bluuebunny/crossref_metadata_2025 huggingface dataset:
Immobilization Effect of Morphological, Thermal and Optical Properties in Biotemplate on Zinc Oxide Nanocomposite from Chitosan
Authors: Karpuraranjith M. , Thambidurai S.
Published: July 2017

Biotemplate-based zinc oxide nanocomposite was effectively prepared via simple chemical precipitation route. The functional groups of amino (–NH2), hydroxyl (–OH) and O–Zn–O were confirmed and characterized by FTIR spectroscopy. The structural and morphological properties were confirmed by XRD, UV–Vis DRS, HR-SEM and TEM analyses. The elemental composition of carbon, nitrogen, zinc and oxygen was confirmed by energy-dispersive X-ray analysis (EDAX) and Brunauer–Emmett–Teller high surface area of materials was estimated to be 52.49[Formula: see text]m2/g, respectively. Thermogravimetric analysis (TGA) shows that biotemplate on zinc oxide nanocomposite has higher thermal stability than chitosan matrix. The results demonstrate that biotemplate on zinc oxide matrix causes immobilization effect among the two components. Therefore, chitosan–ZnO nanocomposite has a microcrystalline morphological structure and also good thermal stability, so it can be a promising material for sensors, medical, tissue engineering and wastewater treatment applications.
HUMAN RESOURCES AND INNOVATIVE BEHAVIOUR: IMPROVING NURSING PERFORMANCE
Authors: XERRI MATTHEW J. , REID STUART R. M.
Published: July 2017

This study examines, using the social exchange theory, the mediating effect of employees’ perception of wellbeing on the relationship between two human resource (HR) management factors (satisfaction with teamwork and satisfaction with training opportunities) and innovative behaviour of nurses working in Australian public and private hospitals. Current nurse shortages and limited budgets have increased the need for hospitals to improve their efficiency and cost-effectiveness. It is proposed that fostering innovative behaviour is one way that hospitals can improve the efficiency and effectiveness of nurses. A cross-sectional self-report survey was completed by 220 nurses working within Australian hospitals. The results show that an employee’s perception of their wellbeing completely mediated the relationship between satisfaction with training opportunities and their innovative behaviour and partially mediated the relationship between satisfaction with teamwork and innovative behaviour. The findings shed new light on how HR management factors can foster innovative behaviour. The results raise new implications for managers seeking to stimulate innovative behaviour, highlighting the importance of cultivating an organisational environment conducive to positive perceptions of wellbeing.
The Great Shift of Globalization: From the Transatlantic Axis towards China and Emerging Asia
Authors: Steinbock Dan
Published: July 2017

Since the mid-2010s, global economic integration, as measured by world trade, investment and migration, has come to a standstill. During the global crisis of 2008–2009, the negative demand shock in the advanced West and the drastic trade plunge in the emerging East highlighted the increasing inter-dependency in the global economy. Nevertheless, in the past few years, world trade has been falling; world investment continues to stagnate while slower migration has given rise to elevated global displacement and refugee crises, despite peace time conditions. In the Trump era, the eclipse of the U.S. postwar trading regime is accompanied with the rise of new protectionism that has a historical precedent. While China seeks to promote globalization, the White House is moving from multilateral free trade toward bilateral deficit targeting, despite its ongoing secular rebalancing and associated cyclical fluctuations. Although the first Trump-Xi Summit suggests that there may be more room for policy compromises than initially anticipated, the eclipse of U.S. globalism will make any reconciliation difficult. Nevertheless, the global economy is now amid a secular transition that is characterized by increasing South-to-South trade, investment and migration. In this new era, globalization, responsibility and accountability in the international community can no longer be subject mainly to the interests of major advanced economies. While global economic integration was initiated by advanced economies in the 20th century, it will be completed by emerging economies in the 21st century. The drivers of globalization are moving from the transatlantic axis to China and emerging Asia.
Syntrophy Goes Electric: Direct Interspecies Electron Transfer
Authors: Lovley Derek R.
Published: July 2017

Direct interspecies electron transfer (DIET) has biogeochemical significance, and practical applications that rely on DIET or DIET-based aspects of microbial physiology are growing. Mechanisms for DIET have primarily been studied in defined cocultures in which Geobacter species are one of the DIET partners. Electrically conductive pili (e-pili) can be an important electrical conduit for DIET. However, there may be instances in which electrical contacts are made between electron transport proteins associated with the outer membranes of the partners. Alternatively, DIET partners can plug into conductive carbon materials, such as granular activated carbon, carbon cloth, and biochar, for long-range electron exchange without the need for e-pili. Magnetite promotes DIET, possibly by acting as a substitute for outer-surface c-type cytochromes. DIET is the primary mode of interspecies electron exchange in some anaerobic digesters converting wastes to methane. Promoting DIET with conductive materials shows promise for stabilizing and accelerating methane production in digesters, permitting higher organic loading rates. Various lines of evidence suggest that DIET is important in terrestrial wetlands, which are an important source of atmospheric methane. DIET may also have a role in anaerobic methane oxidation coupled to sulfate reduction, an important control on methane releases. The finding that DIET can serve as the source of electrons for anaerobic photosynthesis further broadens its potential environmental significance. Microorganisms capable of DIET are good catalysts for several bioelectrochemical technologies and e-pili are a promising renewable source of electronic materials. The study of DIET is in its early stages, and additional investigation is required to better understand the diversity of microorganisms that are capable of DIET, the importance of DIET to carbon and electron flow in anaerobic environments, and the biochemistry and physiology of DIET.
Material Perception
Authors: Fleming Roland W.
Published: July 2017

