bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Quantitative Determination of Resin Acids from Corsican Pinus pinasterAiton Oleoresin Using 13C‐NMR Spectroscopy
Authors: Ottavioli Joséphine , Paoli Mathieu , Casanova Joseph , Tomi Félix , Bighelli Ange
Published: January 2019

Twenty‐three resin samples have been obtained by tapping from individual Pinus pinaster adult trees grown in Corsica and submitted to acido‐basic partition. Identification and quantitative determination of resin acids has been carried out using 13C‐NMR spectroscopy following a method developed by our group. The main components were dehydroabietic acid (up to 37.6 %), levopimaric acid (up to 35.5 %) and abietic acid (up to 24.7 %). A lignan, pinoresinol, has been identified in some samples. Within the 23 compositions, submitted to k‐means analysis and Principal Component Analysis, two clusters have been perfectly differentiated, whose compositions were dominated by dehydroabietic acid (Group I, M=23.5 %, SD=6.3) and levopimaric acid (Group II, M=21.2 %; SD=6.2), respectively. Both compositions have been observed in the three locations of harvest.
Epigenetic Players of Chromatin Structure Regulation in Plasmodium falciparum
Authors: Jabeena C. A. , Rajavelu Arumugam
Published: January 2019

The protozoan parasite Plasmodium has evolved to survive in different hosts and environments. The diverse strategies of adaptation to different niches involve differential gene expression mechanisms mediated by chromatin plasticity that are poorly characterized in Plasmodium. The parasite employs a wide variety of regulatory mechanisms to complete their life cycle and survive inside hosts. Among them, epigenetic‐mediated mechanisms have been implicated for controlling chromatin organization, gene regulation, morphological differentiation, and antigenic variation. The differential gene expression in parasite is largely dependent on the nature of the chromatin structure. The histone core methylation marks and methyl mark readers contribute to chromatin dynamics. Here, we review the recent developments on various epigenetic marks and its enzymes in the Plasmodium falciparum, how these marks play a key role in the regulation of transcriptional activity of variable genes and coordinate the differential gene expression. We also discuss the possible roles of these epigenetic marks in chromatin structure regulation and plasticity at various stages of its development.
Calycosin stimulates the osteogenic differentiation of rat calvarial osteoblasts by activating the IGF1R/PI3K/Akt signaling pathway
Authors: Fang Yaoyao , Xue Zhiyuan , Zhao Lianggong , Yang Xiuyan , Yang Yafei , Zhou Xianglin , Feng Shilan , Chen Keming
Published: January 2019

Calycosin has been reported to have a strong osteogenic activity and a positive correlation with anti‐osteoporosis effects. However, its precise mechanism of action remains unclear. Since insulin‐like growth factor 1 receptor (IGF1R) signaling and phosphatidylinositol 3‐kinase/Akt (PI3K/Akt) signaling have been shown to play a pivotal role in regulating osteogenesis, we hypothesized that the osteogenic activity of calycosin is mediated by these signaling pathways. Rat calvarial osteoblasts (ROBs) were cultured in osteogenic medium containing calycosin with or without GSK1904529A (GSK) or LY294002 (LY) (inhibitors of IGF1R and PI3K, respectively). The effects on cell proliferation, alkaline phosphatase (ALP) activity, calcified nodules, mRNA or protein expression of osteogenic genes [alkaline phosphatase (Alpl), collagen type I (Col1a1), runt‐related transcription factor 2 (Runx2), Osterix, and bone morphogenetic protein 2 (Bmp2)], and phosphorylation of IGF1R and Akt were examined. The present results showed that calycosin enhanced cell proliferation, ALP activity and Alizarin Red‐S staining in a dose‐dependent manner in the range of 10−8–10−6 M, while an inhibitory effect was observed at 10−5 M. Treatment at the optimal concentration (10−6 M, a physiologically achievable concentration) increased mRNA levels of osteogenic genes and phosphorylation of IGF1R and Akt. Furthermore, treatment with GSK or LY partly reversed the effects of calycosin on ROBs, as indicated by the decreases in calycosin‐induced ALP activity, calcified nodules and osteogenic gene expression. These results suggest that the osteogenic effect of calycosin partly involves the IGF1R/PI3K/Akt signaling pathway.
Hemoglobin: A New Biocatalyst for the Synthesis of 2‐substituted Benzoxazoles via Oxidative Cyclization
Authors: Li Fengxi , Li Zhengqiang , Tang Xuyong , Cao Xinyu , Wang Chunyu , Li Jialin , Wang Lei
Published: January 2019

Efficient and mild synthesis of a series of 2‐substituted benzoxazoles via oxidative cyclization catalyzed by hemoglobins reported here for the first time. Satisfactory yields (84 %–97 %) and mild reaction conditions make this method highly viable for practical applications.
Metal‐Organic Frameworks as Hosts for Fluorinated Azobenzenes: A Path towards Quantitative Photoswitching with Visible Light
Authors: Hermann Daniela , Schwartz Heidi A. , Werker Melanie , Schaniel Dominik , Ruschewitz Uwe
Published: January 2019

