bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of 3D printing in treating craniomaxillofacial congenital anomalies
Authors: Lopez Christopher D. , Witek Lukasz , Torroni Andrea , Flores Roberto L. , Demissie David B. , Young Simon , Cronstein Bruce N. , Coelho Paulo G.
Published: May 2018

Craniomaxillofacial congenital anomalies comprise approximately one third of all congenital birth defects and include deformities such as alveolar clefts, craniosynostosis, and microtia. Current surgical treatments commonly require the use of autogenous graft material which are difficult to shape, limited in supply, associated with donor site morbidity and cannot grow with a maturing skeleton. Our group has demonstrated that 3D printed bio‐ceramic scaffolds can generate vascularized bone within large, critical‐sized defects (defects too large to heal spontaneously) of the craniomaxillofacial skeleton. Furthermore, these scaffolds are also able to function as a delivery vehicle for a new osteogenic agent with a well‐established safety profile. The same 3D printers and imaging software platforms have been leveraged by our team to create sterilizable patient‐specific intraoperative models for craniofacial reconstruction. For microtia repair, the current standard of care surgical guide is a two‐dimensional drawing taken from the contralateral ear. Our laboratory has used 3D printers and open source software platforms to design personalized microtia surgical models. In this review, we report on the advancements in tissue engineering principles, digital imaging software platforms and 3D printing that have culminated in the application of this technology to repair large bone defects in skeletally immature transitional models and provide in‐house manufactured, sterilizable patient‐specific models for craniofacial reconstruction.
Potential of Continuous Manufacturing for Liposomal Drug Products
Authors: Worsham Robert D. , Thomas Vaughan , Farid Suzanne S.
Published: May 2018

Over the last several years, continuous manufacturing of pharmaceuticals has evolved from bulk APIs and solid oral dosages into the more complex realm of biologics. The development of continuous downstream processing techniques has allowed biologics manufacturing to realize the benefits (e.g., improved economics, more consistent quality) that come with continuous processing. If relevant processing techniques and principles are selected, the opportunity arises to develop continuous manufacturing designs for additional pharmaceutical products including liposomal drug formulations. Liposome manufacturing has some inherent aspects that make it favorable for a continuous process. Other aspects such as formulation refinement, materials of construction, and aseptic processing need development, but present an achievable challenge. This paper reviews the current state of continuous manufacturing technology applicable to liposomal drug product manufacturing and an assessment of the challenges and potential of this application.
Development of an HPLC‐DAD method for the determination of five alkaloids in Stephania yunnanensis Lo and in rat plasma after oral dose of Stephania yunnanensis Lo extracts
Authors: Xin Aiyi , Zhang Yaming , Zhang Yanxia , Di Duolong , Liu Junxi
Published: May 2018

For the rational utilization and the quantitative quality control of the Stephania yunnanensis Lo, an HPLC‐DAD method was developed for the quantitative and simultaneous determination of five alkaloids in rat plasma (stepharine, sinomenine, palmatine, isocorydine and tetrahydropalmatine), which were the main active chemical constituents of this plant and belong to four kinds of isoquinoline‐type alkaloids (protoberberine, morphine, aporphine and protaporphine alkaloids). The contents of five alkaloids ranged from 0.09 to 2.32% (w/w). The method validation was tested for the linearity (r2 > 0.9975), precision (intra‐day RSD < 4.8% and inter‐day RSD < 4.9%), extraction recovery (85.49 ± 2.29% to 99.21 ± 1.48%) and stability (98.5 ± 5.3% to 101.2 ± 3.4%). We developed an HPLC‐DAD method to simultaneously measure these alkaloids in rat plasma after oral administration of the extract of this plant to rats. The results supported the hypothesis that isoquinoline alkaloids were the compounds responsible for the main pharmacological activities for anti‐inflammatory and analgesic.
Oral phase dysphagia in facial onset sensory and motor neuronopathy
Authors: Watanabe Mitsuru , Shiraishi Wataru , Yamasaki Ryo , Isobe Noriko , Sawatsubashi Motohiro , Yasumatsu Ryuji , Nakagawa Takashi , Kira Jun‐ichi
Published: May 2018

Introduction

Facial onset motor and sensory neuronopathy (FOSMN) is a rare disease whose cardinal features are initial asymmetrical facial sensory deficits followed by bulbar symptoms and spreading of sensory and motor deficits from face to scalp, neck, upper trunk, and upper extremities in a rostral–caudal direction. Although bulbar involvement is frequently observed in FOSMN, dysphagia in these patients has not been fully described. In this study, we aimed to characterize dysphagia as a prognostic factor in FOSMN by investigating our institutional case series.

Methods

We retrospectively reviewed the medical records, including swallowing function tests, of six patients with FOSMN (three men and three women) who were thoroughly examined at Kyushu University Hospital between 1 January 2005 and 30 November 2017.

Results

Average age at onset was 58.5 years; average disease duration was 5.7 years. All patients developed bulbar dysfunction and dysphagia (at an average of 1.8 and 2.6 years from onset, respectively), resulting in choking episodes in three patients, percutaneous endoscopic gastrostomy placement in three, and recurrent aspiration pneumonia in one. Four of five patients evaluated with videofluoroscopic swallowing studies had poor oral retention, leading to bolus flowing into the pharynx before swallowing; the fifth patient showed poor lingual transfer. Fiberoptic endoscopic evaluation of swallowing revealed leakage of blue‐dyed water from the mouth to the pharynx in three patients because of poor oral retention, but only mild pharyngeal phase dysphagia in all four cases evaluated.

