bluuebunny/crossref_metadata_2025_split huggingface dataset:
MedPServer: A database for identification of therapeutic targets and novel leads pertaining to natural products
Authors: Potshangbam Angamba Meetei , Polavarapu Raja , Rathore Ravindranath Singh , Naresh Damuka , Prabhu Nagu Prakash , Potshangbam Nongdam , Kumar Pravind , Vindal Vaibhav 
Published: November 2018

AbstractNatural products have been the source of treatment for various human diseases from time immemorial. Interests in natural product‐based scaffolds for the discovery of modern drugs have grown in recent years. However, research on exploring the traditional medicinal systems for modern therapeutics is severely limited due to our incomplete understanding of the therapeutic mechanism of action. One possible solution is to develop computational approaches, based on ligand‐ and structure‐based screening tools, for fast and plausible target identification, leading to elucidation of the therapeutic mechanism. In the present work, we present two methods based on shape‐based and pharmacophore search to predict targets of natural products and elucidate their mechanism, and to identify natural product‐based leads. These methods were tested on an in‐house developed database of medicinal plants that include information from a largely unexplored North‐East region of India, known as one of the twelve mega biodiversity regions. However, depending on the choice of the lead molecules, any existing databases can be used for screening. MedPServer is an open access resource available at http://bif.uohyd.ac.in/medserver/.
Preliminary application of micro‐SPECT/CT imaging by 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met for non‐small‐cell lung cancer
Authors: Zhang Yiqiu , Meng Lanfang , Li Beilei , Tan Hui , Lin Qing‐Yu , Cheng Dengfeng , Shi Hongcheng 
Published: November 2018

AbstractObjectiveA novel 99mTc‐tricine‐EDDA‐Hynic‐c‐Met molecular probe was synthetized, and nude mice models of human non‐small‐cell lung cancer (NSCLC) were established in order to preliminarily investigate that whether the molecular probe can be used to screen c‐Met inhibitor for targeted drug therapy in NSCLC.MethodsWith Hynic as the chelating agent, 99mTcO4‐labeled c‐Met receptor was used to synthetize 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met. Two nude mice successfully transplanted with H1993 tumor and two nude mice transplanted with H292 tumor were injected with 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met through the tail vein. After 2 and 4 hr, micro‐SPECT/CT imaging was performed.Resultsmicro‐SPECT/CT imaging of nude mice transplanted with H1993 and H292 tumors using 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met showed that uptake of 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met was high in H1993 tumor, while it was mild in H292 tumor both at 2 and 4 hr postinjection. Semiquantitative analysis of the ratio of radioactivity intensity at tumor site to radioactivity intensity of adjacent muscles (T/N value) showed that the average T/N value of H1993 and H292 tumors at 2 hr was 3.90 and 2.85, while it was 4.88 and 2.36 at 4 hr.Conclusionmicro‐SPECT/CT imaging through 99mTc‐tricine‐EDDA‐HYNIC‐c‐Met can be used to screen c‐Met indicators of NSCLC in H1993 nude mice models for targeted drug therapy.
The peripheral immune response after stroke—A double edge sword for blood‐brain barrier integrity
Authors: Li Yan , Zhu Zi‐Yu , Huang Ting‐Ting , Zhou Yu‐Xi , Wang Xin , Yang Li‐Qun , Chen Zeng‐Ai , Yu Wei‐Feng , Li Pei‐Ying 
Published: November 2018

SummaryThe blood‐brain barrier (BBB) is a highly regulated interface that separates the peripheral circulation and the brain. It plays a vital role in regulating the trafficking of solutes, fluid, and cells at the blood‐brain interface and maintaining the homeostasis of brain microenvironment for normal neuronal activity. Growing evidence has led to the realization that ischemic stroke elicits profound immune responses in the circulation and the activation of multiple subsets of immune cells, which in turn affect both the early disruption and the later repair of the BBB after stroke. Distinct phenotypes or subsets of peripheral immune cells along with diverse intracellular mechanisms contribute to the dynamic changes of BBB integrity after stroke. This review focuses on the interaction between the peripheral immune cells and the BBB after ischemic stroke. Understanding their reciprocal interaction may generate new directions for stroke research and may also drive the innovation of easy accessible immune modulatory treatment strategies targeting BBB in the pursuit of better stroke recovery.
Effects of Common CYP1A2 Genotypes and Other Key Factors on Intraindividual Variation in the Caffeine Metabolic Ratio: An Exploratory Analysis
Authors: Tian Dan‐Dan , Natesan Senthil , White John R. , Paine Mary F. 
Published: November 2018

