bluuebunny/crossref_metadata_2025 huggingface dataset:
Gold‐Catalyzed Cross‐Coupling Reactions: An Overview of Design Strategies, Mechanistic Studies, and Applications
Authors: Nijamudheen A. , Datta Ayan
Published: October 2019

Transition‐metal‐catalyzed cross‐coupling reactions are central to many organic synthesis methodologies. Traditionally, Pd, Ni, Cu, and Fe catalysts are used to promote these reactions. Recently, many studies have showed that both homogeneous and heterogeneous Au catalysts can be used for activating selective cross‐coupling reactions. Here, an overview of the past studies, current trends, and future directions in the field of gold‐catalyzed coupling reactions is presented. Design strategies to accomplish selective homocoupling and cross‐coupling reactions under both homogeneous and heterogeneous conditions, computational and experimental mechanistic studies, and their applications in diverse fields are critically reviewed. Specific topics covered are: oxidant‐assisted and oxidant‐free reactions; strain‐assisted reactions; dual Au and photoredox catalysis; bimetallic synergistic reactions; mechanisms of reductive elimination processes; enzyme‐mimicking Au chemistry; cluster and surface reactions; and plasmonic catalysis. In the relevant sections, theoretical and computational studies of AuI/AuIII chemistry are discussed and the predictions from the calculations are compared with the experimental observations to derive useful design strategies.
Exploiting Synergistic Catalysis for an Ambient Temperature Photocycloaddition to Pyrazoles
Authors: Lakeland Christopher P. , Watson David W. , Harrity Joseph P. A.
Published: October 2019

Sydnone‐based cycloaddition reactions are a versatile platform for pyrazole synthesis, however they operate under harsh conditions (high temperature and long reaction times). Herein we report a strategy that addresses this limitation utilizing the synergistic combination of organocatalysis and visible‐light photocatalysis. This new approach proceeds under ambient conditions and with excellent levels of regiocontrol. Mechanistic studies suggest that photoactivation of sydnones, rather than enamines, is key to the successful implementation of this process.
Evidence for a Proton‐Coupled Electron Transfer Mechanism in a Biomimetic System for Monoamine Oxidase B Catalysis
Authors: Nakamura Akiko , Latif Marwa Abdel , Deck Paul A. , Castagnoli Neal , Tanko James M.
Published: October 2019

Mechanistic studies with 5‐ethyl‐3‐methyllumiflavinium (Fl+) perchlorate, a biomimetic model for flavoenzyme monoamine oxidase B (MAO‐B) catalysis, and the tertiary, allyl amine 1‐methyl‐4‐(1‐methyl‐1 H‐pyrrol‐2‐yl)‐1,2,3,6‐tetrahydropyridine (MMTP) reveal that proton‐coupled electron transfer (PCET) may be an important pathway for MAO catalysis. The first step involves a single‐electron transfer (SET) leading to the free radicals Fl. and MMTP., the latter produced by deprotonation of the initially formed and highly acidic MMTP.+. Molecular oxygen (O2) is found to play a hitherto unrecognized role in the early steps of the oxidation. MMTP and several structurally similar tertiary amines are the only tertiary amines oxidized by MAO, and their structural/electronic properties provide the key to understanding this behavior. A general hypothesis about the role of SET in MAO catalysis, and the recognition that PCET occurs with appropriately substituted substrates is presented.
Trifluoromethyl Dihydrothiazine‐Based β‐Secretase (BACE1) Inhibitors with Robust Central β‐Amyloid Reduction and Minimal Covalent Binding Burden
Authors: Anan Kosuke , Iso Yasuyoshi , Oguma Takuya , Nakahara Kenji , Suzuki Shinji , Yamamoto Takahiko , Matsuoka Eriko , Ito Hisanori , Sakaguchi Gaku , Ando Shigeru , Morimoto Kenji , Kanegawa Naoki , Kido Yasuto , Kawachi Tomoyuki , Fukushima Tamio , Teisman Ard , Urmaliya Vijay , Dhuyvetter Deborah , Borghys Herman , Austin Nigel , Van Den Bergh An , Verboven Peter , Bischoff Francois , Gijsen Harrie J. M. , Yamano Yoshinori , Kusakabe Ken-ichi
Published: October 2019