Conclusions

Oral phase dysphagia predominates in the early stage of FOSMN.
Pristimerin targeting NF‐κB pathway inhibits proliferation, migration, and invasion in esophageal squamous cell carcinoma cells
Authors: Tu Yuanqing , Tan Fuxing , Zhou Jingfeng , Pan Jingxuan
Published: May 2018

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer‐related death with poor prognosis in China. Identifying novel targeted therapies in ESCC is urgently needed. The aberrant activation of NF‐κB signalling pathway is critical for prognosis and recurrence of ESCC, which make it a potential target in the treatment of ESCC. Here, we found that pristimerin inhibited ESCC cell proliferation, migration, invasion, induced cell apoptosis, and eliminated cancer stem‐like cells (CSCs). It also showed a synergistic effect on ESCC when combined with 5‐fluorouracil (5‐FU). Moreover, pristimerin potently inhibited the growth of ESCC xenograft in nude mice. The anti‐ESCC effects of pristimerin were demonstrated to be associated with the inhibition of NF‐κB pathway by suppressing tumour necrosis factor α (TNFα)‐induced IκBα phosphorylation, p65 translocation, and NF‐κB‐dependent gene expression. This study provides an evidence for the development of pristimerin to be a new therapeutic agent for ESCC.

Significance of the study

Although several approaches including surgery, chemotherapy, and radiotherapy had been applied in the treatment of ESCC, more effective targeted chemotherapies are required to increase the survival rates of patients. This study suggested that inhibiting NF‐κB signalling pathway could be an effective approach for the treatment of ESCC. Pristimerin, a potent NF‐κB inhibitor, exerted potent anti‐ESCC effects both in vitro and in vivo, which may be a promising therapeutic agent for ESCC.
A Crown‐Shaped Ru‐Substituted Arsenotungstate for Selective Oxidation of Sulfides with Hydrogen Peroxide
Authors: Han Mengdan , Niu Yanjun , Wan Rong , Xu Qiaofei , Lu Jingkun , Ma Pengtao , Zhang Chao , Niu Jingyang , Wang Jingping
Published: May 2018

An acetate‐bridged Ru‐substituted arsenotungstate [H2N(CH3)2]14[As4W40O140{Ru2(CH3COO)}2]⋅22 H2O (1) has been synthesized and structurally characterized. Four Ru atoms occupy the respective lacunary S2 sites of the crown‐shaped polyanion [As4W40O140]28−, and each Ru atom is coordinated by one As atom and five μ2‐O atoms, comprising four from the S2 site and one from the acetate ligand. To the best of our knowledge, this coordination of the Ru atom, with an Ru−As bond length of 2.377(3)–2.387(3) Å, is unprecedented in polyoxometalate (POM) chemistry. Notably, 1 exhibits high efficiency, excellent selectivity, and good recyclability for the oxidation of sulfides with hydrogen peroxide (H2O2). Catalytic oxidation of various sulfides in the presence of 1 gives superior conversion and selectivity for sulfones in acetonitrile, whereas sulfoxides are obtained in methanol.
C−H Borylation/Cross‐Coupling Forms Twisted Donor–Acceptor Compounds Exhibiting Donor‐Dependent Delayed Emission
Authors: Crossley Daniel L. , Kulapichitr Pakapol , Radcliffe James E. , Dunsford Jay J. , Vitorica‐Yrezabal Inigo , Kahan Rachel J. , Woodward Adam W. , Turner Michael L. , McDouall Joseph J. W. , Ingleson Michael J.
Published: May 2018

Benzothiadiazole (BT) directed C−H borylation using BCl3, followed by B−Cl hydrolysis and Suzuki–Miyaura cross‐coupling enables facile access to twisted donor–acceptor compounds. A subsequent second C−H borylation step provides, on arylation of boron, access to borylated highly twisted D−A compounds with a reduced bandgap, or on B−Cl hydrolysis/cross‐coupling to twisted D‐A‐D compounds. Photophysical studies revealed that in this series there is long lifetime emission only when the donor is triphenylamine. Computational studies indicated that the key factor in observing the donor dependent long lifetime emission is the energy gap between the S1/T2 excited states, which are predominantly intramolecular charge‐transfer states, and the T1 excited state, which is predominantly a local excited state on the BT acceptor moiety.
Stereoselective HPLC separation of alvimopan on cellulose‐based immobilized polysaccharide as a chiral stationary phase
Authors: Dhekale Nitin H. , Gunjal Dattatray B. , Gore Anil H. , Komaravolu Yagnakirankumar , Hima Bindu K. , Kolekar Govind B.
Published: May 2018

Chiral separation by normal phase high performance liquid chromatography is one of the most powerful technique to quantify the chiral purity of the compounds. In this study, a novel, simple, and specific analytical method was proposed to ascertain the chiral purity of alvimopan (ALV). The normal phase HPLC method was developed based on cellulose tris (3,5‐dichlorophenylcarbamate) stationary phase. The separation of ALV isomers achieved by using column CHIRALPAK IC (250 × 4.6 mm, 5 μm), mobile phase n‐hexane: isopropyl alcohol: ethanol: diethylamine (650:200:150:5 v/v), column oven temperature 30°C, flow rate 1.0 mL min−1, injection volume was 10 μL, chromatographic response monitored at 273 nm. The developed method was validated as per the ICH guidelines and found precise, accurate, and linear. The advantage of the method is a good separation of ALV isomers within 35 minutes of the analysis time. Therefore, this method is suitable for routine determination of chiral purity of ALV active pharmaceutical ingredient.
Preoperative dobutamine stress echocardiography in patients undergoing orthotopic liver transplantation
Authors: Patel Krishna K. , Young Laura , Carey William , Kohn Kathryn A. , Grimm Richard A. , Rodriguez L. Leonardo , Griffin Brian P. , Desai Milind Y.
Published: May 2018

Background

Coronary artery disease (CAD) is associated with increased mortality in patients who undergo orthotopic liver transplantation (OLT). Chronic vasodilatory state and poor exercise tolerance in patients with end‐stage liver disease make dobutamine stress echocardiography (DSE) preferred for preoperative evaluation of CAD prior to OLT. We studied the incidence of positive DSE results and the association between DSE results and perioperative and longer‐term events.

