bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroreductive Intermolecular Coupling of Chromones with Benzophenones: Synthesis of 2‐Diarylmethylchromones and Tetrasubstituted Furans
Authors: Kise Naoki , Nagamine Hiroaki , Sakurai Toshihiko
Published: May 2019

The electroreductive coupling of chromones with benzophenones in the presence of TMSCl gave adducts reacted at the 2‐position of chromones as trimethylsilyl ethers. From 3‐methyl‐ and 3‐phenylchromones, 2,3‐cis‐adducts were formed predominantly. The cis‐adducts were isomerized to trans‐ones by treatment with DBU. The detrimethylsilylation of the adducts with 1 M HCl aq/dioxane produced the corresponding alcohols. The dehydrosiloxylation of the adducts or dehydration of the desilylated alcohols brought about 2‐diarylmethylchromones. The detrimethylsilylation of the adducts with TBAF and subsequent treatment with NaH afforded ring‐opening products. The dehydration of the ring‐opening products obtained from 3‐methyl‐ and 3‐phenylchromons brought about tetrasubstituted furans or dihydrobenzofuran‐3‐ones. The dehydrogenation of the adducts with DDQ and subsequent desilylation with 1 M HCl aq/dioxane gave 2‐(diarylhydroxymethyl)chromones.
Towards a Synthetic Strategy for the Ten Canonical Carrageenan Oligosaccharides – Synthesis of a Protected γ‐Carrageenan Tetrasaccharide
Authors: Kinnaert Christine , Clausen Mads H.
Published: May 2019

Herein, we report a synthetic strategy aiming at synthesizing the ten canonical carrageenan oligosaccharides from one single precursor. The key β‐(1→4)‐linked disaccharide was synthesized from commercially available galactose pentaacetate. The notoriously difficult formation of β‐(1→4)‐d‐galactan linkages was successfully optimized on the differentially substituted monosaccharides to afford the desired disaccharide in 55 % yield. Following a convergent strategy, two disaccharides were then glycosylated to form the fully protected α‐(1→4)‐linked tetrasaccharide backbone of the carrageenans. The careful selection of protecting groups provides the opportunity to access all ten carrageenan substructures identified in polysaccharides isolated from red algae. Here, we demonstrate how one such target oligosaccharide can be obtained in a protected form.
Peptidomics and proteomics based on CE‐MS as a robust tool in clinical application: The past, the present, and the future
Authors: Latosinska Agnieszka , Siwy Justyna , Mischak Harald , Frantzi Maria
Published: May 2019

Capillary electrophoresis combined with mass spectrometry (CE‐MS) has been used for several years for the investigation of proteins and peptides as biomarkers for diagnosis and prognosis of diseases. In addition, the technology has recently been introduced to support the stratification of patients in clinical trials and in large clinical studies. In this review, we aim at presenting the development of CE‐MS over the last 20 years, by focusing on the clinical potential of proteome and peptidome analysis and highlighting some of the key technical issues and advancements that have been made in this context towards implementation. Based on the reviewed literature, it has become evident that CE‐MS is now an accepted tool in clinical application in several disease areas. Apart from a critical overview on the current state‐of‐the‐art in CE‐MS, we also indicate the expected developments for potential future use.
Functionalized gold nanoparticles for sample preparation: A review
Authors: Liu Siyao , Lämmerhofer Michael
Published: May 2019

Sample preparation is a crucial step for the reliable and accurate analysis of both small molecule and biopolymers which often involves processes such as isolation, pre‐concentration, removal of interferences (purification), and pre‐processing (e.g., enzymatic digestion) of targets from a complex matrix. Gold nanoparticle (GNP)‐assisted sample preparation and pre‐concentration has been extensively applied in many analytical procedures in recent years due to the favorable and unique properties of GNPs such as size‐controlled synthesis, large surface‐to‐volume ratio, surface inertness, straightforward surface modification, easy separation requiring minimal manipulation of samples. This review article primarily focuses on applications of GNPs in sample preparation, in particular for bioaffinity capture and biocatalysis. In addition, their most common synthesis, surface modification and characterization methods are briefly summarized. Proper surface modification for GNPs designed in accordance to their target application directly influence their functionalities, e.g., extraction efficiencies, and catalytic efficiencies. Characterization of GNPs after synthesis and modification is worthwhile for monitoring and controlling the fabrication process to ensure proper quality and functionality. Parameters such as morphology, colloidal stability, and physical/chemical properties can be assessed by methods such as surface plasmon resonance, dynamic light scattering, ζ‐potential determinations, transmission electron microscopy, Taylor dispersion analysis, and resonant mass measurement, among others. The accurate determination of the surface coverage appears to be also mandatory for the quality control of functionality of the nanoparticles. Some promising applications of (functionalized) GNPs for bioanalysis and sample preparation are described herein.
Effect of Electrolyte Composition on Performance and Stability of Lithium–Sulfur Batteries
Authors: Ishino Yuki , Takahashi Keitaro , Murata Wataru , Umebayashi Yasuhiro , Tsuzuki Seiji , Watanabe Masayoshi , Kamaya Minori , Seki Shiro
Published: May 2019

