bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise interventions for improving objective physical function in patients with end-stage kidney disease on dialysis: a systematic review and meta-analysis
Authors: Clarkson Matthew J. , Bennett Paul N. , Fraser Steve F. , Warmington Stuart A.
Published: February 2019

Patients with end-stage kidney disease on dialysis have increased mortality and reduced physical activity, contributing to impaired physical function. Although exercise programs have demonstrated a positive effect on physiological outcomes such as cardiovascular function and strength, there is a reduced focus on physical function. The aim of this review was to determine whether exercise programs improve objective measures of physical function indicative of activities of daily living for patients with end-stage kidney disease on dialysis. A systematic search of Medline, Embase, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature identified 27 randomized control trials. Only randomized control trials using an exercise intervention or significant muscular activation in the intervention, a usual care, nonexercising control group, and at least one objective measure of physical function were included. Participants were ≥18 yr of age, with end-stage kidney disease, undergoing hemo- or peritoneal dialysis. Systematic review of the literature and quality assessment of the included studies used the Cochrane Collaboration’s tool for assessing risk bias. A meta-analysis was completed for the 6-min walk test. Data from 27 studies with 1,156 participants showed that exercise, regardless of modality, generally increased 6-min walk test distance, sit-to-stand time or repetitions, and grip strength as well as step and stair climb times or repetitions, dynamic mobility, and short physical performance battery scores. From the evidence available, exercise, regardless of modality, improved objective measures of physical function for end-stage kidney disease patients undergoing dialysis. It is acknowledged that further well-designed randomized control trials are required.
Respiratory system reactance reflects communicating lung volume in chronic obstructive pulmonary disease
Authors: Milne Stephen , Jetmalani Kanika , Chapman David G. , Duncan Joseph M. , Farah Claude S. , Thamrin Cindy , King Gregory G.
Published: February 2019

Respiratory system reactance (Xrs) measured by the forced oscillation technique (FOT) is theoretically and experimentally related to lung volume. In chronic obstructive pulmonary disease (COPD), the absolute volume measured by body plethysmography includes a proportion that is inaccessible to pressure oscillations applied via the mouth, that is, a “noncommunicating” lung volume. We hypothesized that in COPD the presence of noncommunicating lung would disrupt the expected Xrs-volume relationship compared with plethysmographic functional residual capacity (FRCpleth). Instead, Xrs would relate to estimates of communicating volume, namely, expiratory reserve volume (ERV) and single-breath alveolar volume (VaSB). We examined FOT and lung function data from people with COPD ( n = 51) and from healthy volunteers ( n = 40). In healthy volunteers, we observed an expected inverse relationship between reactance at 5 Hz (X5) and FRCpleth. In contrast, there was no such relationship between X5 and FRCplethin COPD subjects. However, there was an inverse relationship between X5 and both ERV and VaSB. Hence the theoretical Xrs-volume relationship is present in COPD but only when considering the communicating volume rather than the absolute lung volume. These findings confirm the role of reduced communicating lung volume as an important determinant of Xrs and therefore advance our understanding and interpretation of FOT measurements in COPD.

NEW & NOTEWORTHY To investigate the determinants of respiratory system reactance (Xrs) measured by the forced oscillation technique (FOT) in chronic obstructive pulmonary disease (COPD), we examine the relationship between Xrs and lung volume. We show that Xrs does not relate to absolute lung volume (functional residual capacity) in COPD but instead relates only to the volume of lung in communication with the airway opening. This communicating volume may therefore be fundamental to our interpretation of FOT measurements in COPD and other pulmonary diseases.
Tidal breathing flow volume profiles during sleep in wheezing infants measured by impedance pneumography
Authors: Gracia-Tabuenca Javier , Seppä Ville-Pekka , Jauhiainen Milla , Kotaniemi-Syrjänen Anne , Malmström Kristiina , Pelkonen Anna , Mäkelä Mika , Viik Jari , Malmberg L. Pekka
Published: February 2019

Overnight analysis of tidal breathing flow volume (TBFV) loops, recorded by impedance pneumography (IP), has been successfully applied in the home monitoring of children with wheezing disorders. However, little is known on how sleep physiology modifies the relationship between TBFV profiles and wheeze. We studied such interactions in wheezing infants. Forty-three infants recruited because of recurrent lower airway symptoms were divided into three groups based on their risk of asthma: high (HR), intermediate (IR), or low (LR). Sedated patients underwent infant lung function testing including assessment of airway responsiveness to methacholine at the hospital and a full-night recording of TBFV profiles at home with IP during natural sleep. Overnight TBFV indexes were estimated from periods of higher and lower respiration variability, presumably belonging to active [rapid eye movement (REM)] and quiet [non-REM (NREM)] sleep, respectively. From 35 valid recordings, absolute time indexes showed intrasubject sleep phase differences. Peak flow relative to time and volume was lower in HR compared with LR only during REM, suggesting altered expiratory control. Indexes estimating the concavity/convexity of flow decrease during exhalation suggested limited flow during passive exhale in HR compared with IR and LR, similarly during NREM and REM. Moreover, during REM convexity was negatively correlated with maximal flow at functional residual capacity and methacholine responsiveness. We conclude that TBFV profiles determined from overnight IP recordings vary because of sleep phase and asthma risk. Physiological changes during REM, most likely decrease in respiratory muscle tone, accentuate the changes in TBFV profiles caused by airway obstruction.

