bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid automatic creation of monodisperse emulsion droplets by microfluidic device with degassed PDMS slab as a detachable suction actuator
Authors: Murata Yuki , Nakashoji Yuta , Kondo Masaki , Tanaka Yugo , Hashimoto Masahiko
Published: August 2017

We previously developed a technique that enabled automatic creation of monodisperse water‐in‐oil droplets with the use of an air‐evacuated PDMS microfluidic device. Although the device generated droplets over a long‐time period, the production rate was slow (∼10 droplets per second). In the current study, we aimed to improve this rate, using the same fluid pumping principle described in our previous work, by remodeling our device configuration. To achieve this aim, we developed a new device with a much larger PDMS surface area‐to‐volume ratio within the air‐trapping void space (178 cm–1), than that of our earlier device (5.0 cm–1). This design approach was based on the idea that a larger PDMS surface area‐to‐volume ratio was likely to create a higher vacuum inside the void space, thereby contributing to faster liquid flow and an increased droplet generation rate. The new device consisting of five layers featuring a degassed PDMS slab as a detachable liquid‐suction actuator, which was stacked on a lower microfluidic layer. In this device, the rate of droplet production increased during the time‐course droplet formation and reached ca. 470 droplets per second immediately before completely consuming the loaded aqueous solution (20 μL).
Hexafluoroisopropanol as a Low‐Boiling Extraction Solvent for 5‐Hydroxymethylfurfural Production
Authors: Weingart Eric , Teevs Linda , Krieg Ramona , Prüße Ulf
Published: August 2017

In this study, we show that the fluorous alcohol hexafluoroisopropanol (HFIP) can act as a superior solvent for the in situ extraction of 5‐hydroxymethylfurfural (HMF) from an aqueous reaction system. HFIP has a far higher partition coefficient for HMF than common extraction solvents such as methyl isobutyl ketone (MIBK) and n‐butanol and has a significantly lower boiling point of 58–59 °C. In a system containing fructose, HCl as the catalyst, and HFIP as the extraction solvent, a high HMF yield of 89 % is achieved, which is far better than the HMF yields in common MIBK/butanol extraction systems. HFIP extracts HMF from the reaction phase without extraction of the fructose educt. In addition, the aqueous catalyst phase can be reused.
New advances in the volatile metabolites of Frullania tamarisci
Authors: Pannequin Anaïs , Tintaru Aura , Desjobert Jean‐Marie , Costa Jean , Muselli Alain
Published: August 2017

The chemical composition of Frullania tamarisci essential oil from Corsica was investigated using GC‐FID, GC–MS and NMR analyses. The essential oil compositions were further studied analyzing samples prepared from three different Corsican locations and during a seasonal vegetative cycle. 40 components, which accounted for 78.3–89.8% of the total amount of F. tamarisci essential oils were identified. The main components were tamariscol coeluted with pacifigorgiol (30.4–41.5%), germacra‐1(10)E,5E–dien‐11‐ol (3.6–7.1%), γ‐cylocostunolide (1.8–20.1%), γ‐dihydrocyclocostunolide (1.2–8.0%) and frullanolide (1.7–4.9%). Among them, germacra‐1(10)E,5E–dien‐11‐ol was never reported in the Frullania genus and pacifigorgiol, a tamariscol GC‐overlapped compound, was for the first time reported in Bryophytes. Finally using 1D and 2D NMR experiments, we reported γ‐dihydrocyclocostunolide as a new natural compound. Two Corsican F. tamarisci essential oils with different GC profiles were assessed for their phytotoxic behavior against onion seeds and seedling in order to evaluate their capacity to inhibit germination and alter the development of plantlets. According to the essential oil‐compositions, a stimulation of the onion seedling was observed when sesquiterpene lactones amount was higher, whilst the inhibition of roots growth occurs when sesquiterpene alcohols were predominantly.
Electrochemical Properties of Al–based Solid Solutions Alloyed by Element Mg, Ga, Zn and Mn under the Guide of First Principles
Authors: Yi Y. , Huo J. , Wang W.
Published: August 2017

Molecular simulation method was firstly used for analyzing the energy of aluminum alloy systems alloyed by Mg, Ga, Zn and Mn. Based on the analyses, Al‐Mg, Al‐Ga, Al‐Zn, Al‐Mn alloys were metallurgically prepared. The structures, electrochemical activities and utilization ratios were characterized by X‐ray diffraction patterns (XRD), anodic polarization measurement and galvanostatic discharge. The calculated energies of the aluminum alloy systems increase in the following order: Al< Al‐Mn < Al‐Mg < Al‐Zn < Al‐Ga. The absolute values of the open circuit potentials of the alloys measured in alkaline solution rank in the following orders: φAl‐Ga alloy > φAl‐Zn alloy > φAl‐Mg alloy > φAl‐Mn alloy and the order is consistent with the calculated energies. The results indicate that molecular simulation based on the first‐principles is a useful method in the alloying design and thermodynamic performance prediction. Alloy additives Zn and Ga effectively change the open circuit potential of metal aluminum to a more negative potential. In addition, alloy additive Zn increases the charge transfer resistance of Al→Al3+, which decreases the discharge current density. Alloy additive Mg diminishes the grain size of the alloy and notably enhances the discharge current density. Alloy additive Mn improves the utilization ratio remarkably when discharging in alkaline solution.
Dealing with the deluge of historical weather data: the example of the TEMPEST database
Authors: Veale Lucy , Endfield Georgina , Davies Sarah , Macdonald Neil , Naylor Simon , Royer Marie‐Jeanne , Bowen James , Tyler‐Jones Richard , Jones Cerys
Published: August 2017