The β‐site amyloid precursor protein cleaving enzyme 1 (BACE1, also known as β‐secretase) is a promising target for the treatment of Alzheimer's disease. A pKa lowering approach over the initial leads was adopted to mitigate hERG inhibition and P‐gp efflux, leading to the design of 6‐CF3 dihydrothiazine 8 (N‐(3‐((4S,6S)‐2‐amino‐4‐methyl‐6‐(trifluoromethyl)‐5,6‐dihydro‐4H‐1,3‐thiazin‐4‐yl)‐4‐fluorophenyl)‐5‐cyanopicolinamide). Optimization of 8 led to the discovery of 15 (N‐(3‐((4S,6S)‐2‐amino‐4‐methyl‐6‐(trifluoromethyl)‐5,6‐dihydro‐4H‐1,3‐thiazin‐4‐yl)‐4‐fluorophenyl)‐5‐(fluoromethoxy)pyrazine‐2‐carboxamide) with an excellent balance of potency, hERG inhibition, P‐gp efflux, and metabolic stability. Oral administration of 8 elicited robust Aβ reduction in dog even at 0.16 mg/kg. Reflecting the reduced hERG inhibitory activity, no QTc prolongation was observed at high doses. The potential for reactive metabolite formation of 15 was realized in a nucleophile trapping assay using [14C]‐KCN in human liver microsomes. Utilizing covalent binding (CVB) in human hepatocytes and the maximum projected human dosage, the daily CVB burden of 15 was calculated to be at an acceptable value of below 1 mg/day. However, hepatotoxicity was observed when 15 was subjected to a two‐week tolerance study in dog, which prevented further evaluation of this compound.
Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series
Authors: Holbrook Kourtney , Lutzky Jose , Davies Michael A. , Davis Jessica Michaud , Glitza Isabella C. , Amaria Rodabe N. , Diab Adi , Patel Sapna P. , Amin Asim , Tawbi Hussein
Published: October 2019

Background

Sixty percent of patients with stage IV melanoma may develop brain metastases, which result in significantly increased morbidity and a poor overall prognosis. Phase 3 studies of melanoma usually exclude patients with untreated brain metastases; therefore, clinical data for intracranial responses to treatments are limited.

Methods

A multicenter, retrospective case series investigation of consecutive BRAF‐mutant patients with melanoma brain metastases (MBMs) treated with a combination of BRAF inhibitor encorafenib and MEK inhibitor binimetinib was conducted to evaluate the antitumor response. Assessments included the intracranial, extracranial, and global objective response rates (according to the modified Response Evaluation Criteria in Solid Tumors, version 1.1); the clinical benefit rate; the time to response; the duration of response; and safety.

Results

A total of 24 patients with stage IV BRAF‐mutant MBMs treated with encorafenib plus binimetinib in 3 centers in the United States were included. Patients had received a median of 2.5 prior lines of treatment, and 88% had prior treatment with BRAF/MEK inhibitors. The intracranial objective response rate was 33%, and the clinical benefit rate was 63%. The median time to a response was 6 weeks, and the median duration of response was 22 weeks. Among the 21 patients with MBMs and prior BRAF/MEK inhibitor treatment, the intracranial objective response rate was 24%, and the clinical benefit rate was 57%. Similar outcomes were observed for extracranial and global responses. The safety profile for encorafenib plus binimetinib was similar to that observed in patients with melanoma without brain metastases.

Conclusions

Combination therapy with encorafenib plus binimetinib elicited intracranial activity in patients with BRAF‐mutant MBMs, including patients previously treated with BRAF/MEK inhibitors. Further prospective studies are warranted and ongoing.
“My doctor says the cancer is worse, but I believe in miracles”—When religious belief in miracles diminishes the impact of news of cancer progression on change in prognostic understanding
Authors: George Login S. , Balboni Tracy A. , Maciejewski Paul K. , Epstein Andrew S. , Prigerson Holly G.
Published: October 2019

Background

News of cancer progression is critical to setting accurate prognostic understanding, which guides patients' treatment decision making. This study examines whether religious belief in miracles modifies the effect of receiving news of cancer progression on change in prognostic understanding.