The development of new electrolytes for lithium–sulfur (Li–S) batteries is important. Electrolytes based on 1:1 glyme:Li+ complexes can be locally destroyed to form free glyme during charge/discharge cycles. Free glyme can cause Li2Sx dissolution, which is a major factor in Li–S battery degradation. To decrease the local generation of free glyme, the glyme:Li+ electrolytes with higher proportions of Li salts are developed to control the Li2Sx dissolution into the electrolyte. The chemical solubility of Li2S8 and the charge/discharge properties of Li–S cells are investigated by varying the glyme:Li salt molar ratio. Nonequimolar (high Li salt concentration) glyme:Li salt mixture electrolytes directly suppress the Li2S8 dissolution and improve the charge/discharge properties (cycling and coulombic efficiency) of Li–S cells. The electrolyte composition can control the chemical stability of reactive intermediates at the Li2Sx electrode and provide high‐performance Li–S cells for next‐generation batteries.
The oldest trees in China and where to find them
Authors: Liu Jiajia , Yang Bao , Lindenmayer David B
Published: May 2019

Extremely old trees are valued and revered by residents in many countries. Yet information about the ages and locations of the oldest living trees is rarely available, especially at the national level. We compiled a series of dendrochronological datasets of the age and location of very old trees (≥1000 years old) across China, and found that there are at least 98 ancient living trees exceeding 1000 years of age in the country. The oldest living individual we identified was a Qilian juniper (Juniperus przewalskii) tree that, as of 2009, was determined to be 2230 years old. The oldest trees occurred most frequently in remote, high‐elevation areas.
The Effects of Interaction between Climate Change and Land‐Use/Cover Change on Biodiversity‐Related Ecosystem Services
Authors: He Xinyue , Liang Jie , Zeng Guangming , Yuan Yujie , Li Xiaodong
Published: May 2019

Climate change and land‐use/cover change (LUCC) are two major types of global environmental change. They are increasingly challenging the main objectives of ecosystem management, which are to provide ecosystem services sustainably to society and maintain biodiversity. However, a comprehensive understanding of how climate–land‐use change affects these primary goals of ecosystem management is still lacking. Here, a global literature review on the impacts of climate change and LUCC on ecosystem services related to biodiversity is presented. In this review, possible ecological responses at species, community, and ecosystem levels, and the effects of interaction mechanisms between climate change and LUCC on biodiversity‐related ecosystem services are identified. The results show possible effects on species facing climate change challenges through affecting distribution/range shifts, interspecific relations, richness, and abundance, and the impacts on biodiversity through increasing extinction rates, nutrient deposition, and habitat fragmentation under LUCC. Climate change may hinder the ability of species to deal with LUCC, and in turn LUCC could reduce resilience to climate change. Understanding of these interactions is necessary to address the increasing pressure on sustainable provisioning of ecosystem services under different climate and land‐use scenarios in the future.
Modelling the differences between El Niño and La Niña years and planktonic larval duration on dispersal across the southeast Australian biogeographic barrier
Authors: Aguilar Lucia A. , Matthews Samuel A. , Ayre David J. , Minchinton Todd E.
Published: May 2019

Phylogeographic and genetic studies have revealed complex variation in connectivity across the Southeast Australian Biogeographic Barrier (SEABB) for intertidal rocky‐shore invertebrates. The objective of this study was to use Connie2 to test whether differences between El Niño and La Niña years alter the probability of larvae crossing the SEABB. The SEABB occurs on the SE corner of Australia and is the convergence site of two major ocean currents (Zeehan and East Australian Currents) as well as an historical land bridge connecting Tasmania to the mainland. It includes extensive sandy shore lacking suitable substrate for rocky‐shore specialists. Study locations included coastal sites from New South Wales, Victoria, and Tasmania categorised into four regions (Barrier, Eastern, Western, and Southern). Connie2, an interactive hydrodynamic modelling tool available online, was used to evaluate connectivity via larval dispersal by comparing the effect of planktonic larval duration (PLD) from five to 120 days, season of spawning, and ENSO variability (comparing La Niña and El Niño years) on the cumulative probability of dispersal between and among populations (regions) arrayed either side of the SEABB. For all years, strong connections were detected among sites within regions, even for low to moderate (less than 20% predicted dispersal) PLDs and irrespective of season. Connectivity across SEABB (between regions) was also strongly influenced by all variables but occurred only at PLD of at least 30 days for summer spawning. Connectivity across the SEABB was strongest from west to east and south to east during La Niña events. Our findings support the importance of SEABB as a barrier to dispersal. Migration across SEABB is predicted only for summer spawners (PLD ≥30 days). Predicted dispersal is only weakly influenced by El Niño and La Niña extremes, but connectivity may be altered by projected changes to the relative strengths of the Zeehan and East Australian Currents.
Positive margin rates and predictors in transoral robotic surgery after federal approval: A national quality study
Authors: Hanna Jonathan , Morse Elliot , Brauer Philip R. , Judson Benjamin , Mehra Saral
Published: May 2019

Background

Purpose of the study is to assess nationwide margin performance in oropharynx transoral robotic surgery (TORS).

Methods

Retrospective review of the National Cancer Database.

Results

Two thousand six hundred sixty‐one patients were included. The national positive margin rate (PMR) was 16.9%. High‐volume facilities had a lower PMR than low‐volume facilities (12.7% vs 21.9%; P < .001). Patients with disease of the tonsil had a lower PMR (15.7%) than base‐of‐the‐tongue (18.2%; P = .14). PMR increased with T classification (T1 = 13.0%, T2 = 17.1%, T3 = 28.2%, T4a = 45.9%, T4b = 58.3%; P < .001). On multivariable regression, factors associated with margin status included only lymph‐vascular invasion (1.63[1.13‐2.36]; P = .01), high volume (0.57[0.36‐0.92]; P = .005), and T classification (as compared to T1, T2: 1.50[1.03‐2.18], T3: 3.11[1.77‐5.46], T4a: 7.03[2.95‐16.75], T4b: 6.72[1.26‐35.93]; P < .001).

