bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of VGLUT3 Produces Circadian-Dependent Hyperdopaminergia and Ameliorates Motor Dysfunction and l-Dopa-Mediated Dyskinesias in a Model of Parkinson's Disease
Authors: Divito Christopher B. , Steece-Collier Kathy , Case Daniel T. , Williams Sean-Paul G. , Stancati Jennifer A. , Zhi Lianteng , Rubio Maria E. , Sortwell Caryl E. , Collier Timothy J. , Sulzer David , Edwards Robert H. , Zhang Hui , Seal Rebecca P. 
Published: November 2015

The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson's disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and locomotor activity, a canonical measure of basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity that is restricted to the waking cycle and is due to an increase in striatal DA synthesis, packaging, and release. Using a conditional VGLUT3 KO mouse, we show that deletion of the transporter from CINs, surprisingly, does not alter evoked DA release in the dorsal striatum or baseline locomotor activity. The mice do, however, display changes in rearing behavior and sensorimotor gating. Elevation of DA release in the global KO raised the possibility that motor deficits in a Parkinson's disease model would be reduced. Remarkably, after a partial 6-hydroxydopamine (6-OHDA)-mediated DA depletion (∼70% in dorsal striatum), KO mice, in contrast to WT mice, showed normal motor behavior across the entire circadian cycle.l-3,4-dihydroxyphenylalanine-mediated dyskinesias were also significantly attenuated. These findings thus point to new mechanisms to regulate basal ganglia function and potentially treat Parkinson's disease and related disorders.SIGNIFICANCE STATEMENTDopaminergic signaling is critical for both motor and cognitive functions in the mammalian nervous system. Impairments, such as those found in Parkinson's disease patients, can lead to severe motor deficits. Vesicular glutamate transporter 3 (VGLUT3) loads glutamate into secretory vesicles for neurotransmission and is expressed by discrete neuron populations throughout the nervous system. Here, we report that the absence of VGLUT3 in mice leads to an upregulation of the midbrain dopamine system. Remarkably, in a Parkinson's disease model, the mice show normal motor behavior. They also show fewer abnormal motor behaviors (dyskinesias) in response tol-3,4-dihydroxyphenylalanine, the principal treatment for Parkinson's disease. The work thus suggests new avenues for the development of novel treatment strategies for Parkinson's disease and potentially other basal-ganglia-related disorders.
Daidzein Augments Cholesterol Homeostasis via ApoE to Promote Functional Recovery in Chronic Stroke
Authors: Kim Eunhee , Woo Moon-Sook , Qin Luye , Ma Thong , Beltran Cesar D. , Bao Yi , Bailey Jason A. , Corbett Dale , Ratan Rajiv R. , Lahiri Debomoy K. , Cho Sunghee 
Published: November 2015

