bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the Readmission of Heart Failure Patients through Data Analytics
Authors: Sohrabi Babak , Vanani Iman Raeesi , Gooyavar Amirsahand , Naderi Nasim
Published: January 2019

Reducing the costs and improving the quality of treatment in hospital systems as well as demands for better treatment from patients in order to keep them away from readmissions are two main issues healthcare systems have faced. In order to solve such challenges, predicting the occurrence of re-hospitalisation with data mining techniques would be so worthwhile. In this study, we are seeking to predict the occurrence of re-hospitalisation of the heart failure patients in two time-horizons (1-month and 3-month) via deployment of classification algorithms (i.e. decision trees, artificial neural networks, support vector machines and logistic regression). Two criterions (as main criterions) such as AUC (area under curve) and ACC (accuracy) have been calculated and assessed for classifying the prediction-power of the models in each time-horizon (outcome/target). We also have calculated some other criterions such as recall, precision and F1-Score. Then, we identified the importance and contribution of the variables for each outcome. Therefore, the variables whose contribution/importance changes over time are differentiated. It is noteworthy to say that this study is done under the scrutiny of an expert cardiologist. Trained nurses and expert cardiologist monitored the dataset every day, which was a hard and valuable measure to conduct. Finally, the dataset does not have missing values and noises. This research can be the basis for prospective medical studies and projects.
Developing a Robot-Guided Interactive Simon Game for Physical and Cognitive Training
Authors: Turp Mısra , González José Carlos , Pulido José Carlos , Fernández Fernando
Published: January 2019

Enveloping cognitive or physical rehabilitation into a game highly increases the patients’ commitment with their treatment. Specially with children, keeping them motivated is a very time-consuming work, so therapists are demanding tools to help them with this task. NAOTherapist is a generic robotic architecture that uses Automated Planning techniques to autonomously drive noncontact upper-limb rehabilitation sessions for children with a humanoid NAO robot. Our aim is to develop more robotic games for this platform to enrich its variability and possibilities of interaction. The goal of this work is to present our first attempt to develop a different, more complex game that reuses the previous architecture. We contribute with the design description of a novel robotic Simon game that employs upper-limb poses instead of colors and could qualify as a cognitive and physical training. Statistics of evaluation tests with 14 adults and 56 children are displayed and the outcomes are analyzed in terms of human–robot interaction (HRI) quality. The results demonstrate the application-domain generalization capabilities of the NAOTherapist architecture and give an insight to further analyze the therapeutic benefits of the new developed Simon game.
Adoption of Hospital Information Systems in Public Hospitals in Turkey: An Analysis with the Unified Theory of Acceptance and Use of Technology Model
Authors: Engin Melih , Gürses Fatih
Published: January 2019

Information and communication technologies (ICTs) has become a tool which cannot be ignored in terms of public administrations, which provides advantage to the administrations as far as they can be adapted. The use of ICTs become widespread in the health sector as it is in all other sectors. In hospitals, hospital information systems (HIS) are used to keep records of patients and hospitals securely, to improve appointment, in-hospital management, decision support and workflow processes. Therefore, HISs are also used to increase efficiency and productivity, to reduce error rates, to increase service quality, to reduce service costs and to realize the specific purposes such as ensuring patient satisfaction. It is necessary that the end users should adopt HISs to obtain the expected benefits and to implement HIS successfully in public hospitals. The adoption of a technology product is also a sociological phenomenon at the same time. In this regard, the issue of adoption in the relevant literature is addressed in the context of a wide variety of models and many variables. This study is also a study of technology adoption. The subject of the study is the adoption of HISs in public hospitals in Turkey. In this context. The study aimed to determine the factors affecting the adoption of HISs by the personnel working in public hospitals in Turkey, in accordance with the Unified Theory of Acceptance and Use of Technology (UTAUT) model in the literature on technology adoption. In the study, the universe of the study consisted of the personnels (physicians, nurses, health officers, medical secretaries] which were working in public hospitals in the Bursa and Balıkesir Metropolitan Municipalities at the time of the study. According to the results of the study, performance expectancy, effort expectancy and social influence variables have positive and significant effects on the behavioral intention of hospital staff for using of HISs. In addition, facilitating conditions and behavioral intention variables have a positive and significant effect on usage behavior. On the other hand, it was found that gender has a moderator effect on the relationship between performance expectancy, effort expectancy and behavioral intention. Experience has a moderator effect on the relationship between the social influence and the behavioral intention while age has a moderator effect on the relationship between facilitating conditions and use behavior.
Is a topology change after a Big Rip possible?
Authors: Oikonomou V. K.
Published: January 2019

Motivated by condensed matter physical systems, in which a finite-time singularity indicates that the topology of the system changes, we critically examine the possibility of the Universe’s topology change at a finite-time cosmological singularity. We emphasize on Big Rip and Type II and IV cosmological singularities, which we classify to future spacelike and timelike singularities. For the Type IV and Type II singularities, since no geodesics incompleteness occurs, no topological change is allowed, by using Geroch’s theorem arguments. However, for the Big Rip case, Tipler’s arguments allow a topology change, if the spacetime in which the topology change occurs is non-compact and the boundary of this region are two topologically distinct three-dimensional spacelike partial Cauchy hypersurfaces. Also, some additional requirements must hold true, among which the weak energy condition, which can be satisfied in a geometric way in the context of a modified gravity. We critically examine Tipler’s arguments for the Big Rip case, and we discuss the mathematical implications of such a topological change, with regard to the final hypersurface on which geodesics incompleteness occurs.
Recurrence relations for polynomials obtained by arithmetic functions
Authors: Heim Bernhard , Luca Florian , Neuhauser Markus
Published: January 2019