Fifteen new photochromic hybrid materials were synthesized by gas phase loading of fluorinated azobenzenes, namely ortho‐tetrafluoroazobenzene (tF‐AZB), 4H,4H′‐octafluoroazobenzene (oF‐AZB), and perfluoroazobenzene (pF‐AZB), into the pores of the well‐known metal‐organic frameworks MOF‐5, MIL‐53(Al), MIL‐53(Ga), MIL‐68(Ga), and MIL‐68(In). Their composition was analysed by elemental (CHNS) and DSC/TGA. For pF‐AZB0.34@MIL‐53(Al), a structural model based on high‐resolution synchrotron powder diffraction data was developed and the host‐guest and guest‐guest interactions were elucidated from this model. These interactions of O−H⋅⋅⋅F and π⋅⋅⋅π type were confirmed by significant shifts of the O−H frequencies in loaded and unloaded MOFs of the MIL‐53 and MIL‐68 series. Most remarkably, all of the synthesized F‐AZB@MOF systems can be switched with visible light, and some of them show almost quantitative (>95 %) photo‐isomerization between its E and Z forms with no significant fatigue after repeated switching cycles.
Acetic Anhydride as an Oxygen Donor in the Non‐Hydrolytic Sol–Gel Synthesis of Mesoporous TiO2 with High Electrochemical Lithium Storage Performances
Authors: Wang Yanhui , Kim Sanghoon , Louvain Nicolas , Alauzun Johan G. , Mutin P. Hubert
Published: January 2019

An original, halide‐free non‐hydrolytic sol–gel route to mesoporous anatase TiO2 with hierarchical porosity and high specific surface area is reported. This route is based on the reaction at 200 °C of titanium(IV) isopropoxide with acetic anhydride, in the absence of a catalyst or solvent. NMR spectroscopic studies indicate that this method provides an efficient, truly non‐hydrolytic and aprotic route to TiO2. Formation of the oxide involves successive acetoxylation and condensation reactions, both with ester elimination. The resulting TiO2 materials were nanocrystalline, even before calcination. Small (about 10 nm) anatase nanocrystals spontaneously aggregated to form mesoporous micron‐sized particles with high specific surface area (240 m2 g−1 before calcination). Evaluation of the lithium storage performances shows a high reversible specific capacity, particularly for the non‐calcined sample with the highest specific surface area favouring pseudo‐capacitive storage: 253 mAh g−1 at 0.1 C and 218 mAh g−1 at 1 C (C=336 mA g−1). This sample also shows good cyclability (92 % retention after 200 cycles at 336 mA g−1) with a high coulombic efficiency (99.8 %). Synthesis in the presence of a solvent (toluene or squalane) offers the possibility to tune the morphology and texture of the TiO2 nanomaterials.
Understanding the engagement of key decision support persons in patient decision making around breast cancer treatment
Authors: Veenstra Christine M. , Wallner Lauren P. , Abrahamse Paul H. , Janz Nancy K. , Katz Steven J. , Hawley Sarah T.
Published: January 2019

Background

Patients with breast cancer involve multiple decision support persons (DSPs) in treatment decision making, yet little is known about DSP engagement in decision making and its association with patient appraisal of the decision process.

Methods

Patients newly diagnosed with breast cancer reported to Georgia and Los Angeles Surveillance, Epidemiology, and End Results registries in 2014‐2015 were surveyed 7 months after their diagnosis. The individual most involved in each respondent's decision making (the key DSP) was surveyed. DSP engagement was measured across 3 domains: 1) informed about decisions, 2) involved in decisions, and 3) aware of patient preferences. Patient decision appraisal included subjective decision quality (SDQ) and deliberation. This study evaluated bivariate associations with chi‐square tests between domains of DSP engagement and independent DSP variables. Analysis of variance and multivariable logistic regression were used to compare domains of DSP engagement with patient decision appraisal.

Results

In all, 2502 patients (68% response rate) and 1203 eligible DSPs (70% response rate) responded. Most DSPs were husbands/partners or daughters, were white, and were college graduates. Husbands/partners were more likely to be more informed, involved, and aware (all P values < .01). English‐ and Spanish‐speaking Latinos had a higher extent of (P = .02) but lower satisfaction with involvement (P < .01). A highly informed DSP was associated with higher odds of patient‐reported SDQ (odds ratio, 1.46; 95% confidence interval, 1.03‐2.08; P = .03). A highly aware DSP was associated with higher odds of patient‐reported deliberation (odds ratio, 1.83; 95% confidence interval, 1.36‐2.47; P < .01).

Conclusions

In this population‐based study, informal DSPs were engaged with and positively contributed to patients’ treatment decision making. To improve decision quality, future interventions should incorporate DSPs.
Progressive resistance training to prevent arm lymphedema in the first year after breast cancer surgery: Results of a randomized controlled trial
Authors: Ammitzbøll Gunn , Johansen Christoffer , Lanng Charlotte , Andersen Elisabeth Wreford , Kroman Niels , Zerahn Bo , Hyldegaard Ole , Wittenkamp Merete Celano , Dalton Susanne Oksbjerg
Published: January 2019

Background

Existing research suggests that progressive resistance training (PRT) after breast cancer (BC) surgery is safe, but the preventive effect on arm lymphedema has yet to be determined.

Methods

Women aged 18 to 75 years who were undergoing BC surgery with axillary lymph node dissection were eligible for the study. Recruited on the day of surgery, participants were allocated to intervention or usual care by computer randomization. The intervention consisted of PRT 3 times per week: in the first 20 weeks as a supervised group exercise and in the last 30 weeks as a self‐administered exercise. The primary outcome was arm lymphedema, which was defined as a >3% increase in the interlimb volume difference by water displacement. Measurements were made at the baseline and at a 12‐month follow‐up by physiotherapists blinded to group allocation. Analyses of effects included t tests and regression models; missing data were addressed by multiple imputation.

Results

Among the 158 randomized women, no mean group difference was found in arm volume (0.3%; 95% confidence interval, –1.7% to 2.3%) or lymphedema incidence (adjusted odds ratio, 1.2; 95% confidence interval, 0.5‐2.8). None of the participants exited the program because of adverse events.