People have long been interested in the history of weather, particularly extremes, and chronologies of past events drawing on information from written records have been compiled and published throughout history. In recent years, concern over current and future weather and climate has triggered a new level of interest in past weather events and their impacts. This interest, alongside the development of digital humanities research methods, has resulted in a rapid growth in the number of online databases relating to historic weather and climate around the world. This paper documents the design, creation and content of one such database, TEMPEST, an online repository for extreme weather history in the UK. TEMPEST has been created as the major output of the AHRC funded project ‘Spaces of Experience and Horizons of Expectation: The Implications of Extreme Weather in the UK, Past, Present and Future’ (2013‐2017). Unlike the majority of existing databases that rely on published materials, TEMPEST's records are drawn from primary research into original documentary sources held in archives around the UK. The c. 18,000 records that TEMPEST currently contains offer personalised and geo‐referenced insights into the relationship between society and extreme weather in the UK spanning a period of over 400 years. In this paper we outline potential applications for TEMPEST and suggest directions for future research and resources in historical weather. We also consider broader issues for the digital humanities relating to the storage, archiving, ownership, and usage of data and the need to ensure connectivity between complementary datasets.
A newly discovered Early Paleozoic ophiolite in Dagele, Eastern Kunlun, China, and its geological significance
Authors: Du Wei , Jiang Changyi , Xia Mingzhe , Xia Zhaode , Zhou Wei , Ling Jinlan , Wang Bangyao
Published: August 2017

This study reports the discovery of an ophiolite located in the Eastern Kunlun Orogen (Dagele, Eastern Kunlun, China) that is mainly composed of isotropic and serpentinized dunite, gabbro, and eclogites. According to the geochemical results, the ophiolite unit is characterized by the depletion of Nb, Ta, and Ti and a slight enrichment in large‐ion lithophile elements, which suggests that the Dagele ophiolite was formed in an island arc environment. To constrain the time of formation of the ophiolite, gabbro samples were selected for sensitive high‐resolution ion microprobe U–Pb zircon dating and yielded an age of 445 ± 4.8 Ma. By integrating the regional geological and geochronological data, we propose that the Dagele ophiolite is a suprasubduction zone‐type. Further studies on this and other ophiolites in the region will provide crucial constraints on the evolution of the Eastern Kunlun Orogen as well as the Proto‐Tethys Ocean in central western China.
Precambrian tectonic affinity of theNorthQinlingMicrocontinent: Constraints from the discovery ofMesoproterozoic magmatic zircons in theQinlingGroup
Authors: Cao Huahua , Li Sanzhong , Zhao Shujuan , Wang Pengcheng , Somerville Ian , Wang Qian
Published: August 2017

This paper presents new results on zircon U–Pb dating of a two‐mica schist from the Qinling Group in the core of the North Qinling Orogenic Belt (NQB), Central China, with the aim of constraining the formation time of the Qinling Group, and the tectonic affinity of the North Qinling Microcontinent. Zircon U–Pb dating indicates that the protolith of the metasedimentary rock in the Qinling Group was deposited later than ~1502 Ma. The Qinling Group in the NQB represents a long‐lived unit, and its formation age can be constrained to the period between the Paleoproterozoic and early Neoproterozoic. The zircon age populations of the studied sample can be divided into two major populations of 1559–1642 and 1470–1548 Ma, and one subordinate population of 1717–1794 Ma, indicating their provenances were mainly attributed to the NQB and subordinately from the North China Craton (NCC) and the Yangtze Craton (YZC). And the distribution of the early Neoproterozoic magmatic events and the Nd–Pb whole‐rock isotopes, zircon Hf isotopes, and trace element compositions of the Precambrian basement rocks in the NQB is significantly different from those in the NCC and YZC, indicating that the NQB cannot be a southern sector of the NCC, or a northern sector of the YZC, and was an independent microcontinent from the Paleoproterozoic to the early Neoproterozoic.
High‐potassium volcanic rocks from the Okinawa Trough: Implications for a cryptic potassium‐rich and DUPAL‐like source
Authors: Zhang Yuxiang , Zeng Zhigang , Li Xiaohui , Yin Xuebo , Wang Xiaoyuan , Chen Shuai
Published: August 2017

Major element, trace element, and Sr–Nd–Pb isotopic compositions of high‐potassium calc‐alkaline rhyolites (the T6 rhyolites) collected from the western slope of the middle Okinawa Trough (MOT) are reported in this article. These high‐potassium rhyolites have similar major and trace elemental compositions as Type 2 rhyolites from the MOT, except that the former contain higher concentrations of K2O, Th, U, and Rb and lower concentrations of Sr and Eu. Experimental data indicate that the T6 rhyolites cannot be sourced from low‐ to mid‐potassium MOT rocks by either fractional crystallization or partial melting processes but are instead derived from a cryptic potassium‐rich source beneath the Okinawa Trough (OT). Considering that high‐potassium volcanic rocks are distributed throughout the East China Sea Shelf, the Ryukyu Arc, and Kyushu Island, the high‐potassium OT rocks could represent an important connection between the OT and its adjacent regions. Compared to volcanic rocks from the MOT axial zone, the T6 rhyolites have more depleted Sr–Nd isotopic compositions (87Sr/86Sr = 0.7035–0.7036, 143Nd/144Nd = 0.51291–0.51297) but much more enriched compositions of 207Pb (207Pb/204Pb = 15.60–15.63) and 208Pb (208Pb/204Pb = 38.45–38.57), thus recording a significant DUPAL‐like signature. These isotopic anomalies cannot be explained by the incorporation of subducting sediments or crustal contamination but instead imply the presence of a DUPAL‐like mantle source beneath the OT. The decrease of the DUPAL‐like anomaly from the T6 rhyolites to the MOT axial zone volcanic rocks is consistent with the injection of an normal mid‐ocean ridge basalt (N‐MORB) mantle source, such as asthenospheric material, into pre‐existing DUPAL‐like mantle during back‐arc extension.
Functional neuroimaging after severe anoxic brain injury in children may reveal preserved, yet covert, cognitive function
Authors: Owen Adrian M.
Published: August 2017