Hypothesis

DSE results pre‐OLT will predict short and long term outcomes.

Methods

We studied 460 patients who underwent DSE within 1 year prior to OLT between 2004 and 2011. Primary events included death and MI at 30 days post‐OLT. We also recorded longer‐term deaths.

Results

Four patients (0.9%) had an ischemic response to DSE, 360 (78%) were normal, and 96 (21%) were nondiagnostic. Fourteen patients (3%) had a primary event at 30 days following OLT (13 deaths and 1 NSTEMI), and there were 108 (24%) deaths at 4.6±2 years of follow‐up. No patient with ischemia on DSE had a 30‐day event. The accuracy, sensitivity, specificity, and positive and negative predictive values of DSE that was not normal (ie, ischemic or nondiagnostic response) to predict 30‐day post‐OLT events were 76%, 14%, 78%, 2%, and 97%, respectively. On Cox survival analysis, only baseline left ventricular ejection fraction (HR: 0.90, 95% CI: 0.85–0.96, P < 0.001) was associated with longer‐term deaths.

Conclusions

Patients undergoing pre‐OLT DSE have very low incidence of an ischemic response on DSE, and it has no association with 30‐day events.
Removal of Acetic Acid from Dimethyl Terephthalate Manufacturing Wastewater with Ion Exchange
Authors: Zeki Omer , Yilmaz Turan
Published: May 2018

Wastewater from dimethyl terephthalate (DMT) manufacturing is treated with weak base anionic resin to remove acetic acid, which causes inhibition during conventional biological treatment. The experimental results show that the ion exchange process can be an effective approach for the pretreatment of DMT wastewater. At the resin dose of 70 g, the removal rate of acetic acid is found to be 86.5% at the equilibrium state. Some equilibrium and kinetic models are applied to the data obtained from the experiments. Among other models, the Freundlich isotherm is found to be the best‐fitting model with a correlation coefficient (R2) value of 0.981. In addition, the pseudo‐second order kinetic model describes the process better than the other kinetic models. The equilibrium and kinetic constants are calculated and the interactions between the acetate, the resin, and the process conditions are determined.
Synthesis and Evaluation of a Series of Bis(pentylpyridinium) Compounds as Antifungal Agents
Authors: Obando Daniel , Koda Yasuko , Pantarat Namfon , Lev Sophie , Zuo Xiaoming , Bijosono Oei Johanes , Widmer Fred , Djordjevic Julianne T. , Sorrell Tania C. , Jolliffe Katrina A.
Published: May 2018

A series of bis(4‐pentylpyridinium) compounds with a variety of spacers between the pyridinium headgroups was synthesised, and the antifungal activity of these compounds was investigated. Lengthening the alkyl spacer between the pentylpyridinium headgroups from 12 to 16 methylene units resulted in increased antifungal activity against C. neoformans and C. albicans, but also resulted in increased hemolytic activity and cytotoxicity against mammalian cells. However, inclusion of an ortho‐substituted benzene ring in the centre of the alkyl spacer resulted in decreased cytotoxicity and hemolytic activity, while maintaining antifungal potency. Replacement of the alkyl and aromatic‐containing spacers by more hydrophilic ethylene glycol groups resulted in a loss of antifungal activity. Some of the compounds inhibited fungal PLB1 activity, but the low correlation of this inhibition with antifungal potency indicates PLB1 inhibition is unlikely to be the predominant mode of antifungal action of this class of compounds, with preliminary studies suggesting they may act via disruption of fungal mitochondrial function.
Moving toward a more rational, evidence‐based approach to PSA screening, diagnosis, and treatment of prostate cancer
Authors: Filson Christopher P.
Published: May 2018

Screening with prostate‐specific antigen (PSA) has decreased since recommendations against its use in 2012, with some claims of subsequent and related increase in metastatic prostate cancer incidence. Competing trends and alternative hypotheses should be investigated before accepting a direct link between a decrease in PSA screening and rise in metastatic prostate cancer.