Conclusions

This study provides no evidence that PRT can prevent arm lymphedema in the first year after BC, but the results corroborate the importance and safety of resistance training for patients, including women at high risk for lymphedema.
Neural system and receptor diversity in the ctenophore Beroe abyssicola
Authors: Norekian Tigran P. , Moroz Leonid L.
Published: January 2019

Although, neurosensory systems might have evolved independently in ctenophores, very little is known about their organization and functions. Most ctenophores are pelagic and deep‐water species and cannot be bred in the laboratory. Thus, it is not surprising that neuroanatomical data are available for only one genus within the group—Pleurobrachia. Here, using immunohistochemistry and scanning electron microscopy, we describe the organization of two distinct neural subsystems (subepithelial and mesogleal) and the structure of different receptor types in the comb jelly Beroe abyssicola—the voracious predator from North Pacific. A complex subepithelial neural network of Beroe, with five receptor types, covers the entire body surface and expands deep into the pharynx. Three types of mesogleal neurons are comparable to the cydippid Pleurobrachia. The predatory lifestyle of Beroe is supported by the extensive development of ciliated and muscular structures including the presence of giant muscles and feeding macrocilia. The obtained cell‐type atlas illustrates different examples of lineage‐specific innovations within these enigmatic marine animals and reveals the remarkable complexity of sensory and effector systems in this clade of basal Metazoa.
A survey of techniques for improving efficiency of mobile web browsing
Authors: Mittal Sparsh , Mattela Venkat
Published: January 2019

Mobile web traffic has now surpassed the desktop web traffic and has become the primary means for service providers to reach out to the billions of end users. Due to this trend, optimization of mobile web browsing (MWB) has gained significant attention. In this paper, we present a survey of techniques for improving the efficiency of web browsing on mobile systems, proposed in the last 6‐7 years. We review the techniques from both the networking domain (eg, proxy and browser enhancements) and the processor architecture domain (eg, hardware customization and thread‐to‐core scheduling). We organize the research works based on key parameters to highlight their similarities and differences. Beyond summarizing the recent works, this survey aims to emphasize the need of architecting for MWB as the first principle, instead of retrofitting for it.
2‐Adamantyl Complexes of Platinum
Authors: Taullaj Fioralba , Armstrong David , Datta Shaishav , Lough Alan J. , Fekl Ulrich
Published: January 2019

The first adamantyl platinum complexes were isolated and characterized, namely [(COD)Pt(2‐Ad)Cl], [(dppe)Pt(2‐Ad)Cl], [(COD)Pt(2‐Ad)Me] and, [(dppe)Pt(2‐Ad)Me] {COD = 1,5‐ cyclooctadiene, dppe = 1,2‐bis(diphenylphosphino)ethane, Ad = adamantyl}. These complexes show considerable stability, including resistance to heating to 125° C in solution for several days. It is therefore concluded that previously existing road blocks to synthesizing platinum adamantyls were due to complications in the transmetallation step, and not due to intrinsic instability of the final product. Counterintuitively, the key to successful transmetallation from ZnIIonto PtIIis imposing slow reaction progress via use of a solvent in which both the platinum chloride precursor and adamantyl anion precursor are poorly soluble.
Trigeminal neuropathic pain development and maintenance in rats are suppressed by a positive modulator of α6 GABAA receptors
Authors: Vasović Dina , Divović Branka , Treven Marco , Knutson Daniel E. , Steudle Friederike , Scholze Petra , Obradović Aleksandar , Fabjan Jure , Brković Božidar , Sieghart Werner , Ernst Margot , Cook James M. , Savić Miroslav M.
Published: January 2019

γ‐Aminobutyric acid type A (GABAA) receptors containing the α6 subunit are located in trigeminal ganglia, and their reduction by small interfering RNA increases inflammatory temporomandibular and myofascial pain in rats. We thus hypothesized that enhancing their activity may help in neuropathic syndromes originating from the trigeminal system. Here, we performed a detailed electrophysiological and pharmacokinetic analysis of two recently developed deuterated structurally similar pyrazoloquinolinone compounds. DK‐I‐56‐1 at concentrations below 1 µM enhanced γ‐aminobutyric acid (GABA) currents at recombinant rat α6β3γ2, α6β3δ and α6β3 receptors, whereas it was inactive at most GABAA receptor subtypes containing other α subunits. DK‐I‐87‐1 at concentrations below 1 µM was inactive at α6‐containing receptors and only weakly modulated other GABAA receptors investigated. Both plasma and brain tissue kinetics of DK‐I‐56‐1 were relatively slow, with half‐lives of 6 and 13 hr, respectively, enabling the persistence of estimated free brain concentrations in the range 10–300 nM throughout a 24‐hr period. Results obtained in two protocols of chronic constriction injury of the infraorbital nerve in rats dosed intraperitoneally with DK‐I‐56‐1 during 14 days after surgery or with DK‐I‐56‐1 or DK‐I‐87‐1 during 14 days after trigeminal neuropathy were already established, demonstrated that DK‐I‐56‐1 but not DK‐I‐87‐1 significantly reduced the hypersensitivity response to von Frey filaments.