Conclusions

National PMR is 16.9%, substantially higher than reported in high‐volume TORS centers. There is a linear association between positive margins and T classification, with T3 and T4 PMRs exceeding 28%. High‐volume facilities are half as likely to yield positive margins compared to low‐volume facilities. There was no association between human papilloma virus status, tumor subsite, or academic facility status and positive margins.
A novel approach to neurologic function sparing surgical management of vagal schwannomas: Continuous intraoperative nerve monitoring of the laryngeal adductor reflex
Authors: Sandler Mykayla L. , Sims John R. , Sinclair Catherine , Ho Rebecca , Yue Lauren E. , Téllez Maria J. , Ulkatan Sedat , Khorsandi Azita S. , Brandwein‐Weber Margaret , Urken Mark L.
Published: May 2019

Background

Vagal schwannomas are rare, benign tumors of the head and neck. Nerve damage during surgical resection is associated with significant morbidity. A new technique of continuous intraoperative nerve monitoring (IONM) that allows for real‐time intraoperative feedback has recently been used for thyroid and cervical spine surgeries but has not previously been used in vagal schwannoma surgery.

Methods

Case series of three patients who underwent vagal schwannoma excision utilizing this novel IONM technique. The recurrent laryngeal and vagus nerves were monitored via the laryngeal adductor reflex (LAR) using an electromyographic endotracheal tube.

Results

Three patients with suspected vagal schwannomas were treated surgically using the intracapsular enucleation approach with a combination of intermittent IONM and continuous IONM of the LAR.

Conclusion

This combination of continuous and intermittent IONM can be used to preserve vagal laryngeal innervation and function and may represent the future standard of care for vagal schwannoma excision.
NMDA receptor activity bidirectionally controls active decay of long‐term spatial memory in the dorsal hippocampus
Authors: Migues Paola Virginia , Wong Jacinda , Lyu Jeongho , Hardt Oliver
Published: May 2019

The time‐dependent forgetting of long‐term spatial memories involves activation of NMDA receptors (NMDARs) in the hippocampus. Here, we tested whether NMDARs regulate memory persistence bidirectionally, decreasing or increasing the rate of forgetting. We found that blocking NMDAR activation with AP5 or the GluN2B‐selective antagonist Ro25‐6981 in the dorsal hippocampus (dHPC) prevented the natural forgetting of long‐term memory for the locations of objects in an open field arena. In contrast, while enhancing NMDAR function with the partial agonist D‐Cycloserine did not affect the speed of forgetting for these types of memories, infusing the NMDAR co‐agonist D‐Serine significantly shortened their persistence. These results suggest that NMDAR activity can modulate the speed of constitutive long‐term memory decay in the dHPC and that regulating NMDAR expression and D‐Serine availability could provide a mechanism to control the duration of long‐term memory.
Oil fouling in double‐pipe heat exchanger under liquid‐liquid dispersion and the influence of copper oxide nanofluid
Authors: Majdi Hasan S. , Alabdly Hussein A. , Hasan Basim O. , Hathal Mustafa M.
Published: May 2019

Dispersions of oil in water are encountered in a variety of industrial processes leading to a reduction in the performance of the heat exchangers when thermally treating such two phase fluids. This reduction is mainly due to changes in the thermal and hydrodynamical behavior of the two phase fluid. In the present work, an experimental investigation was performed to study the effects of light oil fouling on the heat transfer coefficient in a double‐pipe heat exchanger under turbulent flow conditions. The effects of different operating conditions on the fouling rate were investigated including: hot fluid Reynolds number (the dispersion), cold fluid Reynolds number, and time. The oil fouling rate was analyzed by determining the growth of fouling resistance with time and through pressure drop measurements. The influence of copper oxide (CuO) nanofluid on the fouling rate in the dispersion was also determined. It was found that the presence of dispersed oil causes a reduction in heat transfer coefficient by percentages depending on the Reynolds number of both cold and hot fluids and the concentration of oil. In addition, the time history of fouling resistance exhibited different trends with the flow rates of both fluids and its trend was influenced appreciably by the presence of CuO nanofluid.
Cluster analysis identifying clinical phenotypes of preterm birth and related maternal and neonatal outcomes from the Brazilian Multicentre Study on Preterm Birth
Authors: Souza Renato T. , Cecatti Jose G. , Passini Renato , Pacagnella Rodolfo C. , Oliveira Paulo F. , Silva Cleide M. ,   the Brazilian Multicentre Study on Preterm Birth study group
Published: May 2019

Objective

To explore a conceptual framework of clinical conditions associated with preterm birth (PTB) by cluster analysis, assessing determinants for different PTB subtypes and related maternal and neonatal outcomes.

Methods

Secondary analysis of the Brazilian Multicentre Study on Preterm Birth of 33 740 births in 20 maternity hospitals between April 2011 and July 2012. In accordance with a prototype concept based on maternal, fetal, and placental conditions, an adapted k‐means model and fuzzy algorithm were used to identify clusters using predefined conditions. The mains outcomes were phenotype clusters and maternal and neonatal outcomes.

