bluuebunny/crossref_metadata_2025 huggingface dataset:
Steric as well as n→π* Interaction Controls the Conformational Preferences of Phenyl Acetate: Gas‐phase Spectroscopy and Quantum Chemical Calculations
Authors: Singh Santosh K. , Panwaria Prakash , Mishra Kamal K. , Das Aloke
Published: September 2019

Herein, we report that the conformational preference of phenyl acetate is governed by steric effect and n→π* interaction. Conformation‐specific electronic and IR spectroscopy combined with quantum chemistry calculations confirm the presence of only the cis conformer of phenyl acetate in the experiment. The cis conformer of phenyl acetate has n→π* interaction between the lone‐pair electrons on the carbonyl oxygen atom and the π* orbitals of the phenyl group. The n→π* interaction is absent in the trans conformer which has additional steric repulsion between the methyl group and phenyl ring. The trans conformer is higher in energy than the cis conformer by ≈3 kcal mol−1. We have found the effect of methyl substitution on the strength of the n→π* interaction, steric repulsion, and hyperconjugation in phenyl acetate. The red‐shift observed in the cis conformer of phenyl acetate with respect to the trans conformer is affected due to the influence of the methyl substituent on the strength of the n→π* interaction as well as hyperconjugation. The present result demonstrates that the introduction of a bulkier substituent can induce steric as well as electronic control to reduce conformational heterogeneity of a molecular system. Understanding the effect of bulkier substituents to promote defined conformations having specific non‐covalent interactions may have implication in better perception of the optimum structure and function of biomolecules as well as recognition of drugs by biomolecules.
Impact of stent diameter on outcomes following percutaneous coronary intervention with second‐generation drug‐eluting stents: Results from a large single‐center registry
Authors: Plitt Anna , Claessen Bimmer E. , Sartori Samantha , Baber Usman , Chandrasekhar Jaya , Aquino Melissa , Vijay Pooja , Elsayed Sherif , Kovacic Jason C. , Sweeny Joseph , Barman Nitin , Moreno Pedro , Krishnan Prakash , Demopoulos Antonia , Dangas George , Kini Annapoorna S. , Mehran Roxana , Sharma Samin K.
Published: September 2019

Background

In patients treated with bare metal stents and first‐generation drug‐eluting stents (DES) smaller stent diameter (SD) has been associated with worse long term outcomes after percutaneous coronary intervention (PCI). Data on the impact of small SD on outcomes after PCI with second‐generation DES is scarce.

Methods

Consecutive patients treated with second‐generation DES between 2010 and 2016 were included in a single tertiary center. Patients were grouped according to SD: ≤2.50 mm, 2.75 ≤ 3.00 mm, 3.25 ≤ 3.50 mm, and >3.50 mm. One‐year event rates were estimated using the Kaplan–Meier method and adjusted hazard ratios were generated using Cox regression analysis. The primary endpoint was major adverse cardiac events (MACE; death, myocardial infarction [MI], or target vessel revascularization [TVR]).

Results

Of the 17,607 patients who underwent PCI with second‐generation DES, 32.6% (n = 5,741) had SD ≤2.5 mm, 39.1% (n = 6,890) had SD 2.75 ≤ 3.0 mm, 22.2% (n = 3,910) had SD 3.25 ≤ 3.5 mm, and 6.1% (n = 1,066) had SD >3.5 mm. At 1 year, MACE rates were 10.5%, 9.5%, 8.0%, and 8.0%, respectively, with increasing SD (p = .006). TVR rates decreased with increasing SD (7.2%, 5.8%, 4.7%, and 3.3%, respectively [p < .0001]) whereas rates of MI across SD groups were comparable (1.7%, 1.9%, 2.0%, and 1.5%, respectively [p = .60]). After multivariable adjustment, smaller SD remained associated with higher rates of MACE, TVR, and target lesion revascularization.

Conclusion

In a large cohort of patients undergoing PCI with second‐generation DES, smaller SD was associated with increased MACE, driven by higher rates of repeat revascularization. Further research into the optimal treatment of small coronary arteries is warranted.
Towards Stable and Conductive Titanium Oxynitride High‐Surface‐Area Support for Iridium Nanoparticles as Oxygen Evolution Reaction Electrocatalyst
Authors: Bele Marjan , Stojanovski Kevin , Jovanovič Primoz , Moriau Leonard , Koderman Podboršek Gorazd , Moškon Jože , Umek Polona , Sluban Melita , Dražič Goran , Hodnik Nejc , Gaberšček Miran
Published: September 2019

The rational design of electrochemical oxygen evolution reaction (OER) electrocatalyst is essential for the development of efficient and sustainable electrochemical energy conversion, storage and electrolysis applications. One of the remaining limitations of the low‐temperature electrolyzers is the large amounts of highly scarce and expensive iridium used as the OER electrocatalysts. This could be solved by applying much smaller amounts of iridium on efficient and stable support. Here we present a very promising functionality of titanium oxynitride (TiONx) high‐surface‐area support that effectively disperses the iridium nanoparticles, exhibits good intrinsic electrical conductivity and stability and thus promises efficient reduction of the noble‐metal loading in electrolyzers gas diffusion electrodes. The new nanocomposite made of approximately 3 nm‐sized iridium nanoparticles finely dispersed on TiONx support is produced using a novel synthetic route. Extensive characterization shows that the new composites exhibit an electronic interaction with the support and, ultimately, a high OER performance in acidic media.
Construction of Biaryls from Aryl Sulfoxides and Anilines by Means of a Sigmatropic Rearrangement
Authors: Yanagi Tomoyuki , Nogi Keisuke , Yorimitsu Hideki
Published: September 2019