A growing body of evidence has confirmed that, after severe brain injury in adults, motoric and task‐dependent factors that are essential for reliable communication, frequently interfere with an accurate assessment of cognitive status. In the current study, resting state functional magnetic resonance imaging (fMRI) in children who have sustained an anoxic brain injury following a near drowning incident suggests a similar pattern; preserved cognition amidst severe motoric impairment that effectively precludes accurate clinical diagnosis at the bedside. Hum Brain Mapp 38:4832–4833, 2017. © 2017 Wiley Periodicals, Inc.
Estradiol rapidly increases GluA2‐mushroom spines and decreases GluA2‐filopodia spines in hippocampus CA1
Authors: Avila Jorge A. , Alliger Amber A. , Carvajal Brigett , Zanca Roseanna M. , Serrano Peter A. , Luine Victoria N.
Published: August 2017

Hippocampal dendritic spine density rapidly increases following estradiol (E2) treatment, but the types of spines and trafficking of synaptic markers have received little investigation. We assessed rapid effects of E2 over time on the density of four spine types (stubby, filopodial, long thin, and mushroom) and trafficking of AMPA receptor subunit GluA2 and PSD95 on tertiary, apical dendrites in CA1. Castrated male rats received 20 μg kg−1 of E2 or vehicle and were sacrificed 30 or 120 min later. Images of Golgi‐Cox impregnated and PSD95/GluA2 stained dendrites were captured under the confocal microscope and quantified with IMARIS‐XT. Stubby and filopodial spine densities did not change following treatment. Long‐thin spines significantly decreased at 30 min while mushroom spines significantly increased at 120 min. GluA2, PSD95, and GluA2/PSD95 colocalization levels in stubby or long thin spines did not change, but filopodial spines had significantly reduced GluA2 levels at 30 min. Mushroom spines showed significantly increased levels for GluA2, PSD95 and GluA2/PSD95 colocalization at 120 min. Because GluA2 is important for memory consolidation, current results present novel data suggesting that trafficking of GluA2 to mushroom spines provides one mechanism contributing to estradiol's ability to enhance learning and memory by the PI3 signaling pathway.
A Piece of the Pie? The Effects of Familial Control Enhancements on the Use of Broad‐Based Employee Ownership Programs in Family Firms
Authors: Mullins Frank
Published: August 2017

While family firms tend to be highly committed to their employees, scholars contend that founding family owners are likely hesitant when it comes to sharing ownership broadly with nonfamily employees. Taking a heterogeneous view of family firms, this study investigates the implications of different familial control‐enhancing mechanisms on the use of broad‐based employee ownership programs (BEOPs) among publicly‐traded family firms. Based on a five‐year panel data set of S&P 500 family firms, the findings indicate that certain control‐enhancing mechanisms can cause family owners to frame their decision to use BEOPs differently. Essentially, family firms with family CEOs, regardless of whether the CEO is a founder or descendant, have a decreased likelihood of using BEOPs in spite of the direct control that family owners have over the firm's operations. Conversely, when family owners hold dual‐class shares, which enhance shareholder voting power, family firms are more likely to use BEOPs. Furthermore, the likelihood of family firms with family CEOs using BEOPs increases when the family holds dual‐class shares. Moreover, there is no significant difference between founder and descendant CEOs, as both are less resistant to using BEOPs when a dual‐class share structure is in place. These findings have implications for HR practitioners working in family firms given the influence that family owners can have on the firm's HR activities, namely BEOPs.
Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF‐κB‐mediated IKKβ expression
Authors: Wu Yi‐Hui , Huang Yu‐Fang , Chang Tzu‐Hao , Chou Cheng‐Yang
Published: August 2017

We have shown that collagen type XI alpha 1 (COL11A1) promotes ovarian cancer progression and is associated with chemoresistance to cisplatin and paclitaxel in ovarian cancer cells. Here, we demonstrate how COL11A1 regulates twist family basic helix‐loop‐helix transcription factor 1‐related protein 1 (TWIST1) to induce chemoresistance and inhibit apoptosis in ovarian cancer cells. Small interfering RNA‐mediated reduction in COL11A1 protein levels increased the chemosensitivity to cisplatin and paclitaxel via downregulated TWIST1 expression. TWIST1 messenger RNA levels positively associated with COL11A1 messenger RNA expression levels in ovarian tumors. High TWIST1 expression levels were significantly associated with a progression‐free interval of ≤ 6 months (p = 0.001) and death (p = 0.040). In addition, patients with high TWIST1 mRNA levels had significantly shorter 5‐year overall‐survival (p = 0.004) and progression‐free survival (p = 0.009) rates, compared to patients with low TWIST1 levels. Increased TWIST1 expression caused by COL11A1‐induced transcription of the inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ) gene occurred via increased SP1 phosphorylation and binding to the IKKβ promoter. COL11A1‐mediated nuclear factor‐kappa B activation, via transcriptional activation of IKKβ, promoted TWIST1, Mcl‐1, and GAS6 expression, which were associated with chemoresistance and anti‐apoptosis in ovarian cancer cells. We suggest that IKKβ and TWIST1 can potentially be targeted in patients with COL11A1‐positive ovarian cancer.
Prospective study of urinary prostaglandin E2 metabolite and pancreatic cancer risk
Authors: Cui Yong , Shu Xiao‐Ou , Li Hong‐Lan , Yang Gong , Wen Wanqing , Gao Yu‐Tang , Cai Qiuyin , Rothman Nathaniel , Yin Hui‐Yong , Lan Qing , Xiang Yong‐Bing , Zheng Wei
Published: August 2017