Stroke is the world's leading cause of physiological disability, but there are currently no available agents that can be delivered early after stroke to enhance recovery. Daidzein, a soy isoflavone, is a clinically approved agent that has a neuroprotective effectin vitro, and it promotes axon growth in an animal model of optic nerve crush. The current study investigates the efficacy of daidzein on neuroprotection and functional recovery in a clinically relevant mouse model of stroke recovery. In light of the fact that cholesterols are essential lipid substrates in injury-induced synaptic remodeling, we found that daidzein enhanced the cholesterol homeostasis genetic program, includingLxrand downstream transporters,Apoe,Abca1, andAbcg1genesin vitro. Daidzein also elevated the cholesterol homeostasis genes in the poststroke brain withApoe, the highest expressing transporter, but did not affect infarct volume or hemispheric swelling. Despite the absence of neuroprotection, daidzein improved motor/gait function in chronic stroke and elevated synaptophysin expression. However, the daidzein-enhanced functional benefits and synaptophysin expression were abolished inApoe-knock-out mice, suggesting the importance of daidzein-induced ApoE upregulation in fostering stroke recovery. Dissociation between daidzein-induced functional benefits and the absence of neuroprotection further suggest the presence of nonoverlapping mechanisms underlying recovery processes versus acute pathology. With its known safety in humans, early and chronic use of daidzein aimed at augmenting ApoE may serve as a novel, translatable strategy to promote functional recovery in stroke patients without adverse acute effect.SIGNIFICANCE STATEMENTThere have been recurring translational failures in treatment strategies for stroke. One underlying issue is the disparity in outcome analysis between animal and clinical studies. The former mainly depends on acute infarct size, whereas long-term functional recovery is an important outcome in patients. In an attempt to identify agents that promote functional recovery, we discovered that an FDA-approved soy isoflavone, daidzein, improved stroke-induced behavioral deficits via enhancing cholesterol homeostasis in chronic stroke, and this occurs without causing adverse effects in the acute phase. With its known safety in humans, the study suggests that the early and chronic use of daidzein serves as a potential strategy to promote functional recovery in stroke patients.
Changes in Methionine Metabolism and Histone H3 Trimethylation Are Linked to Mitochondrial Defects in Multiple Sclerosis
Authors: Singhal Naveen Kumar , Li Shuo , Arning Erland , Alkhayer Kholoud , Clements Robert , Sarcyk Zachary , Dassanayake Rohan S. , Brasch Nicola E. , Freeman Ernest J. , Bottiglieri Teodoro , McDonough Jennifer 
Published: November 2015

Mitochondrial changes, including decreased expression of electron transport chain subunit genes and impaired energetic, have been reported in multiple sclerosis (MS), but the mechanisms involved in these changes are not clear. To determine whether epigenetic mechanisms are involved, we measured the concentrations of methionine metabolites by liquid chromatography tandem mass spectrometry, histone H3 methylation patterns, and markers of mitochondrial respiration in gray matter from postmortem MS and control cortical samples. We found decreases in respiratory markers as well as decreased concentrations of the methionine metabolites S-adenosylmethionine, betaine, and cystathionine in MS gray matter. We also found expression of the enzyme betaine homocysteine methyltransferase in cortical neurons. This enzyme catalyzes the remethylation of homocysteine to methionine, with betaine as the methyl donor, and has previously been thought to be restricted to liver and kidney in the adult human. Decreases in the concentration of the methyl donor betaine were correlated with decreases in histone H3 trimethylation (H3K4me3) in NeuN+ neuronal nuclei in MS cortex compared with controls. Mechanistic studies demonstrated that H3K4me3 levels and mitochondrial respiration were reduced in SH-SY5Y cells after exposure to the nitric oxide donor sodium nitroprusside, and betaine was able to rescue H3K4me3 levels and respiratory capacity in these cells. Chromatin immunoprecipitation experiments showed that betaine regulates metabolic genes in human SH-SY5Y neuroblastoma cells. These data suggest that changes to methionine metabolism may be mechanistically linked to changes in neuronal energetics in MS cortex.SIGNIFICANCE STATEMENTFor decades, it has been observed that vitamin B12deficiency and multiple sclerosis (MS) share certain pathological changes, including conduction disturbances. In the present study, we have found that vitamin B12-dependent methionine metabolism is dysregulated in the MS brain. We found that concentrations of the methyl donor betaine are decreased in MS cortex and are correlated with reduced levels of the histone H3 methyl mark H3K4me3 in neurons. Cell culture and chromatin immunoprecipitation-seq data suggest that these changes may lead to defects in mitochondria and impact neuronal energetics. These data have uncovered a novel pathway linking methionine metabolism with mitochondrial respiration and have important implications for understanding mechanisms involved in neurodegeneration in MS.
Incorporating Patient Preferences in the Management of Multiple Long-Term Conditions: Is This a Role for Clinical Practice Guidelines?
Authors: Young Charlotte E. , Boyle Frances M. , Brooker Katie S. , Mutch Allyson J. 
Published: November 2015