An unprecedented S−N variant of the benzidine rearrangement for construction of biaryls has been developed. Aryl sulfoxides underwent dehydrogenative coupling with anilines by successive treatment with trifluoromethanesulfonic anhydride and trifluoromethanesulfonic acid to provide the corresponding 2‐amino‐2′‐sulfanyl‐ and/or 4‐amino‐4′‐sulfanylbiphenyls. Mechanistic studies indicate that the C−C‐bond‐forming sigmatropic rearrangement proceeds intramolecularly from dicationic S−N‐tethered species.
Design and rationale for the “Me & My Heart” (eMocial) study: A randomized evaluation of a new smartphone‐based support tool to increase therapy adherence of patients with acute coronary syndrome
Authors: Krackhardt Florian , Maier Lars S. , Appel Karl‐Friedrich , Köhler Till , Ghanem Alexander , Tschoepe Carsten , Dahl Jürgen vom , Degenhardt Ralf , Niklasson Anna , Ahlqvist Matti , Waliszewski Matthias W. , Jörnten‐Karlsson Magnus
Published: September 2019

A novel smartphone‐based patient support tool was developed to increase the adherence to antiplatelet therapy and lifestyle changes in patients after coronary angioplasty for acute coronary syndrome (ACS). The eMocial study (ClinicalTrials.gov Identifier: NCT02615704) investigates whether an electronic support tool will improve adherence to comedication and lifestyle changes in ACS patients. The primary hypothesis of this trial is that an electronic support tool can increase adherence to comedication (primary endpoint) thereby supporting positive lifestyle changes (secondary endpoints). Patients hospitalized with ACS (ST elevation myocardial infarction [STEMI], non‐ST elevation myocardial infarction [NSTEMI], or unstable angina pectoris) and treated with ticagrelor coadministered with low‐dose acetylsalicylic acid will be randomized 1:1 to an active group receiving the patient support tool via a smartphone‐based application or to a control group without the patient support tool. Patient questionnaires to evaluate lifestyle changes and quality of life will be used at baseline and at the end of the 48‐week observation phase. Patients are asked to fill out questionnaires to determine their adherence, treatment attitudes, health‐care utilization and risk factors on a monthly basis. The study was started in February 2016 and the completion date is scheduled for October 2019. For final analysis 664 patients are expected be available. Preliminary baseline demographics were unstable angina pectoris (13.7%), NSTEMI (49.9%), STEMI (36.4%), male gender (86.3%), and diabetes mellitus (17.6%). Our study could significantly help to understand how inadequate adherence to antiplatelet therapy in ACS patients could be improved with a smartphone‐based application.
Risk of ischemic stroke and utility of CHA2DS2‐VASc score in women and men with atrial fibrillation
Authors: Tomasdottir Maria , Friberg Leif , Hijazi Ziad , Lindbäck Johan , Oldgren Jonas
Published: September 2019

Background

The magnitude of increased risk of stroke in women with atrial fibrillation (AF) remains uncertain.

Hypothesis

We investigated the risk of ischemic stroke and death in women and men with AF, and the risk associated with individual non‐sex CHA2DS2‐VASc risk factors.

Methods

Retrospective cohort study of 231 077 (48.1% women) nonselected patients with AF not receiving oral anticoagulation from 2006 to 2014. Data from cross‐linked national Swedish registers. The outcome was the first occurrence of ischemic stroke or death. Median age was 82 and 75 years in women and men, respectively. Mean follow‐up was 2.5 years.

Results

Hazard ratios, adjusted for non‐sex CHA2DS2‐VASc risk factors, for women vs men were 1.53, 95% CI: 1.49‐1.58 for ischemic stroke and 1.24, 95% CI: 1.22‐1.26 for death, respectively. When divided into age groups the differences in ischemic stroke rates between women and men were attenuated. In patients with only one non‐sex CHA2DS2‐VASc risk factor allotted 1 point, ischemic stroke rates per 100 person‐years were 1.22 in women (n = 9838) and 1.02 in men (n = 15 609), respectively, P < .006. In both women and men, age of 65 to 74 years was associated with higher ischemic stroke risk compared to other non‐sex CHA2DS2‐VASc risk factors allotted 1 point.

Conclusions

The risk of ischemic stroke was 1.5‐fold higher in women compared to men but this association appears to be the result of confounding by age. In the low risk end, the CHA2DS2‐VASc risk score underestimates the ischemic stroke risk conferred by age 65 to 74 years, while it overestimates the risk conferred by female sex.
Auxin‐Inducible Degron System for Depletion of Proteins in Saccharomyces cerevisiae
Authors: Shetty Ameet , Reim Natalia I. , Winston Fred
Published: September 2019

The auxin‐inducible degron (AID) is a powerful tool that is used for depletion of proteins to study their function in vivo. This method can conditionally induce the degradation of any protein by the proteasome simply by the addition of the plant hormone auxin. This approach is particularly valuable to study the function of essential proteins. The protocols provided here describe the steps to construct the necessary strains and to optimize auxin‐inducible depletion in Saccharomyces cerevisiae. © 2019 by John Wiley & Sons, Inc.