Methods

In a multisite, prospective cohort study, 158 patients with advanced cancer, whom oncologists expected to die within 6 months, were assessed before and after the visit at which scan results were discussed. Before the visit, religious belief in miracles was assessed; after the visit, patients indicated what scan results they had received (cancer was worse vs cancer was stable, better, or other). Before and after the visit, prognostic understanding was assessed, and a change score was computed.

Results

Approximately 78% of the participants (n = 123) reported at least some belief in miracles, with almost half (n = 73) endorsing the strongest possible belief. A significant interaction effect emerged between receiving news of cancer progression and belief in miracles in predicting change in prognostic understanding (b = −0.18, P = .04). Receiving news of cancer progression was associated with improvement in the accuracy of prognostic understanding among patients with weak belief in miracles (b = 0.67, P = .007); however, among patients with moderate to strong belief in miracles, news of cancer progression was unrelated to change in prognostic understanding (b = 0.08, P = .64).

Conclusions

Religious belief in miracles was highly prevalent and diminished the impact of receiving news of cancer progression on prognostic understanding. Assessing patients' beliefs in miracles may help to optimize the effectiveness of “bad news” scan result discussions.
Electrical stimulation induces synaptic changes in the peripheral auditory system
Authors: Li Qiang , Lu Tianhao , Zhang Chen , Hansen Marlan R. , Li Shufeng
Published: October 2019

Since a rapidly increasing number of neurostimulation devices are used clinically to modulate specific neural functions, the impact of electrical stimulation on targeted neural structure and function has become a key issue. In particular, the specific effect of electrical stimulation via a cochlear implant (CI) on inner hair cell (IHC) synapses remains unclear. Importantly, CI candidacy has recently expanded to include patients with partial hearing loss. Unfortunately, some CI recipients experience progressive hearing loss after activation of electrical stimulation. The mechanism(s) accounting for loss of residual hearing following electrical stimulation is unknown. Here normal‐hearing guinea pigs were implanted with customized CIs. Intracochlear electrical stimulation with an intensity equal to or above electrically evoked compound action potential (ECAP) threshold decreased the excitability of auditory nerve. Furthermore, the number of synapses between IHCs and the afferent spiral ganglion neurons (SGNs) also decreased after electrical stimulation with higher intensities. However, no significant change was observed in the packing density and perikaryal area of SGNs as well as the quantity of hair cells. These results carry important implications for use of CIs in patients with residual hearing and for an increasing number of patients treated with other neurostimulation devices. Notably, the results were based on acute electrical stimulation. Considering the complex interaction between CIs and targeted tissues, it is urgent to conduct further research to clarify whether the similar changes could be induced by chronic electrical stimulation.
1D Amorphous Tungsten‐Based Ternary Refractory Metal Sulfides for Catalytic Hydrogen Evolution at Soft Interfaces
Authors: Aslan Emre , Sarilmaz Adem , Ozel Faruk , Hatay Patir Imren , Girault Hubert H.
Published: October 2019

Transition metals incorporated into molybdenum sulfide and tungsten sulfide matrixes are promising candidates for hydrogen evolution due to the unique chemical and physical properties. Here, we first describe a general strategy for the synthesis of rod‐like ternary refractory metal sulfides (MWSx; M=Ni, Co, Fe and Mn) through a simple hot‐injection method. The newly developed materials are affirmed as valuable alternatives to noble metal Pt due to their simple fabrication, inexpensive and impressive catalytic performance. We present that highly efficient catalysts for the hydrogen evolution at a polarized water/1,2‐dichloroethane (DCE) interface by using the decamethylferrocene (DMFc). Kinetics of hydrogen evolution studies are monitored by two phase reactions using UV/Vis spectroscopy, and also further proved by gas chromatography. These ternary refractory metal sulfide catalysts show high catalytic activities on hydrogen evolution comparable to platinum. The rate of hydrogen evolution for the MWSx catalysts changed in the order Ni>Co>Fe>Mn according to the type of first row transition metals.
Photochemical Reaction of o‐Phthalaldehyde with Fullerene C60: The Stimulus for the Phthalide Additions to C60
Authors: Tzirakis Manolis D. , Malliaros Nikitas G. , Orfanopoulos Michael
Published: October 2019