NEW & NOTEWORTHY Impedance pneumography was used to investigate overnight tidal breathing flow volume (TBFV) indexes and their interactions with sleep phase [rapid eye movement (REM) vs. non-REM] at home in wheezing infants. The study shows that TBFV indexes vary significantly because of sleep phase and asthma risk of the infant and that during REM the changes in TBFV indexes caused by airway obstruction are accentuated and better associated with lung function of the infant.
Synapse formation: from cellular and molecular mechanisms to neurodevelopmental and neurodegenerative disorders
Authors: Batool Shadab , Raza Hussain , Zaidi Jawwad , Riaz Saba , Hasan Sean , Syed Naweed I.
Published: February 2019

The precise patterns of neuronal assembly during development determine all functional outputs of a nervous system; these may range from simple reflexes to learning, memory, cognition, etc. To understand how brain functions and how best to repair it after injury, disease, or trauma, it is imperative that we first seek to define fundamental steps mediating this neuronal assembly. To acquire the sophisticated ensemble of highly specialized networks seen in a mature brain, all proliferated and migrated neurons must extend their axonal and dendritic processes toward targets, which are often located at some distance. Upon contact with potential partners, neurons must undergo dramatic structural changes to become either a pre- or a postsynaptic neuron. This connectivity is cemented through specialized structures termed synapses. Both structurally and functionally, the newly formed synapses are, however, not static as they undergo consistent changes in order for an animal to meet its behavioral needs in a changing environment. These changes may be either in the form of new synapses or an enhancement of their synaptic efficacy, referred to as synaptic plasticity. Thus, synapse formation is not restricted to neurodevelopment; it is a process that remains active throughout life. As the brain ages, either the lack of neuronal activity or cell death render synapses dysfunctional, thus giving rise to neurodegenerative disorders. This review seeks to highlight salient steps that are involved in a neuron’s journey, starting with the establishment, maturation, and consolidation of synapses; we particularly focus on identifying key players involved in the synaptogenic program. We hope that this endeavor will not only help the beginners in this field to understand how brain networks are assembled in the first place but also shed light on various neurodevelopmental, neurological, neurodegenerative, and neuropsychiatric disorders that involve synaptic inactivity or dysfunction.
HistoNFC: An Innovative Tool for the Practical Teaching of Histology Using NFC Technology
Authors: Jimena Medina I. , Gómez-Luque M. A. , Peña Amaro J. , Luque Ruiz I. , Gómez-Nieto M. A.
Published: February 2019

Despite the development of mobile device technology over recent years, its application in the field of teaching has not yet had a parallel development. For the past two decades teaching subjects such as histology has undergone a change in the digital use of its content and didactic methods based on Web applications, e-learning portals, etc., in which the use of high definition images enables the substitution of the light microscope for a “virtual microscope”. This paper describes a mobile device solution based on the use of Near Field Communication technology for supporting teaching in medical histology. The didactic contents are managed in a database which stores information and images corresponding to the histological slides that are handed out to students in the glass slides for their analysis under a microscope. By associating a single NFC chip to each glass slide and touching this chip with a smartphone, students are given access to all the multimedia information related to the histological slides, without needing a mobile device. The system developed, called HistoNFC, enables access to this information at any moment, as well as the follow-up to the didactic activity and student evaluation. Evaluation of the system has been carried out by histology students of medical degree at the University of Córdoba, assessing aspects of the assisted-learning process as well as technologies, and the results obtained have been very favorable for both, as can be seen in detail in this study.
Developmental Motor Profile in Preschool Children with Primary Stereotypic Movement Disorder
Authors: Valente Francesca , Pesola Chiara , Baglioni Valentina , Teresa Giannini Maria , Chiarotti Flavia , Caravale Barbara , Cardona Francesco
Published: February 2019

Aim. Different neuropsychological dysfunctions have been described in children with primary Stereotypic Movement Disorder (SMD), mainly attention or motor coordination problems. Up to now with no study has evaluated psychomotor functions in preschoolers primary SMD. The aim of this observational study was to gather information on the motor profiles of SMD patients in this age range in comparison with typically developing children. Patients and Methods. Twenty-six children (four girls) aged 36 to 76 months (mean= 53 ±10) with primary SMD were assessed by a structured evaluation including the Movement Assessment Battery for Children-Second Edition (MABC-2), the Beery-Buktenica Developmental test of Visual-Motor Integration (VMI), the Repetitive Behaviour Scale-Revised (RBS-R), the Motor Severity Stereotypy Scale (MSSS), and the Child Behaviour Checklist (CBCL). The diagnoses of Intellectual Disability or Autism Spectrum Disorder were exclusion criteria from the study. A comparison group of twenty-seven (four girls) typically developing children without stereotypies aged 36 to 59 months (mean= 48 ±7) was also examined. Results. The MABC–2 total score was lower than 15th percentile in fifteen children with SMD (58%); the worst performances were observed in Balance and Manual Dexterity subtests. The motor coordination score of VMI was lower than 15th percentile in ten children (38%). The majority of the children with low scores at MABC-2 also had low scores at the motor coordination subscale of VMI. MABC-2 standard scores of the clinical group were significantly lower than those of controls on MABC-2 Total, Balance, and Ball Skills subtests. Conclusion. The finding of widespread dysfunction of gross and fine motor abilities in preschoolers with primary SMD seems to delineate a peculiar phenotype and could provide new approaches to the management of this neurodevelopment disorder.
Combined Extracts of Herba Epimedii and Fructus Ligustri Lucidi Rebalance Bone Remodeling in Ovariectomized Rats
Authors: Chen Yuheng , Li Xiaoxi , Tang Xiufeng , Gao Yingying , Yu Ping , Xu Liping , Liu Renhui
Published: February 2019