Results

Among 4150 PTBs, three clusters of PTB phenotypes were identified: women who had PTB without any predefined conditions; women with mixed conditions; and women who had pre‐eclampsia, eclampsia, HELLP syndrome and fetal growth restriction. The prevalence of different preterm subtypes differed significantly in the three clusters, varying from 80.95% of provider‐initiated PTBs in cluster 3–6.62% in cluster 1 (P<0.001). Although some maternal characteristics differed among the clusters, maternal and neonatal outcomes did not.

Conclusions

The analysis identified three clusters with distinct phenotypes. Women from the different clusters had different subtypes of PTB and maternal and pregnancy characteristics.
Synthesis and assessment of metallic ion migration through a novel calcium carbonate coating for biomedical implants
Authors: Bang Le Thi , Filho Luimar C. , Engqvist Håkan , Xia Wei , Persson Cecilia
Published: May 2019

Titanium (Ti) implants are commonly regarded as well accepted by the body. However, metal ion release is still a cause for concern. A small decrease in pH, which can be caused by inflammation, may produce a large increase in the corrosion rate of Ti implants. Coating the alloy with a buffer layer could have a significant protective effect. In this study, a calcium carbonate coating was developed on commercially pure Ti and a Ti–6Al–4V alloy through a hydrothermal treatment of previously NaOH‐treated surfaces in calcium‐citric acid chelate complexes. The results showed that a superstructured calcite coating layer formed on the Ti substrate after treatment at 170°C for 3 hr. The coating was approx. 1 μm thick and covered the substrate surface uniformly. When prolonging the hydrothermal treatment from 5 hr to 24 hr, the rhombohedral structure of calcite was observed in addition to the superstructure of calcite. Dissolution test results showed no significant differences in solution pH between the coated‐ and un‐coated samples. However, the CaCO3 coating reduced by approx. 2–5 times the Ti and V ion release from the substrate as compared to the uncoated material, at pH 4. CaCO3 and hydroxyapatite (HA) coatings gave nonsignificant effects at neutral pH although the HA coating showed a trend for better results at the longer time points. The reduction in metal ion release from the substrate and the buffering ability of the CaCO3 coating encourage further studies on this coating for clinical applications.
The retinol‐retinoic acid metabolic pathway is impaired in the lumbar spine of a rat model of congenital kyphoscoliosis
Authors: Sonoda Hiroyuki , Iizuka Haku , Ishiwata Sho , Tsunoda Daisuke , Abe Masako , Takagishi Kenji , Chikuda Hirotaka , Koibuchi Noriyuki , Shimokawa Noriaki
Published: May 2019

Although congenital scoliosis is defined as a genetic disease characterized by a congenital and abnormal curvature of the spinal vertebrae, our knowledge of the genetic underpinnings of the disease is insufficient. We herein show that the downregulation of the retinol‐retinoic acid metabolism pathway is involved in the pathogenesis of congenital scoliosis. By analyzing DNA microarray data, we found that the expression levels of genes associated with the retinol metabolism pathway were decreased in the lumbar spine of Ishibashi rats (IS), a rat model of congenital kyphoscoliosis. The expression of Adh1 and Aldh1a2 (alcohol dehydrogenase), two enzymes that convert retinol to retinoic acid in this pathway, were decreased at both the gene and protein levels. Rarα, a receptor of retinoic acid and bone morphogenetic protein 2, which play a central role in bone formation and are located downstream of this pathway, were also downregulated. Interestingly, the serum retinol levels of IS rats were higher than those of wild‐type control rats. These results indicate that the adequate conversion from retinol to retinoic acid is extremely important in the regulation of normal bone formation and it may also be a key factor for understanding the pathogenesis of congenital scoliosis.
Circular RNA circ_0103552 forecasts dismal prognosis and promotes breast cancer cell proliferation and invasion by sponging miR‐1236
Authors: Yang Lixia , Song Chang , Chen Ying , Jing Guilian , Sun Jingwen
Published: May 2019

Breast cancer (BC) is a fatal malignancy, which has a high incidence and mortality across the world. Circular RNAs (circRNAs) have crucial roles in tumor initiation and progression. In this project, a newly found circRNA, circ_0103552 was explored. Quantitative real‐time polymerase chain reaction was applied to measure its expression in the patients' tissue specimens and cells. In addition, Fisher's exact test, Kaplan‐Meier curves and Cox regression model were conducted to discover the clinical significance of circ_0103552. Cell viability, clone‐forming ability, apoptosis, and metastatic properties of BC cells were evaluated by gain/loss‐of‐function assays. Dual luciferase reporter assay was applied to illuminate its mechanisms. As data indicated, circ_0103552 was significantly elevated in BC tissue samples and cells. In addition, its expression correlates with clinical severity and dismal prognosis. Furthermore, circ_0103552 could facilitate cell growth, clone‐forming ability, migration and invasion, and decrease apoptotic cells. For the mechanism exploration, circ_0103552 could directly sponge miR‐1236 to execute oncogenic activities in BC cells. In summary, this study provides a novel circRNA in tumorigeneis and progression of BC and may help to develop effective therapeutic target for this devastating disease.
Fe3O4@NCs/BF0.2: A magnetic bio‐based nanocatalyst for the synthesis of 2,3‐dihydro‐1H‐perimidines
Authors: Mirjalili Bi Bi Fatemeh , Imani Mahnaz
Published: May 2019