The caffeine metabolic ratio is an established marker for cytochrome P450 (CYP) 1A2 activity. Optimal sample size calculation for clinical pharmacokinetic xenobiotic–caffeine interaction studies requires robust estimates of interindividual and intraindividual variation in this ratio. Compared with interindividual variation, factors contributing to intraindividual variation are less defined. An exploratory analysis involving healthy nonsmoking non‐naïve caffeine drinkers (1–3 cups/day; 12 men, 12 women) administered caffeine (160 mg) on five occasions evaluated the effects of CYP1A2 induction status (based on genotype) and other factors on intraindividual variation in CYP1A2 activity. Results were compared with those from previous studies. Regardless of whether a hyperinducer (CYP1A2*1A/*1F or CYP1A2*1F/*1F) or normal metabolizer (CYP1A2*1A/*1A, CYP1A2*1C/*1F, or CYP1A2*1C*1F/*1C*1F), sex, age, oral contraceptive use by women, and smoking status, intraindividual variation was ≤30%. A value of 30% is proposed for optimal design of pharmacokinetic xenobiotic–caffeine interaction studies. Prospective studies are needed for confirmation.
Long‐term regular dental attendance and tooth retention among British adults: A cross‐sectional analysis of national survey data
Authors: Talakey Arwa Ameen , Bernabé Eduardo 
Published: November 2018

AbstractObjectiveTo explore the association between long‐term pattern of dental attendance and tooth retention among British adults.MethodsThis study analysed data from 2970 dentate adults who participated in the Adult Dental Health Survey. Data were collected through home interviews and clinical examinations. Individuals were categorized into four trajectories according to their responses to three questions on dental attendance over their life span. The four trajectories were always, current, former and never regular attenders. Tooth retention was measured as the number of natural teeth retained and having a functional dentition (20 or more teeth). Associations were examined in regression models adjusted for demographic (sex, age and country of residence), socioeconomic (education, equivalized household income and social class) and clinical factors (untreated caries and periodontal disease).ResultsNever and former regular attenders had fewer teeth retained (rate ratios with 95% confidence interval: 0.93 [0.89‐0.97] and 0.97 [0.96‐0.99], respectively) and lower odds of having functional dentition (odds ratios with 95% CI: 0.36 [0.22‐0.60] and 0.53 [0.34‐0.83], respectively) than always regular attenders after adjusting for demographic, socioeconomic and clinical characteristics. However, no differences in number of teeth retained or having a functional dentition were found between always and current regular attenders.ConclusionLong‐term regular dental attendance was associated with greater tooth retention. Never and former regular attenders had fewer teeth retained than always regular attenders. No difference in tooth retention was found between always and current regular attenders.
Thermal and crystallization behavior of SiO2‐PbF2 glass system in the presence of ErF3 and Al2O3
Authors: Torab Ahmadi Pooya , Eftekhari Yekta Bijan , Mohammadi Hesameddin , Golestani‐Fard Farhad 
Published: November 2018