See also pages 2733‐9.
Channel estimation based on learning automata for OFDM systems
Authors: Salehi Fateme , Majidi Mohammad‐Hassan , Neda Naaser
Published: May 2018

The abundant benefits of Orthogonal Frequency‐Division Multiplexing and its high flexibility have resulted in its widespread applications in many telecommunication standards. One important parameter for improving wireless system's efficiency is the accurate estimation of channel state information. In the literatures, many techniques have been studied in order to estimate the channel state information. Nowadays, the techniques based on intelligent algorithms such as genetic algorithm and particle swarm optimization (PSO) have attracted attention of researchers. With a very low pilot overhead, these techniques are able to estimate the channel frequency response properly only using the received signals. Unfortunately, each of these techniques suffers a common weakness: they have a slow convergence rate. In this paper, a new intelligent and different method has been presented for channel estimation using learning automata, entitled LA estimator, where the learning automata are search agents, and each pair is responsible for searching 1 complex coefficient of the channel frequency response. This method can achieve an accurate channel estimation with a moderate computational complexity in comparison with GA and PSO estimators. Furthermore, with higher convergence rate, our proposed method is capable of providing the same performance as GA and PSO. For a 2‐path fast fading channel, simulation results demonstrate the robustness of our proposed scheme according to the bit error rate and the mean square error.
Profiling of new psychoactive substances by using stable isotope ratio mass spectrometry: Study of the synthetic cannabinoid 5F‐PB‐22
Authors: Münster‐Müller S. , Scheid N. , Holdermann T. , Schneiders S. , Pütz M.
Published: May 2018

In this paper, the results of a pilot study on the profiling of the synthetic cannabinoid receptor agonist 5F‐PB‐22 (5F‐QUPIC, pentylfluoro‐1H‐indole‐3‐carboxylic acid‐8‐quinolinyl ester) via isotope ratio mass spectrometry are presented. It focuses on δ13C, δ15N and δ2H isotope ratios, which are determined using elemental analyser (EA) and high temperature elemental analyser (TC/EA) coupled to an isotope ratio mass spectrometer (IRMS). By means of a sample of pure material of 5F‐PB‐22, it is shown that the extraction of 5F‐PB‐22 from herbal material, a rapid clean‐up procedure, or preparative column chromatography had no influence on the isotope ratios. Furthermore, 5F‐PB‐22 was extracted from 14 different herbal blend samples (“Spice products” from police seizures) and analysed via IRMS, yielding 3 clusters containing 7, 5, and 2 samples, distinguishable through their isotopic composition, respectively. It is assumed that herbal blends in each cluster have been manufactured from individual batches of 5F‐PB‐22.
Local weather and body condition influence habitat use and movements on land of molting female southern elephant seals (Mirounga leonina)
Authors: Chaise Laureline L. , Prinet Iris , Toscani Camille , Gallon Susan L. , Paterson William , McCafferty Dominic J. , Théry Marc , Ancel André , Gilbert Caroline
Published: May 2018

Southern elephant seals (Mirounga leonina) are known to move and aggregate while molting, but little is known about their behavior on land during this time. In this study, 60 adult females were monitored (23 with GPS tags) during four molting seasons, between 2012 and 2016 at Kerguelen Archipelago, Indian Ocean. Population surveys were recorded each year (N = 230 daily counts), and habitat use was analyzed in relation to the stage of the molt and local weather. Based on stage of molt, habitat use, and movements on land, we classified the molt of elephant seals into three phases: (1) a “search phase” at the initial stage of molt when grass and wallow habitats were used and characterized by greater mean distances travelled on land per day compared with the two other phases; (2) a “resident phase”: during initial and mid‐stage of molt when animals were found in grass and wallow habitats but with less distance moved on land; and (3) a “termination phase” at the final stage of molt where grass and beach habitats were occupied with no change in distances. Windchill and solar radiation influenced individual distances moved per day (mean 590 ± 237.0 m) at the mid‐ and final stage of molt such that animals travelled greater distances on days of low windchill or high solar radiation. Individual variation in distance moved and relative habitat use were also linked to body mass index (BMI) at arrival on the colony, as females with higher BMI moved less and preferred beach habitat. Moreover, the individual rate of molt increased with the use of wallows. Aggregation rate tended to be negatively correlated with distances moved. We therefore suggest that individuals face an energetic trade‐off while molting, balancing energy expenditure between movement and thermoregulation.
Improving geographically extensive acoustic survey designs for modeling species occurrence with imperfect detection and misidentification
Authors: Banner Katharine M. , Irvine Kathryn M. , Rodhouse Thomas J. , Wright Wilson J. , Rodriguez Rogelio M. , Litt Andrea R.
Published: May 2018

Acoustic recording units (ARUs) enable geographically extensive surveys of sensitive and elusive species. However, a hidden cost of using ARU data for modeling species occupancy is that prohibitive amounts of human verification may be required to correct species identifications made from automated software. Bat acoustic studies exemplify this challenge because large volumes of echolocation calls could be recorded and automatically classified to species. The standard occupancy model requires aggregating verified recordings to construct confirmed detection/non‐detection datasets. The multistep data processing workflow is not necessarily transparent nor consistent among studies. We share a workflow diagramming strategy that could provide coherency among practitioners. A false‐positive occupancy model is explored that accounts for misclassification errors and enables potential reduction in the number of confirmed detections. Simulations informed by real data were used to evaluate how much confirmation effort could be reduced without sacrificing site occupancy and detection error estimator bias and precision. We found even under a 50% reduction in total confirmation effort, estimator properties were reasonable for our assumed survey design, species‐specific parameter values, and desired precision. For transferability, a fully documented r package, OCacoustic, for implementing a false‐positive occupancy model is provided. Practitioners can apply OCacoustic to optimize their own study design (required sample sizes, number of visits, and confirmation scenarios) for properly implementing a false‐positive occupancy model with bat or other wildlife acoustic data. Additionally, our work highlights the importance of clearly defining research objectives and data processing strategies at the outset to align the study design with desired statistical inferences.
The bacterial community structure and functional profile in the heavy metal contaminated paddy soils, surrounding a nonferrous smelter in South Korea
Authors: Tipayno Sherlyn C. , Truu Jaak , Samaddar Sandipan , Truu Marika , Preem Jens‐Konrad , Oopkaup Kristjan , Espenberg Mikk , Chatterjee Poulami , Kang Yeongyeong , Kim Kiyoon , Sa Tongmin
Published: May 2018