This study aimed to investigate the osteoprotective effect and the possible molecular mechanisms of the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi on postmenopausal osteoporosis (PMOP). Forty-eight female SD rats were sham-operated (Sham, n = 8) or ovariectomized (OVX, n = 40). Then after a week, OVX rats were divided randomly into five groups (n = 8 in each group): OVX, extracts of Herba Epimedii (HE, 0.35 g/kg), extracts of Fructus Ligustri Lucidi (FLL, 0.35 g/kg), combined extracts of HE and FLL (HE & FLL, 0.20 g/kg HE plus 0.15 g/kg FLL), and Raloxifene hydrochloride (RH, 6.25 mg/kg) groups. All groups were administered once daily for 12 weeks. Indicators related to bone remodeling were detected, including estradiol (E2), bone mineral density (BMD), maximal load, ultimate deflection, micro-CT properties, tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP) levels in serum and bone, and the protein and mRNA expression of bone turnover markers (RANKL, M-CSF, Wnt5a, Atp6v0d2, OPG, IGF-1, TGF-β1, and Bmp-2). Results showed that the combined extracts could increase serum E2 levels and BMD, enhance bone strength, reserve bone microstructure degeneration, promote bone formation, and inhibit bone resorption through upregulating the mRNA and protein expression of OPG, IGF-1, TGF-β1, and Bmp-2, while downregulating RANKL, M-CSF, Wnt5a, and Atp6v0d2. These findings demonstrated that the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi with bone protective effects on OVX rats might be an alternative medicine for the treatment of PMOP.
An LC-MS/MS Method for Simultaneous Determination of the Toxic and Active Components of Cortex Periplocae in Rat Plasma and Application to a Pharmacokinetic Study
Authors: Li Zhen , Li Yang , Li Jin , Liu Rui , Hao Jia , He Jun , Chang Yan-xu
Published: February 2019

A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the toxic and other active components including isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract to rats. Plasma samples were prepared by protein precipitation with methanol. All compounds were separated on a C18 column with gradient elution using acetonitrile and formic acid aqueous solution (0.1%, v/v) as the mobile phase at a flow rate of 0.3 mL/min. The detection of all compounds was accomplished by multiple-reaction monitoring (MRM) in the positive electrospray ionization mode. The LC-MS/MS method exhibited good linearity for five analytes. The lower limit of quantification (LLOQ) was 0.48 ng/mL for scopoletin, periplogenin, and periplocymarin; 2.4 ng/mL for isovanillin and periplocin. The extraction recoveries of all compounds were more than 90% and the RSDs were below 10%. It was found that the absorption of scopoletin and periplocin was rapid in vivo after oral administration of cortex periplocae extract. Furthermore, periplocymarin possessed abundant plasma exposure. The results demonstrated that the validated method was efficiently applied for the pharmacokinetic studies of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract.
Pineapple Bark Performance in Dyes Adsorption: Optimization by the Central Composite Design
Authors: Fegousse Ahlam , El Gaidoumi Abdelali , Miyah Youssef , El Mountassir Rabea , Lahrichi Anissa
Published: February 2019

This work is concerned with the study of the adsorption in aqueous medium of a three-dye mixture which contains Methylene Blue, Brilliant Green, and Congo Red on the pineapple bark. This adsorbent material has been characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The experimental design methodology, based on the response surface methodology (RSM) by the central composite design (CCD), has been applied for the optimization of the parameters, namely, the temperature, dose of the adsorbent, and pH. The yield reached 98.91% under optimal conditions (T = 30°C; adsorbent dose = 2.5 g·L−1; pH = 9.8) at an initial concentration of 20 mg·L−1.
Dynamic Analysis of Flexible Shaft and Elastic Disk Rotor System Based on the Effect of Alford Force
Authors: Yang Wenjun , Yuan Huiqun , Hui Li , Zhang Kaifeng
Published: February 2019

Taken the flexible shaft and elastic disk rotor system as the research object, vibration differential equations are established by the modal synthesis method. Based on the Runge–Kutta method of direct integration, dynamic equations are solved successfully. Then, the effects of Alford force caused by the airflow excitation are researched on the stability and dynamic response. The results show modal vibration of the disk takes a great effect on the coupled natural frequency of shaft transverse vibration in the high rotational speed region. The effect of shaft‐disk coupling makes rotor frequency to decrease, and different rotational speeds have little effect on rotor frequency. Eccentric distance is sensitive to the amplitude of rotor response, but it has little effect on rotor stability, motion law, and relative relationship of two response frequencies. The proportion of rotor responses caused by aerodynamic excitation force becomes larger with the increase of rotational speed and disk radius. However, the proportion decreases with the second support moving to the right, and it is helpful for the stable operation of the rotor system.
Bearing Fault Diagnosis Based on Spatial Features of 2.5 Dimensional Sound Field
Authors: Hou Junjian , Ma Jun , Fang Zhanpeng , Ming Wuyi , He Wenbin
Published: February 2019