AbstractOxyfluoride glass‐ceramics have been introduced as one of the best bulk hosts for upconversion process of rare‐earth ions. However, less attention to the technological topics in the process of glass crystallization has hindered the development of them in industrial scale applications. In this research, SiO2–PbF2 glasses were investigated to clarify the ambiguous role of rare‐earth ions and alumina content in the microstructure and crystallization behavior. Results indicated that Er3+ addition caused a liquid‐liquid phase separation via nucleation and growth mechanism, which led to single phase crystallization of β‐PbF2:Er3+ solid solution. Moreover, Er3+ had a significant effect on the crystallite size, size distribution, and PbF2 crystallization temperature. On the other hand, increasing Al2O3 content enhanced the transparency and thermal stability of glass samples, whereas it reduced the amount of fluorine loss and increased the dissolution of Er3+ in fluoride crystalline structure. These results address some of the most controversial issues about crystallization behavior of rare‐earth‐doped oxyfluoride glasses.
Dynein axonemal intermediate chain 2 plays a role in gametogenesis by activation of Stat3
Authors: Yang Zhaojuan , Xu Bo , Hu Xiaopeng , Yao Xiaoying , Tang Yunhui , Qian Cuifeng , Wang Shuzeng , Chen Haifeng , Bai Xiaohui , Wu Ji 
Published: November 2018

AbstractWe previously identified the mouse dynein axonemal intermediate chain 2 (Dnaic2) gene. This gene expresses a component of the axonemal dynein complex that functions in cilia or flagella. We found that overexpression of Dnaic2 results in female subfertility and male infertility. In this study, we generated Dnaic2 knockdown (KD) mice and identified the potential regulatory mechanisms involved in Dnaic2 function. For phenotype analysis, we found that body weight was lighter and size was smaller in Dnaic2 KD mice than in wild‐type mice. A total of 45% of these Dnaic2 KD mice were infertile due to sperm abnormalities in males, or had oocyte abnormalities and pathological changes in the tunica mucosa in the oviduct of females. Moreover, Dnaic2 overexpression enhanced the expression of proliferating cell nuclear antigen (PCNA) in the ovaries, which suggested that Dnaic2 stimulated proliferation of cells in the ovaries. However, PCNA expression in the testis of Dnaic2‐overexpressed mice was lower than that in controls. Additionally, the ratio of Bax/B‐cell lymphoma‐2(Bcl‐2) in the testis of Dnaic2‐overexpressed mice was higher than that in controls, which suggested that Dnaic2 inhibited cellular proliferation in the testis. To examine the molecular action of Dnaic2, immunoprecipitation analysis was used and showed that Dnaic2 protein interacted with signal transducer and activator of transcription 3 (Stat3). Molecular modelling analysis showed that Dnaic2 bound with the linker and SH2 domains of Stat3. Furthermore, overexpression of Dnaic2 promoted phosphorylation of Stat3. In conclusion, our study suggests that Dnaic2 plays a role in oogenesis and spermatogenesis by activation of Stat3.
High health care costs among adults with intellectual and developmental disabilities: a population‐based study
Authors: Lunsky Y. , De Oliveira C. , Wilton A. , Wodchis W. 
Published: November 2018

AbstractObjectiveWhile it is generally accepted that adults with intellectual and developmental disabilities (IDDs) use health services to a greater extent than the general population, there is remarkably little research that focuses on the costs associated with their health care. Using population‐based data from adults with IDD in Ontario, this study aimed to estimate overall health care costs, classify individuals into high and non‐high cost categories and describe differences in the demographics, clinical profiles and health care use patterns between these groups.DesignA retrospective cohort study based in Ontario, Canada, was conducted with the use of linked administrative health data.MethodsA costing algorithm developed for the general population in Ontario was applied to estimate health care costs of adults with IDD under age 65 for 2009 and 2010. Individuals were categorised into two groups according to whether their total annual health care costs were among the highest decile in the general population. These groups were compared on demographic and clinical variables, and relative mean costs for six types of health care services in the two groups were computed. In addition, we computed the proportion of individuals who remained in the high cost group over 2 years.ResultsAmong adults with IDD, 36% had annual health care expenditures greater than $2610 CAD (top decile of all Ontario adults under 65). These individuals were more likely to be female, to be in the oldest age groups, to live in group homes and to be receiving disability income support than individuals whose expenditures were below the high cost threshold. In addition, they had higher rates of all the physical and mental health conditions studied. Greatest health care expenses were due to hospitalisations, especially psychiatric hospitalisations, continuing care/rehabilitation costs and medication costs. The majority of individuals whose health care costs placed them in the high cost category in 2009 remained in that category a year later.DiscussionAdults with IDD are nearly 4 times as likely to incur high annual health care costs than those without IDD. Individuals with IDD and high health care costs have unique health and demographic profiles compared with adults with IDD whose annual health care costs are below the high cost threshold. Attending to their health care needs earlier in their health care trajectory may be an opportunity to improve health and reduce overall health care costs. It is important that we explore how to best meet their needs. Models proposed to meet the needs of adults with high health care costs in the general population may not apply to this unique group.
Muscle tenderness score in temporomandibular disorders patients: A case‐control study
Authors: Almoznino Galit , Zini Avraham , Zakuto Avraham , Zlutzky Hulio , Bekker Stav , Shay Boaz , Haviv Yaron , Sharav Yair , Benoliel Rafael 
Published: November 2018