Under typical viewing conditions, human observers effortlessly recognize materials and infer their physical, functional, and multisensory properties at a glance. Without touching materials, we can usually tell whether they would feel hard or soft, rough or smooth, wet or dry. We have vivid visual intuitions about how deformable materials like liquids or textiles respond to external forces and how surfaces like chrome, wax, or leather change appearance when formed into different shapes or viewed under different lighting. These achievements are impressive because the retinal image results from complex optical interactions between lighting, shape, and material, which cannot easily be disentangled. Here I argue that because of the diversity, mutability, and complexity of materials, they pose enormous challenges to vision science: What is material appearance, and how do we measure it? How are material properties estimated and represented? Resolving these questions causes us to scrutinize the basic assumptions of mid-level vision.
Changes in microvascular density differentiate metabolic health outcomes in monkeys with prior radiation exposure and subsequent skeletal muscle ECM remodeling
Authors: Fanning K. M. , Pfisterer B. , Davis A. T. , Presley T. D. , Williams I. M. , Wasserman D. H. , Cline J. M. , Kavanagh K.
Published: July 2017

Radiation exposure accelerates the onset of age-related diseases such as diabetes, cardiovascular disease, and neoplasia and, thus, lends insight into in vivo mechanisms common to these disorders. Fibrosis and extracellular matrix (ECM) remodeling, which occur with aging and overnutrition and following irradiation, are risk factors for development of type 2 diabetes mellitus. We previously demonstrated an increased incidence of skeletal muscle insulin resistance and type 2 diabetes mellitus in monkeys that had been exposed to whole body irradiation 5–9 yr prior. We hypothesized that irradiation-induced fibrosis alters muscle architecture, predisposing irradiated animals to insulin resistance and overt diabetes. Rhesus macaques ( Macaca mulatta, n = 7–8/group) grouped as nonirradiated age-matched controls (Non-Rad-CTL), irradiated nondiabetic monkeys (Rad-CTL), and irradiated monkeys that subsequently developed diabetes (Rad-DM) were compared. Prior radiation exposure resulted in persistent skeletal muscle ECM changes, including a relative overabundance of collagen IV and a trend toward increased transforming growth factor-β1. Preservation of microvascular markers differentiated the irradiated diabetic and nondiabetic groups. Microvascular density and plasma nitrate and heat shock protein 90 levels were lower in Rad-DM than Rad-CTL. These results are consistent with a protective effect of abundant microvasculature in maintaining glycemic control within radiation-induced fibrotic muscle.
Effect of endurance training and branched-chain amino acids on the signaling for muscle protein synthesis in CKD model rats fed a low-protein diet
Authors: Yoshida Takuya , Kakizawa Sachika , Totsuka Yuri , Sugimoto Miho , Miura Shinji , Kumagai Hiromichi
Published: July 2017

A low-protein diet (LPD) protects against the progression of renal injury in patients with chronic kidney disease (CKD). However, LPD may accelerate muscle wasting in these patients. Both exercise and branched-chain amino acids (BCAA) are known to increase muscle protein synthesis by activating the mammalian target of rapamycin (mTOR) pathway. The aim of this study was to investigate whether endurance exercise and BCAA play a role for increasing muscle protein synthesis in LPD-fed CKD (5/6 nephrectomized) rats. Both CKD and sham rats were pair-fed on LPD or LPD fortified with a BCAA diet (BD), and approximately one-half of the animals in each group was subjected to treadmill exercise (15 m/min, 1 h/day, 5 days/wk). After 7 wk, renal function was measured, and soleus muscles were collected to evaluate muscle protein synthesis. Renal function did not differ between LPD- and BD-fed CKD rats, and the treadmill exercise did not accelerate renal damage in either group. The treadmill exercise slightly increased the phosphorylation of p70s6 kinase, a marker of mTOR activity, in the soleus muscle of LPD-fed CKD rats compared with the sham group. Furthermore, BCAA supplementation of the LPD-fed, exercise-trained CKD rats restored the phosphorylation of p70s6 kinase to the same level observed in the sham group; however, the corresponding induced increase in muscle protein synthesis and muscle mass was marginal. These results indicate that the combination of treadmill exercise and BCAA stimulates cell signaling to promote muscle protein synthesis; however, the implications of this effect for muscle growth remain to be clarified.
Differential contributions to the interception of occluded ballistic trajectories by the temporoparietal junction, area hMT/V5+, and the intraparietal cortex
Authors: Delle Monache Sergio , Lacquaniti Francesco , Bosco Gianfranco
Published: July 2017

The ability to catch objects when transiently occluded from view suggests their motion can be extrapolated. Intraparietal cortex (IPS) plays a major role in this process along with other brain structures, depending on the task. For example, interception of objects under Earth’s gravity effects may depend on time-to-contact predictions derived from integration of visual signals processed by hMT/V5+ with a priori knowledge of gravity residing in the temporoparietal junction (TPJ). To investigate this issue further, we disrupted TPJ, hMT/V5+, and IPS activities with transcranial magnetic stimulation (TMS) while subjects intercepted computer-simulated projectile trajectories perturbed randomly with either hypo- or hypergravity effects. In experiment 1, trajectories were occluded either 750 or 1,250 ms before landing. Three subject groups underwent triple-pulse TMS (tpTMS, 3 pulses at 10 Hz) on one target area (TPJ | hMT/V5+ | IPS) and on the vertex (control site), timed at either trajectory perturbation or occlusion. In experiment 2, trajectories were entirely visible and participants received tpTMS on TPJ and hMT/V5+ with same timing as experiment 1. tpTMS of TPJ, hMT/V5+, and IPS affected differently the interceptive timing. TPJ stimulation affected preferentially responses to 1-g motion, hMT/V5+ all response types, and IPS stimulation induced opposite effects on 0-g and 2-g responses, being ineffective on 1-g responses. Only IPS stimulation was effective when applied after target disappearance, implying this area might elaborate memory representations of occluded target motion. Results are compatible with the idea that IPS, TPJ, and hMT/V5+ contribute to distinct aspects of visual motion extrapolation, perhaps through parallel processing.