A new, simple, and rapid photochemical reaction of o‐phthalaldehyde with C60 has been disclosed. This reaction afforded exclusively the unanticipated C60‐phthalide derivative 11 in good yield. The formation of this product is consistent with the intervention of a key free‐radical intermediate –a benzylic radical– in the course of the reaction. The structure of 11 has been determined by the combined use of experimental and theoretical NMR studies. In the course of this study we further disclosed a new mode of radical reactivity of C60 with a series of substituted phthalides (2, 15–17) catalyzed by tetrabutylammonium decatungstate.
Voltammetric Determination of Isoniazid Drug in Various Matrix by Using CuOx Decorated MW‐CNT Modified Glassy Carbon Electrode
Authors: Özdokur K. Volkan
Published: October 2019

Copper oxide decorated multi‐walled carbon nanotube (MWCNT) modified glassy carbon electrode (GCE) was prepared for determination of isoniazid (INZ) in various matrices. The electrochemical behavior of INZ was tested with the aid of Cyclic Voltammetry (CV) and quantitative experiments were performed by using Linear Sweep Voltammetry (LSV). Morphological and structural characterization of the modified electrode was performed by utilizing Scanning Electron Microscopy (SEM), X‐Ray Photoelectron Spectroscopy (XPS) while electrochemical characterization was performed by using CV and Electrochemical Impedance spectroscopy (EIS). The proposed sensor exhibited well defined anodic peak at 0.30 V for INZ at pH 6.0 medium. Under the optimum conditions, a linear relation between INZ concentration and peak current was observed in the range of 2.0×10−7 to 5.0×10−5 M. Limit of detection was calculated as 1.0×10−8 M and repeatability and accuracy was found as 5.60 % and 91.0 % for 5.0 10−7 M INZ by using 3 successive measurement, respectively. Then, the analytic performance of the electrode developed was tested by analyzing commercial tablets, artificial human serum and urine samples. The results indicated that satisfactory recoveries was observed for all issue.
Effect of valve opening shapes on the performance of a single‐stage Gifford‐McMahon cryocooler
Authors: Panda Debashis , Satapathy Ashok K. , Sarangi Sunil K.
Published: October 2019

In this work, the effect of the triangular and Gaussian‐shaped opening of the rotary valve (ie, the valve timing diagram of high‐pressure and low‐pressure valves) on the performance of a single‐stage Gifford‐McMahon (GM) cryorefrigerator is numerically investigated. In addition, the effect of waiting time of the rotary valve on its cooling power and coefficient of performance is studied for both types of opening shapes. The governing equations representing the fluid flow and heat transfer behaviors of the refrigerator are solved by using an implicit finite‐volume discretization method. The model considers both primary and secondary loss mechanisms. The developed model is first validated with the published results on GM cryorefrigerators. A very good agreement appears among them. It is observed that no significant change can be appreciated in the cooling power between 40° to 90° of waiting time for both types of opening shapes. On the other hand, in‐between 1° to 40° of waiting time, the cooling power of the Gaussian‐shaped opening of the rotary valve is higher than the one of the triangular opening.
A recommender system for selecting potential industrial training organizations
Authors: Ogunde Adewale Opeoluwa , Idialu Joy Oseremen
Published: October 2019