Background Clinical practice guidelines provide an evidence-based approach to managing single chronic conditions, but their applicability to multiple conditions has been actively debated. Incorporating patient-preference recommendations and involving consumers in guideline development may enhance their applicability, but further understanding is needed. Objectives To assess guidelines that include recommendations for comorbid conditions to determine the extent to which they incorporate patient-preference recommendations; use consumer-engagement processes during development, and, if so, whether these processes produce more patient-preference recommendations; and meet standard quality criteria, particularly in relation to stakeholder involvement. Design A review of Australian guidelines published from 2006 to 2014 that incorporated recommendations for managing comorbid conditions in primary care. Document analysis of guidelines examined the presence of patient-preference recommendations and the consumer-engagement processes used. The Appraisal of Guidelines for Research and Evaluation instrument was used to assess guideline quality. Results Thirteen guidelines were reviewed. Twelve included at least one core patient-preference recommendation. Ten used consumer-engagement processes, including participation in development groups (seven guidelines) and reviewing drafts (ten guidelines). More extensive consumer engagement was generally linked to greater incorporation of patient-preference recommendations. Overall quality of guidelines was mixed, particularly in relation to stakeholder involvement. Conclusions Guidelines do incorporate some patient-preference recommendations, but more explicit acknowledgement is required. Consumer-engagement processes used during guideline development have the potential to assist in identifying patient preferences, but further research is needed. Clarification of the consumer role and investment in consumer training may strengthen these processes.
Cardiometabolic Health in African Immigrants to the United States: A Call to Re-examine Research on African-descent Populations
Authors: Commodore-Mensah, PhD, RN Yvonne , Dennison Himmelfarb, PhD, ANP, RN Cheryl , Agyemang, PhD, MPH Charles , Sumner, MD Anne E. 
Published: November 2015

<p> </p><p> In the 20th century, Africans in Sub-Saharan Africa had lower rates of cardiometabolic disease than Africans who migrated. How­ever, in the 21st century, beyond infectious diseases, the triple epidemics of obesity, diabetes and hypertension have taken hold in Africa. Therefore, Africans are acquiring these chronic diseases at different rates and different intensity prior to migration. To ensure optimal care and health outcomes, the United States practice of grouping all African-descent populations into the “Black/ African American” category without regard to country of origin masks socioeconomic and cultural differences and needs re-evalu­ation. Overall, research on African-descent populations would benefit from a shift from a racial to an ethnic perspective. To dem­onstrate the value of disaggregating data on African-descent populations, the epide­miologic transition, social, economic, and health characteristics of African immigrants are presented. <em>Ethn Dis. </em>2015;25(3):373- 380.</p>
Neighborhood Social Predictors of Weight-related Measures in Underserved African-Americans in the PATH Trial
Authors: McDaniel Tyler , Wilson Dawn K. , Coulon Sandra M. , Hand Gregory A. , Siceloff E. Rebekah 
Published: November 2015

<p class="Default"> </p><p>African Americans have the highest rate of obesity in the United States relative to other ethnic minority groups. Bioecologi­cal factors including neighborhood social and physical environmental variables may be important predictors of weight-related measures specifically body mass index (BMI) in African American adults. Baseline data from the Positive Action for Today’s Health (PATH) trial were collected from 417 African American adults. Overall a multiple regression model for BMI was significant, showing positive associations with average daily moderate-to-vigorous physical activity (MVPA) (B =-.21, <em>P</em>&lt;.01) and neighbor­hood social interaction (B =-.13, <em>P</em>&lt;.01). Consistent with previous literature, results show that neighborhood social interac­tion was associated with healthier BMI, highlighting it as a potential critical factor for future interventions in underserved, African American communities. <em>Ethn Dis. </em>2015; 25(4):405-412; doi:10.18865/ed.25.4.405</p>
Behind-Casing Cement Void Volumetric Evaluation
Authors: Hu Yike , Guo Weijun 
Published: November 2015