NEW & NOTEWORTHY Visual extrapolation represents a potential neural solution to afford motor interactions with the environment in the face of missing information. We investigated relative contributions by temporoparietal junction (TPJ), hMT/V5+, and intraparietal cortex (IPS), cortical areas potentially involved in these processes. Parallel organization of visual extrapolation processes emerged with respect to the target’s motion causal nature: TPJ was primarily involved for visual motion congruent with gravity effects, IPS for arbitrary visual motion, whereas hMT/V5+ contributed at earlier processing stages.
Enhancement of phase-locking in rodents. I. An axonal recording study in gerbil
Authors: Wei Liting , Karino Shotaro , Verschooten Eric , Joris Philip X.
Published: July 2017

The trapezoid body (TB) contains axons of neurons in the anteroventral cochlear nucleus projecting to monaural and binaural nuclei in the superior olivary complex (SOC). Characterization of these monaural inputs is important for the interpretation of response properties of SOC neurons. In particular, understanding of the sensitivity to interaural time differences (ITDs) in neurons of the medial and lateral superior olive requires knowledge of the temporal firing properties of the monaural excitatory and inhibitory inputs to these neurons. In recent years, studies of ITD sensitivity of SOC neurons have made increasing use of small animal models with good low-frequency hearing, particularly the gerbil. We presented stimuli as used in binaural studies to monaural neurons in the TB and studied their temporal coding. We found that general trends as have been described in the cat are present in gerbil, but with some important differences. Phase-locking to pure tones tends to be higher in TB axons and in neurons of the medial nucleus of the TB (MNTB) than in the auditory nerve for neurons with characteristic frequencies (CFs) below 1 kHz, but this enhancement is quantitatively more modest than in cat. Stronger enhancement is common when TB neurons are stimulated at low frequencies below CF. It is rare for TB neurons in gerbil to entrain to low-frequency stimuli, i.e., to discharge a well-timed spike on every stimulus cycle. Also, complex phase-locking behavior, with multiple modes of increased firing probability per stimulus cycle, is common in response to low frequencies below CF.

NEW & NOTEWORTHY Phase-locking is an important property of neurons in the early auditory pathway: it is critical for the sensitivity to time differences between the two ears enabling spatial hearing. Studies in cat have shown an improvement in phase-locking from the peripheral to the central auditory nervous system. We recorded from axons in an output tract of the cochlear nucleus and show that a similar but more limited form of temporal enhancement is present in gerbil.
Differential expression of long-term potentiation among identified inhibitory inputs to dopamine neurons
Authors: Simmons DeNard V. , Petko Alyssa K. , Paladini Carlos A.
Published: July 2017

The in vivo firing pattern of ventral tegmental area (VTA) dopamine neurons is controlled by GABA afferents originating primarily from the nucleus accumbens (NAc), rostromedial tegmental nucleus (RMTg), and local GABA neurons within the VTA. Although different forms of plasticity have been observed from GABA inputs to VTA dopamine neurons, one dependent on cyclic GMP synthesis and the other on adenylyl cyclase activation, it is unknown whether plasticity is differentially expressed in each. Using an optogenetic strategy, we show that identified inhibitory postsynaptic currents (IPSCs) from local VTA GABA neurons and NAc afferents exhibit a cyclic GMP-dependent long-term potentiation (LTP) that is capable of inhibiting the firing activity of dopamine neurons. However, this form of LTP was not induced from RMTg afferents. Only an adenylyl cyclase-mediated increase in IPSCs was exhibited by all three inputs. Thus discrete plasticity mechanisms recruit overlapping but different subsets of GABA inputs to VTA dopamine neurons.

NEW & NOTEWORTHY We describe a mapping of plasticity expression, mediated by different mechanisms, among three distinct GABA afferents to ventral tegmental area (VTA) dopamine neurons: the rostromedial tegmental nucleus, the nucleus accumbens, and the local GABA neurons within the VTA known to synapse on VTA dopamine neurons. This work is the first demonstration that discrete plasticity mechanisms recruit overlapping but different subsets of GABA inputs to VTA dopamine neurons.
Novel channel-mediated choline transport in cholinergic neurons of the mouse retina
Authors: Ishii Toshiyuki , Homma Kohei , Mano Asuka , Akagi Takumi , Shigematsu Yasuhide , Shimoda Yukio , Inoue Hiroyoshi , Kakinuma Yoshihiko , Kaneda Makoto
Published: July 2017

Choline uptake into the presynaptic terminal of cholinergic neurons is mediated by the high-affinity choline transporter and is essential for acetylcholine synthesis. In a previous study, we reported that P2X2 purinoceptors are selectively expressed in OFF-cholinergic amacrine cells of the mouse retina. Under specific conditions, P2X2 purinoceptors acquire permeability to large cations, such as N-methyl-d-glucamine, and therefore potentially could act as a noncanonical pathway for choline entry into neurons. We tested this hypothesis in OFF-cholinergic amacrine cells of the mouse retina. ATP-induced choline currents were observed in OFF-cholinergic amacrine cells, but not in ON-cholinergic amacrine cells, in mouse retinal slice preparations. High-affinity choline transporters are expressed at higher levels in ON-cholinergic amacrine cells than in OFF-cholinergic amacrine cells. In dissociated preparations of cholinergic amacrine cells, ATP-activated cation currents arose from permeation of extracellular choline. We also examined the pharmacological properties of choline currents. Pharmacologically, α,β-methylene ATP did not produce a cation current, whereas ATPγS and benzoyl-benzoyl-ATP (BzATP) activated choline currents. However, the amplitude of the choline current activated by BzATP was very small. The choline current activated by ATP was strongly inhibited by pyridoxalphosphate-6-azophenyl-2′,4′-sulfonic acid. Accordingly, P2X2 purinoceptors expressed in HEK-293T cells were permeable to choline and similarly functioned as a choline uptake pathway. Our physiological and pharmacological findings support the hypothesis that P2 purinoceptors, including P2X2 purinoceptors, function as a novel choline transport pathway and may provide a new regulatory mechanism for cholinergic signaling transmission at synapses in OFF-cholinergic amacrine cells of the mouse retina.