Basic Protocol 1: Construction of TIR1‐expressing strains by transformation

Basic Protocol 2: Tagging a yeast protein of interest with an auxin‐inducible degron

Support Protocol: Construction of depletion strains by genetic crosses

Basic Protocol 3: Optimization for depletion of the auxin‐inducible‐degron‐tagged protein
Formal and informal institutional pressures on corporate social responsibility: A cross‐country analysis
Authors: Tolmie Carri Reisdorf , Lehnert Kevin , Zhao Hongxin
Published: September 2019

This study examines the influences of cross‐country institutional pressures on multinational enterprises' corporate social responsibility (CSR). Building on institutional and stakeholder theory, we propose that different formal and informal environments have direct impacts on firm CSR. Specifically, we investigate informal institutions as they relate to self‐transcendent and self‐enhancement values. We propose that the firm's consideration of multiple stakeholder expectations moderates these complex formal and informal institutional relationships. Utilizing hierarchical linear modeling, this study analyzes institutional constraints on nearly 1,000 firms in 47 different countries. The empirical results reveal that informal values that are aligned with the firm's strategies and stakeholder desires have a strong impact on firms' CSR actions. Multiple stakeholder consideration strengthens this important relationship. These findings provide insight on how managers can utilize informal institutions to meet the global challenge of satisfying profit needs and still maintain social responsibility.
Infant emotional responses to challenge predict empathic behavior in toddlerhood
Authors: Noten Malou M. P. G. , van der Heijden Kristiaan B. , Huijbregts Stephan C. J. , van Goozen Stephanie H. M. , Swaab Hanna
Published: September 2019

Although emotional responses are theorized to be important in the development of empathy, findings regarding the prediction of early empathic behavior by infant behavioral and physiological responses are mixed. This study examined whether behavioral and physiological responses to mild emotional challenge (still face paradigm and car seat task) in 118 infants at age 6 months predicted empathic distress and empathic concern in response to an empathy‐evoking task (i.e, experimenter's distress simulation) at age 20 months. Correlation analyses, corrected for sex and baseline levels of physiological arousal, showed that stronger physiological and behavioral responses to emotional challenge at age 6 months were positively related to observed empathic distress, but not empathic concern, at age 20 months. Linear regression analyses indicated that physiological and behavioral responses to challenge at 6 months independently predicted empathic distress at 20 months, which suggests an important role for both physiological and behavioral emotional responses in empathy development. In addition, curvilinear regression analyses showed quadratic associations between behavioral responses at 6 months, and empathic distress and empathic concern at 20 months, which indicates that moderate levels of behavioral responsivity predict the highest levels of empathic distress and empathic concern.
Steviol glucuronide, a metabolite of steviol glycosides, potently stimulates insulin secretion from isolated mouse islets: Studies in vitro
Authors: Gu Wenqian , Rebsdorf Andreas , Anker Camilla , Gregersen Søren , Hermansen Kjeld , Geuns Jan M. C. , Jeppesen Per Bendix
Published: September 2019

Aims

Steviol glycosides are the sweet components extracted from medicinal plant Stevia rebaudiana Bertoni, which have antihyperglycaemic effects. Steviol glucuronide (SVG) is the metabolite excreted in human urine after oral administration of steviol glycosides. We aimed to clarify whether SVG exerts direct insulin stimulation from pancreatic islets and to explore its mode of action.

Materials and Methods

Insulin secretion was measured after 60 minutes static incubation of isolated mouse islets with (a) 10−9‐10−5 mol/L SVG at 16.7 mmol/L glucose and (b) 10−7 mol/L SVG at 3.3‐16.7 mmol/L glucose. Islets were perifused with 3.3 or 16.7 mmol/L glucose in the presence or absence of 10−7 mol/L SVG. Gene transcription was measured after 72 hours incubation in the presence or absence of 10−7 mol/L SVG.

Results

SVG dose‐dependently increased insulin secretion from mouse islets with 10−7 mol/L exerting the maximum effect in the presence of 16.7 mmol/L glucose (P < .001). The insulinotropic effect of SVG was critically dependent on the prevailing glucose concentration, and SVG (10−7 mol/L) enhanced insulin secretion at or above 11.1 mmol/L glucose (P < .001) and showed no effect at lower glucose concentrations. During perifusion of islets, SVG (10−7 mol/L) had a long‐acting and apparently reversible insulinotropic effect in the presence of 16.7 mmol/L glucose (P < .05). Gene‐transcript levels of B2m and Gcgr were markedly altered.

Conclusion

This is the first report to demonstrate that SVG stimulates insulin secretion in a dose‐ and glucose‐dependent manner from isolated mouse islets of Langerhans. SVG may be the main active metabolite after oral intake of steviol glycosides.
Artificial Biocatalytic Cascade with Three Enzymes in One Pot for Asymmetric Synthesis of Chiral Unnatural Amino Acids
Authors: Zhou Haisheng , Meng Lijun , Yin Xinjian , Liu Yayun , Xu Gang , Wu Jianping , Wu Mianbin , Yang Lirong
Published: September 2019

