arrays formed functional networks after 4 weeks postimplantation but lost the prepatterned architecture. However, maintenance of uniaxial physical constraints during postangiogenesis remodeling of the implanted neovasculatures produced networks with aligned microvessels, as well as an altered proportional distribution of arterioles, capillaries, and venules.

Conclusion—
Here we show that network topology resulting from implanted microvessel precursors is independent from prepatterning of precursors but can be influenced by a patterning stimulus involving tissue deformation during postangiogenesis remodeling and maturation.
Renin–Angiotensin System Modulators Modestly Reduce Vascular Risk in Persons With Prior Stroke
Authors: Lee Meng , Saver Jeffrey L. , Hong Keun-Sik , Hao Qing , Chow Jessica , Ovbiagele Bruce 
Published: November 2011

Background and Purpose—
Although the efficacy of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in reducing future vascular events for patients with coronary heart disease is established, less is known about the precise benefit of these agents among patients with stroke. We evaluated whether use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers reduces future vascular events in persons with prior stroke.

Methods—
We searched PubMed, Cochrane Central Register of Controlled Trials, and bibliographies of relevant trials and recent review articles to identify randomized controlled trials. Relative risk with 95% CI was used as a measure of the association between use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and risks of major vascular event (nonfatal stroke, nonfatal myocardial infarction, or death from cardiovascular causes) or stroke (ischemic or hemorrhagic) after pooling data across trials.

Results—

Eight randomized controlled trials with 29 667 participants were identified. Use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in persons with prior stroke was associated with lower risks of future major vascular events (relative risk, 0.91; 95% CI, 0.87–0.97;
P
=0.001; number needed to treat=71) and recurrent stroke (relative risk, 0.93; 95% CI, 0.86–0.99;
P
=0.03; number needed to treat=143). Heterogeneity was found among studies for end points of major vascular events (
P
=0.02, I
2
=61%) but not recurrent stroke (
P
=0.38, I
2
=6%). In subgroup analyses, there was generally no obvious heterogeneity among different study characteristics.

Conclusions—
Treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker has a clear but rather modest effect on reducing vascular risk in persons with prior stroke.
Forecasting Sun versus Shade in Complex Terrain for the 2010 Winter Olympic and Paralympic Games
Authors: Howard Rosie , Stull Roland 
Published: November 2011

During the 2010 Vancouver Winter Olympic and Paralympic Games in Canada, there were 10 mostly sunny days at the outdoor Olympic venues. The warmth and sunshine, possibly a result of El Niño conditions at the time, significantly reduced snow cover at one venue and weakened the snowpack at the other two venues, much to the chagrin of the event organizers. Solar radiation affects ski racing via its effect on snow-surface friction, abrasion, and mechanical strength. Ski technicians and athletes compensate via the choice of ski and wax. For these reasons, sun-versus-shade forecasts were produced for Canadian ski and snowboard teams.
A theodolite was used to survey the horizon elevation angles around the full azimuth circles at 133 locations spaced roughly 150 m apart along race pistes (compacted ski runs) at three Olympic venues. This survey was important for including the shadowing effects of the tall evergreen trees that border the pistes. This would not be properly accounted for if only digital elevation data were used. These data, along with the astronomical equations for solar elevation and azimuth, were used to calculate whether each survey point would be in the sun or the shade in cloudless conditions for any time and date during the Olympics. Half-hourly output was provided to ski and snowboard technicians and coaches via a graphical user interface delivered on the Internet.
Energetics of Barotropic and Baroclinic Tides in the Monterey Bay Area
Authors: Kang Dujuan , Fringer Oliver 
Published: November 2011