NEW & NOTEWORTHY Choline transport across the membrane is exerted by both the high-affinity and low-affinity choline transporters. We found that choline can permeate P2 purinergic receptors, including P2X2 purinoceptors, in cholinergic neurons of the retina. Our findings show the presence of a novel choline transport pathway in cholinergic neurons. Our findings also indicate that the permeability of P2X2 purinergic receptors to choline observed in the heterologous expression system may have a physiological relevance in vivo.
Aging does not affect the intralimb coordination elicited by slip-like perturbation of different intensities
Authors: Aprigliano Federica , Martelli Dario , Tropea Peppino , Pasquini Guido , Micera Silvestro , Monaco Vito
Published: July 2017

This study was aimed at verifying whether aging modifies intralimb coordination strategy during corrective responses elicited by unexpected slip-like perturbations delivered during steady walking on a treadmill. To this end, 10 young and 10 elderly subjects were asked to manage unexpected slippages of different intensities. We analyzed the planar covariation law of the lower limb segments, using the principal component analysis, to verify whether elevation angles of older subjects covaried along a plan before and after the perturbation. Results showed that segments related to the perturbed limbs of both younger and older people do not covary after all perturbations. Conversely, the planar covariation law of the unperturbed limb was systematically held for younger and older subjects. These results occurred despite differences in spatio-temporal and kinematic parameters being observed among groups and perturbation intensities. Overall, our analysis revealed that aging does not affect intralimb coordination during corrective responses induced by slip-like perturbation, suggesting that both younger and older subjects adopt this control strategy while managing sudden and unexpected postural transitions of increasing intensities. Accordingly, results corroborate the hypothesis that balance control emerges from a governing set of biomechanical invariants, that is, suitable control schemes (e.g., planar covariation law) shared across voluntary and corrective motor behaviors, and across different sensory contexts due to different perturbation intensities, in both younger and older subjects. In this respect, our findings provide further support to investigate the effects of specific task training programs to counteract the risk of fall.

NEW & NOTEWORTHY This study was aimed at investigating how aging affects the intralimb coordination of lower limb segments, described by the planar covariation law, during unexpected slip-like perturbations of increasing intensity. Results revealed that neither the aging nor the perturbation intensity affects this coordination strategy. Accordingly, we proposed that the balance control emerges from an invariant set of control schemes shared across different sensory motor contexts and despite age-related neuromuscular adaptations.
Broadband Enhancement of Optical Frequency Comb Using Cascaded Four-Wave Mixing in Photonic Crystal Fiber
Authors: Eltaif Tawfig
Published: July 2017

A cascaded intensity modulator (IM) and phase modulator (PM) are used to modulate a continuous-wave (CW) laser and generate an optical frequency comb (OFC). Thus, the generated comb is utilized as an initial seed and combined with another CW-laser to generate four-wave mixing (FWM) in photonic crystal fiber (PCF). Results show that an initial flat 30 GHz OFC of 29, 55 lines within power fluctuation of 0.8 dB and 2 dB, respectively, can be achieved by setting the ratio of the DC bias to amplitude of sinusoidal signal at 0.1 and setting the modulation indices of both IM and PM at 10. Moreover, the 1st order of FWM created through 14 m of PCF has over 68 and 94 lines with fluctuation of 0.8 dB and 2 dB, respectively. Hence, the generated wavelengths of 1st left and right order of FWM can be tuned in a range from ~1500 nm to ~1525 nm and ~1590 nm to ~1604 nm, respectively.
Characterization of Extruded Poly(lactic acid)/Pecan Nutshell Biocomposites
Authors: Álvarez-Chávez C. R. , Sánchez-Acosta D. L. , Encinas-Encinas J. C. , Esquer J. , Quintana-Owen P. , Madera-Santana T. J.
Published: July 2017

Pecan nutshells are a solid form of waste obtained from the pecan nut production and they have been explored as an inexpensive filler for incorporation by melt blending into the poly(lactic acid) (PLA) matrix. The pecan nutshells contain polyphenols, proteins, tannins, sugars, and lipids; some of these components must be released in order to improve adhesion with a polymeric matrix. The physicochemical characterization of the extruded biocomposites of pecan nutshell powder (PNSP) at 0, 5, and 7.5% wt. with two treatments (untreated and defatted) into PLA is presented in this work. The incorporation of PNSP into the PLA matrix caused a variation in color and density and increased the water absorption. However, some mechanical and thermal parameters of the biocomposites showed a significant decrease. The morphological analysis showed good dispersion and adhesion of the PNSP to the PLA matrix. Based on the results of the characterization, biocomposites formulated with defatted PNSP have a potential to be used as sustainable fillers in PLA biocomposites. These biocomposites have a potential application as food containers, packaging trays, or disposable items.
Area Spectral Efficiency and Energy Efficiency Tradeoff in Ultradense Heterogeneous Networks
Authors: Xiang Lanhua , Chen Hongbin , Zhao Feng
Published: July 2017