Two biocatalytic reactions, transamination catalyzed by transaminases and reductive amination catalyzed by amino acid dehydrogenases, can be used for asymmetric synthesis of optically pure unnatural amino acids. However, although transaminases show a great diversity and broad substrate spectrum, most transaminase reactions are reversible, while amino acid dehydrogenases catalyze reductive amination irreversibly but with strict substrate specificity. Accordingly, herein we developed a tri‐enzyme one‐pot reaction system to exploit the respective advantages of transaminases and amino acid dehydrogenases, while overcoming the disadvantages of each. In this work, representatives of all four subgroups of transaminases coupled with different amino acid dehydrogenases to produce five l‐ and four d‐ unnatural amino acid products, using ammonia and the co‐enzyme NAD(P)H, which is regenerated by a robust alcohol dehydrogenase with 2‐propanol as cheap cosubstrate. The complete conversion and high enantiopurity (ee > 99 %) of the products, demonstrated it as an ideal alternative for asymmetric synthesis of chiral amino acid compounds.
Genotoxic Assessment of the Dry Decoction of Myracrodruon urundeuva Allemão (Anacardiaceae) Leaves in Somatic Cells of Drosophila melanogaster by the Comet and SMART Assays
Authors: de Amorim Érima Maria , de Santana Samuel Lima , da Silva André Severino , de Aquino Nayara Coriolano , Silveira Edilberto Rocha , Ximenes Rafael Matos , Rohde Claudia
Published: September 2019

Medicinal plants are worldwide used as an efficient treatment of many diseases. Myracrodruon urundeuva Allemão (Anacardiaceae) is widely used Brazilian folk medicine to treat inflammations and infections of the female genital tract, conditions of the stomach and throat, and to heal wounds on the skin and mucous membranes. Several pharmacological properties of extracts and compounds isolated from M. urundeuva are found in the literature, corroborating its uses as antiulcer and gastroprotective, anti‐inflammatory and analgesic, as well as antimicrobial. Despite these many uses in traditional herbal medicine, there are few reports of its toxic‐genetic effect. This work aimed to investigate the genotoxic and mutagenic potential in vivo of the dry decoction of M. urundeuva leaves on somatic cells of Drosophila melanogaster, through the Comet assay and somatic mutation and recombination test (SMART). Six concentrations (0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 mg/mL) were studied after feeding individuals for 24 hr in culture medium hydrated with extracts of M. urundeuva. In the Comet assay, all concentrations showed a genotoxic effect significantly higher than the negative control group, treated with distilled water. The two highest concentrations were also superior to the positive control group, treated with cyclophosphamide (1 mg/mL). In the SMART, there was a mutagenic effect at all concentrations tested, with a clear dose‐dependent relationship. Both recombination and mutation account for these mutagenic effects. The set of results indicate that the dry decoction of M. urundeuva leaves is genotoxic and mutagenic for D. melanogaster under the experimental conditions of this study. Environ. Mol. Mutagen. 61:329–337, 2020. © 2019 Wiley Periodicals, Inc.
CompRess: Composing overlay service resources for end‐to‐end network slices using semantic user intents
Authors: Chen Xi , Yu Hongfang , Xu Shizhong , Du Xiaojiang
Published: September 2019

Network slicing is considered as a promising approach to bring flexible overlay services to end users, especially in the emerging 5G networks. Vertical network slices have been introducing new players into the arena of networked service provisioning such as automobile, healthcare, etc. Software‐Defined Networking (SDN) and Network Function Virtualization (NFV) are the key enabling technologies for network slicing. The combination of SDN and NFV brings benefits such as network programmability, flexible resources composition, etc; nevertheless, it also introduces complexity in expressing resources composition logics. Following the Intent‐Based Networking (IBN) ideology, this paper presents CompRess, an IBN practice and implementation of overlay service resources composition for end‐to‐end network slices based on Semantic Web techniques in SDN/NFV networks. Web Ontology Language and Resource Description Framework are used for resources modeling and description whereas SPARQL, a structural human‐readable query language, is adopted for user intent expression to bring high‐level abstraction and coarser‐grained encapsulation of low‐level operations. Meanwhile, back‐end K Shortest Paths–based algorithms are derived to compose a multichain Virtual Network Function Forwarding Graph (VNF‐FG) in an IBN flavor where several service function chains can be orchestrated for traffic steering under the hood of front‐end SPARQL‐expressed user intents. The simulation results demonstrate CompRess' applicability in multichain VNF‐FG composition for end‐to‐end network slices.
Multiobjective cooperative swarm intelligence algorithm for uplink resource allocation in LTE‐A networks
Authors: Moses M. Leeban , Kaarthick B.
Published: September 2019

Nowadays, Long‐Term Evolution Advanced (LTE‐A) network is the primary innovation in 4G networks. The LTE‐A networks convey exceptional data rates and low latency for few sorts of application. Sometimes, in LTE‐A, the multiobjective uplink resource allocation is the perplexing optimization problem, and this problem is considered as 0‐1 multiobjective knapsack trouble. In order to overcome this trouble, a multiobjective cooperative swarm intelligence algorithm for resource allocation is proposed in this paper. In our proposed work, hybrid firefly algorithm (FFA) and particle swarm optimization (PSO) algorithm are utilized to solve 0‐1 multiobjective knapsack problem. Initially, a priority and urgency factor (urgency of packets)–based user ranking and quantifying scheme is designed for scheduling process. After the scheduling process, the resource allocations employ three objective functions, such as maximization of resource utilization, maximization of quality of service (QoS), and interference minimization. The optimization problem is overcome by using the hybrid FFA and PSO algorithm. The experimental outcomes demonstrate that it has the best QoS and less interference in the resource allocation in LTE‐A network than state‐of‐art methods in the proposed strategy.
Interplay of the long axis of the hippocampus and ventromedial prefrontal cortex in schema‐related memory retrieval
Authors: Guo Dingrong , Yang Jiongjiong
Published: September 2019