The difficulty in securing students industrial work experience scheme (SIWES) placements has negatively affected the final grades of some undergraduates. A recommender system is hereby proposed to solve this problem. This system will use past SIWES data to recommend potential organizations to future SIWES students. Research data collection was through an online questionnaire, with 200 respondents. The data was divided into a training data set (70%) and test data set (30%). Collaborative filtering recommendation approach was employed using the C4.5 algorithm to classify the data and generate a decision tree model from the training data set. The model generated was used to predict the class label of the test data set. Results from the data analysis carried out revealed that Kappa statistics was 0.7839, mean absolute error = 0.0058, and root mean squared error = 0.0586. In addition, true positive rate = 0.788, recall = 0.788, precision = 0.749, F‐measure = 0.755, MCC = 0.760, ROC = 0.985, and PRC = 0.813. The high values obtained indicates that the model was predicting with a high level of accuracy, ie, 78.84% correctly classified instances. The developed model was used as a knowledge base to develop a very beneficial front‐end web application, tagged “RecommendIT” where students can enter their preferences and view company recommendations.
Ammonium Fluoride Interface Modification for High‐Performance and Long‐Term Stable Perovskite Solar Cells
Authors: Zhu Qianjin , Wu Jihuai , Yuan Pengqiang , Zhang Mingjing , Dou Yanfei , Wang Xiaobing , Zou Jinjun , Sun Weihai , Fan Leqing , Lan Zhang
Published: October 2019

As a new generation of promising photovoltaic devices, perovskite solar cells (PSCs) have rapidly evolved in efficiency from 3.8% in 2009 to 23.5% recently. Numerous studies indicate that interface defects and the recombination of charge carrier at the interface, which hinders the improvement of photovoltaic performance and stability of PSCs, remains an important research area. Herein, a novel method for modifying the interface between the electron transport layer and the perovskite layer with ammonium fluoride (NH4F) is presented. After the TiO2 film is modified with NH4F, the TiO2/perovskite interface defects are mitigated and passivated, the carrier recombination decreases, and the electron extraction and injection capacity increase. Consequently, the planar PSC interface modified with an optimal NH4F concentration maintains over 95% initial efficiency for 32 days at 20% relative humidity, and achieves a champion power conversion efficiency of 20.47%, whereas the pristine device achieves an efficiency of 18.59% under the same conditions. This work demonstrates a low‐cost and efficient strategy to obtain high‐performance and stable PSCs.
Refractory epilepsy and nonadherence to drug treatment
Authors: Henning Oliver , Lossius Morten I. , Lima Maren , Mevåg Morten , Villagran Antonia , Nakken Karl O. , Johannessen Landmark Cecilie
Published: October 2019

In patients with epilepsy, nonadherence to agreed antiepileptic drug (AED) treatment may result in seizure relapse, and at worst sudden unexpected death. The aim of this study was to examine the extent of both unintentional and intentional nonadherence among Norwegian patients with refractory epilepsy and try to identify possible risk factors. At the National Centre for Epilepsy in Norway, 333 consecutive adult in‐ and outpatients with refractory epilepsy participated in an anonymous survey about adherence to drug treatment. Twenty‐two percentages admitted that they sometimes or often forgot to take their drugs as scheduled, and 19% reported that they, rarely, sometimes or often intentionally did not follow the AED treatment plan agreed upon with their physician. Young age and depression were significantly correlated with unintentional nonadherence. Intentional nonadherence was associated with young age (36 years or younger). We found nonadherence not to be associated with any specific AED. In conclusion, about one‐fifth of patients with refractory epilepsy admitted that they did not adhere to the agreed drug treatment plan, either intentionally or unintentionally. Measures to reduce nonadherence in this patient group may improve seizure control and should be tailored to address both unintentional and intentional lack of adherence.
Time‐transgressive cryoplanation terrace development through nivation‐driven scarp retreat
Authors: Nyland Kelsey E. , Nelson Frederick E.
Published: October 2019