The pollution of agricultural soils by the heavy metals affects the productivity of the land and has an impact on the quality of the surrounding ecosystems. This study investigated the bacterial community structure in the heavy metal contaminated sites along a smelter and a distantly located paddy field to elucidate the factors that are related to the alterations of the bacterial communities under the conditions of heavy metal pollution. Among the study sites, the bacterial communities in the soil did not show any significant differences in their richness and diversity. The soil bacterial communities at the three study sites were distinct from one another at each site, possessing a distinct set of bacterial phylotypes. Among the study sites, significant changes were observed in the abundances of the bacterial phyla and genera. The variations in the bacterial community structure were mostly related to the general soil properties at the phylum level, while at the finer taxonomic levels, the concentrations of arsenic (As) and lead (Pb) were the significant factors, affecting the community structure. The relative abundances of the genera Desulfatibacillum and Desulfovirga were negatively correlated to the concentrations of As, Pb, and cadmium (Cd) in the soil, while the genus Bacillus was positively correlated to the concentrations of As and Cd. According to the results of the prediction of bacterial community functions, the soil bacterial communities of the heavy metal polluted sites were characterized by the more abundant enzymes involved in DNA replication and repair, translation, transcription, and the nucleotide metabolism pathways, while the amino acid and lipid metabolism, as well as the biodegradation potential of xenobiotics, were reduced. Our results showed that the adaptation of the bacterial communities to the heavy metal contamination was predominantly attributed to the replacement process, while the changes in community richness were linked to the variations in the soil pH values.
Convergence in reduced body size, head size, and blood glucose in three island reptiles
Authors: Sparkman Amanda M. , Clark Amanda D. , Brummett Lilly J. , Chism Kenneth R. , Combrink Lucia L. , Kabey Nicole M. , Schwartz Tonia S.
Published: May 2018

Many oceanic islands harbor diverse species that differ markedly from their mainland relatives with respect to morphology, behavior, and physiology. A particularly common morphological change exhibited by a wide range of species on islands worldwide involves either a reduction in body size, termed island dwarfism, or an increase in body size, termed island gigantism. While numerous instances of dwarfism and gigantism have been well documented, documentation of other morphological changes on islands remains limited. Furthermore, we lack a basic understanding of the physiological mechanisms that underlie these changes, and whether they are convergent. A major hypothesis for the repeated evolution of dwarfism posits selection for smaller, more efficient body sizes in the context of low resource availability. Under this hypothesis, we would expect the physiological mechanisms known to be downregulated in model organisms exhibiting small body sizes due to dietary restriction or artificial selection would also be downregulated in wild species exhibiting dwarfism on islands. We measured body size, relative head size, and circulating blood glucose in three species of reptiles—two snakes and one lizard—in the California Channel Islands relative to mainland populations. Collating data from 6 years of study, we found that relative to mainland population the island populations had smaller body size (i.e., island dwarfism), smaller head sizes relative to body size, and lower levels of blood glucose, although with some variation by sex and year. These findings suggest that the island populations of these three species have independently evolved convergent physiological changes (lower glucose set point) corresponding to convergent changes in morphology that are consistent with a scenario of reduced resource availability and/or changes in prey size on the islands. This provides a powerful system to further investigate ecological, physiological, and genetic variables to elucidate the mechanisms underlying convergent changes in life history on islands.
Cu(II) complex of phenylthiosemicarbazone: An in situ catalyst for formation of C‐N bond between different N‐based neucleophiles with arylboronic acids at room temperature
Authors: Gogoi Nibedita , Borah Geetika , Gogoi Pradip K.
Published: May 2018

We have reported here a new synthetic protocol for the formation of C‐N bond catalyzed by a thiosemicarbazone complex of copper. This in situ complex has been found to be very effective for Chan‐Lam C‐N cross‐coupling reaction of anilines and various imidazoles at room temperature. Pyrazole and 4‐bromoindole were also activated for C‐N bond formation by using this protocol at room temperature. This catalytic system gave good‐to‐excellent yield using a mixture of DMF and water as solvent in a 1:1 proportion.
Consumer price sensitivity and health plan choice in a regulated competition setting
Authors: Bischof Tamara , Schmid Christian P.R.
Published: May 2018

We estimate premium elasticities in a regulated competition market based on a quasi‐exogenous premium increase for young adults in Switzerland. We exploit that individuals born before the turn of the year (“treatment group”) face a larger increase in premiums than individuals born after the turn of the year (“control group”). We find that the treatment group is 1.5 times more likely to switch their health plan than the control group. Overall, individuals respond to premium increases by choosing more frequently health plans with managed care features, increasing the deductible, and by switching the insurer. Regarding health plan choice, we find an average elasticity of −0.56 with regard to the relative premium difference of any plan to the status quo contract. The elasticity is up to 5 times larger for the treated (−1.03) than for the controls (−0.19). Our results are not driven by health status as measured by health care expenditures and chronic conditions. Rather, our findings suggest that the difference in the premium elasticity is driven by the salience of the premium increase. We argue that this finding is of high relevance for health care policies that aim at fostering health plan competition.
Molecular magnetic resonance imaging accurately measures the antifibrotic effect of EDP‐305, a novel farnesoid X receptor agonist
Authors: Erstad Derek J. , Farrar Christian T. , Ghoshal Sarani , Masia Ricard , Ferreira Diego S. , Chen Yin‐Ching Iris , Choi Ji‐Kyung , Wei Lan , Waghorn Phillip A. , Rotile Nicholas J. , Tu Chuantao , Graham‐O'Regan Katherine A. , Sojoodi Mozhdeh , Li Shen , Li Yang , Wang Guogiang , Corey Kathleen E. , Or Yat Sun , Jiang Lijuan , Tanabe Kenneth K. , Caravan Peter , Fuchs Bryan C.
Published: May 2018