In order to meet the demand of explosive data traffic, ultradense base station (BS) deployment in heterogeneous networks (HetNets) as a key technique in 5G has been proposed. However, with the increment of BSs, the total energy consumption will also increase. So, the energy efficiency (EE) has become a focal point in ultradense HetNets. In this paper, we take the area spectral efficiency (ASE) into consideration and focus on the tradeoff between the ASE and EE in an ultradense HetNet. The distributions of BSs in the two-tier ultradense HetNet are modeled by two independent Poisson point processes (PPPs) and the expressions of ASE and EE are derived by using the stochastic geometry tool. The tradeoff between the ASE and EE is formulated as a constrained optimization problem in which the EE is maximized under the ASE constraint, through optimizing the BS densities. It is difficult to solve the optimization problem analytically, because the closed-form expressions of ASE and EE are not easily obtained. Therefore, simulations are conducted to find optimal BS densities.
Reachable Set Estimation for a Class of Nonlinear Time-Varying Systems
Authors: Sun Yuangong , Meng Fanwei
Published: July 2017

This paper studies the problem of reachable set estimation for a class of nonlinear time-varying systems with disturbances. New necessary and (or) sufficient conditions are derived for the existence of a ball such that all the solutions of the system converge asymptotically within it. Explicit estimation on the decay rate is also presented. The method used in this paper is motivated by that for positive systems, which is different from the conventional Lyapunov-Krasovskii functional method. A numerical example is given to illustrate the effectiveness of the obtained result.
Dahuang Zhechong Pill Combined with Doxorubicin Induces Cell Death through Regulating Energy Metabolism in Human Hepatocellular Carcinoma Cells
Authors: Wu Li , Zhao Jiayu , Cai Hao , Wang Jiaqi , Chen Zhipeng , Li Weidong , Liu Xiao
Published: July 2017

Many physiological activities such as cell survival, proliferation, defense, adaptation, and metabolism need to consume energy. Hepatoma cells can quickly start stress responses like multidrug resistance (MDR) requiring adenosine triphosphate (ATP) consumption after administration of chemotherapeutics. We employed CCK‐8 assay to evaluate cell viability and the flow cytometry to confirm apoptosis and necrosis. ELISA kit was used to determine intracellular levels of ATP in lysates. Western blot was employed to analyze the expressions of key enzymes involved in energy metabolism. We found that doxorubicin (DOX) potently stimulated apoptosis at a low dose and even induced necrosis at a high dose in SMMC‐7721. DHZCP combined with DOX at low or middle dose enhanced the synergistic antihepatoma effect. Results indicated that Dahuang Zhechong Pill (DHZCP) inhibited the expressions of several key enzymes involved in oxidative phosphorylation and reduced intracellular ATP levels. The combination of DHZCP with DOX reversed the elevation of intracellular ATP levels, and a significantly synergistic antitumor effect was observed. DHZCP could not only strengthen the therapeutic effects of chemotherapeutic drugs but also decrease the doses of chemotherapeutic drugs and the incidences of adverse reactions, providing novel strategies for clinical treatment of liver cancer.
Joint Torque and Mechanical Power of Lower Extremity and Its Relevance to Hamstring Strain during Sprint Running
Authors: Zhong Yunjian , Fu Weijie , Wei Shutao , Li Qing , Liu Yu
Published: July 2017

The aim of this study was to quantify the contributions of lower extremity joint torques and the mechanical power of lower extremity muscle groups to further elucidate the loadings on hamstring and the mechanics of its injury. Eight national-level male sprinters performed maximum-velocity sprint running on a synthetic track. The 3D kinematic data and ground reaction force (GRF) were collected synchronously. Intersegmental dynamics approach was used to analyze the lower extremity joint torques and power changes in the lower extremity joint muscle groups. During sprinting, the GRF during the stance phase and the motion-dependent torques (MDT) during the swing phase had a major effect on the lower extremity movements and muscle groups. Specifically, during the stance phase, torque produced and work performed by the hip and knee muscles were generally used to counteract the GRF. During the swing phase, the role of the muscle torque changed to mainly counteract the effect of MDT to control the movement direction of the lower extremity. Meanwhile, during the initial stance and late swing phases, the passive torques, namely, the ground reaction torques and MDT produced by the GRF and the inertial movement of the segments of the lower extremity, applied greater stress to the hamstring muscles.
The Association of Mammographic Density and Molecular Breast Cancer Subtype
Authors: Edwards Brandy L. , Atkins Kristen A. , Stukenborg George J. , Novicoff Wendy M. , Larson Krista N. , Cohn Wendy F. , Harvey Jennifer A. , Schroen Anneke T.
Published: July 2017

Background: Mammographic density (MD) is associated with increased breast cancer risk, yet limited data exist on an association between MD and breast cancer molecular subtypes.

Methods: Women ages 18 years and older with breast cancer and available mammograms between 2003 and 2012 were enrolled in a larger study on MD. MD was classified by the Breast Imaging Reporting and Data System (BI-RADS) classification and by volumetric breast percent density (Volpara Solutions). Subtype was assigned by hormone receptor status, tumor grade, and mitotic score (MS). Subtypes included: Luminal-A (ER/PR+ and grade = 1; ER/PR+ and grade = 2 and MS = 1; ER+/PR− and grade = 1; n = 233); Luminal-B (ER+ and grade = 3 or MS = 3; ER+/PR− and grade = 2; ER/PR+ and grade = 2 and MS = 2; n = 79); Her-2-neu+ (H2P; n = 59); triple-negative (ER/PR−, Her-2−; n = 86). Precancer factors including age, race, body mass index (kg/m2), family history of breast cancer, and history of lobular carcinoma in situ were analyzed.