When new information is relevant to prior knowledge or schema, it can be learned and remembered better. Rodent studies have suggested that the hippocampus and ventromedial prefrontal cortex (vmPFC) are important for processing schema‐related information. However, there are inconsistent findings from human studies on the involvement of the hippocampus and its interaction with the vmPFC in schema‐related memory retrieval. To address these issues, we used a human analog of the rodent spatial schema task to compare brain activity during immediate retrieval of paired associations (PAs) in schema‐consistent and schema‐inconsistent conditions. The results showed that the anterior hippocampus was more involved in retrieving PAs in the schema‐consistent condition than in the schema‐inconsistent condition. Connectivity analyses showed that the anterior hippocampus had stronger coupling with the vmPFC when the participants retrieved newly learned PAs successfully in the schema‐consistent (vs. schema‐inconsistent) condition, whereas the coupling of the posterior hippocampus with the vmPFC showed the opposite. Taken together, the results shed light on how the long axis of the hippocampus and vmPFC interact to serve memory retrieval via different networks that differ by schema condition.
Verteporfin targeting YAP1/TAZ‐TEAD transcriptional activity inhibits the tumorigenic properties of gastric cancer stem cells
Authors: Giraud Julie , Molina‐Castro Silvia , Seeneevassen Lornella , Sifré Elodie , Izotte Julien , Tiffon Camille , Staedel Cathy , Boeuf Hélène , Fernandez Solène , Barthelemy Philippe , Megraud Francis , Lehours Philippe , Dubus Pierre , Varon Christine
Published: September 2019

Gastric carcinomas (GC) are heterogeneous tumors, composed of a subpopulation of cluster of differentiation‐44 (CD44)+ tumorigenic and chemoresistant cancer stem cells (CSC). YAP1 and TAZ oncoproteins (Y/T) interact with TEA domain family member 1 (TEAD) transcription factors to promote cell survival and proliferation in multiple tissues. Their activity and role in GC remain unclear. This work aimed to analyze Y/T‐TEAD activity and molecular signature in gastric CSC, and to assess the effect of verteporfin, a Food and Drug Administration‐approved drug preventing Y/T‐TEAD interaction, on gastric CSC tumorigenic properties. Y/T‐TEAD molecular signature was investigated using bioinformatical (KmPlot database), transcriptomic and immunostaining analyses in patient‐derived GC and cell lines. Verteporfin effects on Y/T‐TEAD transcriptional activity, CSC proliferation and tumorigenic properties were evaluated using in vitro tumorsphere assays and mouse models of patient‐derived GC xenografts. High expressions of YAP1, TAZ, TEAD1, TEAD4 and their target genes were associated with low overall survival in nonmetastatic human GC patients (n = 444). This Y/T‐TEAD molecular signature was enriched in CD44+ patient‐derived GC cells and in cells resistant to conventional chemotherapy. Verteporfin treatment inhibited Y/T‐TEAD transcriptional activity, cell proliferation and CD44 expression, and decreased the pool of tumorsphere‐forming CD44+/aldehyde dehydrogenase (ALDH)high gastric CSC. Finally, verteporfin treatment inhibited GC tumor growth in vivo; the residual tumor cells exhibited reduced expressions of CD44 and ALDH1, and more importantly, they were unable to initiate new tumorspheres in vitro. All these data demonstrate that Y/T‐TEAD activity controls gastric CSC tumorigenic properties. The repositioning of verteporfin targeting YAP1/TAZ‐TEAD activity could be a promising CSC‐based strategy for the treatment of GC.
IGF‐1R pathway activation as putative biomarker for linsitinib therapy to revert tamoxifen resistance in ER‐positive breast cancer
Authors: Kruger Dinja T. , Alexi Xanthippi , Opdam Mark , Schuurman Karianne , Voorwerk Leonie , Sanders Joyce , van der Noort Vincent , Boven Epie , Zwart Wilbert , Linn Sabine C.
Published: September 2019

Preclinical studies indicate that activated IGF‐1R can drive endocrine resistance in ER‐positive (ER+) breast cancer, but its clinical relevance is unknown. We studied the effect of IGF‐1R signaling on tamoxifen benefit in patients and we searched for approaches to overcome IGF‐1R‐mediated tamoxifen failure in cell lines. Primary tumor blocks from postmenopausal ER+ breast cancer patients randomized between adjuvant tamoxifen versus nil were recollected. Immunohistochemistry for IGF‐1R, p‐IGF‐1R/InsR, p‐ERα(Ser118), p‐ERα(Ser167) and PI3K/MAPK pathway proteins was performed. Multivariate Cox models were employed to assess tamoxifen efficacy. The association between p‐IGF‐1R/InsR and PI3K/MAPK pathway activation in MCF‐7 and T47D cells was analyzed with Western blots. Cell proliferation experiments were performed under various growth‐stimulating and ‐inhibiting conditions. Patients with ER+, IGF‐1R‐positive breast cancer without p‐IGF‐1R/InsR staining (n = 242) had tamoxifen benefit (HR 0.41, p = 0.0038), while the results for p‐IGF‐1R/InsR‐positive patients (n = 125) were not significant (HR 0.95, p = 0.3). High p‐ERα(Ser118) or p‐ERα(Ser167) expression was associated with less tamoxifen benefit. In MCF‐7 cells, IGF‐1R stimulation increased phosphorylation of PI3K/MAPK proteins and ERα(Ser167) regardless of IGF‐1R overexpression. This could be abrogated by the dual IGF‐1R/InsR inhibitor linsitinib, but not by the IGF‐IR‐selective antibody 1H7. In MCF‐7 and T47D cells, stimulation of the IGF‐1R/InsR pathway resulted in cell proliferation regardless of tamoxifen. Abrogation of cell growth was regained by addition of linsitinib. In conclusion, p‐IGF‐1R/InsR positivity in ER+ breast cancer is associated with reduced benefit from adjuvant tamoxifen in postmenopausal patients. In cell lines, stimulation rather than overexpression of IGF‐1R is driving tamoxifen resistance to be abrogated by linsitinib.
Approaches to triage optimization in HPV primary screening: Extended genotyping and p16/Ki‐67 dual‐stained cytology—Retrospective insights from ATHENA
Authors: Stoler Mark H. , Baker Ed , Boyle Sean , Aslam Shagufta , Ridder Ruediger , Huh Warner K. , Wright Thomas C.
Published: September 2019