SummaryBackgroundThe total tenderness score (TTS) is commonly used in headache practice and contributes valuable information.ObjectiveTo assess muscle tenderness scores in patients diagnosed with Temporomandibular disorders (TMD) and analyse their associations with various demographic and clinical parameters.MethodsMasticatory (MTS), cervical (CTS) and TTSs were analysed in this case‐control study among 192 TMD patients and 99 controls. The study included a questionnaire and a clinical examination following RDC/TMD guidelines. Data were analysed using: Pearson's chi‐square, analysis of variance, t test and Bonferroni post hoc. To examine the factors associated with MTS score in a multivariate manner, a conceptual hierarchical multiple regression model was adopted.ResultsMasticatory and TTS differed between TMD sub‐groups and controls. Muscle tenderness was positively associated with: female sex, whiplash history, parafunction, co‐morbid pains such as headaches and body pain, pain intensity, onset, frequency and duration. In the conceptual hierarchical multiple regression model, pain onset, frequency and duration, co‐morbid pains were mediators in the relationship between TMD diagnosis and MTS.ConclusionMuscle tenderness scores were positively associated with TMD disease characteristics and co‐morbid pain conditions, which may reflect associations with disease severity. MTS differed between TMD populations and may be used in routine patient workup, to assess MMD severity and changes over time as well as treatments response and as a research tool. MTS can be used as a common methodology to describe both headaches and masticatory muscle disorders and to facilitate interprofessional research and crosstalk between a headache and oro‐facial pain practitioners.
How mandatory is the mandatory reporting of children at risk?
Authors: Isaacs David , Britton Philip N , Kilham Henry A , Bag Shopna , Marks Susan 
Published: November 2018

AbstractAlthough mandatory reporting of suspected child abuse was first introduced over 50 years ago, there are no quantitative studies addressing whether or not it achieves better outcomes for children. We report two cases of maternal infection, one with tuberculosis (TB) and one with human immunodeficiency virus (HIV), where the mothers' failure to attend follow‐up appointments raised the possibility of significant harm if their infants were infected. Some health professionals argued strongly that mandatory reporting meant the mothers should be reported to child protection authorities. Others argued that the risk was not critically imminent and an immediate report could seriously compromise maternal confidentiality, risked maternal disengagement and a worse outcome. An alternative was to make more vigorous efforts to contact the mothers and report only if these failed. In the TB case, reporting to child protection was deferred in favour of making more strenuous efforts at communication, which proved successful. In the HIV case, a case worker reported the case to child protection, but when the doctor contacted child protection authorities they agreed not to contact the mother unless the doctor's vigorous attempts to communicate with her failed. We do not advocate for breaking the law regarding mandatory reporting, but we do argue for a considered approach to the timing of reporting and for a collaborative approach with child protection services.
Energy Consumption and Total Vehicle Efficiency Calculation Procedure for Electric Vehicles (EV, HEV and PHEV)
Authors: Alcázar-García Désirée , Romeral Martínez Luis 
Published: November 2018