Families of polynomials associated to arithmetic functions [Formula: see text] are studied. The case [Formula: see text], the divisor sum, dictates the non-vanishing of the Fourier coefficients of powers of the Dedekind eta function. The polynomials [Formula: see text] are defined by [Formula: see text]-term recurrence relations. For the case that [Formula: see text] is a polynomial of degree [Formula: see text], we prove that at most a [Formula: see text] term recurrence relation is needed. For the special case [Formula: see text], we obtain explicit formulas and results.
Areca Plant Extracts as a Green Corrosion Inhibitor of Carbon Steel Metal in 3 M Hydrochloric Acid: Gasometric, Colorimetry and Atomic Absorption Spectroscopy Views
Authors: Raghavendra Narasimha
Published: January 2019

The corrosion inhibition of carbon steel (CS) in 3 M HCl was thoroughly investigated in the presence and absence of areca plant extracts as a green corrosion inhibitor. The effect of solution temperature and different amounts of areca plant extracts was examined through gasometric, colorimeter and atomic absorption spectroscopy techniques. Surface studies were screened by scanning electron microscopy (SEM) technique. The results of these techniques show that areca plant extracts (arecanut husk extract, arecanut seed extract and areca flower extract) behave as a nontoxic corrosion inhibitor for CS in 3 M HCl solution. Areca plant extract (arecanut husk extract, arecanut seed extract and areca flower extracts) shows maximum protection efficiency at 4 g/L extract amount.
Superconducting Quantum Critical Phenomena
Authors: Tao Yong
Published: January 2019

When the superconducting transition temperature [Formula: see text] sufficiently approaches zero, quantum fluctuations are expected to be overwhelmingly amplified around zero temperature so that the mean-field approximation may break down. This implies that quantum critical phenomena may emerge in highly underdoped and overdoped regions, where the transition temperature [Formula: see text] is sufficiently low. By using Gor’kov’s Green function method, we propose a superconducting quantum critical equation (SQCE) for describing such critical phenomena. For two-dimensional (2D) overdoped materials, SQCE shows that the transition temperature [Formula: see text] and the zero-temperature superfluid phase stiffness [Formula: see text] will obey a two-class scaling combined by linear and parabolic parts, which agrees with the existing experimental investigation [I. Božović et al., Dependence of the critical temperature in overdoped copper oxides on superfluid density, Nature 536 (2016) 309–311]. For three-dimensional (3D) overdoped materials, SQCE predicts that the two-class scaling will be replaced by the linear scaling. Furthermore, we show that SQCE can be applied into highly underdoped region by using Anderson’s non-Fermi liquid model.
Law of Creation and Grand Unification Theory
Authors: Sha Zhi Gang , Xiu Rulin
Published: January 2019

The understanding about the creation of our universe is explored in many philosophies, natural sciences, religions, ideologies, traditions and many other disciplines. Currently, natural science cannot answer this question at the most fundamental level. In this work, based on the ancient Chinese Tao wisdom about creation, we propose the Law of Tao Yin–Yang Creation. This law states that everything is created from emptiness through yin–yang interaction. Yin and yang are the two basic elements that make up everything. Yin and yang are opposite, relative, co-created, inseparable and co-dependent. The Law of Tao Yin–Yang Creation gives us a deeper insight about space and time. We propose that space and time are two basic measurements we conduct. Time relates to the measurement of movement and change. Space relates to the measurement of stillness and solidity. Space and time are a yin–yang pair. Interaction of two fundamental yin–yang pairs, the space and time yin–yang pair and the inclusion and exclusion duality pair, create our universe. We demonstrate that from this insight, one can derive string theory, superstring or M-theory and the universal wave function interpretation of string theory. We suggest that the Law of Tao Yin–Yang Creation presents the exact process how “it from bit” and it could be the fundamental principle leading to the grand unification theory and the theory of everything.
Structural interpretation of gravity, topography and seismicity
Authors: Patton Regan L. , Watkinson A. John
Published: January 2019

Global geophysical observations constrain all theories of terrestrial dynamics. We jointly interpret EGM2008 gravity, RET2014 topography and the Global Centroid Moment Tensor database from a structural point of view. We hypothesize that lateral variations of gravity and topography reflect the scale-dependent competence of rocks. We compare the spectral and spatial characteristics of the observed fields with structural predictions from the mechanics of differential grade-2 (DG-2) materials. The results indicate that these viscoelastic materials are a powerful tool for exploring dynamic processes in the Earth. We demonstrate that the known spectral range of Earth's gravity and topography can be explained by the folding, shear banding, faulting and differentiation of the crust, lithosphere and mantle. We show that the low-amplitude long-wavelength bias apparent in the disturbance field can be explained by perturbations to Earth's overall ellipsoidal shape, induced by internal slab loading of the mantle. We find by examining the directional isotropy of the data that the zonal energy in Earth's gravity disturbance is maximized about an axis coincident with the shape-perturbation minimum. The symmetry of tectonic features about this axis, extending from eastern Borneo to Brazil, and its coincidence with the equator suggest the coupling of current plate motions to true polar wander.
LineUp
Authors: Yu Minjing , Ye Zipeng , Liu Yong-Jin , He Ying , Wang Charlie C. L.
Published: January 2019