Significance

Neuropathic pain induced by trigeminal nerve damage is poorly controlled by current treatments. DK‐I‐56‐1 that positively modulates α6 GABAA receptors is appropriate for repeated administration and thus may represent a novel treatment option against the development and maintenance of trigeminal neuropathic pain.
Comparison of two different electrophoretic methods in studying the genetic diversity among plantains (Musa spp.) using ISSR markers
Authors: Marimuthu Somasundaram Saraswathi , Subbaraya Uma , Durairajan Sharmila Gayatri , Rajendran Soundaryan , Gopalakrishnan Jithu , Shahul Hameed Bahrudeen , Palani Durai , Suthanthiram Backiyarani
Published: January 2019

Inter simple sequence repeat markers were employed for the genotyping of 16 plantain ecotypes. Two different electrophoretic systems namely conventional gel electrophoresis (CVGE) and fully automated high‐resolution CGE were used to evaluate the genetic diversity. Comparative analysis indicated that all parameters related to marker informativeness were higher in CGE except polymorphic information content. But genetic diversity parameters like effective number of alleles, Nei's gene diversity (1973) and Shannon's information index showed higher values (1.52 ± 0.12, 0.34 ± 0.05 and 0.52 ± 0.05, respectively) in CVGE as against CGE (1.29 ± 0.04, 0.22 ± 0.02 and 0.38 ± 0.03, respectively) system. The unweighed pair group method with arithmetic averages was used to obtain the dendrogram for both analyses. The results of dendrogram and principal component analysis were found to be consistent in both systems except for some minor disagreements. The clone‐specific bands could be used in the identification and development of SCAR markers. Inter simple sequence repeat markers used in this study provided sufficient polymorphism and reproducible banding pattern for evaluating the genetic diversity of different plantain ecotypes. Lack of accuracy and consistency of the CVGE warrants the employment of high‐throughput CGE for diversity analysis as it provided better separation of bands with higher resolution.
Security outage performance of partial relay selection in AF mixed RF/FSO system with outdated channel state information
Authors: Odeyemi Kehinde O. , Owolawi Pius A.
Published: January 2019

In this paper, the secrecy outage performance of a partial relay selection–based mixed radio frequency/free‐space optical (RF/FSO) system with outdated channel state information is studied. All the RF links are modeled in Rayleigh fading, and the FSO link is subjected to Gamma‐Gamma fading with/or without pointing errors in relation to the two detection techniques such as heterodyne detection and intensity modulation with direct detection. It is assumed that the relay nodes employ fixed gain and variable gain amplified‐and‐forward relaying protocols. Thus, unified cumulative distribution functions of the equivalent end‐to‐end signal to noise ratio for both the AF relaying schemes are then derived. Utilizing the cumulative distribution functions, the closed‐form expressions for the lower bound secrecy outage probability under the two relaying protocols are then obtained for the concerned system. Moreover, the impacts of turbulence, pointing errors, detection techniques, outdated channel state information, and relay selection are investigated. The finding demonstrated that the variable gain relaying mixed RF/FSO system offers much better secrecy performance compared with the fixed gain relaying system. Monte Carlo simulation results are provided to validate the accuracy of the analysis.
Repair Schwann cell update: Adaptive reprogramming, EMT, and stemness in regenerating nerves
Authors: Jessen Kristjan R , Arthur‐Farraj Peter
Published: January 2019

Schwann cells respond to nerve injury by cellular reprogramming that generates cells specialized for promoting regeneration and repair. These repair cells clear redundant myelin, attract macrophages, support survival of damaged neurons, encourage axonal growth, and guide axons back to their targets. There are interesting parallels between this response and that found in other tissues. At the cellular level, many other tissues also react to injury by cellular reprogramming, generating cells specialized to promote tissue homeostasis and repair. And at the molecular level, a common feature possessed by Schwann cells and many other cells is the injury‐induced activation of genes associated with epithelial–mesenchymal transitions and stemness, differentiation states that are linked to cellular plasticity and that help injury‐induced tissue remodeling. The number of signaling systems regulating Schwann cell plasticity is rapidly increasing. Importantly, this includes mechanisms that are crucial for the generation of functional repair Schwann cells and nerve regeneration, although they have no or a minor role elsewhere in the Schwann cell lineage. This encourages the view that selective tools can be developed to control these particular cells, amplify their repair supportive functions and prevent their deterioration. In this review, we discuss the emerging similarities between the injury response seen in nerves and in other tissues and survey the transcription factors, epigenetic mechanisms, and signaling cascades that control repair Schwann cells, with emphasis on systems that selectively regulate the Schwann cell injury response.
Trait Openness and serotonin 2A receptors in healthy volunteers: A positron emission tomography study
Authors: Stenbæk Dea Siggaard , Kristiansen Sara , Burmester Daniel , Madsen Martin Korsbak , Frokjaer Vibe Gedsoe , Knudsen Gitte Moos , Fisher Patrick MacDonald
Published: January 2019

Recent research found lasting increases in personality trait Openness in healthy individuals and patients after administration of the serotonin 2A receptor (5‐HT2AR) agonist psilocybin. However, no studies have investigated whether 5‐HT2AR availability as imaged using positron emission tomography (PET) is associated with this trait. In 159 healthy individuals (53 females), the association between 5‐HT2AR binding in neocortex imaged with [18F]altanserin or [11C]Cimbi‐36 PET and personality trait Openness was investigated using linear regression models. In these models the influence of sex on the association was also investigated. Trait Openness was assessed with the NEO Personality Inventory‐Revised. No significant associations between neocortical 5‐HT2AR binding and trait Openness were found for [18F]altanserin (p = 0.5) or [11C]Cimbi‐36 (p = 0.8). Pooling the data in a combined model did not substantially change our results (p = 0.4). No significant interactions with sex were found (p > 0.35). Our results indicate that differences in 5‐HT2AR availability are not related to variations in trait Openness in healthy individuals. Although stimulation of the 5‐HT2AR with compounds such as psilocybin may contribute to long‐term changes in trait Openness, there is no evidence in favor of an association between 5‐HT2AR and trait Openness.
Treatment modalities and outcomes of Fanconi anemia patients with head and neck squamous cell carcinoma: Series of 9 cases and review of the literature
Authors: Beckham Thomas H. , Leeman Jonathan , Jillian Tsai Chiaojung , Riaz Nadeem , Sherman Eric , Singh Bhuvanesh , Lee Nancy , McBride Sean , Higginson Daniel S.
Published: January 2019

Background

Fanconi anemia (FA) is associated with an increased risk of developing head and neck squamous cell cancer (HNSCC) and presents a treatment dilemma due to concerns of increased toxicities from chemotherapy and radiation therapy (RT).