The cyclooxygenase 2 (COX‐2) pathway is upregulated in many pancreatic cancer cells, and it is believed that carcinogenetic effects of COX‐2 upregulation are largely through prostaglandin E2 (PGE2) overproduction. We tested this hypothesis by evaluating the association between urinary PGE2 metabolites (PGE‐M), a biomarker of in vivo PGE2 overproduction, and pancreatic cancer risk. We conducted a case–control study with 722 subjects (239 cases and 483 controls) nested within two prospective cohort studies, the Shanghai Women's Health Study (SWHS) and Shanghai Men's Health Study (SMHS). Pre‐diagnosis urine samples were measured for PGE‐M using a liquid chromatography/tandem mass spectrometric method. Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence intervals (95%CI), with adjustment for potential confounders. Compared to those with the lowest urine level of PGE‐M (the first quartile), individuals with higher urine levels of PGE‐M had an increased risk of developing pancreatic cancer, with adjusted ORs (95%CI) of 1.63 (0.98–2.73), 1.55 (0.90–2.69) and 1.94 (1.07–3.51), for the second to the fourth quartile groups, respectively (p for trend = 0.054). This dose–response positive association was more evident among those who had BMI <25 kg/m2 than overweight individuals (p for interaction = 0.058). After excluding cases diagnosed in the first year of follow‐up and their matched controls, this positive association persisted (p for trend = 0.037) and the interaction became statistically significant (p for interaction = 0.017). Our study adds additional evidence that the COX‐2 pathway is involved in pancreatic carcinogenesis and suggests that urinary PGE‐M may serve as a biomarker for predicting pancreatic cancer risk.
Comparison of regional cerebral blood flow in Parkinson's disease with depression and major depression
Authors: Kim Young‐Do , Jeong Hyeonseok S. , Kim Yong‐Duk
Published: August 2017

Diagnosis of depression in Parkinson's disease (PD) patients is complicated due to the overlapping symptoms of the two disorders. We investigated regional cerebral blood flow (rCBF) in patients with only major depression (MD) and PD patients with (PDMD) and without MD (PDNMD) using 99mTc hexamethylpropyleneamine oxime single photon emission computed tomography (HMPAO‐SPECT). A total of 103 patients (38 PDMD, 46 PDNMD, and 19 MD patients) underwent brain HMPAO‐SPECT scans. Voxel‐wise whole‐brain analysis was conducted to compare rCBF of the PDMD group with that of the PDNMD and MD groups. The scores of the Geriatric Depression Scale (GDS) and Neuropsychiatric Inventory (NPI) were significantly higher in the PDMD group than in the PDNMD group. The PDMD group showed significant hypoperfusion in the subcallosal cortex than the PDNMD group. The MD group showed significant hypoperfusion in the brainstem and inferomedial frontal region compared with the PDMD group. Our findings suggest that dysfunction of the inferomedial frontal cortex may be involved in the pathogenesis of depression in PD patients.
Fuzzy generalized fast marching method for 3D segmentation of brain structures
Authors: Baghdadi Mohamed , Benamrane Nacéra , Sais Lakhdar
Published: August 2017

The aim of this work is to develop a new model for segmentation of brain structures in medical brain MR images. Brain segmentation is a challenging task due to the complex anatomical structure of brain structures as well as intensity nonuniformity, partial volume effects and noise. Generally the structures of interest are of relatively complicated size and have significant shape variations, the structures boundaries may be blurry or even missing, and the surrounding background is full of irrelevant edges. Segmentation methods based on fuzzy models have been developed to overcome the uncertainty caused by these effects. In this study, we propose a robust and accurate brain structures segmentation method based on a combination of fuzzy model and deformable model. Our method breaks up into two great parts. Initially, a preliminary stage allows to construct the various information maps, in particular a fuzzy map, used as a principal information source, constructed using the Fuzzy C‐means method (FCM). Then, a deformable model implemented with the generalized fast marching method (GFMM), evolves toward the structure to be segmented, under the action of a normal force defined from these information maps. In this sense, we used a powerful evolution function based on a fuzzy model, adapted for brain structures. Two extensions of our general method are presented in this work. The first extension concerns the addition of an edge map to the fuzzy model and the use of some rules adapted to the segmentation process. The second extension consists of the use of several models evolving simultaneously to segment several structures. Extensive experiments are conducted on both simulated and real brain MRI datasets. Our proposed approach shows promising and achieves significant improvements with respect to several state‐of‐the‐art methods and with the three practical segmentation techniques widely used in neuroimaging studies, namely SPM, FSL, and Freesurfer.
A look at random access for machine‐type communications in 5th generation cellular networks
Authors: Grassi Alessandro , Piro Giuseppe , Boggia Gennaro
Published: August 2017