In this article, we introduce a novel method that can generate a sequence of physical transformations between 3D models with different shape and topology. Feasible transformations are realized on a chain structure with connected components that are 3D printed. Collision-free motions are computed to transform between different configurations of the 3D printed chain structure. To realize the transformation between different 3D models, we first voxelize these input models into a similar number of voxels. The challenging part of our approach is to generate a simple path—as a chain configuration to connect most voxels. A layer-based algorithm is developed with theoretical guarantee of the existence and the path length. We find that collision-free motion sequence can always be generated when using a straight line as the intermediate configuration of transformation. The effectiveness of our method is demonstrated by both the simulation and the experimental tests taken on 3D printed chains.
Knittable Stitch Meshes
Authors: Wu Kui , Swan Hannah , Yuksel Cem
Published: January 2019

We introduce
knittable stitch meshes
for modeling complex 3D knit structures that can be fabricated via knitting. We extend the concept of stitch mesh modeling, which provides a powerful 3D design interface for knit structures but lacks the ability to produce actually knittable models. Knittable stitch meshes ensure that the final model can be knitted. Moreover, they include novel representations for handling important shaping techniques that allow modeling more complex knit structures than prior methods. In particular, we introduce
shift paths
that connect the yarn for neighboring rows, general solutions for properly connecting pieces of knit fabric with mismatched knitting directions without introducing seams, and a new structure for representing
short rows
, a shaping technique for knitting that is crucial for creating various 3D forms, within the stitch mesh modeling framework. Our new 3D modeling interface allows for designing knittable structures with complex surface shapes and topologies, and our knittable stitch mesh structure contains all information needed for fabricating these shapes via knitting. Furthermore, we present a scheduling algorithm for providing step-by-step hand knitting instructions to a knitter, so that anyone who knows how to knit can reproduce the complex models that can be designed using our approach. We show a variety of 3D knit shapes and garment examples designed and knitted using our system.
Achieving Business Process Improvement via Ubiquitous Decision-Aware Business Processes
Authors: Yousfi Alaaeddine , Batoulis Kimon , Weske Mathias
Published: January 2019

Business process improvement is an endless challenge for many organizations. As long as there is a process, it must be improved. Nowadays, improvement initiatives are driven by professionals. This is no longer practical because people cannot perceive the enormous data of current business environments. Here, we introduce ubiquitous decision-aware business processes. They pervade the physical space, analyze the ever-changing environments, and make decisions accordingly. We explain how they can be built and used for improvement. Our approach can be a valuable improvement option to alleviate the workload of participants by helping focus on the crucial rather than the menial tasks.
The Moment of Truth: A Review, Synthesis, and Research Agenda for the Customer Service Experience
Authors: Groth Markus , Wu Yu , Nguyen Helena , Johnson Anya
Published: January 2019

Customer service is a central feature of the service context. As service research has evolved into a burgeoning multidisciplinary field, management scholars have developed an impressive body of research regarding the antecedents, processes, and outcomes of customer service. We provide an integrative review and synthesis of the literature with a focus on three important and interrelated aspects of customer service that specifically focus on the interpersonal service interaction between employees and customers: ( a) affect in customer service, including emotional labor and emotional contagion processes; ( b) customer mistreatment, the low-quality interpersonal treatment of customers toward service employees; and ( c) customer service behaviors, including customer orientation and service-oriented citizenship behaviors. We review theoretical perspectives for each of these streams of research and summarize the current knowledge regarding empirical findings. We provide a critical assessment of the literature and conclude with a discussion of future research agendas and practical implications for service managers.
Team-Level Constructs
Authors: Chan David
Published: January 2019

Studies of team-level constructs can produce new insights when researchers explicitly take into account several critical conceptual and methodological issues. This article explicates the conceptual bases for multilevel research on team constructs and discusses specific issues relating to conceptual frameworks, measurement, and data analysis. To advance programmatic research involving team-level constructs, several future research directions concerning issues of substantive content (i.e., changes in the nature of work and teams, member-team fit, linking team-level constructs to higher-level constructs) and strategic approaches (i.e., the construct's theoretical roles, dimensionality and specificity, malleability and changes over time, relationships with Big Data) are proposed.
Diet Composition Differentially Affects Insulin Pathway Compromised and Control Flies
Authors: Otero-Moreno Deyannira , Murillo-Maldonado Juan Manuel , Riesgo-Escovar Juan R.
Published: January 2019