Nanocellulose (NC) materials have some unique properties, which make them attractive as organic or inorganic supports for catalytic applications. Nanocatalysts with diameters of less than 100 nm are difficult to separate from the reaction mixture, therefore, magnetic nanoparticles (MNPs) were used as catalysts to overcome this problem. Fe3O4@NCs/BF0.2 as a green, bio‐based, eco‐friendly, and recyclable catalyst was synthesized and characterized using fourier‐transform infrared spectroscopy (FT‐IR), vibrating sample magnetometer (VSM), X‐ray diffraction (XRD), X‐ray fluorescence (XRF), Brunauer–Emmett–Teller (BET), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and thermal gravimetric analysis (TGA) techniques. Fe3O4@NCs/BF0.2 was employed for the synthesis of 2,3‐dihydro‐1H‐perimidine derivatives via a reaction of 1,8‐diaminonaphthalene with various aldehydes at room temperature under solvent‐free conditions. The present procedure offers several advantages including a short reaction time, excellent yields, easy separation of catalyst, and environmental friendliness.
Circ_0005075 promotes hepatocellular carcinoma progression by suppression of microRNA‐335
Authors: Yang Xiangyu , Song Hang , Zi Zhenguo , Kou Jiantao , Chen Shuhua , Dai Yang , Wang Jiangfeng , Yuan Liudi , Gao Kun
Published: May 2019

Accumulating evidence suggests that noncoding RNAs play a vital role in cancer biology. Circular RNAs (circRNAs), a newly defined class of endogenously widespread noncoding RNAs, have been intensively reported to influence cell function and development, and even cancer prognosis by sponging microRNAs in various types of cancer. Nevertheless, the circRNAs research in hepatocellular carcinoma (HCC) still remains far insufficient. Herein, we investigated the role of a newly defined circRNAs, circ_0005075, in HCC development. We found circ_0005075 was upregulated in HCC tissues. HCC progression was suppressed by downregulation of circ_0005075 in vitro and in vivo, and the suppression was partially reversed by inhibition of microRNA‐335 (miR‐335) expression. Further, we found the expression of mitogen‐activated protein kinase 1 (MAPK1) was substantially regulated by circ_0005075 and miR‐335. Mechanically, it was demonstrated that circ_0005075 could directly bind to miR‐335 and miR‐335 could bind to MAPK1. Our data provide evidence that circ_0005705 promotes the HCC progression by sponging miR‐335 and further regulating MAPK1 expression.
Friend or foe: Multiple roles of adipose tissue in cancer formation and progression
Authors: Wang Yu‐Xiang , Zhu Neng , Zhang Chan‐Juan , Wang Yi‐Kai , Wu Hong‐Tao , Li Qun , Du Ke , Liao Duan‐Fang , Qin Li
Published: May 2019

Obesity is well‐known as the second factor for tumorigenesis after smoking and is bound up with the malignant progression of several kinds of cancers, including esophageal cancer, liver cancer, colorectal cancer, kidney cancer, and ovarian cancer. The increased morbidity and mortality of obesity‐related cancer are mostly attributed to dysfunctional adipose tissue. The possible mechanisms connecting dysfunctional adipose tissue to high cancer risk mainly focus on chronic inflammation, obesity‐related microenvironment, adipokine secretion disorder, and browning of adipose tissue, and so forth. The stromal vascular cells in adipose tissue trigger chronic inflammation through secreting inflammatory factors and promote cancer cell proliferation. Hypertrophic adipose tissues lead to metabolic disorders of adipocytes, such as abnormal levels of adipokines that mediate cancer progression and metastasis. Cancer patients often show adipose tissue browning and cancerous cachexia in an advanced stage, which lead to unsatisfied chemotherapy effect and poor prognosis. However, increasing evidence has shown that adipose tissue may display quite opposite effects in cancer development. Therefore, the interaction between cancers and adipose tissue exert a vital role in mediates adipose tissue dysfunction and further leads to cancer progression. In conclusion, targeting the dysfunction of adipose tissue provides a promising strategy for cancer prevention and therapy.
Ultrasound assessment of muscle mass in response to exercise training in chronic kidney disease: a comparison with MRI
Authors: Gould Douglas W. , Watson Emma L. , Wilkinson Thomas J. , Wormleighton Joanne , Xenophontos Soteris , Viana Joao L. , Smith Alice C.
Published: May 2019

Background

Chronic kidney disease (CKD) is a catabolic condition associated with muscle wasting and dysfunction, which associates with morbidity and mortality. There is a need for simple techniques capable of monitoring changes in muscle size with disease progression and in response to interventions aiming to increase muscle mass and function. Ultrasound is one such technique; however, it is unknown how well changes in muscle cross‐sectional area (CSA) measured using ultrasound relate to changes in whole muscle volume measured using magnetic resonance imaging. We tested whether rectus femoris CSA (RF‐CSA) could be used as a valid indication of changes in quadriceps muscle volume as a single measure of muscle size and following a 12 week exercise intervention that resulted in muscle hypertrophy.

Methods

Secondary analysis of data was collected from the ExTra CKD study (ISRCTN 36489137). Quadriceps muscle size was assessed from 36 patients with non‐dialysis CKD before and after 12 weeks of supervised exercise that resulted in muscle hypertrophy.