Abstract
A detailed energy analysis of the barotropic and baroclinic M2 tides in the Monterey Bay area is performed. The authors first derive a theoretical framework for analyzing internal tide energetics based on the complete form of the barotropic and baroclinic energy equations, which include the full nonlinear and nonhydrostatic energy flux contributions as well as an improved evaluation of the available potential energy. This approach is implemented in the Stanford Unstructured Nonhydrostatic Terrain-Following Adaptive Navier–Stokes Simulator (SUNTANS). Results from three-dimensional, high-resolution SUNTANS simulations are analyzed to estimate the tidal energy partitioning among generation, radiation, and dissipation. A 200 km × 230 km domain including all typical topographic features in this region is used to represent the Monterey Bay area. Of the 152-MW energy lost from the barotropic tide, approximately 133 MW (88%) is converted into baroclinic energy through internal tide generation, and 42% (56 MW) of this baroclinic energy radiates away into the open ocean. The tidal energy partitioning depends greatly on the topographic features. The Davidson Seamount is most efficient at baroclinic energy generation and radiation, whereas the Monterey Submarine Canyon acts as an energy sink. Energy flux contributions from nonlinear and nonhydrostatic effects are also examined. In the Monterey Bay area, the nonlinear and nonhydrostatic contributions are quite small. Moreover, the authors investigate the character of internal tide generation and find that in the Monterey Bay area the generated baroclinic tides are mainly linear and in the form of internal tidal beams. Comparison of the modeled tidal conversion to previous theoretical estimates shows that they are consistent with one another.
Transcending the Adaptation/Mitigation Climate Change Science Policy Debate: Unmasking Assumptions about Adaptation and Resilience
Authors: Jennings Tori L. 
Published: November 2011

AbstractThe two principal policy approaches to global climate change include mitigation and adaption. In recent years, the interest in adaptation and “resilience” has increased significantly in part because anthropogenic climate change appears unavoidable and mitigation agreements are difficult to achieve. This article takes a critical look at the emerging discourse over climate change adaptation and resilience. By drawing upon critiques of environmental resource management and adaptive comanagement, this paper argues that taking the concept of adaptation for granted as an appropriate bottom-up strategy for coping with anthropogenic climate change not only ignores the political and economic contexts in which this environmental strategy developed, but might also unintentionally subvert the vulnerable communities it intends to benefit. Using an ethnographic case study of the 2004 Boscastle Harbour flood in North Cornwall, England, this paper explores the paradoxical way in which adaptation and resilience work within the apparatus of the neoliberal state, which aims to shift responsibility for social and environmental problems to the individual. By better understanding the political and economic processes embedded in the concepts of adaptation and resilience, researchers will be more effective at finding equitable solutions to human ecological problems.Adaptation to the adverse effects of climate change is vital in order to reduce the impacts of climate change that are happening now and increase resilience to future impacts (United Nations Framework Convention on Climate Change).
Paraprofessionals’ perceptions on delivering infant feeding lessons to disadvantaged mothers via a self-directed computer-supported method
Authors: Singleterry Lisa R , Horodynski Mildred A 
Published: November 2011

Objective: To ascertain paraprofessionals’ perceptions regarding a self-directed computer-supported nutrition educational intervention to disadvantaged mothers of infants. Design: Qualitative focus group study. Setting: Three county extension programs in a Midwestern state, which serve disadvantaged families. Method: Sixteen paraprofessional nutrition educators, affiliated with Extended Food and Nutrition Programs (EFNEP), took part in three focus groups led by a facilitator following a semi-structured questioning route. Results: Three themes emerged: (1) paraprofessionals’ perceptions of personal connections with learners; (2) paraprofessionals’ perceptions of lesson plans; and (3) paraprofessionals’ perceptions of self-directed lessons. Conclusions: Data provided exemplars of paraprofessional teaching strategies used with the disadvantaged populations they service, a recommendation to develop a blended curriculum, and insight regarding technology. A preventive nutrition education program, focusing on the reduction of childhood obesity though informed infant feeding practices, can be delivered using a combination of direct contact paraprofessional education and self-directed computer-supported lessons.
Inhibition of α Folate Receptor Resulting in a Reversal of Taxol Resistance in Nasopharyngeal Carcinoma
Authors: Li Wei , Tan Guolin , Ma Yanhong , Li Heqing , He Guangxiang 
Published: November 2011