The insulin pathway is an anabolic pathway that controls, amongst other things, glucose homeostasis. It is an evolutionarily conserved pathway. Disruptions in insulin pathway functions can lead to diabetic states. Diabetes, a very common occurrence in modern life, afflicts a significant portion of the population of developed and developing countries worldwide. Yet, few studies have addressed the evolution of diabetic states on a long-term basis. Here, we cultured three different insulin pathway signaling compromised flies (heteroallelic mutant combinations, akin to diabetes mellitus type II) and wild type control flies, for the extent of one generation in different isocaloric diets fed at libitum, with or without extra methionine added. All fly stocks have a homogenized genetic background. We measured weight, total lipid, and carbohydrate content of adults at two different time points, and survival of adults reared in some of the different diets. Results show that, despite the fact that all diet regimes allow survival of at least a fraction of flies to adulthood, life histories are significantly different. Higher protein content diets promote better survival compared to higher percentage lipid and carbohydrate diets, and added methionine promotes survival in moderately reduced protein content diets. In mutants, survival is significantly reduced, and added methionine generally has an effect, albeit a more modest one. Our results highlight the value of higher percentage protein diets, and differences in effects in “healthy” versus “diabetic” states. They also show that added methionine, proposed as a “sensor” for protein content in food for flies, leads to differential effects depending on the adequacy of the diet regime.
Root Coverage for Single Deep Gingival Recessions: Outcomes Based on a Decision-Making Algorithm
Authors: César Neto João B. , Cavalcanti Marília C. , Sekiguchi Ricardo T. , Pannuti Claudio M. , Romito Giuseppe A. , Tatakis Dimitris N.
Published: January 2019

Aim. The aim of this study is to report root coverage outcomes in single deep gingival recessions (GR) following a proposed decision-making algorithm. Materials and Methods. A retrospective, practice-based study included single deep (≥5 mm) Miller Class II and III defects. The step-by-step decision-making algorithm led to a choice among three different flap designs (coronally advanced flap (CAF), double papilla envelope flap (DPE) or modified lateral sliding flap (LSF)) used with a connective tissue graft. Recession depth (RD) at 6 months follow-up and the corresponding root coverage (RC) were the primary outcomes assessed. Results. Sixteen GR defects were included, with baseline RD of 6.7 ± 1.8 mm. Six months postoperatively, RD was significantly reduced to 1.2 ± 0.8 mm (p<0.05). Mean RC was 81.7 ± 13.0%, without significant differences between Miller Class II (87.1 ± 9.2%; n=9) and Class III (74.6 ± 14.5%; n=7) GRs (p=0.07). Postoperatively, keratinized tissue width increase was greater for LSF (3.5 ± 1.1) and DPE (4.2 ± 1.4 mm) than for CAF (1.9 ± 0.9 mm). Conclusions. Following the proposed decision-making algorithm, root coverage outcomes for GR defects ≥5 mm were comparable to outcomes reported for shallow defects. Prospective clinical trials are needed to validate the proposed approach and techniques. Practical Implications. The proposed algorithm allows the clinician to select the appropriate surgical technique for treatment of single deep gingival recessions with good predictability.
Peroxynitrite and 4-Hydroxynonenal Inactivate Breast Cancer Resistance Protein/ABCG2
Authors: Verenich Svetlana , Gerk Phillip M.
Published: January 2019

Oxidative stress may arise from a variety of pathologies and results in the formation of toxic and reactive chemical species. Extensive research has been done to establish mechanisms of formation and cytotoxic effects of a number of different products of oxidation stress including peroxynitrite (PN) and 4-hydroxynonenal (4HNE). However, relatively few studies have investigated their effects on ATP-binding cassette (ABC) transporters. The objective of this investigation was to determine the effects of PN and 4HNE on BCRP/ABCG2. To eliminate the effect of metabolic enzymes, the experiments were carried out with inside-outSf9membrane vesicles overexpressing BCRP/ABCG2 using riboflavin as a substrate. The experiments revealed that PN produced IC50of about 31.2 ± 2.7μM, based upon initial concentrations. The IC50for 4HNE was estimated to be 92 ± 1.4μM. Preincubation of membrane vesicles with either PN or 4HNE caused the maximal rate of transport (Vmax) to drop drastically, up to 19 times, with no or much smaller effect onKm. Thus, PN and 4NE can inhibit BCRP transport activity.
Automatic Extraction of Two Regions of Creases from Palmprint Images for Biometric Identification
Authors: Yaacob Roszaharah , Ooi Chok Dong , Ibrahim Haidi , Nik Hassan Nik Fakhuruddin , Othman Puwira Jaya , Hadi Helmi
Published: January 2019

Palmprint has become one of the biometric modalities that can be used for personal identification. This modality contains critical identification features such as minutiae, ridges, wrinkles, and creases. In this research, feature from creases will be our focus. Feature from creases is a special salient feature of palmprint. It is worth noting that currently, the creases-based identification is still not common. In this research, we proposed a method to extract crease features from two regions. The first region of interest (ROI) is in the hypothenar region, whereas another ROI is in the interdigital region. To speed up the extraction, most of the processes involved are based on the processing of the image that has been a downsampled image by using a factor of 10. The method involved segmentations through thresholding, morphological operations, and the usage of the Hough line transform. Based on 101 palmprint input images, experimental results show that the proposed method successfully extracts the ROIs from both regions. The method has achieved an average sensitivity, specificity, and accuracy of 0.8159, 0.9975, and 0.9951, respectively.
Translation and Initial Validation of the Chinese Version of the Action Research Arm Test in People with Stroke
Authors: Zhao Jiang-Li , Chen Pei-Ming , Li Wen-Feng , Bian Rui-Hao , Ding Ming-Hui , Li Hai , Lin Qiang , Xu Zhi-Qin , Mao Yu-Rong , Huang Dong-Feng
Published: January 2019