The traditional acoustic‐based diagnosis (ABD) technique based on single‐channel testing has a significant engineering value. Since its diagnosis robustness is sensitive to sound signal acquisition location, it develops slowly. To solve this problem, the 2‐dimensional (2D) sound field variation near the machine is adopted for diagnosis by the near‐field acoustic holography (NAH)‐ based fault diagnosis method with array measurement. However, its performance is limited due to the neglect of the sound field normal change information. To dig the sound field fault information further, a 2.5‐dimensional (2.5D) acoustic field diagnosis method is presented in this paper and its performance compared with the 2D technology is verified by the bearing diagnostic test. Different from the 2D technique with only one source image, the 2.5D acoustic field model consists of source image, holographic sound image, and the differences between them, and its effective feature model is constructed by Gabor wavelet feature extraction and random forest feature reduction algorithm. The diagnostic effect of the 2.5D technique compared with the 2D technique increases more than 11% in the bearing diagnostic test. It provides new ideas for the development of the NAH‐based fault diagnosis method, and further improves the ABD technique‐based array measurement.
Experimental Study on Nano‐SiO2 Improving Concrete Durability of Bridge Deck Pavement in Cold Regions
Authors: Cheng Youkun , Shi Zhenwu
Published: February 2019

In order to reduce early damage of bridge deck pavement concrete in cold regions, a certain content of nano‐SiO2 is added into the concrete to enhance its durability. Through tests on four durability indexes, strength, frost resistance, resistance to Cl− ion permeability, and abrasion resistance of concrete with 1% nano‐SiO2 content and concrete without nano‐SiO2, the ability of nano‐SiO2 to improve the concrete durability of bridge deck pavement is evaluated. The results of tests and analysis show that the incorporation of nano‐SiO2 greatly improves the four durability indexes. Nano‐SiO2 effectively absorbs the calcium hydroxide released early by the hydration of cement, increases the calcium silicate hydrate content, and elevates the interface between the paste and aggregate of the hardened cement, which improves the durability of the concrete.
On Positioning and Vibration Control Application to Robotic Manipulators with a Nonideal Load Carrying
Authors: Lima Jeferson J. , Balthazar José M. , Rocha Rodrigo T. , Janzen Frederic C. , Bernardini Davide , Litak Grzegorz , Bassinello Dailhane G. , Tusset Angelo M.
Published: February 2019

In recent years, the evolution of artificial intelligence techniques has widely grown such that it gives new ways to improve human life, not only at work but also living. Nowadays, to the human being, physical human‐robot interactions (PHRIs) have been presented very important and present itself as a major challenge for the current engineering. Therefore, this work designs and analyses a two‐degree‐of‐freedom robotic arm with flexible joints driven by a DC motor. Due to the interaction between the robot links and flexible joints, the arm may present overshoots when it is moved such that it becomes difficult to manipulate the arm. Therefore, Magnetorheological dampers (MR damper or MR brake) are attached to the links of the arm in order to control such overshoot and provide a way to adjust the mechanical limitations of the arm. The dynamics of the system will be investigated, showing the appearance of chaotic behavior due to the coupling of the manipulator to the motors. After that, the feedback control is obtained through the state‐dependent Riccati equation (SDRE) aiming the control of the positioning of the manipulator and the torque applied on the MR damper. Numerical results showed that the proposed control using hybrid actuators, DC motor, and MR brake was effective to control the position and behavior of the flexible joints of the manipulators.
Castleman Disease in a Patient with Common Variable Immunodeficiency
Authors: Ricciardi Luisa , Furci Fabiana , Ieni Antonio , Macrì Antonio
Published: February 2019

Common variable immunodeficiency (CVID) is a primary immunodeficiency due to a disorder of the adaptive immune system which causes hypogammaglobulinemia and therefore an increased susceptibility to infection; noninfectious, inflammatory conditions including systemic autoimmunity and lymphoproliferative complications are also commonly associated with CVID. Castleman disease (CD) is a systemic disease clinically characterized by diffuse lymphadenopathy, splenomegaly, anemia, and systemic inflammatory symptoms. This makes CD a great mimicker of more common benign and malignant masses in the neck, chest, abdomen, and pelvis. A novel case of primary immunodeficiency (CVID) in a middle-aged woman, who developed multicentric CD (MDC) with splenomegaly, is described. The authors suggest that the onset of MCD and of the correlated splenomegaly was due to incorrect management of the hypogammaglobulinemia as immunoglobulin G (IgG) levels were not kept within normal ranges. Correct management of the hypogammaglobulinemia allowed splenectomy to be performed without any infectious surgical complications. MCD is reported for the first time in association with an adult case of CVID. The above reported case highlights the need for a timely correct diagnosis and treatment of CVID to avoid complications, which could cause recourse to splenectomy, such as in our case or development of malignancies.
Intrasplenic Pancreatic Pseudocyst after Chemoradiation of a Pancreatic Adenocarcinoma Mimicking Progressive Disease: A Case Report and Review of the Literature
Authors: Benter Thomas , Roehr Oliver , Moser Lutz , Kiewe Philipp , Hentschel Leopold , Platzek Ivan , Schuler Markus K.
Published: February 2019