The objective of our study was to assess the performance of different triage strategies for high‐risk human papillomavirus (hrHPV)‐positive results utilizing either extended genotyping or a p16/Ki‐67 dual‐stained cytology (DS) approach, with or without partial genotyping. A subset of women with hrHPV infections participating in the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study were analyzed to determine the number of cervical intraepithelial neoplasia grade 3 or worse (≥CIN3) cases detected, and the absolute risk for ≥CIN3 of each genotype. A clinical utility table was constructed to compare the impact of different triage strategies. In all, 2,339 women with single‐genotype hrHPV infections were identified. Among these were 171 ≥CIN3 cases. The U.S. Food and Drug Administration (FDA)‐approved algorithm (HPV16/18 positive, or 12‐other hrHPV positive and Pap positive, i.e., ≥ atypical squamous cells of undetermined significance) for primary HPV screening detected 132/171 (77.2%) ≥CIN3 cases and required 964 colposcopies (colposcopies per ≥CIN3 ratio: 7.3). An approach that uses DS instead of cytology in the FDA‐approved algorithm detected 147/171 (86.0%) ≥CIN3 cases, requiring 1,012 colposcopies (ratio: 6.9). Utilizing DS for triage of all hrHPV‐positive women identified 126/171 (73.7%) ≥CIN3 cases, requiring 640 colposcopies (ratio: 5.1). A strategy that detected HPV16/18/31/33/35+ captured 130/171 (76.0%) ≥CIN3 cases, requiring 1,025 colposcopies (ratio: 7.9). Inclusion of additional genotypes resulted in greater disease detection at the expense of higher colposcopy ratios. Substituting cytology with a DS triage approach improved disease detection and the colposcopy detection rate. Further reduction of colposcopy rates can be achieved by using DS without partial genotyping. Extended genotyping strategies can identify a comparable number of cases but requires an increased number of colposcopies.
Transfusion practices in the care of pregnant women with sickle cell disease in Ouagadougou
Authors: Zamané Hyacinthe , Sanou Fabienne , Kiemtoré Sibraogo , Kain Dantola Paul , Sawadogo Arnaud Kiswendsida , Bonané‐Thiéba Blandine
Published: September 2019

Objective

To study the contribution of blood transfusion management in the improvement of maternal and perinatal outcomes in pregnant women with sickle cell disease in Ouagadougou.

Methods

A cross‐sectional retrospective study with data collected from February 2012 to January 2014 was used. Patients were differentiated into three groups: patients with at least one exchange transfusion, patients who received blood transfusion, and patients who did not receive any transfusion. Data were collected from patients’ patient care documents.

Results

One hundred and sixty‐four patients were included, of whom 53 were in the first group, 32 in the second group, and 79 in the third group. Maternal complications in the last trimester of pregnancy were significantly less important (P=0.000) in the first group (58.5%) than in the second (78.5%) and third group (91.1%). The same trend was observed for postpartum maternal mortality (5.7%; 12.5%; 12.6%; P=0.009). Fetal complications such as preterm birth and early neonatal death were lower in the first group (15.1%; 1.8%) than in the second (40.6%; 23.1%) and third group (32.9%; 7.6%).

Conclusion

Prophylactic blood transfusion is an important part of the management of pregnant patients with sickle cell disease.
Explore prognostic marker of colorectal cancer based on ceRNA network
Authors: Ke Mu‐Jing , Ji Lian‐Dong , Li Yi‐Xiong
Published: September 2019

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. With the deepening of people's understanding of CRC at the molecular level, the survival and prognosis of CRC have been significantly improved with the help of surgery, radiotherapy, and chemotherapy, molecular targeted biological therapy and early detection of diseases. The research of different disciplines and the development of multihistological analysis in recent years have proved that the occurrence and development of CRC is a complex biological process with the common action of multiple factors, which involves the huge changes of various histological levels such as the genome, transcriptome, and epigenome. At present, the abnormal expression of protein products in the transcription process has attracted more and more attention. Based on the sensitivity and timeliness of its changes, it has become a hot topic to study the occurrence and development mechanism of CRC through transcriptome changes, so as to provide markers for early diagnosis and prognosis. In recent years, competitive endogenous RNA (ceRNA) has become one of the hot topics in cancer research. The ceRNA hypothesis holds that transcripts such as long noncoding RNA can competitively bind microRNA (miRNA), thus preventing miRNA from binding to messenger RNA (mRNA) and thereby regulating the expression of mRNA. At present, the interaction mechanism of ceRNA in CRC is still unclear, and exploring its interaction relationship is of great significance to elucidate the occurrence and development mechanism of CRC. In this study, we used The Cancer Genome Atlas (TCGA) RNA ‐ seq data of colorectal Cancer and microRnas ‐ seq data to construct colorectal Cancer ceRNA topology network to mine key RNAs that influence the prognosis of colorectal cancer, providing potential RNA biomarkers.
Relationship between serum tumor markers and Anaplastic Lymphoma Kinase mutations in stage IV lung adenocarcinoma in Hubei province, Central China
Authors: Tan Qi , Huang Qi , Ma GuanZhou , LV Zhilei , Mei PeiYuan , Mao KaiMin , Wu Feng , Jin Yang
Published: September 2019

Objective

The aim of this study was to explore the predictive value of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCAg), and neuron‐specific enolase (NSE) in the prediction of anaplastic lymphoma kinase (ALK) mutations in advance stage non‐small cell lung cancer (NSCLC).