Purpose. This study aimed to translate the English version of the Action Research Arm Test (ARAT) into Chinese and to evaluate the initial validation of the Chinese version (C-ARAT) in patients with a first stroke.Methods. An expert group translated the original ARAT from English into Chinese using a forward-backward procedure. Forty-four patients (36 men and 8 women) aged 22–80 years with a first stroke were enrolled in this study. The participants were evaluated using 3 stroke-specific outcome measures: C-ARAT, the upper extremity section of the Fugl–Meyer assessment (UE-FMA), and the Wolf Motor Function Test (WMFT). Internal consistency was analysed using Cronbach’sαcoefficients and item-scale correlations. Concurrent validity was determined using Spearman’s rank correlation coefficients. Floor and ceiling effects were considered to be present when more than 20% of patients fell outside the preliminarily set lower or upper boundary, respectively.Results. The C-ARAT items yielded excellent internal consistency, with a Cronbach’sαof 0.98 (p < 0.001) and item-total correlations ranging from 0.727 to 0.948 (p < 0.001). The C-ARAT exhibited good-to-excellent correlations with the UE-FMA and WMFT functional ability (WMFT-FA) scores, with respectiveρvalues of 0.824 and 0.852 (p < 0.001), and an excellent negative correlation with the WMFT performance time (WMFT-time), with aρvalue of -0.940 (p < 0.001). The C-ARAT subscales generally exhibited good-to-excellent correlations with stroke-specific assessments, withρvalues ranging from 0.773 to 0.927 (p < 0.001). However, the gross subscale exhibited moderate-to-good correlations with the UE-FMA and WMFT-FA scores, with respectiveρvalues of 0.665 and 0.720 (p < 0.001). No significant floor effect was observed, and a significant ceiling effect was observed only on the WMFT-time.Conclusions. The C-ARAT demonstrated excellent internal consistency and good-to-excellent concurrent validity. This test could be used to evaluate upper extremity function in stroke patients without cognitive impairment.
Preventive Effects of Evodiamine on Dexamethasone-Induced Osteoporosis in Zebrafish
Authors: Yin Heng , Wang Jianwei , Wu Mao , Ma Yong , Wang Shanfu , Su Qiuju
Published: January 2019

The aim of this study was to investigate the effect of evodiamine (EV) on dexamethasone-induced osteoporosis in zebrafish. Zebrafish larvae were exposed to different concentrations of dexamethasone to obtain the osteoporosis in zebrafish. Calcium, phosphorus, and alizarin red staining determination were performed to evaluate the effects of EV on bone mineralization. Alkaline phosphatase (ALP), hydroxyproline (HP), and tartrate resistant acid phosphatase (TRAP) were also measured by commercial kits. The expression of MMP3-OPN-MAPK pathway in zebrafish was measured by Western blot. RT-PCR was used to determine mRNA levels of MMP3, OPN, and MAPK. EV could significantly increase the content of calcium and phosphorus. The results of alizarin red staining showed that EV could significantly increase the calcium sink of horse fish, increasing the area of bone formation. EV could increase the content of hydroxyproline in zebrafish. EV also increased ALP and TRAP in zebrafish. Western blot and RT-PCR results showed that EV restored the MMP3-OPN-MAPK pathway in zebrafish. In conclusion, we found that EV can alleviate dexamethasone-induced osteoporosis in zebrafish. The mechanism is related to activating MMP3-OPN-MAPK pathway and then activating bone remodeling.
Concentrated Growth Factors as an Ingenious Biomaterial in Regeneration of Bony Defects after Periapical Surgery: A Report of Two Cases
Authors: Malli Sureshbabu Nivedhitha , Selvarasu Kathiravan , V Jayanth Kumar , Nandakumar Mahalakshmi , Selvam Deepak
Published: January 2019

The overall success of a periapical surgery is assessed in terms of regeneration of functional periradicular tissues. The regenerative potential of platelets has been well documented. This article describes the use of concentrated growth factors (CGF), a new family of autologous platelet concentrates, as a sole material for bone regeneration after periapical surgery. 32- and 35-year-old female patients diagnosed with Ellis Class IV, an open apex in 11 with apical periodontitis in 11 and 12 and previously root canal-treated 31 and 41 with a chronic apical abscess, respectively, were managed with endodontic surgery. Subsequent to apicectomy and retrograde filling, the CGF fibrin block and membrane were used before suturing. There was uneventful healing during the immediate post-op and the subsequent follow-up periods. CGF is produced by a differential centrifugation process that results in the formation of a denser fibrin matrix richer in growth factors than those observed in PRF. Reasonable osseous healing was seen as early as 6-month follow-up, thereby recommending the use of CGF as an alternative to bone grafts and membranes in extensive periapical lesions to enhance bone regeneration and to decrease the healing time.
Correlations between Repeated Use of Dry Sauna for 4 x 10 Minutes, Physiological Parameters, Anthropometric Features, and Body Composition in Young Sedentary and Overweight Men: Health Implications
Authors: Podstawski Robert , Borysławski Krzysztof , Clark Cain C. T. , Choszcz Dariusz , Finn Kevin J. , Gronek Piotr
Published: January 2019