Machine‐type communications represent a major challenge for the upcoming 5th generation (5G) technology. Future cellular systems, in fact, will be in charge of supporting a huge number of devices generating sporadic small packets at random times. In this context, the random access channel (RACH) protocol is generally used to initiate the communication sessions, aimed at delivering this kind of traffic. But, occasional peaks of requests, generated when many devices react to the same event, may severely degrade network performance (ie, by increasing the collision probability). This letter investigates, through computer simulations, the performance of well‐known procedures for the RACH, designed for the current 4th generation technology and the upcoming 5G system in challenging scenarios never seen before. Specifically, the evaluation targets access peaks caused by emergency situations, including every phase of the protocol from the initial contention to the transmission of the application payload. Obtained results highlight pros and cons of available solutions, while showing challenging issues that should be carefully addressed in future research activities.
In vitro genotoxicity of airborne Ni‐NP in air–liquid interface
Authors: Latvala Siiri , Vare Daniel , Karlsson Hanna L. , Elihn Karine
Published: August 2017

Studies using advanced toxicological methods enabling in vitro conditions that are more realistic are currently needed for understanding the risks of pulmonary exposure to airborne nanoparticles. Owing to the carcinogenicity of certain nickel compounds, the increased production of nickel nanoparticles (Ni‐NPs) raises occupational safety concerns. The aim of this study was to investigate the genotoxicity of airborne Ni‐NPs using a recently developed air–liquid interface exposure system. The wild‐type Chinese hamster lung fibroblast cell line (V79) was used and cytotoxicity, DNA damage and mutagenicity were studied by testing colony forming efficiency, alkaline DNA unwinding and HPRT mutation assays, respectively. Additionally, co‐exposure to a PARP‐1 inhibitor was performed to test possible involvement of base excision repair (BER) in repair of Ni‐induced DNA damage. The results showed that cell viability was reduced significantly (to 45% and 46%) after 48 hours Ni‐NP exposure at concentrations of 0.15 and 0.32 μg cm−2. DNA damage was significantly increased after Ni‐NP exposure in the presence of the BER inhibitor indicating that Ni‐NP‐induced DNA damages are subsequently repaired by BER. Furthermore, there was no increased HPRT mutation frequency following Ni‐NP exposure. In conclusion, this study shows that Ni‐NP treatment of lung fibroblasts in an air–liquid interface system that mimics real‐life exposure, results in increased DNA strand breaks and reduced cellular viability. These DNA lesions were repaired with BER in an error‐free manner without resulting in mutations. This study also underlines the importance of appropriate quantification of the actual exposure concentrations during air–liquid interface exposure studies.
A novel endpoint for the assessment of chemotherapy‐induced peripheral neuropathy in rodents: biomechanical properties of peripheral nerve
Authors: Liu Chang‐Ning , Berryman Edwin , Zakur David , Shoieb Ahmed M. , Pardo Ingrid D. , Boucher Magalie , Somps Chris J. , Bagi Chedo M. , Cook Jon C.
Published: August 2017

Chemotherapy‐induced peripheral neuropathy (CiPN) is a frequent adverse effect in patients and a leading safety consideration in oncology drug development. Although behavioral assessment and microscopic examination of the nerves and dorsal root ganglia can be incorporated into toxicity studies to assess CiPN risk, more sensitive and less labor‐intensive endpoints are often lacking. In this study, rats and mice administered vincristine (75 μg kg−1 day−1, i.p., for 10 days in rats and 100 μg kg−1 day−1, i.p., for 11 days in mice, respectively) were employed as the CiPN models. Behavioral changes were assessed during the dosing phase. At necropsy, the sural or sciatic nerve was harvested from the rats and mice, respectively, and assessed for mechanical and histopathological endpoints. It was found that the maximal load and the load/extension ratio were significantly decreased in the nerves collected from the animals dosed with vincristine compared with the vehicle‐treated animals (P < 0.05). Additionally, the gait analysis revealed that the paw print areas were significantly increased in mice (P < 0.01), but not in rats following vincristine administration. Light microscopic histopathology of the nerves and dorsal root ganglia were unaffected by vincristine administration. We concluded that ex vivo mechanical properties of the nerves is a sensitive endpoint, providing a new method to predict CiPN in rodent. Gait analysis may also be a useful tool in these pre‐clinical animal models.
Development of a 3‐dimensional tissue lung phantom of a preterm infant for optical measurements of oxygen—Laser‐detector position considerations
Authors: Larsson Jim , Liao Peilang , Lundin Patrik , Krite Svanberg Emilie , Swartling Johannes , Lewander Xu Märta , Bood Joakim , Andersson‐Engels Stefan
Published: August 2017

There is a need to further improve the clinical care of our most vulnerable patients—preterm infants. Novel diagnostic and treatment tools facilitate such advances. Here, we evaluate a potential percutaneous optical monitoring tool to assess the oxygen and water vapor content in the lungs of preterm babies. The aim is to prepare for further clinical studies by gaining a detailed understanding of how the measured light intensity and gas absorption signal behave for different possible geometries of light delivery and receiver. Such an experimental evaluation is conducted for the first time utilizing a specially developed 3‐dimensional‐printed optical phantom based on a geometry model obtained from computer tomography images of the thorax (chest) of a 1700‐g premature infant. The measurements yield reliable signals for source–detector distances up to about 50 mm, with stronger gas absorption signals at long separations and positions related to the lower part of the lung, consistent with a larger relative volume of this. The limitations of this study include the omission of scattering tissue within the lungs and that similar optical properties are used for the wavelengths employed for the 2 gases, yielding no indication on the optimal wavelength pair to use.
The Effect of Depression, Generalized Anxiety, and Selective Serotonin Reuptake Inhibitors on Change in Bone Metabolism in Adolescents and Emerging Adults
Authors: Calarge Chadi A , Mills James A , Janz Kathleen F , Burns Trudy L , Schlechte Janet A , Coryell William H , Zemel Babette S
Published: August 2017