Results: A total of 604 patients had invasive cancer; 457 had sufficient information for analysis. Women with H2P tumors were younger (P = 0.011) and had the highest volumetric percent density (P = 0.002) among subgroups. Multinomial logistic regression (LA = reference) demonstrated that although quantitative MD does not significantly differentiate between all subtypes (P = 0.123), the association between MD and H2P tumors is significant (OR = 1.06; confidence interval, 1.01–1.12). This association was not seen using BI-RADS classification in bivariable analysis but was statistically significant (P = 0.047) when controlling for other precancer factors.

Conclusions: Increased MD is more strongly associated with H2P tumors when compared with LA.

Impact: Delineating risk factors specific to breast cancer subtype may promote development of individualized risk prediction models and screening strategies. Cancer Epidemiol Biomarkers Prev; 26(10); 1487–92. ©2017 AACR.
Targeting AXL and mTOR Pathway Overcomes Primary and Acquired Resistance to WEE1 Inhibition in Small-Cell Lung Cancer
Authors: Sen Triparna , Tong Pan , Diao Lixia , Li Lerong , Fan Youhong , Hoff Jennifer , Heymach John V. , Wang Jing , Byers Lauren Averett
Published: July 2017

Purpose: Drugs targeting DNA repair and cell-cycle checkpoints have emerged as promising therapies for small-cell lung cancer (SCLC). Among these, the WEE1 inhibitor AZD1775 has shown clinical activity in a subset of SCLC patients, but resistance is common. Understanding primary and acquired resistance mechanisms will be critical for developing effective WEE1 inhibitor combinations.

Experimental Design: AZD1775 sensitivity in SCLC cell lines was correlated with baseline expression level of 200 total or phosphorylated proteins measured by reverse-phase protein array (RPPA) to identify predictive markers of primary resistance. We further established AZD1775 acquired resistance models to identify mechanism of acquired resistance. Combination regimens were tested to overcome primary and acquired resistance to AZD1775 in in vitro and in vivo SCLC models.

Results: High-throughput proteomic profiling demonstrate that SCLC models with primary resistance to AZD1775 express high levels of AXL and phosphorylated S6 and that WEE1/AXL or WEE1/mTOR inhibitor combinations overcome resistance in vitro and in vivo. Furthermore, AXL, independently and via mTOR, activates the ERK pathway, leading to recruitment and activation of another G2-checkpoint protein, CHK1. AZD1775 acquired resistance models demonstrated upregulation of AXL, pS6, and MET, and resistance was overcome with the addition of AXL (TP0903), dual-AXL/MET (cabozantinib), or mTOR (RAD001) inhibitors.

Conclusions: AXL promotes resistance to WEE1 inhibition via downstream mTOR signaling and resulting activation of a parallel DNA damage repair pathway, CHK1. These findings suggest rational combinations to enhance the clinical efficacy of AZD1775, which is currently in clinical trials for SCLC and other malignancies. Clin Cancer Res; 23(20); 6239–53. ©2017 AACR.
Die Rolle der Talgdrüsen bei psoriatischer Alopezie: Ein unterschätzter Faktor
Authors: Philipp Sandra
Published: July 2017

Hintergrund: Psoriasis ist eine chronisch-entzündliche Hauterkrankung, die durch Plaques mit Entzündung, Infiltration, Hyper-/Parakeratosis und Desquamation gekennzeichnet ist. Mikroskopische Befunde aus früheren Studien belegen ein gewisses Maß an Atrophie der Talgdrüsen bei Patienten mit Psoriasis vulgaris und psoriatischer Alopezie. Ziel: Das Ziel dieser Studie war es, mögliche Veränderungen der Talgdrüsen bei Patienten mit Psoriasis-Plaques und insbesondere psoriatischer Alopezie zu untersuchen. Methoden: Es wurden Proben betroffener und nicht-betroffener Haut von 14 Patienten mit Psoriasis entnommen und im Anschluss histologisch und stereologisch analysiert. Die Stereologie dient der Erkennung und Quantifizierung dreidimensionaler Strukturen ex vivo. Darüber hinaus wurde der Differenzierungsprozess der Sebozyten bei weiteren 14 Psoriasis-Patienten mittels Immunhistochemie von beteiligten und unbeteiligten Hautproben untersucht. Ergebnisse: In den Psoriasis-Läsionen wurde im Vergleich zur nicht durch Psoriasis geschädigten Haut eine signifikante Reduktion der Anzahl der Talgdrüsen sowie des Volumens der einzelnen Talgdrüsen festgestellt. Darüber hinaus erschien es als wahrscheinlich, dass Sebozyten in psoriatischen Läsionen sich nicht ordnungsgemäß differenzieren. Schlussfolgerung: Diese Ergebnisse deuten darauf hin, dass die Talgdrüsen möglicherweise eine aktive Rolle in der Entwicklung von Psoriasis-Läsionen und insbesondere der Entstehung von psoriatischer Alopezie spielen.
Feld- versus Flächentherapie bei aktinischen Keratosen mittels Photodynamischer Therapie
Authors: Braun-Falco Markus
Published: July 2017