Results

Strong positive correlations were observed between RF‐CSA and quadriceps volume at baseline (r2 = 0.815, CI 0.661 to 0.903; P < 0.001) and following 12 week exercise (r2 = 0.845, CI 0.700 to 0.923; P < 0.001). A moderate positive association was also observed between changes in RF‐CSA and quadriceps following exercise training (rho = 0.441, CI 0.085 to 0.697; P = 0.015). Bland–Altman analysis revealed a small bias (bias 0.6% ± 12.5) between the mean percentage changes in RF‐CSA and quadriceps volume but wide limits of agreement from −24 to 25.

Conclusions

Rectus femoris CSA appears to be a reliable index of total quadriceps volume as a simple measure of muscle size, both as a single observation and in response to exercise training in non‐dialysis CKD patients.
Preclinical assessment of 68Ga‐PSMA‐617 entrapped in a microemulsion delivery system for applications in prostate cancer PET/CT imaging
Authors: Mandiwana Vusani , Kalombo Lonji , Lemmer Yolandy , Labuschagne Philip , Semete‐Makokotlela Boitumelo , Sathekge Mike , Ebenhan Thomas , Zeevaart Jan Rijn
Published: May 2019

It has in recent years been reported that microemulsion (ME) delivery systems provide an opportunity to improve the efficacy of a therapeutic agent whilst minimising side effects and also offer the advantage of favourable treatment regimens. The prostate‐specific membrane antigen (PSMA) targeting agents PSMA‐11 and PSMA‐617, which accumulate in prostate tumours, allow for [68Ga]Ga3+‐radiolabelling and positron emission tomography/computed tomography (PET) imaging of PSMA expression in vivo. We herein report the formulation of [68Ga]Ga‐PSMA‐617 into a ME ≤40 nm including its evaluation for improved cellular toxicity and in vivo biodistribution. The [68Ga]Ga‐PSMA‐617‐ME was tested in vitro for its cytotoxicity to HEK293 and PC3 cells. [68Ga]Ga‐PSMA‐617‐ME was administered intravenously in BALB/c mice followed by microPET/computed tomography (CT) imaging and ex vivo biodistribution determination. [68Ga]Ga‐PSMA‐617‐ME indicated negligible cellular toxicity at different concentrations. A statistically higher tolerance towards the [68Ga]Ga‐PSMA‐617‐ME occurred at 0.125 mg/mL by HEK293 cells compared with PC3 cells. The biodistribution in wild‐type BALB/C mice showed the highest amounts of radioactivity (%ID/g) presented in the kidneys (31%) followed by the small intestine (10%) and stomach (9%); the lowest uptake was seen in the brain (0.5%). The incorporation of [68Ga]Ga‐PSMA‐617 into ME was successfully demonstrated and resulted in a stable nontoxic formulation as evaluated by in vitro and in vivo means.
Empirical comparison of univariate and multivariate meta‐analyses in Cochrane Pregnancy and Childbirth reviews with multiple binary outcomes
Authors: Price Malcolm J. , Blake Helen A. , Kenyon Sara , White Ian R. , Jackson Dan , Kirkham Jamie J. , Neilson James P. , Deeks Jonathan J. , Riley Richard D.
Published: May 2019

Background

Multivariate meta‐analysis (MVMA) jointly synthesizes effects for multiple correlated outcomes. The MVMA model is potentially more difficult and time‐consuming to apply than univariate models, so if its use makes little difference to parameter estimates, it could be argued that it is redundant.

Methods

We assessed the applicability and impact of MVMA in Cochrane Pregnancy and Childbirth (CPCB) systematic reviews. We applied MVMA to CPCB reviews published between 2011 and 2013 with two or more binary outcomes with at least three studies and compared findings with results of univariate meta‐analyses. Univariate random effects meta‐analysis models were fitted using restricted maximum likelihood estimation (REML).

Results

Eighty CPCB reviews were published. MVMA could not be applied in 70 of these reviews. MVMA was not feasible in three of the remaining 10 reviews because the appropriate models failed to converge. Estimates from MVMA agreed with those of univariate analyses in most of the other seven reviews. Statistical significance changed in two reviews: In one, this was due to a very small change in P value; in the other, the MVMA result for one outcome suggested that previous univariate results may be vulnerable to small‐study effects and that the certainty of clinical conclusions needs consideration.

Conclusions

MVMA methods can be applied only in a minority of reviews of interventions in pregnancy and childbirth and can be difficult to apply because of missing correlations or lack of convergence. Nevertheless, clinical and/or statistical conclusions from MVMA may occasionally differ from those from univariate analyses.
EEG analysis of mixed‐reality music rehabilitation system for post‐stroke lower limb therapy
Authors: Chang Wei‐Chiao , Ko Li‐Wei , Yu Kuen‐Han , Ho Yu‐Chun , Chen Chia‐Hsin , Jong Yuh‐Jyh , Huang Yi‐Pai
Published: May 2019

Lots of evidence and guidelines recommended that stroke patients have to do the rehabilitation all the time, but in fact, the ratio of patients doing the rehabilitation is usually less than one third. In order to enhance the rehabilitation efficacy, we develop an innovative mixed‐reality music rehabilitation (MR2) system, which is consisted of an MR goggle, inertial measurement unit sensors, and an EEG system. Several music contents with different levels are implemented into the MR system. While doing the rehabilitation task, our system can monitor patient's both gait information and electroencephalographic (EEG) signals to understand the rehabilitation performance in both central and peripheral nervous systems. The MR2 system has been pilot testing on two stroke patients and three healthy controls. Experiment results show that the patient's motor function is significantly activating when wearing the MR2 system during the rehabilitation task. Furthermore, the gait analysis results also show that flexion angle of the hemiplegic knee during walking was significantly improved when following the tempo of the MR music content in the rehabilitation. The pilot testing results provide new insights into the understanding of complex brain functions of patients actively and continuously performing the rehabilitation ordinary tasks within the mixed‐reality applications.
Early versus late salvage abdominoperineal resection for anal squamous cell carcinoma: Is there a difference in survival?
Authors: Fields Adam C. , Melnitchouk Nelya , Senturk James , Irani Jennifer , Bleday Ronald , Goldberg Joel
Published: May 2019