Subjects and Methods

A total of 482 cases with untreated lung adenocarcinoma were retrospectively reviewed. Finally, 72 patients with stage IV were enrolled because of intact data of the detection of ALK rearrangement and serum tumor markers, as well they have not received any previous anticancer therapy. We used the one‐way ANOVA analysis, correlation analysis, and multiple logistic regression analysis to evaluate the relationship between the level of serum tumor markers and ALK mutations.

Results

Fifteen cases with ALK mutations and 57 cases without mutations were identified. The result of the one‐way ANOVA analysis showed only CEA was significantly associated with ALK mutations (95% CI:39.05‐148.88; P = .001). The area under the ROC curve (AUC) of CEA was 0.705 (95%CI:0.567‐0.843; P = .015). However, no significant association was observed between CEA and ALK mutations though the result of correlation analysis (P = .069) and multivariate logistic regression analysis (OR = 0.988, 95% CI: 0.972‐1.003, P = .111).

Conclusions

In our study, we performed on the patients with stage IV lung adenocarcinoma in our region and found preoperative serum levels of SCCAg, CYRF21‐1, and NSE not suitable for the detection of ALK mutation. Although we observed a significant association between CEA and ALK mutations; however, it was not strong enough to distinguish ALK status for the patients in our region.
Effects of Adding Pentoxifylline to Captopril on Primary Hypertension: A Pilot Randomized Clinical Trial
Authors: Namdar Hossein , Khani Elnaz , Pourrashid Mohammad Hassan , Entezari‐Maleki Taher
Published: September 2019

Because of the key role blood viscosity plays in the regulation of blood pressure (BP) and the hemorheological effects of pentoxifylline (PTX), this study was conducted to evaluate whether PTX can reduce BP when added to captopril in patients with stage 1 hypertension. In this randomized clinical trial 62 patients with stage 1 hypertension were entered. The intervention group (n = 30) received 1200 mg PTX in 3 divided doses plus 25 mg captopril 3 times a day, whereas the control group (n = 32) received only 75 mg captopril in 3 divided doses. Measurements of BP were done at baseline and in the first and second months after entering the study. Major adverse cardiac events during this period were recorded. When the systolic BP levels in the intervention and the control groups were compared, no significant differences at baseline (150.4 ± 6.03 versus 150.4 ± 6.2, P = .98) or first (138.4 ± 9.4 versus 142.3 ± 5.6, P = .08) or second (134.6  ± 8.9 versus 137.4 ± 6.0, P = .20) month of the study were noted. Similarly no significant difference was observed in the diastolic BP at baseline (91.7 ± 3.9 versus 92.0 ± 3.7, P = .84) or first (85.5 ± 5.1 versus 86.9  ± 3.8, P = .27) or second (82.6  ± 5.7 versus 84.0  ± 3.5, P = .31) month. Based on the results of present study, adding PTX as a hemorheological agent to captopril could not significantly reduce blood pressure in the patients with stage 1 hypertension.
Spatial assessment of meteorological drought features over different climate regions in Iran
Authors: Sharafati Ahmad , Nabaei Sina , Shahid Shamsuddin
Published: September 2019

Iran has a predominantly arid and semi‐arid climate where the drought hazards and their variability are the crucial concerns for water resources management. This study assesses the characteristics and trends of meteorological droughts features in different climate regions of Iran. Monthly rainfall data are analysed using Standardized Precipitation Index (SPI) to reconstruct meteorological droughts for different time steps (1, 3, 6, 9 and 12). The drought events are decomposed into three features, namely Severity (S), Duration (D) and Peak (P) to assess their spatial variations in different climate regions. The Mann–Kendall (MK) test is used to detect the trends in drought features in different climate regions. The percentage area (PA) of increasing/decreasing trend in drought features is computed to assess the spatial variations of trends in each region. Besides, SPI is compared with Standardized Precipitation Evapotranspiration Index (SPEI) to understand the importance of evapotranspiration on meteorological droughts. The high correlations between SPI and SPEI indicate that the results obtained using SPI would not vary if a similar analysis is conducted using SPEI. The results obtained using SPI reveal that short‐duration droughts (6 months or less) are more frequent and severe in the northwest and the north along the Caspian plains while the longer‐duration droughts (more than 6 months) are more frequent and severe in the south, southeast and southwest. Overall, the northwest region of Iran is found most susceptible to droughts in terms of S, P and D. Moderate (40% < PA < 60%) or significant (PA > 60%) increase in the drought features are observed in all climate regions for shorter SPI (3 months or less) except northwest, while no drought feature is found to increase significantly for SPI‐12. Overall, the higher increase in drought S, P and D are found in the central arid region and at higher altitudes.
Hard and soft tissue evaluation of titanium dental implants and abutments with nanotubes in canines
Authors: Garrett Phillip W. , Johnston Gary W. , Bosshardt Dieter D. , Jones Archie A. , Sasada Yuya , Ong Joo L. , Cochran David L.
Published: September 2019

Background

Little is known regarding the interaction of dental implant surface nanotubes and oral soft and hard tissues. The purpose of this study was to evaluate both histologically and radiographically the qualitative and quantitative effects of dental implant surface nanotubes on hard and soft tissue in a canine model.