Abstract
During the completion of well drilling, cement is pumped into the annulus between the casing and formation to provide zonal isolation and a pressure barrier. The cement integrity inside the annulus is crucial for environmental and safety concerns. One aspect in the evaluation of cement integrity includes the determination of how much void exists inside the cement. This manuscript describes a sub-surface evaluation technique to estimate the cement void volume behind the casing using a gamma ray spectra indicator. The tool includes a radioactive gamma source, a gamma ray detector, and associated electronics. The target under investigation is a layered structure that consists of single or multiple layers of casing, cement in the annulus space, and the formation.
Monte Carlo N-Particle (MCNP) modeling, based on high energy photons transport, was conducted to simulate the energy spectrum deposited on the gamma ray detector. The various cement integrities were represented by a different void volume inside the cement. The detector responses change as the void volume within the cement changes. A spectra indicator was defined to describe the change of the spectra shape. The correspondence between the cement void volume and the spectra indicator, known as the quality curve, was generated through analysis of detector responses from a series of basic structures of known cement integrity, which were built through extensive computer modeling. When cement of unknown integrity is investigated, its spectra indicator can be computed from the recorded gamma ray detector spectra. The cement void volume behind the casing is determined by correlating the spectra indicator with the pre-generated quality curve.
A Novel Cementing Technique In Mid-deep Heavy Oil Reservoirs
Authors: Wang Lei , Liu Huiqing , Pang Zhanxi , Cen Xueqi , Xia Jing , Wen Liangfan , Wang Hao , Guan Yuting , Chen Yihe , Wang Jun 
Published: November 2015

Abstract
At present, thermal recovery is an important method for developing heavy oil reservoirs effectively. However, the leakage of cement slurry into the formation during cementing and steam leakage through cement in the annular space around a cemented casing during production have become a problem to be urgently solved in heavy oil reservoir thermal recovery production.
The solutions to these problems are usage of two-stage cement slurry system and the dynamic vibration cementing. The well section from 100 metres above the top of oil layer to the wellhead is cemented by a novel foam cement slurry system, and the rest of the barefoot interval is cementedby the good thermal-stability cement slurry system by using the dynamic vibration cementing technique. The objective of usage of two-stagecement slurry system is to reduceannulus fluid column pressure, and the objective of the dynamic vibration cementing is to achieve a stable hydraulic seal.
The consequences of the pressure reduction in the cement columnare evident. Not only the difficulty of leakage in cementing is settled by applying the low-density foam cement slurry, of which the density is 1.40 g/cm3, but also the heat loss of wellbore is decreased because of reduction of thermal conductivity. The performance of thermal-stability hardened cement paste before and aftersteam vapor curing was compared by lab experiments. The result shows that the compression strength, tensile strength and shear stress of hardened cement paste and of hardened cement pastehad little change. SEM photographs indicate that the microstructure of hardening cement after vibration action is more compact.
These results had been validated on site test. Through the comparison and analysis of cementing quality of two wells in the same block, it has proved that the well with this novel cementing technique is better quality than the other one. The CBL/VDL test report revealed that acoustic amplitude value of the well is less than 10%. The formation wave of the well is clearer than the other and casing wave is weaker.
Through usage of two-stagecement slurry system, not only the difficulty of leak formation in cementing is settled, but also the wellbore heat loss have come down significantly during the course of thermodynamic oil exploitation. And the dynamic vibration cementing can achieve a good thermal-stability hydraulic seal in the annulus space.
Factors Contributing to SAGD Start-Up Performance
Authors: Kaiser T. M. , Taubner S. P. 
Published: November 2015