Methods

We reviewed the literature on HNSCC in FA patients and report on our experience treating 9 FA patients with HNSCC.

Results

Surgery was generally well‐tolerated and surgery alone resulted in durable local control for 2 patients. Four patients received adjuvant RT that was tolerable in most cases, although 1 patient required a treatment break and early cessation of RT. Three of the irradiated patients received concurrent cetuximab.

Conclusions

In patients with adverse features, adjuvant radiation with concurrent cetuximab may be feasible with careful monitoring, although local disease control is infrequent. Early detection via screening permitting a surgery‐alone approach represents the best opportunity for cure in FA patients with HSNCC.
Ultraviolet light‐related DNA damage mutation signature distinguishes cutaneous from mucosal or other origin for head and neck squamous cell carcinoma of unknown primary site
Authors: Chan Jason W. , Yeh Iwei , El‐Sayed Ivan H. , Algazi Alain P. , Glastonbury Christine M. , Ha Patrick K. , Yom Sue S. , van Zante Annemieke
Published: January 2019

Background

Head and neck squamous cell carcinoma of unknown primary site (HNSCCUP) is a diagnostic challenge. Identification of an ultraviolet (UV) light‐related DNA damage signature using next‐generation sequencing (NGS) can classify the primary site of origin as cutaneous.

Methods

A 62‐year‐old male was seen with 2 months of left neck swelling. He was a lifetime nonsmoker but had a history of cutaneous squamous cell carcinoma (SCC) of the left helix. He was also found to have left hilar adenopathy. He had a p16‐negative HNSCCUP on fine needle aspiration (FNA) biopsy of the left neck.

Results

NGS of the FNA specimen revealed a high number of somatic mutations that were mostly C to T transitions, indicating a UV mutation signature and confirming the diagnosis of cutaneous SCC.

Conclusions

Identification of a UV DNA damage signature with NGS distinguishes HNSCCUP of cutaneous vs mucosal or other squamous cell carcinoma origin.
Projected glacier meltwater and river run‐off changes in the Upper Reach of the Shule River Basin, north‐eastern edge of the Tibetan Plateau
Authors: Zhang Zhihua , Deng Shifan , Zhao Qiudong , Zhang Shiqiang , Zhang Xiaowen
Published: January 2019

Glacier meltwater change in the north‐eastern edge of the Tibetan Plateau is greatly important for the projection of the impact of future climate change on local water resource management. Although the glaciated area is only approximately 4% of the Upper Reach of the Shule River Basin (URSRB), the average glacier meltwater contribution to river run‐off was approximately 23.6% during the periods 1971/1972 to 2012/2013. A new glacier melting module coupled with the macroscale hydrologic Variable Infiltration Capacity model (VIC‐CAS) was adopted to simulate and project changes in the glacier meltwater and river run‐off of the URSRB forced by downscaled output of the BCC‐CSM1.1(m), CANESM2, GFDL‐CM3, and IPSL‐CM5A‐MR models. Comparisons between the observed and simulated river run‐offs and glacier area changes during the periods 2000/2001, 2004/2006, 2008/2009, and 2012/2013 suggest that the simulation is reasonable. Due to increases in precipitation, the annual total run‐off is projected to increase by approximately 2.58–2.73 × 108 m3 in the 2050s and 0.28–1.87 × 108 m3 in the 2100s compared with run‐off in the 2010s based on the RCP2.6 (low greenhouse gas emission) and RCP4.5 (moderate greenhouse gas emission) scenarios, respectively. The contribution of glacier meltwater to river run‐off will more likely decrease to approximately 10% and less than 5% during the 2050s and 2100s, respectively.
Novel findings on ultrastructural protection of skeletal muscle fibers during hibernation of Daurian ground squirrels: Mitochondria, nuclei, cytoskeleton, glycogen
Authors: Wang Zhe , Jiang Shan‐Feng , Cao Jin , Liu Kun , Xu Shen‐Hui , Arfat Yasir , Guo Quan‐Ling , Chang Hui , Goswami Nandu , Hinghofer‐Szalkay Helmut , Gao Yun‐Fang
Published: January 2019

We examined ultrastructure protective phenomena and mechanisms of slow and fast muscles in hibernating Daurian ground squirrels (Spermophilus dauricus). Some degenerative changes such as slightly decreased sarcomere length and vacuolization occurred in hibernation, but periaxonal capsular borders in intrafusal fibers remained distinct and the arrangement of extrafusal fibers and Z‐lines unscathed. In soleus samples, the number of glycogenosomes more than tripled during hibernation. The expression of phosphorylated glycogen synthase remained unaltered while that of glycogen phosphorylase decreased during hibernation. The number of extensor digitorum longus glycogenosomes decreased and the expression of phosphorylated glycogen synthase decreased, while glycogen phosphorylase expression remained unaltered. The nuclei number remained unchanged. Kinesin and desmin, preventors of nuclear loss and damage, were maintained or just slightly reduced in hibernation. The single‐fiber mitochondrial concentration and sub‐sarcolemmal mitochondrial number increased in both muscle types. The expression of vimentin, which anchors mitochondria and maintains Z‐line integrity, was increased during and after hibernation. Also, dynamin‐related protein 1, mitochondrial fission factor, and adenosine triphosphate synthase were elevated in both muscle types. These findings confirm a remarkable ultrastructure preservation and show an unexpected increase in mitochondrial capacity in hibernating squirrels.
Efficient osteogenic differentiation of the dental pulp stem cells on β‐glycerophosphate loaded polycaprolactone/polyethylene oxide blend nanofibers
Authors: Hosseini Fatemeh Sadat , Enderami Seyedeh Elnaz , Hadian Ali , Abazari Mohammad Foad , Ardeshirylajimi Abdolreza , Saburi Ehsan , Soleimanifar Fatemeh , Nazemisalman Bahareh
Published: January 2019