Background/Objectives

The first‐line treatment for anal squamous cell carcinoma is Nigro protocol chemoradiotherapy. Some patients will fail curative intent chemoradiotherapy and have persistent disease while others may have an initial response followed by disease recurrence. The goal of this study is to investigate survival in anal squamous cell carcinoma patients who fail first‐line treatment.

Methods

The National Cancer Database (2004‐2013) was used to identify patients with anal squamous cell carcinoma. The primary outcome was overall survival.

Results

There were 256 patients in the early salvage group who underwent abdominoperineal resection (APR) within 6 months of completing chemoradiotherapy and 181 patients in the late salvage group who had APR 6 months or more after completion of chemoradiotherapy. Both groups of patients had similar tumor size (45  vs 50 mm; P = 0.07) and rate of positive margins (21.5% vs 15.6%;P = 0.13). There was no significant difference in overall survival between early and late salvage APR (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.50‐1.32; P = 0.40).

Conclusions

The overall survival of anal squamous cell carcinoma patients undergoing early vs late salvage APR after failure of chemoradiotherapy is similar. As a result, patients with persistent disease should be offered surgery just as readily as those with recurrent disease.
Simulated performance of multi‐year harvest regulation cycles for wild turkeys
Authors: Manning Sydney E. , Stevens Bryan S. , Williams David M.
Published: May 2019

Wild turkeys (Meleagris gallopavo) are a prolific species and valuable game animal throughout the United States. Stochastic simulations are commonly used to inform harvest management, and we used simulation to test performance of fall harvest management that included 1‐, 3‐, and 5‐year cycles of population assessment and updating of harvest targets, respectively. To assess robustness of our conclusions, we replicated analyses across 18 combinations of model parameters that included population productivity (3 levels), sex‐specific vulnerability to fall harvest (3 levels), and magnitude of spring harvest (2 levels). Performance of multi‐year cycles, measured using abundance of males and annual harvest, depended on the context of model parameters that interacted to determine responses of populations to harvest. One‐ and 3‐year cycles had similar performance so long as female harvests were less than or equal to male harvests. However, when harvest of females was greater than males, or when 5‐year regulation cycles were implemented, there was greater risk due to nonlinear population responses to increased harvest. For example, nonlinearity resulted in thresholds where declines to abundance and harvest could occur with small increases to harvest rates, and thus the sustainability of fall harvests was less robust for multi‐year cycles with time‐lagged assessment and decision making. Moreover, the harvest rate resulting in threshold responses depended on model parameters and often occurred within the range of harvest rates recommended by earlier modeling studies (7–15%). Our results imply that multi‐year cycles can be a viable approach to harvest management. Monitoring that provides information on sex‐specific harvest is recommended, however, to determine if nonlinear population responses should be anticipated. Ideally, information on population‐specific vital rates would also be available to allow managers to avoid harvest rates near thresholds that are expected to result in population declines. © The Wildlife Society, 2019
Reaction kinetics and thermochemistry of the chemically activated and stabilized primary ethyl radical of methyl ethyl sulfide, CH3SCH2CH2•, with O2 to CH3SCH2CH2OO•
Authors: Song Guanghui , Bozzelli Joseph W
Published: May 2019

Oxidation of methyl ethyl sulfide (CH3SCH2CH3, methylthioethane, MES) under atmospheric and combustion conditions is initiated by hydroxyl radicals, MES radicals, generated after loss of a H atom via OH abstraction, will further react with O2 to form chemically activated and stabilized peroxyl radical adducts. The kinetics of the chemically activated reaction between the CH3SCH2CH2• radical and molecular oxygen are analyzed using quantum Rice‐Ramsperger‐Kassel theory for k(E) with master equation analysis and a modified strong‐collision approach to account for further reactions and collisional deactivation. Thermodynamic properties of reactants, products, and transition states are determined by the B3LYP/6‐31+G(2d,p), M062X/6‐311+G(2d,p), ωB97XD/6‐311+G(2d,p) density functional theory, and CBS‐QB3, G3MP2B3, and G4 composite methods. The reaction of CH3SCH2CH2• with O2 forms an energized peroxy adduct CH3SCH2CH2OO• with a calculated well depth of 34.1 kcal mol−1 at the CBS‐QB3 level of theory. Thermochemical properties of reactants, transition states, and products obtained under CBS‐QB3 level are used for calculation of kinetic parameters. Reaction enthalpies are compared between the methods. The temperature and pressure‐dependent rate coefficients for both the chemically activated reactions of the energized adduct and the thermally activated reactions of the stabilized adducts are presented. Stabilization and isomerization of the CH3SCH2CH2OO• adduct are important under high pressure and low temperature. At higher temperatures and atmospheric pressure, the chemically activated peroxy adduct reacts to new products before stabilization. Addition of the peroxyl oxygen radical to the sulfur atom followed by sulfur‐oxygen double bond formation and elimination of the methyl radical to form S(= O)CCO• + CH3 (branching) is a potentially important new pathway for other alkyl‐sulfide peroxy radical systems under thermal or combustion conditions.
Laryngeal distribution of adult‐onset recurrent respiratory papillomatosis: A longitudinal study
Authors: Hu Lizbeth , Benedict Peter A. , Garber David , Wang Binhuan , Amin Milan R. , Branski Ryan C.
Published: May 2019

Objectives/Hypothesis

To describe recurrence patterns in patients with recurrent respiratory papillomatosis (RRP) following surgical intervention.