Abstract
SAGD start-up has considerations for both well integrity and warm-up efficiency. Interest in using insulated tubing to address issues related to both considerations is evolving. The scope of this work is to demonstrate how start-up performance is affected by the use of tubing insulation, both in terms of well integrity and reservoir warming efficiency. Both of these considerations are sensitive to operational and reservoir factors that are specific to the implementation. The basis for using insulated tubing for start-up insulation should therefore take those factors into consideration.
This paper demonstrates the use of wellbore thermo-hydraulics modelling to determine the sensitivity of primary metrics of well integrity and SAGD start-up efficiency to the configuration of tubing, insulation, reservoir injectivity, and various thermal characteristics of casing, cement and formations. The wellbore thermo-hydraulics model includes heat transfer across tubing and casing, between fluid conduits and into the formation. Furthermore, it incorporates a convective heat transfer model to take into account fluid injection association with partial or full "bull-heading" into the reservoir. Boundary conditions allow injection rates to be ramped up consistent with field operations, and and the model calculates the pressure ramp-up associated with the transient mass flow rate applied to the well.
The results include a comprehensive description of the transient temperature in the casing, corresponding to the applied mass injection transient. This information can be used for well integrity interpretations, and start-up rates can be evaluated to manage the risk associated with start-up. Furthermore, the injection temperature and steam quality distribution in the tubing strings and tubing/liner annulus can be determined over the start-up period and during the circulation phase as a basis for determining circulation duration required to reach conditions for SAGD start-up. Temperature distributions in the reservoir can also be determined at prescribed distances from the wellbore.
Slotted Liner Design Optimization for Sand Control in SAGD Wells
Authors: Xie Jueren 
Published: November 2015

Abstract
To recover heavy oil and bitumen from the highly unconsolidated reservoirs of the Western Canada oilsands fields using the horizontal well method, and in particular the thermal in situ method of Steam Assisted Gravity Drainage (SAGD), some forms of sand control, such as slotted liners and wire-wrapped screens (WWS), are generally required to limit sand production and maintain well productivity. Over the past two decades, a number experimental and analytical studies have been performed for developing industry guidelines and best practices for the structural and hydraulic design and evaluation of sand control liners under the challenging conditions of SAGD steam injection and production wells. The vast majority of SAGD applications, estimated at about 90% (RPS 2009), employ slotted liners as the sand control method. Design efforts to address the structural and serviceability requirements, however, often oppose one other, presenting significant challenges to the design of slotted liners. For example, in order to maintain sufficient torque, collapse and strain-absorbing capacities, traditional slotted liners are often designed to have low Open Flow Areas (OFA) around 1%, although a larger OFA is desired for production efficiency.
This paper reviews current design requirements for SAGD wells, as well as puts forward a new slotted liner design consideration for the optimized performance under installation and operational loads. Using Finite Element Analysis (FEA) modeling, the effect of key design parameters, such as slot length and slot pattern, are studied. This paper focuses on the feasibility study of achieving higher OFA than the currently-used limit, while maintaining sufficient torque, collapse and strain-absorbing capacities under thermal well load conditions.
Integrity Assessment of Thermal Horizontal Well Liners Using Torque and Drag
Authors: Scot Buell R. 
Published: November 2015

Abstract
Time-lapse, cased hole torque and drag (T&D) measurements and soft string T&D modeling were undertaken in two experimental horizontal steam injection wells for the purpose of assessing the integrity of the slotted liner completions over a 20 month period. A series of progressively complex completions were installed in the wells to manage steam conformance and measure steam injection flow profiles in this mobile, heavy oil application. This T&D work was done to understand if sand influx, scale and asphaltene deposition, or thermal strain damage was occurring within the slotted liner thus increasing the deployment and recovery risk of the tubing-deployed completions. For each injector, T&D measurements were repeatedly obtained at the same depths during each workover with the same 3-1/2 inch (89 mm) tubing string.
T&D data is inexpensive and easy to acquire during rig operations. Commercial software is readily available to model T&D and estimate cased hole friction factors (CHFF). Analysis of T&D in these wells did provide insights for sand influx and scale deposition. However, T&D analysis did not provide insights into all integrity problems encountered which included metal clamp debris that would not allow packers to be landed at the target depth and corrosion failures resulting in parted tubing. T&D measurement analysis is a useful integrity diagnostic in horizontal injectors, but needs to be supplemented with other information to get a complete picture of wellbore conditions. Considering the general lack of information that heavy oil operators get from the horizontal section of their wells, it is recommended that baseline cased hole T&D measurements be acquired on horizontal wells during initial completion with 0.1 Kip precision. Comparing both T&D measurements and CHFF's on subsequent workovers did provide insights on the stability of horizontal wellbore conditions.