Hintergrund: Bei aktinischen Keratosen (AK) wird oft von Herd zu Herd separat behandelt. In den letzten Jahren sind jedoch AK vermehrt als Flächenerkrankungen beschrieben worden, die nicht auf die einzelnen klinisch erkennbaren Läsionen begrenzt sind. Entsprechend sollte auch feldweise behandelt werden, um so möglicherweise das Risiko weiterer AK-Läsionen, Sekundärtumoren und lokaler Rezidivierung zu verringern. Ziel: Das Primärziel der Studie war die Ermittlung der Anzahl neuer Läsionen 9 Monate nach der Photodynamischen Therapie mit Methylaminolävulinat (MAL-PDT). Als Sekundärziele ermittelten wir die Anzahl neuer Läsionen 3 und 6 Monate nach der Therapie sowie die prozentuale Reduktion der AK gegenüber Studienbeginn 3, 6 und 9 Monate nach der MAL-PDT. Methoden: Es handelte sich um eine monozentrische, prospektive, randomisierte, für den Prüfer verblindete Pilotstudie im Seitenvergleich mit einer Studiendauer von einem Jahr. Die Studienpopulation bestand aus Patienten mit AK des Gesichts oder der Kopfschwarte, mit maximal 10 AK-Läsionen pro Seite. Eine Seite wurde mit einer Sitzung einzelläsionsorientierter MAL-PDT behandelt (LT-Seite) und die andere Seite mit einer Sitzung MAL-PDT-Feldtherapie (FT-Seite). Ergebnisse: Nach 9 Monaten waren unter FT signifikant weniger neue Läsionen zu verzeichnen. Zu allen Zeitpunkten der Nachbeobachtung lag eine signifikante Reduktion der Anzahl AK-Läsionen sowohl auf der LT- als auch auf der FT-Seite vor. Nach 3 und 6 Monaten stellten wir keine signifikanten Unterschiede zwischen den Seiten fest. Nach 9 Monaten waren jedoch unter LT signifikant weniger verbleibende AK-Läsionen zu verzeichnen, unter FT hingegen signifikant weniger neue Läsionen. Schlussfolgerungen: Die FT führt im Vergleich zur LT zu einer signifikanten Reduktion der Anzahl neu auftretender AK- Läsionen.
Aktinische Keratose: Photodynamische Therapie mit MAL-PDT zeigt Überlegenheit gegenüber Ingenolmebutat
Authors: Lehmann Percy
Published: July 2017

Hintergrund: Photodynamische Therapie in Verbindung mit Methylamino-Lävulinsäure (MAL-PDT) und mit Ingenolmebutat-Gel (IMB) sind zugelassene therapeutische Optionen bei multiplen aktinischen Keratosen (AK). Ziel: Das Ziel dieser randomisierten klinischen Studie mit intraindividuellem Halbseitenvergleich war es, die Behandlungsergebnisse von MAL-PDT und IMB zu vergleichen. Methoden: Zwei symmetrische kontralaterale Areale mit einer vergleichbaren Zahl AK-Läsionen wurden ausgewählt und per Randomisierung der Behandlung entweder mit einem 3-tägigen IMB-Zyklus oder einer einzelnen MAL-PDT-Sitzung zugeteilt. Am nächsten Tag wurde ein Score zur Beurteilung der lokalen Hautreaktionen (LHR) erhoben. Die Patienten beurteilten die Schmerzen und die Heilungsdauer der behandelten Areale. Ergebnisse: Nach 90 Tagen wurden der Anteil der Läsionen in Vollremission, die Anzahl der Patienten mit Vollremission aller Läsionen, das kosmetische Ergebnis und die Präferenz des Patienten beurteilt. Schlussfolgerung: Unseren Ergebnissen zufolge zeigten IMB und MAL-PDT vergleichbare Wirksamkeit, allerdings war das kosmetische Ergebnis nach MAL-PDT besser. Die Schmerzen waren unter PDT stärker, aber unter IMB waren die LHR ausgeprägter und die Heilung dauerte länger. Die Patienten bevorzugten die MAL-PDT.
Lebensqualität bei Vitiligo: Besondere Umstände bei Kindern und Menschen mit psychiatrischen Erkrankungen
Authors: Zschocke Ina
Published: July 2017

Hintergrund: Vitiligo kann sich negativ auf die Lebensqualität (LQ) eines Patienten auswirken. Ein spezieller Fragebogen dazu, der VitiQoL (vitiligo-specific quality-of-life instrument), wurde in englischer Sprache entwickelt und validiert. Das Instrument wurde ins brasilianische Portugiesisch übersetzt, kulturspezifisch adaptiert und validiert (VitiQoL-PB). Ziel: Das Ziel dieser Studie war die Beurteilung der LQ einer Stichprobe von Patienten mit Vitiligo; bei erwachsenen Patienten mittels VitiQoL und DLQI (Dermatology Life Quality Index) und bei Kindern und Jugendlichen mittels CDLQI (Children's Dermatology Life Quality Index). Methoden: Die Teilnehmer wurden an einer ambulanten dermatologischen Klinik und einer Privatpraxis in Porto Alegre ausgewählt. Die LQ der Kinder wurde mit dem CDLQI-Fragebogen evaluiert. Bei den erwachsenen Patienten verwendeten wir den VitiQoL-PB- und den DLQI-Fragebogen. Ergebnisse: Zwischen den Scores des Gesamt-VitiQoL und des DLQI war eine starke Korrelation zu verzeichnen (r = 0,81; p < 0,001). Der Faktor, der sich am stärksten auf das Endergebnis des VitiQoL auswirkte, war das Stigma. In unserer Stichprobe erzielten Frauen höhere Scores als Männer (p < 0,05). Psychische Probleme waren mit geringerer LQ assoziiert. Bei den Kindern betrug der CDLQI-Score im Median 3 (Quartilsabstand 1,3-7,3). Zwischen dem Alter des Kindes/Jugendlichen und dem CDLQI-Score bestand eine statistisch signifikante Korrelation (rs = 0,41; p = 0,044). Schlussfolgerung: Diese Studie bestätigt, dass der VitiQoL einfach einzusetzen ist und wichtige zusätzliche Informationen zur Auswirkung der Vitiligo auf eine südamerikanische Patientenpopulation liefert. Stigmatisierung spielt bei dieser Krankheit eine sehr große Rolle. Manche Patientengruppen sind hierfür besonders anfällig, z.B. Frauen, Patienten mit psychischen Erkrankungen und Jugendliche.
Anfängliche Fehldiagnose eines oralen malignen Melanoms als ethniespezifische Pigmentierung: Ein Fallbericht
Authors: Martinelli-Kläy Carla Patrícia , Laporte Marcel Leandro , Martinelli Celso Ricardo , Martinelli Celso , Lombardi Tommaso
Published: July 2017