An important question regarding vehicles design optimization and environmental care are energy management strategy and efficiency determination.
Automotive brands work with a wide range of technologies and electrified mobility is considered to be one of the solutions to the growing environmental question. The present paper develops a mathematical model to predict the light-duty electric vehicle overall consumed energy depending on architecture and configuration of vehicles with different degrees of electrification (e.g. electric vehicle and hybrid electric vehicle), on the type of electric motor (e.g. hybrid synchronous electric motor, permanent magnet motor or induction motor) and engine (e.g. gasoline (Otto or Atkinson) or Diesel), on technology of energy-storage system (e.g. lithium-ion or nickel-metal hydride battery) and on weight and geometry of the car being flexible drive cycles and for all types of wheel drive (four wheel, front and rear). The method is verified making a component-to-component revision through real automobiles that are available in the market to demonstrate the validity of the system.
A Vibration Damping Analysis Method of Turbine Blade Shroud Dampers Based on a Given Eigen-Mode
Authors: Jiazhe Zhao , Yanrong Wang , Yanbin Luo , Xiaojie Zhang 
Published: November 2018

High cycle fatigue damage caused by resonance and forced vibration can significantly affect the life and reliability of turbine rotor blades in aero-engines. The friction damper has been widely used to reduce the resonant stress of blades, on which the turbine blade shroud dampers are highly used.
In order to solve the problems of vibration damping analysis and design of shrouded blades dampers, an analytical method without complex and time-consuming nonlinear vibration response has been proposed based on a given eigen-mode in this paper. For the serrated shrouded damper, two typical friction models, namely macro-slip model, and micro-slip model, have been introduced. Additionally, a complete set of damping analysis method has been introduced by the energy method, based on the vibration dynamics principle and eigen-mode analyzed by finite element method. Combined with the analysis of the natural vibration characteristics of the shrouded turbine blade, the law of the damping ratio with the relevant design parameters, such as the vibration stress, the pre-twist angle, the friction coefficient and the nodal diameter, was obtained through a calculation example. The method can also provide an important reference for the parameterized design of dampers.
Improvement of the Balancing Accuracy in Gravity Compensators Based on the Inverted Slider Crank Mechanism
Authors: Arakelyan Vigen , Zhang Yang 
Published: November 2018

The static balancing of mechanical systems is an important issue because it allows significant reduction of torques. However the literature review shows that in many cases the gravity balancing of mechanical systems is carried out by neglecting the masses of auxiliary links associated to the principal mechanism. For many balancing schemes it is the source of errors.
This paper deals with an improved solution for gravity compensators based on the inverted slider crank mechanism considering the masses of the rocker and the spring. For this purpose, the torques due to auxiliary links are determined. Then, they are introduced into the balancing equation for minimization of the residual unbalance. In this way, a more accurate balancing of gravity compensators is achieved. The efficiency of the suggested approach is illustrated by numerical simulations.
Coupled Multi-Material and Joint Topology Optimization: A Proof of Concept
Authors: Florea Vlad , Shah Vishrut , Roper Stephen , Vierhout Garrett , Kim Il Yong 
Published: November 2018

Over the past decade there has been an increasing demand for light-weight components for the automotive and aerospace industries. This has led to significant advancement in Topology Optimization methods, especially in developing new algorithms which can consider multi-material design. While Multi-Material Topology Optimization (MMTO) can be used to determine the optimum material layout and choice for a given engineering design problem, it fails to consider practical manufacturing constraints. One such constraint is the practical joining of multi-component designs.
In this paper, a new method will be proposed for simultaneously performing MMTO and Joint Topology Optimization (JTO). This algorithm will use a serial approach to loop through the MMTO and JTO phases to obtain a truly optimum design which considers both aspects.
A case study is performed on an automotive ladder frame chassis component as a proof of concept for the proposed approach. Two loops of the proposed process resulted in a reduction of components and in the number of joints used between them. This translates into a tangible improvement in the manufacturability of the MMTO design.
Ultimately, being able to consider additional manufacturing constraints in the Topology Optimization process can greatly benefit research and development efforts. A better design is reached with fewer iterations, thus driving down engineering costs. Topology Optimization can help in determining a cost effective and efficient design which address existing structural design challenges.