We examined a novel farnesoid X receptor agonist, EDP‐305, for its antifibrotic effect in bile duct ligation (BDL) and choline‐deficient, L‐amino acid‐defined, high‐fat diet (CDAHFD) models of hepatic injury. We used molecular magnetic resonance imaging with the type 1 collagen‐binding probe EP‐3533 and the oxidized collagen‐specific probe gadolinium hydrazide to noninvasively measure treatment response. BDL rats (n = 8 for each group) were treated with either low or high doses of EDP‐305 starting on day 4 after BDL and were imaged on day 18. CDAHFD mice (n = 8 for each group) were treated starting at 6 weeks after the diet and were imaged at 12 weeks. Liver tissue was subjected to pathologic and morphometric scoring of fibrosis, hydroxyproline quantitation, and determination of fibrogenic messenger RNA expression. High‐dose EDP‐305 (30 mg/kg) reduced liver fibrosis in both the BDL and CDAHFD models as measured by collagen proportional area, hydroxyproline analysis, and fibrogenic gene expression (all P < 0.05). Magnetic resonance signal intensity with both EP‐3533 in the BDL model and gadolinium hydrazide in the CDAHFD model was reduced with EDP‐305 30 mg/kg treatment (P < 0.01). Histologically, EDP‐305 30 mg/kg halted fibrosis progression in the CDAHFD model. Conclusion: EDP‐305 reduced fibrosis progression in rat BDL and mouse CDAHFD models. Molecular imaging of collagen and oxidized collagen is sensitive to changes in fibrosis and could be used to noninvasively measure treatment response in clinical trials. (Hepatology Communications 2018;2:821‐835)
Delayed injury of hippocampal interneurons after neonatal hypoxia‐ischemia and therapeutic hypothermia in a murine model
Authors: Chavez‐Valdez Raul , Emerson Paul , Goffigan‐Holmes Janasha , Kirkwood Alfredo , Martin Lee J. , Northington Frances J.
Published: May 2018

Delayed hippocampal injury and memory impairments follow neonatal hypoxia‐ischemia (HI) despite the use of therapeutic hypothermia (TH). Death of hippocampal pyramidal cells occurs acutely after HI, but characterization of delayed cell death and injury of interneurons (INs) is unknown. We hypothesize that injury of INs after HI is: (i) asynchronous to that of pyramidal cells, (ii) independent of injury severity, and (iii) unresponsive to TH. HI was induced in C57BL6 mice at p10 with unilateral right carotid ligation and 45 min of hypoxia (FiO2 = 0.08). Mice were randomized to normothermia (36 °C, NT) or TH (31 °C) for 4 hr after HI and anesthesia‐exposed shams were use as controls. Brains were studied at 24 hr (p11) or 8 days (p18) after HI. Vglut1, GAD65/67, PSD95, parvalbumin (PV) and calbindin‐1 (Calb1) were measured. Cell death was assessed using cresyl violet staining and TUNEL assay. Hippocampal atrophy and astroglyosis at p18 were used to assess injury severity and to correlate with number of PV + INs. VGlut1 level decreased by 30% at 24 hr after HI, while GAD65/67 level decreased by ∼50% in forebrain 8 days after HI, a decrease localized in CA1 and CA3. PSD95 levels decreased in forebrain by 65% at 24 hr after HI and remained low 8 days after HI. PV + INs increased in numbers (per mm2) and branching between p11 and p18 in sham mice but not in NT and TH mice, resulting in 21–52% fewer PV + INs in injured mice at p18. Calb1 protein and mRNA were also reduced in HI injured mice at p18. At p18, somatodendritic attrition of INs was evident in all injured mice without evidence of cell death. Neither hippocampal atrophy nor astroglyosis correlated with the number of PV + INs at p18. Thus, HI exposure has long lasting effects in the hippocampus impairing the development of the GABAergic system with only partial protection by TH independent of the degree of hippocampal injury. © 2018 Wiley Periodicals, Inc.
Informal caregivers in hospitals: Opportunities and threats
Authors: Amiresmaili Mohammadreza , Emrani Zahra
Published: May 2018

Objective

High hospital costs are a challenge that health system face. Additionally, studies identified manpower deficiency as a problem in health system. Hospital is a place where patients with different physical and mental conditions come to. Their families and friends' companionship can facilitate this situation for them. This study illustrates the roles of informal caregivers in hospital.

Method

This is a phenomenological qualitative study. Data were gathered through semistructured interviews. We interviewed 22 informal caregivers and 9 nurse staffs from different departments of hospital. They were selected through purposeful and snowball sampling approach. The framework method was used for data analysis.

Results

We found 3 main themes including (a) roles of informal caregivers, (b) opportunities of presence of the informal caregivers in the hospital, and (c) threats of presence of informal caregivers.