ObjectiveTo further determine the role of FOLR1 in taxol resistance of nasopharyngeal carcinoma (NPC) and whether inhibition of FOLR1 expression reverses the taxol‐resistant phenotype.Study DesignCorrelation study between gene expression and cancer cell survival.SettingUniversity hospital.Subjects and MethodsThree taxol‐resistant sub–cell lines with a different resistant index were established from the parental CNE‐1 NPC cell line. The correlation between FOLR1 expression and taxol sensitivity was statistically analyzed. Inhibition of FOLR1 expression was carried out by RNA interference and by a FOLR1‐specific monoclonal antibody, and taxol sensitivity was examined by colony formation assays. FOLR1 expression was also examined in 72 NPC patient specimens by immunohistochemistry.ResultsThe levels of FOLR1 expression were positively and significantly correlated with a taxol resistance phenotype (P <. 05). Inhibition of FOLR1 expression resulted in a significantly increased sensitivity of taxol to taxol‐resistant NPC cells (P <. 05). An increase of FOLR1 expression by gene transfection caused a taxol‐resistant phenotype in parental NPC cells. The level of FOLR1 expression was found to be related to clinical stage in NPC tissue samples.ConclusionThese results suggest that FOLR1 plays an important role in taxol resistance of NPC cells.
A Closed‐Loop Stimulation System Supplemented with Motoneurone Dynamic Sensitivity Replicates Natural Eye Blinks
Authors: Frigerio Alice , Cavallari Paolo 
Published: November 2011

ObjectiveThe authors are designing an implantable device that will electrically stimulate a paretic eyelid when electrodes implanted into the contralateral healthy orbicularis oculi muscle detect a spontaneous blink activity. As a novelty, the stimulation pattern includes the dynamic sensitivity of motor units, thus obtaining complete eyelid closure, tailored on the kinematics of the natural eye blink.Study DesignA preliminary study was performed on 10 healthy subjects, to observe, first, the kinematics of their natural eye blink and, second, the eye blink stimulated by a dynamic vs nondynamic pattern.SettingA microaccelerometer taped onto the left upper eyelid detected its kinematics. A dedicated LabView software built up and triggered the stimulation pattern. A webcam recorded the behavioral effect.Subjects and MethodsThe kinematics of spontaneous eye blinks was detected. Then, an epicutaneous stimulation of the facial nerve branch for the left orbicularis oculi muscle was performed on the same subjects. Muscle recruitment curves were studied, and acceleration of the bionic blink was measured and compared with the natural one.ResultsKinematics of the natural eyelid is highly variable within subjects. The stimulation pattern frequency was set case by case in order to obtain the desired eyelid acceleration of the contralateral eye. A custom‐fit dynamic stimulation leads to a symmetrical natural‐like eye blink.ConclusionsBy adding the dynamic pulse, the authors were able to tailor a bionic eye blink, which was hardly distinguishable from the subject’s natural one.
Feeling severely affected by Multiple Sclerosis: What does this mean?
Authors: Strupp Julia , Hartwig Alexander , Golla Heidrun , Galushko Maren , Pfaff Holger , Voltz Raymond 
Published: November 2011