Background. The effect of thermal stress on the physiological parameters of young overweight and sedentary men who sporadically use the sauna remains insufficiently investigated. Aim. The aim of the study was to determine the effect of sauna bathing on the physiological parameters of young overweight, physically inactive men and to test the correlations between physiological parameters versus anthropometric features and body composition parameters. Materials and Methods. Forty-five overweight and sedentary men aged 20.76±2.4 y were exposed to four sauna sessions of 10 minutes each (temperature: 90-91°C; relative humidity: 14-16 %) with four 5-minute cool-down breaks. Body composition was determined before sauna, and body mass and blood pressure were measured before and after sauna. Physiological parameters were monitored during four 10-minute sauna sessions. Results. A significant (p<0.0001) increase in all analyzed physiological parameters was observed during four successive 10-minute sauna sessions. Heart rate, energy expenditure, blood pressure, and body mass loss were most strongly correlated with anthropometric parameters (body mass, body mass index, and body surface area) and body composition parameters (percent body fat, body fat mass, and visceral fat level). The 60-minute treatment resulted in a significant reduction in body mass (0.65 kg). Conclusions. Repeated use of Finnish sauna induces significant changes in the physiological parameters of young sedentary overweight men, and these changes are intensified during successive treatments. Deleterious cardiovascular adaptations were most prevalent in men characterized by the highest degree of obesity and the largest body size.
Tapered Cuff versus Conventional Cuff for Ventilator-Associated Pneumonia in Ventilated Patients: A Meta-Analysis of Randomized Controlled Trials
Authors: Huang Wei Min , Huang Xu An , Du Yan Ping , Li Liu Xia , Wu Fang Fang , Hong Shao Qing , Tang Fang Xuan , Ye Zhang Qiang
Published: January 2019

Background. Microaspiration of secretions around the tracheal cuff is a multifactorial process. Tracheal cuff shape might take a major part in its occurrence. The rationale for producing a taper-shaped cuff is established on the assumption that compared to a conventional cuff with a single fixed diameter, a continuum of minimum-to-maximum diameter sections might better fit the tracheal walls. Objectives. The primary objective of this meta-analysis was to compare ventilator-associated pneumonia (VAP) between tapered-cuff intubation and conventional-cuff intubation. The secondary objective was to compare intensive care unit (ICU) mortality between tapered-cuff intubation and conventional-cuff intubation. Methods. We searched the Cochrane Library, Embase, MEDLINE database through the PubMed search engine, and CINAHL from inception to April 2018. Randomized trials comparing VAP and ICU mortality between tapered-cuff intubation and conventional-cuff intubation in intubated adults were included. Two review authors assessed study quality and abstracted databasing on prespecified criteria independently. Results. We pooled summary estimates from 5 trials evaluating tapered-cuff involving 774 participants. Compared to VAP, no statistically significant difference was observed between the tapered-cuff and conventional-cuff groups (OR 0.82, CI 0.61–1.12, z = 1.24, and p=0.21). No statistically significant difference was observed between the tapered-cuff and conventional-cuff groups with ICU mortality (OR 0.77, CI 0.55–1.08, z = 1.49, and p=0.14). Conclusions. In this meta-analysis, the tapered-cuff tracheal tube may not be superior to the standard-cuff tracheal tube in reducing VAP and ICU mortality.
Radiation Degradation of β-Glucan Extracted from Brewer’s Yeast for Enhancing Growth Promotion and Immunostimulant Activities on Broilers
Authors: Long Nguyen Thanh , Ha Tran Le Truc , Nghia Son Hoang , Luan Le Quang
Published: January 2019

Water-soluble low molecular weight β-glucan (WSLMG) was successfully prepared via γ-irradiation of insoluble β-glucan extracted from brewer’s yeast cell walls. The WSLMG content in an irradiated sample increased as the irradiation dose increased. The WSLMGs with a molecular weight (Mw) of 49, 25, and 11 kDa, obtained at correlative doses of 100, 200, and 300 kGy, respectively, were tested using growth promotion and immune stimulant effects in broilers. Supplementation with 500 ppm WSLMGs not only increased the survival rate (33.3%) and average body weight (40%) but also reduced the feed conversion rate (35.4%) in tested broilers. In addition, WSLMGs enhanced both nonspecific and specific immune components in the blood of supplemented broilers. The WSLMG with Mw ~25 kDa showed the highest effect on the growth performance and immunomodulatory capability in the immune systems of the tested broilers. In conclusion, this product demonstrates substantial promise as an immunostimulant and growth-promoting additive for poultry.
Laminin as a Potent Substrate for Large-Scale Expansion of Human Induced Pluripotent Stem Cells in a Closed Cell Expansion System
Authors: Paccola Mesquita Fernanda C. , Hochman-Mendez Camila , Morrissey Jacquelynn , Sampaio Luiz C. , Taylor Doris A.
Published: January 2019