Conclusions

This study shows some roles for informal caregivers including mental supports, consultation, decision‐making, and care roles. Concerning the shortage of manpower in Iran's hospitals, nurses have less time to take care of each patient; therefore, using informal caregivers as an implicit strategy to overcome nursing shortage and to reduce hospital costs seems to be beneficial. We suggest that an appropriate plan is necessary to make use of them for filling this gap to some extent, as well as providing training sessions and facilities for companions acting as informal caregivers.
Development and evaluation of screening dysphagia tools for observational studies and routine care in cancer patients
Authors: Borean Michael , Shani Kishan , Brown M. Catherine , Chen Judy , Liang Mindy , Karkada Joel , Kooner Simranjit , Doherty Mark K. , O'Kane Grainne M. , Jang Raymond , Elimova Elena , Wong Rebecca K. , Darling Gail E. , Xu Wei , Howell Doris , Liu Geoffrey
Published: May 2018

Background and aims

Dysphagia can be associated with significant morbidity in cancer patients. We aimed to develop and evaluate dysphagia screener tools for use in observational studies (phase 1) and for routine symptom monitoring in clinical care (phase 2).

Methods

Various dysphagia or odynophagia screening questions, selected after an expert panel reviewed the content, criterion, and construct validity, were compared with either functional assessment of cancer therapy ‐ esophageal cancer (FACT‐E) Swallowing Index Cut‐Off Values or to questions adapted from the Patient Reported Outcomes for Common Terminology Criteria for Adverse Events. Sensitivity, specificity, and patient acceptability were assessed.

Results

In Phase 1 (n = 178 esophageal cancer patients), the screening question “How are you currently eating?” had the highest sensitivities and specificities against various Swallowing Index Cut‐Off Value cut‐offs, with the best optimal cutoff associated with weight loss (80% sensitivity and 75% specificity). In phase 2 (255 head and neck, gastro‐esophageal, and thoracic cancer patients), a single question screener (“Do you experience any difficulty or pain upon swallowing?”) versus a Patient Reported Outcomes for Common Terminology Criteria for Adverse Events–like gold standard generated sensitivities between 86% and 94% and specificities between 93% and 100%. This screening question (+/− follow‐up questions) had a median completion time of under 2 minutes, and >90% of patients were willing to complete the survey electronically, did not feel that survey made clinic visit more difficult, and did not find the questions upsetting or distressful.

Conclusion

Our results demonstrate that these screener tools (“How are you currently eating?”, “Do you experience any difficulty or pain upon swallowing?”) can effectively screen dysphagia symptoms without increasing cancer outpatient clinic burden, both in observational studies and for routine clinical monitoring.
Identifying predictive behavioral markers: A demonstration using automatically reinforced self‐injurious behavior
Authors: Hagopian Louis P. , Rooker Griffin W. , Yenokyan Gayane
Published: May 2018

Predictive biomarkers (PBioMs) are objective biological measures that predict response to medical treatments for diseases. The current study translates methods used in the field of precision medicine to identify PBioMs to identify parallelpredictive behavioral markers (PBMs),defined as objective behavioral measures that predict response to treatment. We demonstrate the utility of this approach by examining the accuracy of two PBMs for automatically reinforced self‐injurious behavior (ASIB). Results of the analysis indicated both functioned asgood to excellentPBMs. We discuss the compatibility of this approach with applied behavior analysis, describe methods to identify additional PBMs, and posit that variables related to the mechanisms of problem behavior and putative mechanism of treatment action hold the most promise as potential PBMs. We discuss how this technology could guide individualized treatment selection, inform our understanding of problem behavior and mechanisms of treatment action, and help determine the conditional effectiveness of clinical procedures.
Resveratrol relieves particulate matter (mean diameter < 2.5 μm)‐induced oxidative injury of lung cells through attenuation of autophagy deregulation
Authors: Li Yuan , Qian Weiwei , Wang Dengdian , Meng Yu , Wang Xiaoqian , Chen Yue , Li Xiaoting , Xie Chunfeng , Zhong Caiyun , Fu Suming
Published: May 2018

Oxidative stress and inflammation are critically implicated in ambient fine particulate matter (mean diameter < 2.5 μm; PM2.5)‐induced lung injury. Autophagy, playing a crucial role in various physiopathological conditions, modulates cellular homeostasis and stress adaptation. Resveratrol is a phytoalexin that exerts potent antioxidant effects on cardiopulmonary diseases. To date, the mechanisms by which resveratrol protects against PM2.5 remain to be elucidated. In the present study, we investigated the effect of resveratrol on PM2.5‐induced oxidative injury. The potential role of nuclear factor erythroid‐2‐related factor 2 and autophagy in this progress was explored. Human bronchial epithelial cells were treated with PM2.5 and the cytotoxicity and oxidative stress markers were determined. The results showed that PM2.5 decreased cell viability and elevated the level of lactate dehydrogenase. The levels of malondialdehyde and reactive oxygen species were increased by PM2.5 exposure. PM2.5 also induced a significant increase of the inflammatory cytokines including interleukin (IL)‐6, IL‐8, IL‐1β and tumor necrosis factor α. Meanwhile, PM2.5 triggered autophagy formation and alteration of the nuclear factor erythroid‐2‐related factor 2 pathway. Furthermore, human bronchial epithelial cells were co‐treated with PM2.5 and resveratrol in the presence or absence of 3‐methylamphetamine, an inhibitor of autophagic formation. It was revealed that resveratrol intervention abolished PM2.5‐induced oxidative injury partially through the suppression of autophagy deregulation. Findings from this study could provide new insights into the molecular mechanisms of pulmonary intervention during PM2.5 exposure.
MicroRNA‐508 suppresses epithelial‐mesenchymal transition, migration, and invasion of ovarian cancer cells through the MAPK1/ERK signaling pathway
Authors: Hong Lan , Wang Yifeng , Chen Wangsheng , Yang Shuying
Published: May 2018