The purpose of this study was to prospectively examine the independent contribution of major depressive disorder (MDD), generalized anxiety disorder (GAD), and selective serotonin reuptake inhibitors (SSRIs) use to changes in bone metabolism in older adolescents and emerging adults. Medically healthy 15- to 20-year-olds who were unmedicated or within 1 month of starting an SSRI were prospectively followed. Psychiatric functioning and medication treatment were assessed monthly. Every 4 months, trabecular and cortical volumetric bone mineral density (vBMD) at the radius and markers of bone metabolism were evaluated. Every 8 months, total body less head areal bone mineral content and lumbar spine (LS) areal BMD (aBMD) were determined. Linear mixed-effects regression analysis examined associations between bone measures on the one hand and MDD, GAD, and SSRI indices on the other. A total of 264 participants were followed for 1.51 ± 0.76 years. After adjusting for age, sex, vitamin D concentration, physical activity, lean mass or grip strength, and time in the study, MDD severity was associated with increasing LS aBMD. Similarly, SSRI use was associated with increasing LS aBMD and bone formation in female participants. In contrast, SSRI use was associated with decreasing LS aBMD in males. After accounting for depression, GAD was independently, albeit weakly, associated with increased bone mineralization. In older adolescents and emerging adults, MDD and GAD are associated with increasing bone mass, particularly in the lumbar spine and in females, whereas SSRIs are associated with increasing bone mass in females but decreasing bone mass in males. © 2017 American Society for Bone and Mineral Research.
Impact Microindentation: Consistency of Serial Measurements and Alterations in Patients With Paget's Disease of the Tibia
Authors: Malgo Frank , Hamdy Neveen AT , Papapoulos Socrates E , Appelman-Dijkstra Natasha M
Published: August 2017

Impact microindentation (IMI) is a new technique for the in vivo measurement of tissue-level properties of cortical bone in humans. To address issues related to the proper application of IMI in clinical practice and to directly examine cortical bone properties in patients with tibia pathology, we studied 11 subjects without tibia pathology and nine patients with Paget's disease of the tibia in biochemical remission after bisphosphonate treatment. Serial indentations in the tibias of both legs were performed in all subjects by a single operator until 10 adequate measurements were obtained in each tibia. In patients without Paget's disease (7 men and 4 women; mean age, 61.9 years; range, 51 to 72 years), there was no difference in mean bone material strength index (BMSi) between the dominant and nondominant leg (82.1 ± 1.3 and 81.4 ± 1.3, respectively; p = 0.606). In each individual subject studied, sequential indentations in both legs showed no trends for higher or lower values with time. The standard deviation of unnormalized bone material strength (BMSu) was also comparable between the dominant and nondominant tibia (5.3 and 4.5, respectively; p = 0.657). In patients with Paget's disease (4 men and 5 women; mean age, 69.5 years; range, 55 to 87 years), mean BMSi of the Pagetic tibia was lower, albeit nonsignificantly, than that of the contralateral nonaffected tibia (74.7 ± 1.7 and 78.7 ± 1.3, respectively; p = 0.120). In contrast to subjects without Paget's disease, the SD of adequate BMSu values was significantly larger in the Pagetic tibia compared to that of the non-Pagetic tibia (7.6 versus 5.0, respectively, p = 0.008). These results highlight the consistency of serial IMI measurements as performed by a single operator in the presence as well as absence of tibia pathology and illustrate that the method is able to capture alterations of tissue-level cortical bone properties in patients with Paget's disease of the tibia. © 2017 The Authors.Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
Bone marrow and adipose mesenchymal stem cells attenuate cardiac fibrosis induced by methotrexate in rats
Authors: Fikry Ebtehal Mohammad , Hassan Wedad A. , Gad Amany M.
Published: August 2017

Mesenchymal stem cells (MSCs) are an ideal adult stem cell with capacity for self‐renewal and differentiation with an extensive tissue distribution. The present study evaluates the therapeutic effects of bone marrow mesenchymal stem cells (BM‐MSCs) or adipose‐derived mesenchymal stem cells (AD‐MSCs) against the development of methotrexate (MTX)‐induced cardiac fibrosis versus dexamethasone (DEX). Rats were allocated into five groups; group 1, received normal saline orally; group 2, received MTX (14 mg/kg/week for 2 weeks); groups 3 and 4, treated once with 2 × 106 cells of MTX + BM‐MSCs and MTX + AD‐MSCs, respectively; and group 5, MTX + DEX (0.5 mg/kg, for 7 days, P.O.). MTX induced cardiac fibrosis as marked changes in oxidative biomarkers and elevation of triglyceride, cholesterol, aspartate aminotransferase, gamma‐glutamyl transferase, creatine kinase, and caspase‐3, as well as deposited collagen. These injurious effects were antagonized after treatment with MSCs. So, MSCs possessed antioxidant, antiapoptotic, as well antifibrotic effects, which will perhaps initiate them as notable prospective for the treatment of cardiac fibrosis.
Attenuation of DNA damage and mRNA gene expression in hypoxic rats using natural antioxidants
Authors: Fadda Laila Mohamed , Attia Hala A. , Al‐Rasheed Nouf Mohamed , Ali Hanaa Mahmoud , Aldossari Manal
Published: August 2017