Hard tissue lesion treatment in oral and maxillofacial has been challenging because of tissue complexities. This study aimed to investigate novel biopolymeric construct effects on the osteogenic differentiation potential of the dental pulp stem cells (DPSCs) for introducing a cell copolymer bioimplant. A blended polycaprolactone (PCL)‐polyethylene oxide (PEO) was fabricated using electrospinning, simultaneously filled by β‐glycerophosphate (β‐GP). After that biocompatibility and release kinetics of the PCL‐PEO+β‐GP was evaluated and compared with PCL‐PEO and then the osteogenic differentiation potential of the DPSCs was examined while being cultured on the scaffolds and compared with those cultured on the culture plate. The results demonstrated that scaffolds have not any cytotoxicity and β‐GP can release in a long‐term manner. Alkaline phosphatase activity and calcium content were significantly increased in DPSCs while being cultured on the PCL‐PEO+β‐GP compared with the other groups. Runt‐related transcription factor 2, collagen type‐I, osteonectin, and osteocalcin (OSC) genes expression was upregulated in DPSCs cultured on the PCL‐PEO+β‐GP and was significantly higher than those cultured on the PCL‐PEO. Immunocytochemistry result also confirmed the positive effects of PCL‐PEO+β‐GP on the osteogenic differentiation of the DPSCs by presenting a higher OSC protein expression. According to the results, incorporation of the β‐GP in PCL‐PEO makes a better construct for osteogenic induction into the stem cells and it could be also considered as a great promising candidate for bone, oral, and maxillofacial tissue engineering applications.
Pectolinarigenin prevents bone loss in ovariectomized mice and inhibits RANKL‐induced osteoclastogenesis via blocking activation of MAPK and NFATc1 signaling
Authors: Xiao Yu , Li Kai , Wang Ziyi , Fu Fangsheng , Shao Siyuan , Song Fangming , Zhao Jinmin , Chen Weiwei , Liu Qian , Xu Jiake
Published: January 2019

Osteoporosis (OP) is a metabolic disease caused by multiple factors, which is characterized by a reduction of bone mass per unit volume and destruction of bone microstructure. Aberrant osteoclast function is the main cause of OP, therefore, regulating the differentiation and function of osteoclast is one of the treatment strategies for OP. Pectolinarigenin (PEC) is a medicinal implant isolated from Fragrant Eupatorium. Our experimental data showed that PEC was able to inhibit receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis in vitro, by tartrate‐resistant acid phosphatase (TRAcP) staining, Fibrous actin ring formation, and hydroxyapatite resorption assays. In terms of mechanism, PEC inhibited the expression of the osteoclastogenesis‐related gene, including cathepsin K (Ctsk), matrix metalloproteinase 9 (Mmp9), and TRAcP (Acp5). Western blot analysis demonstrated that PEC could significantly block the activation of RANKL‐induced mitogen‐activated protein kinase signaling cascades and was able to suppress the protein expression of nuclear factor of activated T‐cells and c‐Fos. Meanwhile, the intracellular reactive oxygen species levels were also reduced by PEC in a concentration‐dependent manner. Further, PEC could prevent the ovariectomy‐induced bone loss in vivo. Summarizing all, our data suggested that PEC inhibits osteoclast formation and function and RANKL signaling pathways, and thus could potentially be used in the treatment the osteoclast‐related bone loss diseases.
LncRNA UCA1 sponges miR‐206 to exacerbate oxidative stress and apoptosis induced by ox‐LDL in human macrophages
Authors: Hu Xiaorong , Ma Ruisong , Fu Wenwen , Zhang Changjiang , Du Xianjin
Published: January 2019

Long noncoding RNA UCA1 has exerted a significant effect in cardiovascular disease. The biological role of UCA1 in atherosclerosis is unclear. Our study was to identify the potential mechanisms in the progression of atherosclerosis. Here, we observed that ox‐LDL increased UCA1 expression greatly in THP‐1 cells. Knockdown of UCA1 greatly inhibited CD36 expression, a crucial biomarker in atherosclerosis. Meanwhile, 20 μg/ml ox‐LDL induced foam cell formation, which can be reversed by downregulation of UCA1. In addition, TC and TG levels induced by ox‐LDL was rescued by UCA1 small interfering RNA. Accumulating studies have indicated that oxidative stress contributes to atherosclerosis progression. Here, we also found that reactive oxygen species, MDA, and THP‐1 cell apoptosis were restrained by decreased of UCA1 with an increase of the superoxide dismutase activity. Moreover, miR‐206 was predicted as a target of UCA1 and knockdown of UCA1 was able to repress miR‐206 expression. Furthermore, overexpression of miR‐206 inhibited oxidative stress process and it was reversed by UCA1 upregulation in vitro. In conclusion, we indicated that UCA1 sponged miR‐206 to exacerbate atherosclerosis events induced by ox‐LDL in THP‐1 cells.
Characterization of the Effect of Renal Impairment on Upadacitinib Pharmacokinetics
Authors: Mohamed Mohamed‐Eslam F. , Trueman Sheryl , Feng Tian , Anderson Jaclyn , Marbury Thomas C. , Othman Ahmed A.
Published: January 2019