Study Design

Single‐center, retrospective, longitudinal case series.

Methods

Initial and follow‐up laryngoscopic examinations of seven previously untreated adult‐onset RRP patients were reviewed. Patients were followed longitudinally for periods ranging from 3 months to 7 years. Lesion locations were recorded using a twenty‐one region laryngeal schematic, and maps were generated to illustrate the distribution of disease before and after cold‐knife or potassium‐titanyl‐phosphate laser intervention. Univariate and multivariate analyses were employed to examine variables affecting recurrence patterns.

Results

Across all patients, a statistically significant correlation between initial distribution and primary recurrence was observed. Seventy‐five percent of new lesions were adjacent to regions with preexisting disease; 83% of new glottic lesions were adjacent to preexisting glottic lesions, and 66% of supraglottic lesions were adjacent to preexisting supraglottic regions. No statistically significant differences in recurrence rate were observed across sites.

Conclusions

In previously untreated patients with adult‐onset recurrent respiratory papillomatosis, lesions tended to recur either in the same regions or regions adjacent to those affected at the time of initial surgery.

Level of Evidence

4

Laryngoscope, 129:1993–1997, 2019
Quantifying vocal fold wound‐healing biomechanical property changes
Authors: Dion Gregory R. , Guda Teja , Mukudai Shigeyuki , Bing Renjie , Lavoie Jean‐Francois , Branski Ryan C.
Published: May 2019

Objectives

Development of novel vocal fold (VF) therapeutics is limited by a lack of standardized, meaningful outcomes. We hypothesize that automated microindentation‐based VF biomechanical property mapping matched to histology permits quantitative assessment.

Study Design

Ex vivo.

Methods

Twelve anesthetized New Zealand white rabbits underwent endoscopic right VF injury. Larynges were harvested/bisected day 7, 30, or 60 (n = 4/group), with four uninjured controls. Biomechanical measurements (normal force, structural stiffness, and displacement at 1.96 mN) were calculated using automated microindentation mapping (0.3 mm depth, 1.2 mm/s, 2 mm spherical indenter) with a grid overlay (>50 locations weighted toward VF edge, separated into 14 zones). Specimens were marked/fixed/sectioned, and slides matched to measurement points.

Results

In the injury zone, normal force/structural stiffness (mean, standard deviation [SD]/mean, SD) increased from uninjured (2.2 mN, 0.64/7.4 mN/mm, 2.14) and day 7 (2.7 mN, 0.75/9.0 mN/mm, 2.49) to day 30 (4.3 mN, 2.11/14.2 mN/mm, 7.05) and decreased at 60 days (2.7 mN, 0.77/9.1 mN/mm, 2.58). VF displacement decreased from control (0.28 mm, 0.05) and day 7 (0.26 mm, 0.05) to day 30 (0.20 mm, 0.05), increasing at day 60 (0.25 mm, 0.06). A one‐way ANOVA was significant; Tukey's post hoc test confirmed day‐30 samples differed from other groups (P < 0.05), consistent across adjacent zones. Zones far from injury remained similar across groups (P = 0.143 to 0.551). These measurements matched qualitative histologic variations.

Conclusion

Quantifiable VF biomechanical properties can be linked to histology. This technological approach is the first to simultaneously correlate functional biomechanics with histology and is ideal for future preclinical studies.

Level of Evidence

NA Laryngoscope, 130:454–459, 2020
Efficient 169Yb high‐dose‐rate brachytherapy source production using reactivation
Authors: Flynn Ryan T. , Adams Quentin E. , Hopfensperger Karolyn M. , Wu Xiaodong , Xu Weiyu , Kim Yusung
Published: May 2019

Purpose

To present and quantify the effectiveness of a method for the efficient production of 169Yb high‐dose‐rate brachytherapy sources with 27 Ci activity upon clinical delivery, which have about the same dose rate in water at 1 cm from the source center as 10 Ci 192Ir sources.

Materials

A theoretical framework for 169Yb source activation and reactivation using thermal neutrons in a research reactor and 168Yb‐Yb2O3 precursor is derived and benchmarked against published data. The model is dependent primarily on precursor 168Yb enrichment percentage, active source volume of the active element, and average thermal neutron flux within the active source.

Results

Efficiency gains in 169Yb source production are achievable through reactivation, and the gains increase with active source volume. For an average thermal neutron flux within the active source of 1 × 1014 n cm−2 s−1, increasing the active source volume from 1 to 3 mm3 decreased reactor‐days needed to generate one clinic‐year of 169Yb from 256 days yr−1 to 59 days yr−1, and 82%‐enriched precursor dropped from 80 mg yr−1 to 21 mg yr−1. A resource reduction of 74%–77% is predicted for an active source volume increase from 1 to 3 mm3.

Conclusions

Dramatic cost savings are achievable in 169Yb source production costs through reactivation if active sources larger than 1 mm3 are used.