Chemoradiation is one of the therapeutic options in palliative treatment of locally advanced pancreatic adenocarcinoma, with a well-known safety profile. In this case report, we describe the treatment-related occurrence of an intrasplenic pancreatic pseudocyst which was successfully removed by gastrocystic drainage. This rare complication should be considered in the follow-up and clinical management of patients, particularly if left-sided complaints occur.
Short Nylon Fibers Waste Modified with Glycidyl 3-Pentadecenyl Phenyl Ether to Reinforce Styrene Butadiene Rubber Tread Compounds
Authors: Cen Lan , Lv Guo-zheng , Tan Xin-wen , Gong Zhan-lin
Published: February 2019

The utilization of waste fibers represents an important environmental benefit and great economic savings for the community. In this study short nylon fibers waste was modified with Glycidyl 3-Pentadecenyl Phenyl Ether (GPPE) in the presence of Triethylamine/Ammonium persulfate by a simple two-step procedure. The reinforcing effects of modified fibers (MNSF-2) on the vulcanization characteristics, mechanical properties, dynamic mechanical properties, and the wear resistant property of Styrene Butadiene Rubber (SBR) tread compounds were investigated. The addition of the MNSF-2 resulted in slightly lower minimum torque (ML) and maximum torque (MH), as well as longer cure time (t90) and scorch time (t10) of tread compounds. The deterioration of tensile strength and elongation at break of the tread compound containing short nylon fibers waste (NSF) was apparent. Conversely, the modified fibers showed reinforcing effect on tread compounds. The tensile strength values of compounds increased with MNSF-2 content, passed through a maximum value, and then reduced slightly. The modulus and the tear strength of compounds increased significantly with fiber loadings. The highest tear strength value was observed in 8phr MNSF-2 reinforced SBR compounds, 31.9% higher than that of the gum compound. Meanwhile elongation at break of MNSF-2 compound maintained a relative high value than that of NSF/SBR compound. The addition of NSF exaggerated wear volume of compounds. However, the wear resistance of MNSF-2 compounds was superior to that of NSF compounds and comparable with that of the gum compound. The DMA results reveal that E′ and tan⁡δ values decreased at elevated temperature. Meanwhile enhanced storage modulus in MNSF-2/SBR tread compound can be observed. It is worth highlighting that MNSF-2/SBR compounds show higher tan⁡δ at 0°C, indicating improved wet traction of tread compounds, while tan⁡δ at 60°C maintains almost the same value as that of the gum sample. The results of this study are encouraging, demonstrating that the use of short nylon fibers waste in composites offers promising potential for the green tire application.
Influence of Duodenal–Jejunal Implantation on Glucose Dynamics: A Pilot Study Using Different Nonlinear Methods
Authors: Cuesta-Frau David , Novák Daniel , Burda Vacláv , Abasolo Daniel , Adjei Tricia , Varela Manuel , Vargas Borja , Mraz Milos , Kavalkova Petra , Benes Marek , Haluzik Martin
Published: February 2019

Diabetes is a disease of great and rising prevalence, with the obesity epidemic being a significant contributing risk factor. Duodenal–jejunal bypass liner (DJBL) is a reversible implant that mimics the effects of more aggressive surgical procedures, such as gastric bypass, to induce weight loss. We hypothesized that DJBL also influences the glucose dynamics in type II diabetes, based on the induced changes already demonstrated in other physiological characteristics and parameters. In order to assess the validity of this assumption, we conducted a quantitative analysis based on several nonlinear algorithms (Lempel–Ziv Complexity, Sample Entropy, Permutation Entropy, and modified Permutation Entropy), well suited to the characterization of biomedical time series. We applied them to glucose records drawn from two extreme cases available of DJBL implantation: before and after 10 months. The results confirmed the hypothesis and an accuracy of 86.4% was achieved with modified Permutation Entropy. Other metrics also yielded significant classification accuracy results, all above 70%, provided a suitable parameter configuration was chosen. With the Leave–One–Out method, the results were very similar, between 72% and 82% classification accuracy. There was also a decrease in entropy of glycaemia records during the time interval studied. These findings provide a solid foundation to assess how glucose metabolism may be influenced by DJBL implantation and opens a new line of research in this field.
The Effect of Cu Doping on the Transformation from Rutile to Anatase and Cu Occupation Tendency in TiO2 Solid Solution
Authors: Chen Jun-Yu , Yan Ji-Kang , Gan Guo-You
Published: February 2019

TiO2 doped with different amounts of Cu2+ ions (from 0 to 3 mol%) was synthesized by sol-gel method. The samples were characterized by X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). The XRD analysis showed that the Cu-doped TiO2 samples exhibit anatase and rutile phases. The lattice parameters remain unchanged, independent of Cu2+ content. Diameter of TiO2 increased significantly with increasing concentrations of Cu2+. The investigated results indicate that a greater portion of the Cu2+ ions are well incorporated into the anatase and rutile TiO2 lattices. The stretching vibration frequencies of the interatomic bonds were calculated by the electronegativity principle. The calculated data were compared with infrared spectra. The results show that in the rutile and anatase phases, O atoms in the TiO2 lattice and some interstitial Cu atoms form Cu-O bond, and other substitutional Cu that replaces Ti atoms in TiO2 lattice form Cu-O bond with O atoms in the TiO2 lattice.
Highly Porous pH-Responsive Carboxymethyl Chitosan-Grafted-Poly (Acrylic Acid) Based Smart Hydrogels for 5-Fluorouracil Controlled Delivery and Colon Targeting
Authors: Khan Samiullah , Anwar Naveed
Published: February 2019