Upadacitinib is a novel selective Janus kinase 1 inhibitor developed for treatment of rheumatoid arthritis and other autoimmune diseases. The objective of this study was to assess the pharmacokinetics and safety of a single upadacitinib dose in subjects with normal renal function and in subjects with renal impairment. A total of 24 subjects between the ages of 18 and 75 years were assigned to 1 of 4 renal function groups based on estimated glomerular filtration rate (normal, mild, moderate, severe; N = 6/group). A single 15‐mg dose of upadacitinib extended‐release formulation was administered under fasting conditions. Serial plasma and urine samples were assayed to evaluate the effect of renal impairment on upadacitinib exposure through regression analysis and analysis of covariance. The primary analysis was the regression analysis of upadacitinib exposures versus estimated glomerular filtration rate. The point estimates for upadacitinib plasma exposure ratios (90% confidence interval [CI]) in subjects with mild, moderate, and severe renal impairment were 1.18 (90%CI, 1.06–1.32), 1.33 (90%CI, 1.11–1.59), and 1.44 (90%CI, 1.14–1.82) for area under the plasma concentration–time curve and 1.06 (90%CI, 0.92–1.23), 1.11 (90%CI, 0.88–1.40), and 1.14 (90%CI, 0.84–1.56) for maximum observed plasma concentration, respectively, relative to subjects with normal renal function based on the regression analysis. The analysis of covariance categorical analysis provided consistent results. Upadacitinib was well tolerated by all subjects, and no safety issues were identified in subjects with renal impairment. Renal impairment has a limited effect on upadacitinib pharmacokinetics. This is in agreement with the known limited role of urinary excretion in upadacitinib elimination. Based on the limited impact on exposure, no dose adjustment is necessary for upadacitinib in subjects with impaired renal function.
Pharmacokinetic Evaluation of Nimotuzumab in Patients With Autosomal Dominant Polycystic Kidney Disease
Authors: de Castro‐Suárez Niurys , Rodríguez‐Vera Leyanis , Villegas Carlos , Dávalos‐Iglesias José M. , Bacallao‐Mendez Raymed , Llerena‐Ferrer Betsy , Leyva‐de la Torre Christian , Lorenzo‐ Luaces Patricia , Troche‐Concepción Mayelin , Ramos‐Suzarte Mayra
Published: January 2019

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by an overexpression and mislocalization of epidermal growth factor receptor (EGFR) to the apical membranes of cystic epithelial cells. Nimotuzumab is a humanized antibody that recognizes an extracellular domain III of human EGFR. The aim of this study was to assess the pharmacokinetic behavior of nimotuzumab in patients with ADPKD given as a single dose. A phase I, single‐center, and noncontrolled open clinical study was conducted. Five patients were enrolled at each of the following fixed‐dose levels: 50, 100, 200, and 400 mg. Intravenous continuous infusions of nimotuzumab were administered every 14 days during a year, except the first administration, when blood samples were drawn during 28 days for pharmacokinetic assessments. Subjects were closely monitored during the trial and at completion of the administration of nimotuzumab, including the anti‐idiotypic response. For the first time, nimotuzumab was used for treating a nononcological disease. The administration of nimotuzumab showed dose‐dependent kinetics. Nimotuzumab does not develop anti‐idiotypic response against the murine portion present in the hypervariable region of the antibody present in the serum of the patients treated. No significant differences were found in the systemic clearance between the 100‐ and 400‐mg dose, which indicates that the optimal biological dose is in this range of dose.
Design and Synthesis of Novel C4‐Linked Substituted 2H‐Chromen‐2‐one‐hypoxanthine Hybrids as Potential Antimicrobial Agents: An Approach to Molecular Docking Studies
Authors: Naik Soniya D. , Hosamani Kallappa M.
Published: January 2019

We present here design and synthesis of very efficient, high‐yielded and simple approach of a series of C4‐linked coumarin–hypoxanthine pharmacophores 1(a–j) with moderate to excellent in vitro antimicrobial activity. According to earlier studies, potential modification at C4‐position of coumarin ring provided excellent bioactive molecules. All the titled compounds were characterized by spectroscopic and elemental analyses. Titled compounds have been developed via systematic tuning of coumarin ring substitutions, which are prepared from the well‐known Pechmann condensation reaction. The addition of a pendent nucleobase in hypoxanthine group improved the in vitro antimicrobial activity. Computational studies were also mimicking the potent biomolecules. A good pharmacokinetic profile is suggested by theoretical calculation of absorption, distribution, metabolism, and excretion properties. Therefore, synthesis of these titled compounds provided an insight towards better antimicrobial agents.
Sex‐based outcomes in type I thyroplasty for nonparalytic glottic incompetence
Authors: Farzal Zainab , Overton Lewis J. , Farquhar Douglas R. , Stephenson Elizabeth D. , Shah Rupali N. , Buckmire Robert A.
Published: January 2019

Objective

Clinical outcomes for type I Gore‐Tex thyroplasty (GMT) for nonparalytic glottic incompetence (GI) have been reported in the literature. Given differences in male and female laryngeal anatomy, sex‐based outcomes should also be evaluated. We endeavored to evaluate sex‐specific post‐GMT voice outcomes.

Methods

We performed a retrospective review of patients undergoing GMT for nonparalytic GI. Multidimensional voice outcome measures including voice‐related quality of life (VRQOL), Glottal Function Index (GFI), and grade/roughness/breathiness/asthenia/strain (GRBAS) were analyzed at postoperative time frames: 0 to 3 months, 3 to 9 months, and 9 to 18 months.