Background: The situation for people feeling severely affected by Multiple Sclerosis (MS) remains largely unexamined and the term ‘severe MS’ is not clearly defined. Aim: Our study describes this sub-group of patients utilizing exclusively a subjective inclusion criterion to analyse their reasons for feeling severely affected and document their perceived unmet needs. Design: A questionnaire with open- and closed-ended items addressing only patients feeling severely affected was sent out nationwide. Expanded Disability Status Score (EDSS) and subjectively severe affectedness were analysed for correlation. After dichotomizing both scores by a median split, the answers were allocated to these groups and tested for significant differences. Setting/participants: 1,110 questionnaires were analysed regarding the closed-ended questions while a subsample of 40% ( n = 445) was analysed regarding the open-ended questions. Average age of participants was 51.87 years. Average time since diagnosis was 16.6 years. Main course of the disease was secondary progressive (35.5%). Results: The most frequently mentioned reasons for feeling severely affected were lack of mobility (56.4%) and fatigue (27.4%). Significant percentages for unmet needs were seen in the categories of funding services (31.0%), better social integration (24.7%) and medical support (25.2%). A significant correlation was observed between EDSS and subjectively felt affectedness ( p ≤ 0.01). Motor disorders explained differences in patient needs behind a higher EDSS score; higher severe affectedness referred to other issues like dependency and immobility. Conclusions: EDSS is insufficient for usage as the sole instrument for measuring severe affectedness as it does not take into account other potential reasons. Complex patient needs necessitate multi-professional care as offered by palliative medicine.
Treatment with folic acid ameliorated the histopathological alterations caused by propylthiouracil-induced hypothyroid rat testes
Authors: Tousson Ehab , Ali Ehab MM , Ibrahim Wafaa , Mansour Mohammed A 
Published: November 2011

Hypothyroidism is an underactive thyroid gland that cannot make enough thyroid hormone to keep the body running normally. Here we studied the histopathological, immunohistochemical, and ultrastructural changes in the hypothyroid rat testes at the postpubertal stage, in addition to the ameliorating role of folic acid in enhancing spermatogenesis, boosting sperm concentration and building up the antioxidant status against the oxidants. A total of 50 male albino rats were equally divided into 5 groups; the first and second groups comprised the control and folic acid groups, respectively; while the third group comprised the hypothyroid group in which rats received 6- n-propyl-2-thiouracil in drinking water for 6 weeks to induce hypothyroidism. The fourth and fifth groups comprised hypothyroid rats treated with folic acid for 4 weeks and dissected after 6 and 10 weeks, respectively. Testes in the hypothyroid rats showed marked morphological and histological changes in the seminiferous tubules with a reduction in sperm count. Our results indicate that hypothyroidism adversely affects spermatogenesis, suggesting that thyroid hormone might play an important role not only in controlling normal testicular development but also in maintaining normal testicular function and spermatogenesis. Further, we suggested an ameliorating role of folic acid in the relief of testicular tissue from changes due to hypothyroidism. However, we found that the best results were found in cases where folic acid was used as an adjuvant therapy for returning to the euthyroid state.
Occupational genotoxicity among copper smelters
Authors: De Olivera Juliana Viégas Duarte , Boufleur Liana Appel , Santos Carla Eliete Iochims Dos , Dias Johnny Ferraz , Squeff Cíntia Haag , Silva Guilherme Ruivo Gonçalves , Ianistcki Martus , Benvegnú Vinícius Cosmos , Silva Juliana Da 
Published: November 2011

Occupational exposure in a copper smelting industry may produce various adverse health effects including cancer. Despite a number of well-documented studies reporting an increased risk of cancer among copper smelter workers, the data on genotoxic effects in this industry are scarce. In view of the above, an assessment of DNA damage in peripheral blood leukocytes by Comet assay from copper smelter workers was undertaken. Additionally, the proton-induced X-ray emission (PIXE) analysis was assessed to determine the metal content of samples. The study was conducted with all workers from a copper smelter (males; n = 11), and a control group ( n = 11) was recruited. The results of our study showed a significant increase ( p < 0.001; Mann-Whitney test) in DNA damage in peripheral blood lymphocytes of smelter workers, compared to the controls ( p < 0.001; Mann-Whitney test). No correlation between DNA damage or metal concentration and age mean or time of exposure was found under study. Our findings indicate that copper smelter workers have increased levels of DNA damage in somatic cells, suggesting a potential health risk for the workers. PIXE results show the presence of copper, iron, and other metals.