In the present investigation, new formulations of CMCS/AA hydrogels with varying composition of Carboxymethyl chitosan, acrylic acid, and ethylene glycol dimethacrylate (EGDMA) were prepared by free radical polymerization technique using benzoyl peroxide as catalyst. The bioavailability of 5-FU through the oral route is very limited owing to its rapid metabolism and clearance from the general circulation. Current work was aimed at increasing the bioavailability of 5-FU via smart hydrogels and at investigating their potential in delivering 5-FU to target colon cancer. Swelling studies were carried out on dried hydrogel discs in different USP phosphate buffer solutions of various pH values. Porosity and gel fraction of all the samples were measured. 5-FU was used as a model drug and loaded in selected hydrogel samples. The amount of drug loaded and released was determined. Experimental data was fitted to various model equations, and corresponding parameters were calculated to study the release mechanism. Many structural parameters were calculated. The prepared hydrogels were also characterized by FTIR and SEM to study the structure, crystallinity, compatibility, and morphology of the smart hydrogels. The biocompatibility and cytotoxic potential blank and drug-loaded hydrogels were assessed through MTT assay. The prepared hydrogels were found to be an excellent carrier for 5-FU in targeting colon cancer.
Coal Reservoir Characterization in a Tectonic Setting and the Effects of Tectonism on the Coalbed Methane (CBM) Content
Authors: Ye Zhenni , Hou Enke , Duan Zhonghui , Li Zengjiang
Published: February 2019

Research on the relationships among tectonics, micropores, microfractures, and coalbed methane (CBM) content is important for the optimal selection of CBM production areas. In this study, micropore-microfracture structural parameters of coal samples from the Guojiahe coalfield are determined through the use of X-ray photography, an image recognition algorithm, and a liquid nitrogen adsorption method. The relationship between the micropore-microfracture characteristics of the reservoir and the gas content is quantitatively assessed using the Grassberger and Procaccia (GP) algorithm to calculate the correlation dimension of the parameters. Micropore-microfracture development varies in different tectonic zones. Additionally, the CBM content varies according to the characteristic parameters of hysteresis loops and the pore diameter. The correlation dimension is an effective indicator of the nonlinear relationship between reservoir micropore-microfracture characteristics and the gas content.
Propofol Reduced Mammosphere Formation of Breast Cancer Stem Cells via PD-L1/Nanog In Vitro
Authors: Zhang Xiaobei , Li Fangxuan , Zheng Ying , Wang Xiaokun , Wang Kaiyuan , Yu Yue , Zhao Hongwei
Published: February 2019

Several researches revealed that propofol, a hypnotic intravenous anesthesia agent, could inhibit the cancer cell proliferation and tumor formation, which might affect cancer recurrence or metastasis and impact patients’ prognosis. Cancer stem cells (CSCs) comprised a tiny fraction of tumor bulk and played a vital role in cancer recurrence and eventual mortality. This study investigates the effect of propofol on breast cancer stem cells (BCSCs) in vitro and the underlying molecular mechanisms. Tumor formation of CSCs was measured by mammosphere culture. Cultured BCSCs were exposed to different concentrations and durations of propofol. Cell proliferation and self-renewal capacity were determined by MTT assays. Expressions of PD-L1 and Nanog were measured using western blotting and real-time PCR. We knocked down the PD-L1 expression in MDA-MB-231 cells by lentivirus-mediated RNAi technique, and the mammosphere-forming ability of shControl and shPD-L1 under propofol treatment was examined. Mammosphere culture could enrich BCSCs. Compared with control, cells exposed to propofol for 24 h induced a larger number of mammosphere cells (P=0.0072). Levels of PD-L1 and Nanog were downregulated by propofol. Compared with shControl stem cells, there was no significant difference in the inhibitory effect of propofol on the mammosphere-forming ability of shPD-L1 stem cells which indicated that the inhibition of propofol could disappear in PD-L1 knockdown breast stem cells. Propofol could reduce the mammosphere-forming ability of BCSCs in vitro. Mechanism experiments indicated that the inhibition of propofol in mammosphere formation of BCSCs might be mediated through PD-L1, which was important to maintain Nanog.
Model of the DGEBA-EDA Epoxy Polymer: Experiments and Simulation Using Classical Molecular Dynamics
Authors: Gavrielides Andreas , Duguet Thomas , Aufray Maëlenn , Lacaze-Dufaure Corinne
Published: February 2019

Polyepoxy samples are synthesized from diglycidylether of bisphenol A (DGEBA) and ethylene diamine (EDA) monomers at a stoichiometric ratio of 2 DGEBA : 1 EDA in model conditions in order to promote a high degree of polymerization and a low density of defects and to try to approach the ideal models obtained by simulation. A slow polymerization (>24 h at ambient temperature) and a postcuring achieved in an inert atmosphere lead to a conversion degree of 92±2% and a midpoint glass transition temperature of 391±1 K. In parallel, a model is created with a multistep cross-linking procedure. In this work, all-atom molecular dynamics (MD) simulations are performed with LAMMPS and the GAFF 1.8 force field. In the initial liquid mixture of reactants (600 molecules), proper mixing is demonstrated by the calculation of the partial radial distribution functions (RDF), which show a minimum intermolecular distance of 2.8 Å and similar distributions for EDA-EDA, DGEBA-DGEBA, and DGEBA-EDA molecules in the simulation boxes. Then, in alternation with MD equilibrations, cross-linking is performed on frozen configurations by creating covalent bonds between reactive pairs within a reaction radius of 3 Å. The resulting boxes show conversion rates of 90-93% and densities close to the experimental value. Finally, a cooling ramp from 700 K to 25 K is applied in order to monitor the specific volume and the coefficient of volumetric thermal expansion (CVTE) of the polymer and to derive the glass transition temperature. Experimental thermomechanical analyses (TMA) compares well with simulations for both the specific volume and the CVTE evolutions with temperature. Whereas the uncertainty remains high with the fitting procedure used, we calculate a glass transition temperature of 390±8 K which compares very well with the experimental values (391±1 K from DSC and 380 K from TMA).
Six Sigma Application in Healthcare Logistics: A Framework and A Case Study
Authors: Al-Qatawneh Lina , Abdallah Abdallah A. A. , Zalloum Salam S. Z.
Published: February 2019