This study aimed to explore the efficiency of carnosine (Cs) and/or l‐arginine (Agn) in the downregulation of apoptotic and inflammatory molecule expression and DNA damage caused hepatic injury in response to sodium nitrite (Sd)‐induced hypoxia in rats. Rats were injected with Sd; Agn or/and Cs were administrated prior to Sd intoxication. Sd significantly decreased hemoglobin concentration and Bcl‐2 mRNA expression, while increased expressions of apoptotic markers (Bax and caspase), tumor necrosis factor‐α, nuclear factor kappa B, and C‐reactive protein and the oxidative DNA damage in hepatic tissue. Moreover, administration of Agn or/and Cs exhibited a modulation of the previous parameters. However, concurrent treatment with the forementioned antioxidants modulated these levels. It was concluded that the treatment with the combination of Agn and Cs was the most effective regimen in ameliorating Sd toxicity accompanied by hypoxic stress.
Prophylactic effects of ellagic acid and rosmarinic acid on doxorubicin‐induced neurotoxicity in rats
Authors: Rizk Hanan A. , Masoud Marwa A. , Maher Omar W.
Published: August 2017

Doxorubicin (DOX) is a chemotherapeutic agent widely used in human malignancies. Its long‐term use cause neurobiological side effects. The aim of the present study was to investigate the prophylactic effect exerted by daily administration of ellagic acid (EA) and rosmarinic acid (RA) on DOX‐induced neurotoxicity in rats. Our data showed that DOX‐induced significant elevation of brain malondialdehyde, tumor necrosis factor‐alpha (TNF‐α), inducible nitric oxide synthase (iNOS), caspase‐3, and cholinesterase associated with significant reduction in reduced glutathione, monoamines namely serotonin, dopamine, as well as norepinephrine. Concomitant administration of EA (10 mg/kg/day, p.o. for 14 days) and/or RA (75 mg/kg/day, p.o. for 14 days) with DOX significantly mitigated the neural changes induced by DOX. Meanwhile, treatment ameliorated pro‐inflammatory cytokines as TNF‐α, iNOS, and attenuated oxidative stress biomarkers as well as brain monoamines. In conclusion, EA and RA can effectively protect against DOX‐induced neurotoxicity, and the mechanisms underlying the neuroprotective effect are potentially associated with its antioxidant, anti‐inflammatory, and antiapoptotic properties.
A potential high risk for fatty liver disease was found in mice generated after assisted reproductive techniques
Authors: Gu Leilei , Zhang Jingjing , Zheng Meimei , Dong Guoying , Xu Jingyi , Zhang Wuyue , Wu Yibo , Yang Yang , Zhu Hui
Published: August 2017

Abnormal gametogenesis and embryonic development may lead to poor health status of the offspring. The operations involved in the assisted reproductive technologies (ARTs) occur during the key stage of gametogenesis and early embryonic development. To assess the potential risk of abnormal lipid metabolism in the liver of adult ARTs offspring, two ARTs mice models derived from preimplantation genetic diagnosis (PGD group) and in vitro cultured embryos without biopsy (IVEM group) were constructed. And control mice were from in vivo naturally conceived (Normal group). The results showed that ARTs offspring had increased body weight and body fat content comparing to normal group. An increasing volume and amount of lipid droplets as well as lipid droplet fusion were found in the hepatocytes of ARTs mice, and a significantly increased liver TG content was also shown in the ARTs mice, which due to the increased TG synthesis and decreased TG transport in the liver. All the results indicated that the manipulations involved in ARTs might play an important role in the lipid accumulation of adult offspring. By analyzing the DNA methylation profiles of 7.5dpc embryos, we proposed that methylation deregulation of the genes related to liver development in ARTs embryos might contribute to the abnormal phenotype in the offspring. The study demonstrated that ARTs procedures have adverse effect on liver development which resulted in abnormal lipid metabolism and induced the potential high risk of fatty liver in adulthood.
New insight into the control of peptic ulcer by targeting the histamine H2 receptor
Authors: Singh Vijai , Gohil Nisarg , Ramírez‐García Robert
Published: August 2017

Peptic ulcer disease is one of the major challenges in public health globally and new evidence shows that it can be controlled by targeting the histamine H2 receptor (H2R). Recently, a number of H2R antagonists have been synthesized and used to block the action of histamine on the parietal cells in the stomach and decrease the acid production. In this study, we modeled the H2R by homology modeling using the 3‐D crystal structure and this model was validated based on free energy and amino acid residues present in the allowed regions of a Ramachandran plot. We used this 3‐D model for screening of highly potent drugs using molecular docking. We found cimetidine, cimetex, and famotidine as the most potent drugs based on the binding affinity of drug‐protein interactions. We also generated a cellular network for H2R that could be useful for better understanding of cellular mechanism and drug targets. These findings provide a new insight into the development of suitable, specific, and effective anti‐ulcer drugs for a most effective treatment of ulcerous diseases.
Rapid Screening of Haloacetonitriles in Water Samples by Optimized Vortex‐assisted Liquid–Liquid Microextraction
Authors: Guo Yi‐Min , Ding Erica Ming‐Chieh , Ding Wang‐Hsien
Published: August 2017