The number of high-quality cells required for engineering an adult human-sized bioartificial organ is greater than one billion. Until the emergence of induced pluripotent stem cells (iPSCs), autologous cell sources of this magnitude and with the required complexity were not available. Growing this number of cells in a traditional 2D cell culture system requires extensive time, resources, and effort and does not always meet clinical requirements. The use of a closed cell culture system is an efficient and clinically applicable method that can be used to expand cells under controlled conditions. We aimed to use the Quantum Cell Expansion System (QES) as an iPSC monolayer-based expansion system. Human iPSCs were expanded (up to 14-fold) using the QES on two different coatings (laminin 521 (LN521) and vitronectin (VN)), and a karyotype analysis was performed. The cells were characterized for spontaneous differentiation and pluripotency by RT-PCR and flow cytometry. Our results demonstrated that the QES provides the necessary environment for exponential iPSC growth, reaching 689.75 × 106 ± 86.88 × 106 in less than 7 days using the LN521 coating with a population doubling level of 3.80 ± 0.19. The same result was not observed when VN was used as a coating. The cells maintained normal karyotype (46-XX), expressed pluripotency markers (OCT4, NANOG, LIN28, SOX2, REX1, DPPA4, NODAL, TDGFb, TERT3, and GDF), and expressed high levels of OCT4, SOX2, NANOG, SSEA4, TRA1-60, and TRA1-81. Spontaneous differentiation into ectoderm (NESTIN, TUBB3, and NEFH), mesoderm (MSX1, BMP4, and T), and endoderm (GATA6, AFP, and SOX17) lineages was detected by RT-PCR with both coating systems. We conclude that the QES maintains the stemness of iPSCs and is a promising platform to provide the number of cells necessary to recellularize small human-sized organ scaffolds for clinical purposes.
Genetic Diversity and Structure ofCoix lacryma-jobiL. from Its World Secondary Diversity Center, Southwest China
Authors: Fu Yu-Hua , Yang Chenglong , Meng Qiuyi , Liu Fanzhi , Shen Gang , Zhou Mingqiang , Ao Maohong
Published: January 2019

Coix lacryma-jobiL. is an important minor cereal with a high nutritional and medicinal value in Asian countries. The hilly region of South China is the secondary center of diversity ofCoix lacryma-jobiL. In the present study, we took a sample of 139Coix lacryma-jobiL. genotypes from four geographical regions in Southwest China and analyzed the genetic diversity and population structure using AFLP markers. Six primer combinations detected a total of 743 (89.52%) polymorphic loci. The percentage of polymorphic bands within the four geographical populations ranged from 56.02% (Guangxi) to 86.75% (Guizhou). The overall genetic diversity of 139Coix lacryma-jobiL. was relatively low (hranged from 0.1854 to 0.2564). The neighbor-joining method grouped allCoix lacryma-jobiL. genotypes into two clusters with no geographical affinity observed among genotypes within the same group. The Fst indicated the two clusters existed great genetic differentiation. AMOVA analysis showed the molecular variation within populations was much higher than that among populations of geographical regions and subpopulations derived from STRUCTURE. Human activities and the natural outcrossing system ofCoix lacryma-jobiL. may have a great influence on its distribution, genetic diversity, and population structure. Our study provides useful information for local breeding programs ofCoix lacryma-jobiL. as well.
Role of Tumor-Associated Macrophages in the Clinical Course of Pancreatic Neuroendocrine Tumors (PanNETs)
Authors: Cai Lei , Michelakos Theodoros , Deshpande Vikram , Arora Kshitij S. , Yamada Teppei , Ting David T. , Taylor Marty S. , Castillo Carlos Fernandez-del , Warshaw Andrew L. , Lillemoe Keith D. , Ferrone Soldano , Ferrone Cristina R.
Published: January 2019

Purpose:

This study evaluated the potential role of immune cells and molecules in the pathogenesis and clinical course of pancreatic neuroendocrine tumors (PanNET).

Experimental Design:

Surgically resected PanNETs (N = 104) were immunohistochemically analyzed for Ki67 index, mitotic rate, macrophage, CD4+ cells, and CD8+ T-cell infiltration, as well as HLA class I, PD-L1, and B7-H3 expression. Results were correlated with clinicopathologic characteristics as well as with disease-free (DFS) and disease-specific (DSS) survival.

Results:

The median age of the 57 WHO grade 1 and 47 WHO grade 2 patients was 55 years. High intratumoral CD8+ T-cell infiltration correlated with prolonged DFS (P = 0.05), especially when the number of tumor-associated macrophages (TAM) was low. In contrast, high peritumoral CD4+ cell and TAM infiltration was associated with a worse DFS and DSS. PD-L1 and B7-H3 were expressed in 53% and 78% PanNETs, respectively. HLA class I expression was defective in about 70% PanNETs. HLA-A expression correlated with favorable DSS in PD-L1–negative tumors (P = 0.02). TAM infiltration (P = 0.02), WHO grade (P = 0.04), T stage (P = 0.01), and lymph node positivity (P = 0.04) were independent predictors of DFS. TAM infiltration (P = 0.026) and T stage (P = 0.012) continued to be predictors of DFS in WHO grade 1 PanNET patients. TAM infiltration was the sole independent predictor of DSS for WHO grade 1 and 2 patients (P = 0.02). Therefore, this biomarker may contribute to identifying WHO grade 1 patients with poor prognosis.

Conclusions:

TAM infiltration appears to be the most informative prognostic biomarker in PanNET. It may represent a useful immunotherapeutic target in patients with PanNET.
YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non–Small Cell Lung Cancer
Authors: Yun Jiyeon , Hong Min Hee , Kim Seok-Young , Park Chae-Won , Kim Soyoung , Yun Mi Ran , Kang Han Na , Pyo Kyoung-Ho , Lee Sung Sook , Koh Jong Sung , Song Ho-Juhn , Kim Dong Kyun , Lee Young-Sung , Oh Se-Woong , Choi Soongyu , Kim Hye Ryun , Cho Byoung Chul
Published: January 2019

Purpose:

Given that osimertinib is the only approved third-generation EGFR-TKI against EGFR activating and resistant T790M mutated non–small cell lung cancer (NSCLC), additional mutant-selective inhibitors with a higher efficacy, especially for brain metastases, with favorable toxicity profile are still needed. In this study, we investigated the antitumor efficacy of YH25448, an oral, mutant-selective, irreversible third-generation EGFR-TKI in preclinical models.