Six Sigma is used heavily in various industrial sectors, yet no noticeable applications are seen in healthcare logistics. This paper reveals the special case of healthcare logistics where cost reduction is not the only factor considered in project selection; performance and criticality of each item in the logistics system are of high importance as well. This paper provides a proposed framework to apply Six Sigma in the area of healthcare logistics. It also presents a case study implementing the proposed framework at a Jordanian hospital. In the case study, the paper reveals how the modifications of the define phase to take into consideration the criticality, cost, and performance of items make typical Six Sigma methodology very beneficial for healthcare logistics. In addition, it shows how the Six Sigma project selection can be done to deal effectively with healthcare logistics issues. This paper paves the road for research to elaborate on ways to use Six Sigma in the area of improving healthcare logistics.
Disruption of Endolysosomal RAB5/7 Efficiently Eliminates Colorectal Cancer Stem Cells
Authors: Takeda Mitsunobu , Koseki Jun , Takahashi Hidekazu , Miyoshi Norikatsu , Nishida Naohiro , Nishimura Junichi , Hata Taishi , Matsuda Chu , Mizushima Tsunekazu , Yamamoto Hirofumi , Ishii Hideshi , Doki Yuichiro , Mori Masaki , Haraguchi Naotsugu
Published: February 2019

Given that cancer stem cells (CSC) play a key role in drug resistance and relapse, targeting CSCs remains promising in cancer therapy. Here we show that RAB5/7, which are involved in the endolysosomal pathway, play key roles in the maintenance of CSC survival via regulation of the mitophagic pathway. Inhibition of RAB5/7 efficiently eliminated colorectal CSCs and disrupted cancer foci. In addition, we identified mefloquine hydrochloride, an antimalarial drug, as a novel RAB5/7 inhibitor and promising colorectal CSC-targeting drug. Endolysosomal RAB5/7 and LAMP1/2 mediated parkin-dependent mitochondrial clearance and modulated mitophagy through lysosomal dynamics. In a patient-derived xenograft (PDX) model of colon cancer, treatment with mefloquine resulted in suppression of mitophagic PINK1/PARKIN and increased mitochondrial disorder and mitochondria-induced apoptosis without apparent side effects. These results suggest that the combination of mefloquine with chemotherapeutic agents in the PDX model potentially disrupts the hierarchy of colorectal cancer cells and identify endolysosomal RAB5/7 and LAMP1/2 as promising therapeutic targets in CSCs.

Significance:

These findings show that endosomal/lysosomal RAB5 and RAB7, which regulate mitophagy, are essential for the survival of colon cancer stem cells.
Deoxyribozymes as Catalytic Nanotherapeutic Agents
Authors: Khachigian Levon M.
Published: February 2019

RNA-cleaving deoxyribozymes (DNAzymes) are synthetic single-stranded DNA-based catalytic molecules that can be engineered to bind to and cleave target mRNA at predetermined sites. These have been used as therapeutic agents in a range of preclinical cancer models and have entered clinical trials in Europe, China, and Australia. This review surveys regulatory insights into mechanisms of disease brought about by use of catalytic DNA in vitro and in vivo, including recent uses as nanosensors, nanoflowers, and nanosponges, and the emerging role of adaptive immunity underlying DNAzyme inhibition of cancer growth. DNAzymes represent a promising new class of nucleic acid–based therapeutics in cancer. This article discusses mechanistic and therapeutic insights brought about by DNAzyme use as nanotools and reagents in a range of basic science, experimental therapeutic and clinical applications. Current limitations and future perspectives are also discussed.
Impact of Concomitant Administration of Gastric Acid–Suppressive Agents and Pazopanib on Outcomes in Soft-Tissue Sarcoma Patients Treated within the EORTC 62043/62072 Trials
Authors: Mir Olivier , Touati Nathan , Lia Michela , Litière Saskia , Le Cesne Axel , Sleijfer Stefan , Blay Jean-Yves , Leahy Michael , Young Robin , Mathijssen Ron H.J. , Van Erp Nielka P. , Gelderblom Hans , Van der Graaf Winette T. , Gronchi Alessandro
Published: February 2019

Purpose:

Pazopanib is active in soft-tissue sarcoma (STS). Because pazopanib absorption is pH-dependent, coadministration with gastric acid–suppressive (GAS) agents such as proton pump inhibitors could affect exposure of pazopanib, and thereby its therapeutic effects.