This paper describes an optimized method for the quick screening of low levels of haloacetonitriles (HANs), a nitrogenous disinfection byproduct. The method is especially geared toward screening of water used for drinking and in swimming pools. The method is based on vortex‐assisted liquid–liquid microextraction (VALLME), which is carried out before determination of the gathered samples by gas chromatography‐mass spectrometry (GC‐MS). Factors that can potentially affect the extraction efficiency of the desired trace chemicals from the gathered sample were enhanced using the Box–Behnken design method. The optimal VALLME parameters for a 10‐mL water sample (pH 4, containing 3 g of sodium sulfate), according to the Box–Behnken design method, are extractant 160 μL dichloromethane and vortex extraction time of 1 min at the maximum speed (2500 rpm). The limits of quantitation calculated were 16–35 ng/L. Precision for both intra‐ and inter‐day analysis was also calculated, which was less than 11% on three concentration levels. Mean extraction recovery, otherwise known as trueness, was between 71 and 92%. The developed method was applied successfully to extract HANs from drinking and swimming pool water samples.
Finding the candidate sequence variants for diagnosis of hypertrophic cardiomyopathy in East Slovak patients
Authors: Zigova Michaela , Bernasovska Jarmila , Boronova Iveta , Mydlarova Blascakova Marta , Kmec Jan
Published: August 2017

Background

Hypertrophic cardiomyopathy is a heterogeneous myocardial disease. Mutations appearing in several genes might be a potential cause of the disease. The aim of the study was to analyze selected exons of the sarcomeric and non‐sarcomeric genes, with the purpose to identify potential candidate genetic variants and to understand etiopathogenetic mechanisms of hypertrophic cardiomyopathy in East Slovak patients.

Methods

This study recruited 23 unrelated patients with hypertrophic cardiomyopathy, namely, 13 men and 10 women (mean age of 58.09±15.82 years) and 25 healthy controls in order to determine the candidate sequence variants, in the selected exons of six cardiomyopathy genes (MYBPC3, MYH7, NEBL, SCN5A, TNNI3, TNNT2), by conventional capillary‐based Sanger sequencing method and standard protocols.

Results

Molecular genetic results confirmed the presence of 43 sequence variants in the selected exons of six cardiomyopathy genes, 58.14% of detected variants were novel. The majority of detected sequence variants were confirmed within exon 23 of MYH7 gene. Only 11 genetic alterations were predicted to be potentially pathogenic.

Conclusions

In our study, we identified known and novel sequence variants in 23 unrelated patients with hypertrophic cardiomyopathy, but we did not observe any strong mutation hotspot. The results of our study assumed that exon 23 of MYH7 gene can be in potential affinity to hypertrophic cardiomyopathy in our cohort of patients. The sequence variants identified in this study may be further investigated in order to determine their functions in disease pathogenesis and improve management, diagnosis, and treatment in Slovak patients.
Cognitive psychophysiological treatment of bodily‐focused repetitive behaviors in adults: An open trial
Authors: O'Connor Kieron , Lavoie Marc , Desaulniers Benoît , Audet Jean‐Sébastien
Published: August 2017

Background

Body‐focused repetitive behaviors (BFRBs), such as hair pulling, skin picking, and nail biting, are repetitive, destructive, and nonfunctional habits that cause significant distress. Separate BFRBs form a cohesive group and could be assessed as part of the Tourette/tic spectrum or obsessive‐compulsive spectrum of disorders. The treatment of choice is either antidepressant or behavioral treatment, both of which have shown effectiveness. The cognitive psychophysiological (CoPs) model focuses on the tension and emotional build up that triggers habits by addressing cognitive‐behavioral, emotional and psychophysiological processes preceding onset rather than the habit itself. The CoPs approach has already shown efficacy in treatment of tic and Tourette disorder.

Objective

The aim of the current open trial was to view whether BFRBs can be validly assessed on a standard tic scale (Tourette Symptom Global Scale; TSGS) and evaluate the efficacy of the CoPs intervention on 64 participants (54 completers) with 1 of 3 subtypes of BFRBs (hair pulling, nail biting, and skin picking) compared to a waitlist control.

Method

Participants were assessed at baseline on an adapted TSGS and after receving 14 weeks of CoPs therapy with six months follow up.

Results

The TSGS was reliably and validly adapted to measure BFRBs. The CoPs intervention was effective for all BRFB subtypes with a large effect size (intention‐to‐treat g = 1.54; completers g = 2.04), with 74% of patients showing clinically significant improvement. Mood and self‐esteem also improved posttreatment. The decrease in symptoms was maintained at the 6‐month follow‐up, with a further decrease in perfectionism.

Conclusion

BFRBs can be reliably assessed as a tic spectrum disorder rather than as part of the obsessive‐compulsive spectrum. The CoPs model may offer a complementary treatment for BFRBs.
The many facets of mindfulness and the prediction of change following mindfulness‐based stress reduction (MBSR)
Authors: Gawrysiak Michael J. , Grassetti Stevie N. , Greeson Jeffrey M. , Shorey Ryan C. , Pohlig Ryan , Baime Michael J.
Published: August 2017

Objectives

Mindfulness‐based stress reduction (MBSR) promotes numerous psychological benefits, but few studies have identified for whom MBSR is most effective. The current study tested the hypothesis that lower baseline mindfulness invites more “room to grow” and, thus, predicts greater improvement during MBSR.

Method

We examined three facets of mindfulness (awareness, acceptance, decentering) among 131 MBSR participants prior to enrollment, to test the hypothesis that lower baseline mindfulness predicts greater improvements in perceived stress, positive affect (PA), and negative affect (NA) following MBSR.

Results

Lower acceptance and decentering predicted greater decreases in perceived stress. Higher awareness, acceptance, and decentering predicted greater increases in PA. Higher awareness predicted greater reductions in NA. Lower decentering predicted greater reductions in NA.

Conclusion

Findings partly supported the hypothesis that lower baseline mindfulness predicts greater improvement following MBSR and emphasize the importance of assessing multiple mindfulness facets given their unique, contrasting relations to outcomes.