Experimental Design:

Antitumor activity of YH25448 was investigated in vitro using mutant EGFR-expressing Ba/F3 cells and various lung cancer cell lines. In vivo antitumor efficacy, ability to penetrate the blood–brain barrier (BBB), and skin toxicity of YH25448 were examined and compared with those of osimertinib using cell lines and PDX model.

Results:

Compared with osimertinib, YH25448 showed a higher selectivity and potency in kinase assay and mutant EGFR-expressing Ba/F3 cells. In various cell line models harboring EGFR activating and T790M mutation, YH25448 effectively inhibited EGFR downstream signaling pathways, leading to cellular apoptosis. When compared in vivo at equimolar concentrations, YH25448 produced significantly better tumor regression than osimertinib. Importantly, YH25448 induced profound tumor regression in brain metastasis model with excellent brain/plasma and tumor/brain area under the concentration–time curve value. YH25448 rarely suppressed the levels of p-EGFR in hair follicles, leading to less keratosis than osimertinib in animal model. The potent systemic and intracranial activity of YH25448 has been shown in an ongoing phase I/II clinical trial for advanced EGFR T790M mutated NSCLC (NCT03046992).

Conclusions:

Our findings suggest that YH25448 is a promising third-generation EGFR inhibitor, which may be more effective and better tolerated than the currently approved osimertinib.
Unstable Genome and Transcriptome Dynamics during Tumor Metastasis Contribute to Therapeutic Heterogeneity in Colorectal Cancers
Authors: Cho Sung-Yup , Chae Jeesoo , Na Deukchae , Kang Wonyoung , Lee Ahra , Min Seoyeon , Kang Jinjoo , Choi Boram , Lee Jieun , Sung Chang Ohk , Chuang Jeffrey H. , Lee Charles , Lee Won-Suk , Park Hansoo , Kim Jong-Il
Published: January 2019

Purpose:

Genomic and transcriptomic alterations during metastasis are considered to affect clinical outcome of colorectal cancers, but detailed clinical implications of metastatic alterations are not fully uncovered. We aimed to investigate the effect of metastatic evolution on in vivo treatment outcome, and identify genomic and transcriptomic alterations associated with drug responsiveness.

Experimental Design:

We developed and analyzed patient-derived xenograft (PDX) models from 35 patients with colorectal cancer including 5 patients with multiple organ metastases (MOMs). We performed whole-exome, DNA methylation, and RNA sequencing for patient and PDX tumors. With samples from patients with MOMs, we conducted phylogenetic and subclonal analysis and in vivo drug efficacy test on the corresponding PDX models.

Results:

Phylogenetic analysis using mutation, expression, and DNA methylation data in patients with MOMs showed that mutational alterations were closely connected with transcriptomic and epigenomic changes during the tumor evolution. Subclonal analysis revealed that initial primary tumors with larger number of subclones exhibited more dynamic changes in subclonal architecture according to metastasis, and loco-regional and distant metastases occurred in a parallel or independent fashion. The PDX models from MOMs demonstrated therapeutic heterogeneity for targeted treatment, due to subclonal acquisition of additional mutations or transcriptomic activation of bypass signaling pathway during tumor evolution.

Conclusions:

This study demonstrated in vivo therapeutic heterogeneity of colorectal cancers using PDX models, and suggests that acquired subclonal alterations in mutations or gene expression profiles during tumor metastatic processes can be associated with the development of drug resistance and therapeutic heterogeneity of colorectal cancers.
Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis
Authors: Schwantes-An Tae-Hwi , Liu Sai , Stedman Margaret , Decker Brian S. , Wetherill Leah , Edenberg Howard J. , Vatta Matteo , Foroud Tatiana M. , Chertow Glenn M. , Moe Sharon M.
Published: January 2019

Background: Elevated serum concentrations of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality in patients with chronic kidney disease and those undergoing dialysis. Objectives: We tested the hypotheses that polymorphisms in FGF23, its co-receptor alpha-klotho (KL), and/or FGF23 receptors (FGFR) are associated with cardiovascular events and/or mortality. Methods: We used 1,494 DNA samples collected at baseline from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial, in which patients were randomized to the calcimimetic cinacalcet or placebo for the treatment of secondary hyperparathyroidism. We analyzed European and African Ancestry samples separately and then combined summary statistics to perform a meta-analysis. We evaluated single-nucleotide polymorphisms (SNPs) in FGF23, KL, and FGFR4 as the key exposures of interest in proportional hazards (Cox) regression models using adjudicated endpoints (all-cause and cardiovascular mortality, sudden cardiac death, and heart failure [HF]) as the outcomes of interest. Results: rs11063112 in FGF23 was associated with cardiovascular mortality (risk allele = A, hazard ratio [HR] 1.32, meta-p value = 0.004) and HF (HR 1.40, meta-p value = 0.007). No statistically significant associations were observed between FGF23 rs13312789 and SNPs in FGFR4 or KL genes and the outcomes of interest. Conclusions: rs11063112 was associated with HF and cardiovascular mortality in patients receiving dialysis with moderate to severe secondary hyperparathyroidism.