Patients and Methods:

The EORTC 62043 and 62072 were single-arm phase II and placebo-controlled phase III studies, respectively, of pazopanib in advanced STS. We first compared the outcome of patients treated with pazopanib with or without GAS agents for ≥80% of treatment duration, and subsequently using various thresholds. The impact of concomitant GAS therapy was assessed on progression-free survival (PFS) and overall survival (OS) using multivariate Cox models, exploring and comparing also the potential effect on placebo-treated patients.

Results:

Of 333 eligible patients, 59 (17.7%) received concomitant GAS therapy for >80% of pazopanib treatment duration. Median PFS was shorter in GAS therapy users versus nonusers: 2.8 vs. 4.6 months, respectively [HR, 1.49; 95% confidence interval (CI), 1.11–1.99; P = 0.01]. Concomitant administration of GAS therapy was also associated with a shorter median OS: 8.0 vs. 12.6 months (HR, 1.81; 95% CI, 1.31–2.49; P < 0.01). The longer the overlapping use of GAS agents and pazopanib, the worse the outcome with pazopanib. These effects were not observed in placebo-treated patients (HR, 0.82; 95% CI, 0.51–1.34; P = 0.43 for PFS and HR, 0.84; 95% CI, 0.48–1.48; P = 0.54 for OS).

Conclusions:

Coadministration of long-term GAS therapy with pazopanib was associated with significantly shortened PFS and OS. Withdrawal of GAS agents must be considered whenever possible. Therapeutic drug monitoring of pazopanib plasma concentrations may be helpful for patients on pazopanib and GAS therapy.
Beneficial Effect of Early Intervention with Garenoxacin for Bacterial Infection-Induced Acute Exacerbation of Bronchial Asthma and Chronic Obstructive Pulmonary Disease
Authors: Homma Tetsuya , Kawahara Tomoko , Mikuni Hatsuko , Uno Tomoki , Sato Haruna , Fujiwara Akiko , Uchida Yoshitaka , Fukuda Yosuke , Manabe Ryo , Ida Hitomi , Kuwahara Naota , Kimura Tomoyuki , Hirai Kuniaki , Miyata Yoshito , Jinno Megumi , Yamaguchi Munehiro , Kishino Yasunari , Murata Yasunori , Ohta Shin , Yamamoto Mayumi , Watanabe Yoshio , Yamaguchi Hirofumi , Kusumoto Sojiro , Suzuki Shintaro , Tanaka Akihiko , Yokoe Takuya , Ohnishi Tsukasa , Sagara Hironori
Published: February 2019

Background: Chronic obstructive pulmonary disease (COPD) and asthma have similar clinical features and are both exacerbated by airway infection. Objective: To determine whether garenoxacin mesylate hydrate (GRNX) added to the standard care for bacterial infection-induced acute exacerbation of asthma or COPD in adults has clinical benefits. Method: This single-arm clinical trial was conducted from January 2015 to March 2016. Adults with a history of asthma or COPD for more than 12 months were recruited within 48 h of presentation with fever and acute deterioration of asthma or COPD requiring additional intervention. Participants were administered 400 mg GRNX daily for 7 days without additional systemic corticosteroids or other antibiotics. The primary outcome was efficacy of GRNX based on clinical symptoms and blood test results after 7 days of treatment. Secondary outcomes were: (1) comparison of the blood test results, radiograph findings, and bacterial culture surveillance before and after treatment; (2) effectiveness of GRNX after 3 days of administration; (3) analyzation of patient symptoms based on patient diary; and (4) continued effectiveness of GRNX on 14th day after the treatment (visit 3). Results: The study included 44 febrile patients (34 asthma and 10 COPD). Frequently isolated bacteria included Moraxella catarrhalis (n = 6) and Klebsiella pneumoniae (n = 4). On visit 2, 40 patients responded, and no severe adverse events were observed. All secondary outcomes showed favorable results. Conclusion: GRNX effectively treated asthma and COPD patients with acute bacterial infection without severe adverse events. Further research with a larger study population is needed.
Tumor Cavity Recurrence after Stereotactic Radiosurgery of Surgically Resected Brain Metastases: Implication of Deviations from Contouring Guidelines
Authors: McDermott David M. , Hack Joshua D. , Cifarelli Christoper P. , Vargo John A.
Published: February 2019

Background: Significant heterogeneity exists in target volumes for postoperative stereotactic radiosurgery (SRS) for brain metastases. A set of contouring guidelines was recently published, and we investigated the impact of deviations. Methods: Patients (n = 41) undergoing single-fraction Gamma Knife SRS following surgical resection of brain metastases from 2011 to 2017 were retrospectively reviewed. SRS included the entire contrast-enhancing cavity with heterogeneity in inclusion of the surgical tract and no routine margin along the dura or clinical target volume margin. Follow-up MR imaging was fused with SRS plans to assess patterns of failure. Results: The median follow-up was 11.1 months with a median prescription of 18 Gy. There were 5 local failures: infield (n = 3, 60%), surgical tract (n = 1, 20%), and marginal > 5 mm from the resection cavity (n = 1, 20%). No marginal failures < 5 mm or dural margin failures were noted. For deep lesions (n = 13), 62% (n = 8) had the entire tract covered. The only tract recurrence was in a deep lesion without coverage of the surgical tract (n = 1/5). Conclusion: In this small preliminary experience, despite no routine inclusion of the dural tract or bone flap, no failures were noted in these locations. Omission of the surgical tract in deep lesions may increase failure rates.