Orale maligne Melanome (OMM) sind selten; sie machen weniger als 0,5% aller malignen Erkrankungen im Mundraum aus. Die häufigsten Lokalisationen sind der Gaumen und die maxilläre Gingiva. Die histologische Untersuchung ist von entscheidender Bedeutung für die Diagnosestellung bei verdächtigen pigmentierten Läsionen in der Mundhöhle, vor allem, wenn eine präzise klinische Diagnose nicht möglich ist. Wir stellen einen Fall von OMM vor, der 2 Jahre zuvor in einem anderen Zentrum als ethniespezifische Pigmentierung fehldiagnostiziert worden war. Die klinische Untersuchung ergab multiple Makulae und Noduli auf dem harten und weichen Gaumen, der oberen Alveolarmukosa und Gingiva. Diese Läsionen waren schmerzlos und variierten farblich von dunkelblau bis schwarz. Die histologische Analyse zeigte Lagen und Nester atypischer Melanozyten verschiedener Formen (plasmazytoid, epithelioid, rund) im oberflächlichen Korium mit Ausbreitung in tiefere Gewebeschichten. Manche Tumorzellen enthielten variable Mengen an Melanin. Eingesprosste Blutgefäße oder Nervenfasern waren nicht zu sehen. Die immunhistochemische Analyse ergab, dass die neoplastischen Zellen positiv für HMB-45, Melan-A und S-100 und negativ für AE1/AE3 waren, was die Melanomdiagnose bestätigte. Der Ki-67-Labeling-Index lag bei rund 25%. Die Patientin lehnte jegliche Behandlung ab und verstarb 11 Monate später. Übersetzung aus Dermatopathology 2016;3:1-7 (DOI:10.1159/000444049)
Oncologic Response and Hospitalization Rate of Patients Receiving Cabazitaxel in the Fourth-Line and Beyond in Castration-Resistant Prostate Cancer: Analysis of a Retrospective Cohort and a Structured Literature Review
Authors: von Hardenberg Jost , Schwartz Maike , Werner Thorsten , Fuxius Stefan , Strauss Arne , Worst Thomas Stefan , Nuhn Philipp , Bolenz Christian , Heinrich Elmar
Published: July 2017

Background: Limited data are available for the use of agents in metastatic castration-resistant prostate cancer (mCRPC) beyond the third-line. We provide data during treatment with cabazitaxel (CAB), helping to improve the informed-consent process. Patients and Methods: We retrospectively reviewed patients treated with fourth-line or beyond CAB for mCRPC after failure of previous therapies with docetaxel, abiraterone acetate, enzalutamide and/or radium-223. The progression-free survival (PFS) and the overall survival (OS) were estimated using the Kaplan-Meier method and compared to published data based on a structured literature review. The hospitalization rate was recorded. Factors influencing 6-months OS were analyzed. Results: Fifteen patients were identified at 4 institutions and included in the analysis. The median PFS was 104 days (range 47-397 days). The median time to death was 10 months (range 2-16). PFS and OS data are in accordance with 17 published patients so far. During the therapy, eleven (73%) of the patients were hospitalized. Prostate-specific antigen (PSA, 500 units; hazards ratio [HR] 1.491, 95% CI 1.000-2.0175), white blood cell count (HR 0.425, 95% CI 0.108-0.952), hemoglobin (HR 0.6014, 95% CI 0.2942-1.0758), and alkaline phosphatase (100 units; HR 1.0964, 95% CI 1.000-1.2859) correlate with 6-months OS. Conclusions: CAB beyond the third-line is often accompanied by hospitalization. PFS is a significant proportion of the median time of OS. The baseline laboratory might be a good indicator for the decision between CAB and best-supportive care.
MORPHOLOGICAL CHANGES IN LUNGS, HEART AND LIVER CAUSED BY EXPERIMENTAL ASSOCIATED CHEST AND THIGHS TRAUMA
Authors: Khudobiak M. M. , Marushchak M. I. , Holovatiuk L. M. , Datsko T. I.
Published: July 2017

Background. According to preliminary results obtained, the development of hypoxemia caused by chest trauma affected lipid peroxidation stimulation leading to disruption of cell membranes structure and consequently cell death closing the ‘vicious’ circle, which in our opinion and according to the literature cause multiple organ failure.Objective. The aim of our study was to determine the features of morphological changes in cases of heart, lungs, liver injury after associated chest and both thighs trauma in rats.Methods. For histological examination the pieces of left ventricle tissues of heart, lungs and liver were used, which were fixed in 10% neutral formalin solution, dehydrated and embedded in paraffin blocks.Results. It was established that associated trauma of chest and both thighs in 1 day after the injury is accompanied by disturbances of hemodynamics in parenchymal organs due to venous congestion that occurs during the development of cardiovascular disease caused by traumatic shock. In the most severe period of maximum likelihood of complications, within 3 days, respiratory hypoxia, cardiovascular disorders, metabolic acidosis, and induced programmed cell death may develop.Conclusions. On the background of increasing pulmonary oedema (thickening of inter air sac membranes) caused by associated trauma of chest and both thighs in rats after only one day of the experiment hemodynamic changes in heart (low-blood supply of vessels in epicardium and isolated blood vessels of venous type) and liver (mainly plethora of blood vessels) were observed, which lead to morphological changes of myocardium within 3 days.