Results

Eighty‐five subjects (43 females, 42 males) with mean age 53.5 undergoing GMT for nonparalytic GI from 2005 to 2017 met inclusion criteria. Etiologies included vocal fold hypomobility (N = 36, 42%), paresis (N = 18, 21%), vocal fold atrophy (N = 17, 20%), and scarring (N = 14, 17%). Females had significantly greater improvement on VRQOL at 0 to 3 months and 9 to 18 months timeframes compared to males, with mean change in VRQOL: 41.3 versus 22.4 (P = 0.0002) and 42.5 versus 20.8 (P = 0.002), respectively. Similarly, women had significantly greater improvement in GFI at 0 to 3 months follow‐up (mean difference − 10.8 vs. −4.9, respectively, P = 0.0002). There was no statistically significant sex difference in GRBAS at any follow‐up interval.

Conclusion

Following GMT, females had greater improvement in patient‐reported voice outcomes in the early postoperative period. No significant difference between sexes was noted in perceptual measures (GRBAS). Sex‐specific outcomes should be evaluated for clinical interventions to improve specificity of preoperative counseling.

Level of Evidence

4. Laryngoscope, 129:2543–2548, 2019
Basaloid nasopharyngeal carcinoma: A population‐based analysis of a rare tumor
Authors: Unsal Aykut A. , Booth J. Renee , Rossi Nicholas A. , Byrd J. Kenneth , Kountakis Stilianos E.
Published: January 2019

Objectives

Basaloid nasopharyngeal carcinoma (BNPC) is an extremely rare malignancy with a paucity of cases reported in the literature. This analysis represents the largest cohort of BNPC to date.

Study Design

Retrospective population‐based analysis.

Methods

The Surveillance, Epidemiology, and End Results registry from 2001 to 2015 was utilized to extract a total of 82 cases of BNPC. Data were analyzed for incidence trends, demographic, and tumor characteristics, as well as potential outcome prognosticators.

Results

White male patients between the ages of 40 to 79 years were most commonly affected. The incidence was measured at 0.06 per 100 thousand people. The majority of tumors were considered high grade (grade III/IV; 92.2%). At presentation, patients were most commonly advanced stage (American Joint Committee on Cancer [AJCC] stage IV) at 29.3%, followed by AJCC stages II and III (20.7%, respectively). T2 tumors were most common at 28.8%. Cervical node involvement and distant metastasis were measured at 53.7% and 10.4%, respectively. One‐year, 5‐year, and 10‐year disease‐specific survival was 87.7%, 60.7%, and 29.8%, respectively. No prognostic factors were identified in this study.

Conclusion

Basaloid squamous cell carcinoma represents a histologic subtype of nasopharyngeal carcinoma with excellent short‐term outcomes but poor survival at 10 years when compared to conventional squamous cell carcinomas.

Level of Evidence

NA Laryngoscope, 129:2727–2732, 2019
Outcomes of transmastoid resurfacing for superior canal dehiscence using a cartilage overlay technique
Authors: Al Afif Ayham , Farmer Robert , Bance Manohar
Published: January 2019

Objective

Superior semicircular canal dehiscence is a well‐described syndrome with potentially debilitating symptoms. We report on the audiologic and long‐term symptom outcomes of 10 patients (12 ears) undergoing a cartilage overlay transmastoid resurfacing technique.

Methods

Retrospective chart review and cross‐sectional outcomes recall survey were used. A mailed questionnaire quantifying the effect of surgery on symptom severity and patient satisfaction were used. Nonlinear regression curves of pre‐/postoperative air and bone pure‐tone audiometric data were used to evaluate postoperative changes in hearing. Surgical failure was defined as requiring revision surgery, and rates were estimated over time using a Kaplan‐Meier analysis.

Results

Most patients reported improved symptoms postoperatively and were satisfied overall with the surgical outcomes. However, four of 12 ears (33%) had a second (revision) surgery before achieving these results. Postoperatively, hearing through air and bone conduction tended to decrease at frequencies greater than 2500 Hz. The chance of avoiding a re‐operation at 36 months (and up to 120 months) was estimated to be 57.1% (95% confidence interval [confidence interval]: 100%, 32.6%). The most common surgical complication was intraoperative cerebrospinal fluid (CSF) leak, encountered exclusively during dural elevation, seen in four of 12 ears (33%).

Conclusion

Although subjectively successful at reducing symptoms, in our small sample this surgical approach did not provide a long‐term stable repair and was frequently associated with intraoperative CSF leak. Offering transmastoid resurfacing to patients should involve a detailed discussion on the potential for revision surgery and risks of diminished hearing and CSF leak.

Level of Evidence

4

Laryngoscope, 129:2164–2169, 2019
Electronically Tunable Distributed Feedback (DFB) Laser on Silicon
Authors: Dhoore Sören , Köninger Anna , Meyer Ralf , Roelkens Gunther , Morthier Geert
Published: January 2019

An electronically tunable distributed feedback (DFB) laser heterogeneously integrated on a silicon photonics platform is experimentally demonstrated. Tuning is achieved through carrier injection into the tuning layer of a tunable twin‐guide III–V membrane on silicon. A 2 nm continuous tuning range is achieved with a single tuning current. Continuous‐wave single‐mode laser operation with a side‐mode suppression ratio larger than 44 dB across the tuning range is obtained. Measured wavelength switching times are on the order of 3 ns and non‐return‐to‐zero on‐off keying direct modulation at 12.5 Gbit s−1 is readily achieved. This work can be a major advance toward the realization of optical burst or packet switching systems for future data center networks.