Ovarian cancer (OC) is the sixth most common cancer in women worldwide. Despite advances in detection and therapies, it still represents the most lethal gynecologic malignancy in the industrialized countries. Unfortunately, the molecular events that lead to the development of this highly aggressive disease remain largely unknown. The study explored the ability of microRNA‐508 (miR‐508) to influence proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) in OC cells. We quantified the level of miR‐508 cancer tissues with corresponding adjacent normal tissues collected from 84 patients with OC. Human OC cells SKOV3 and A2780 were treated with negative control (NC), miR‐508 mimics, miR‐508 inhibitors, and miR‐508 inhibitors + a specific MAPK/ERK kinase inhibitor (PD98059) to validate the interaction between miR‐508 and MAPK/ERK signaling. The miR‐508 expression level was lower while MAPK1 and ERK expression levels were higher in the cancer tissues than in the adjacent normal tissues. Dual‐luciferase reporter assay indicated MAPK1 as a target gene of miR‐508. The miR‐508 mimics reduced the expression of MAPK1, p‐MAPK1, ERK, p‐ERK and Vimentin, inhibited cell proliferation, migration and invasion, and increased the expression of E‐cadherin, while the miR‐508 inhibitors resulted in an opposed trend in OC cells. The effects of miR‐508 inhibitors on OC cells were lost when the MAPK1/ERK signaling pathway was inhibited by PD98059. Collectively, our data indicate that miR‐508 plays a tumor suppressor role in the development and progression of OC and may be a novel therapeutic target against OC.
MiR‐1178 regulates mycobacterial survival and inflammatory responses in Mycobacterium tuberculosis‐infected macrophages partly via TLR4
Authors: Shi Ge , Mao Guofeng , Xie Kejie , Wu Dongdong , Wang Wei
Published: May 2018

Tuberculosis is chronic respiratory infectious disease and is caused by the infection of Mycobacterium tuberculosis (M.tb). Macrophages play an important role in host immune response against M.tb infection, which is regulated by various factors, including microRNAs (miRNAs). The present study aimed to examine the in vitro functional role of miR‐1178 in mycobacterial survival and inflammatory responses induced by M.tb infection in human macrophages. Our results showed that M.tb infection increased the expression of miR‐1178 in human macrophages (HTP‐1 and U937 cells) in a concentration‐ and time‐dependent manner. Overexpression of miR‐1178 enhanced the intracellular growth of mycobacteria during M.tb infection, while knockdown of miR‐1178 suppressed the mycobacteria survival. Overexpression of miR‐1178 also significantly attenuated the accumulation of proinflammatory cytokines including interferon‐γ (IFN‐γ), interleukin‐6 (IL‐6), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α) in the M.tb‐infected macrophages, while knockdown of miR‐1178 caused enhancement in these proinflammatory cytokines in the M.tb‐infected macrophage. Bioinformatics analysis and luciferase reporter assay showed that toll‐like receptor 4 (TLR4) was a direct target of miR‐1178, and miR‐1178 negatively regulated the expression of TLR4. In addition, enforced expression of TLR4 attenuated the effects of miR‐1178 overexpression on promoting the production of proinflammatory cytokines including IFN‐γ, IL‐6, IL‐1β, and TNF‐α in the M.tb‐infected macrophages. Collectively, our findings showed that overexpression of miR‐1178 promoted mycobacteria survival and miR‐1178 also modulated the immune response of M.tb‐infected macrophages partly via targeting TLR4.
Effect of estradiol on fibroblasts from postmenopausal idiopathic carpal tunnel syndrome patients
Authors: Yamanaka Yoshiaki , Menuki Kunitaka , Tajima Takafumi , Okada Yasuaki , Kosugi Kenji , Zenke Yukichi , Sakai Akinori
Published: May 2018

Fibrosis of the subsynovial connective tissue (SSCT) is a characteristic finding in patients with idiopathic carpal tunnel syndrome (CTS). Idiopathic CTS frequently occurs in postmenopausal women; therefore, female steroid hormones, especially estrogens, may be involved in its development. In this study, we evaluated the effect of the estradiol on the expression of genes and proteins related to fibrosis of SSCT fibroblasts from patients with idiopathic CTS. This study included 10 postmenopausal women (mean age 76 years). Fibroblasts derived from SSCT were treated with estradiol (10−4–10−12 M), and the expression levels of TGF‐β‐responsive genes were evaluated. The relationships between the expression of untreated estrogen receptor α (ERα) and ERβ and changes in gene expression due to estradiol treatment were examined by quantitative real‐time polymerase chain reaction. The effects of 10−4 M estradiol on collagen type I (Col1) and collagen type III (Col3) protein expression levels were also evaluated by fluorescent staining. The relationships between ERα/β and Col1/3 expression were evaluated by immunohistochemical staining. The reduction in Col1A1 mRNA expression due to estradiol treatment was positively correlated with ERα expression (r = 0.903, p < 0.01). At the protein level, expression of Col1 and Col3 were down‐regulated. These results indicated that ERα‐mediated signaling may be involved in the regulation of Col1A1, and its regulatory effect may be dependent on the ERα expression level. The accurate evaluation of ERα expression level in the SSCT of individual patients with idiopathic CTS might guide the effective use of new estrogen replacement therapy.