Methods

Three subgroups consisting of a combination of test and control implants and abutments (Group A: control implant/control abutment, Group B: control implant/test abutment: Group C: test implant/test abutment) were placed in edentulous mandibles of six large‐breed canines. Implants and abutments were placed on one side at baseline, and on the opposite side of the mandible at week 10; sacrifice occurred at week 12. Quantitative and qualitative analyses were used to measure newly formed hard and soft tissues histologically and radiographically.

Results

The mean radiographic change in marginal bone level from weeks 0 to 12 between implant groups was not statistically significant (P > 0.05). Mean soft tissue contact (junctional epithelium + connective tissue) for Groups A, B, and C were 2.29, 2.33, and 2.31 mm, respectively, with no statistically significant difference (P > 0.05) between the groups. All connective tissue fibers were oriented parallel to the abutment regardless of surface treatment.

Conclusions

The findings of this study suggest that healing of hard and soft tissues around implants and abutments is similar when comparing grit‐blasted surfaces to machined, turned surfaces with nanotubes. Both resulted in similar soft tissue contact values, as well as connective tissue fiber orientation.
Internal demarketing in the U.K. Civil Service since the 2007–2009 financial crisis
Authors: Brown David M. , Dey Bidit Lal , Wäppling Anders , Woodruffe‐Burton Helen
Published: September 2019

In reacting to the Financial Crisis of 2007–2009, the U.K. Civil Service has sought to redefine its relationship with its employees. The U.K. Civil Service appears to have shifted to a model of employer–employee relationship which segments the workforce, markets itself to its perceived core employees, and demarkets itself to its perceived noncore employees. The findings challenge the previously held assumption that internal demarketing constitutes accidental, manager‐level, bungled, but well‐intentioned, attempts at internal marketing.
Comparative study on finance‐growth nexus in Malaysia and Indonesia: Role of institutional quality
Authors: Sohag Kazi , Shams S. M. Riad , Omar Normah , Chandrarin Grahita
Published: September 2019

The impact of financial development (FD) on economic growth in the context of Malaysia and Indonesia has been examined in this study regarding the role of the financial crisis and strategic changes in the institutional setup. Autoregressive distributed lags and threshold regression were applied, and time series data were analyzed for the period between 1984 and 2017 revealing that FD promoted the economic growth in both economies during this period. A nonlinear analysis also revealed that FD and economic growth follow an inverted U‐shape relation in the case of Malaysia whereas, in Indonesia, it followed a U‐shape relation. It was discovered that not all measures of FD promote economic growth. For instance, market capitalization was profound in the Malaysian economy while credit to the private sector and money supply was conducive for the Indonesian economy. The analysis demonstrated that the Asian and global financial crisis adversely affected economic growth in the case of Indonesia due to poor institutional quality (IQ), whereas in Malaysia it was relatively safe from the adversity brought about by the financial crisis due to the presence of IQ and good corporate governance. However, a positive change in IQ was found to have a much greater impact on augmenting economic growth rather than playing a mediating role in connection with FD and economic growth in Malaysia. In the context of Indonesia however, IQ was found to impede economic growth but played a positive and significant mediating role in the nexus of FD and economic growth. The spill‐over analysis revealed that Malaysian FD is positively associated with Indonesian economic growth while Indonesian FD is negatively associated with the Malaysian economy. This study provided all economic and anecdotal explanations in supporting the results of this study.
Using Ultrasound Measurement of the Achilles Tendon in Asymptomatic Runners to Assist in Predicting Tendinopathy
Authors: Kudron Christopher , Carlson Morgan Jake , Meron Adele , Sridhar Balaji , Brakke Holman Rachel
Published: September 2019

Objectives

The Achilles tendon is the strongest tendon in the human body, and Achilles tendinopathy is common in athletes due to the stress imparted by repetitive forces. The prevalence of Achilles tendon abnormalities in asymptomatic elite runners is unknown. Since there is a substantial risk of developing symptomatic tendinopathy in those with abnormal tendons, identifying those asymptomatic athletes with abnormal tendons and characterizing baseline characteristics of elite runners using ultrasound (US) are valuable injury prevention tools.

Methods

This study used US to evaluate the Achilles tendons of 27 asymptomatic National Collegiate Athletic Association Division I cross‐country athletes and performed correlations between dominant and nondominant side tendon size (cross‐sectional area [CSA] and thickness) and athlete characteristics. Tendons were also assessed for signs of abnormalities that were suggestive of Achilles tendinopathy.

Results

The prevalence of tendon abnormalities in asymptomatic collegiate runners was 11%. Among the participants included in this study, dominant and nondominant Achilles tendons did not vary significantly in thickness or CSA (P > .05). The CSA was found to correlate with height, weight, sex, body mass index, and miles run per week (P < .05). Thickness was found to correlate best with miles run per week (P < .05).

Conclusions

A US evaluation of the Achilles tendon has potential to identify changes in tendon size in addition to abnormalities consistent with tendinopathy. As more normative values are identified among various populations, tendon size may have prognostic value for collegiate athletes in the evaluation of Achilles tendinopathy.