Cryoplanation terraces are elevated bedrock features resembling giant staircases, with alternating steep scarps and shallow sloping treads. These landscape‐scale features have long been associated with periglacial environments, but the processes involved in their formation remain vaguely specified and contentious. The two leading hypotheses for the formation of cryoplanation terraces are centered on: (1) geologic structure; and (2) nivation‐driven scarp retreat. The nivation‐formation hypothesis invokes scarp retreat under erosion processes associated with late‐lying snowbanks. To test whether cryoplanation terraces develop through scarp retreat, six relative weathering indices (fracture counts, Cailleux roundness, Cailleux flatness, Krumbein sphericity, rebound, and weathering rind thickness) were measured across well‐developed terraces in unglaciated eastern Beringia (central and western Alaska) at Mt Fairplay, Eagle Summit, and Skookum Pass. Statistically significant differences in relative weathering indices detected through chi‐square and multiple‐comparison procedures indicate that material is less weathered closer to scarps, i.e. that these areas were more recently exposed than those distant from the scarp. Based on these findings, a refined model of time‐transgressive cryoplanation terrace development through nivation‐driven scarp retreat is proposed. This new qualitative model addresses the removal of weathered material from terrace treads down side slopes through piping and gravity‐driven mass‐wasting processes. © 2019 John Wiley & Sons, Ltd.
The impact of storm‐triggered landslides on sediment dynamics and catchment‐wide denudation rates in the southern Central Range of Taiwan following the extreme rainfall event of Typhoon Morakot
Authors: Chen Chia‐Yu , Willett Sean D. , West A. Joshua , Dadson Simon , Hovius Niels , Christl Marcus , Shyu J. Bruce H.
Published: October 2019

Extreme erosion events can produce large short‐term sediment fluxes. Such events complicate erosion rates estimated from cosmogenic nuclide concentrations in river sediment by providing sediment with a concentration different from the long‐term basin average. We present a detrital 10Be study in southern Taiwan, with multiple samples obtained in a time sequence bracketing the 2009 Typhoon Morakot, to assess the impact of landslide sediment on 10Be concentrations (N10Be) in river sediment. Sediment samples were collected from 13 major basins, two or three times over the last decade, to observe the temporal variation of N10Be. Landslide inventories with time intervals of 5–6 years were used to quantify sediment flux changes.

A negative correlation between N10Be and landslide areal density indicates dilution of N10Be by landslide sediment. Denudation rates estimated from the diluted N10Be can be up to three times higher than the lowest rate derived from the same basins. Observed increases imply that, 3 years after the passage of Typhoon Morakot, fluvial channels still contain a considerable amount of sediment provided by hillslope landslides during the event. However, higher N10Be in 2016 samples indicate that the contribution from landslide sediment at the sampled grain size has decreased with time. The correlation between changes in N10Be and landslide area and volume is not strong, likely resulting from the stochastic and complex nature of sediment transport. To simultaneously evaluate the volume of landslide‐derived sediment and estimate the background denudation rate, associated with less impulsive sediment supply, we constructed a sediment‐mixing model with the time series of N10Be and landslide inventories. The spatial pattern of background erosion rate in southern Taiwan is consistent with the regional tectonic framework, indicating that the landscape is evolving mainly in response to the tectonic forcing, and this signal is modified, but not obscured by impulsive sediment supply. © 2019 John Wiley & Sons, Ltd.
Adherence to the Norwegian dietary recommendations in a multi‐ethnic pregnant population prior to being diagnosed with gestational diabetes mellitus
Authors: Garnweidner‐Holme Lisa , Torheim Liv Elin , Henriksen Lena , Borgen Iren , Holmelid Sigrid , Lukasse Mirjam
Published: October 2019

Maternal diet is a modifiable risk factor for the development of gestational diabetes mellitus (GDM). Even though pregnant women are considered to be motivated to eat healthy, previous research found unhealthy eating patterns among some ethnic and lower socio‐economic status groups. This cross‐sectional study assessed adherence to national dietary recommendations prior to GDM diagnosis in a multi‐ethnic population comprising 237 pregnant women. Participants were diagnosed with GDM after performing a two‐hour oral glucose tolerance test ≥ 9 mmol/L. Participants answered a 41‐item Food Frequency Questionnaire about dietary habits prior to being diagnosed with GDM from October 2015 to March 2018. Their scores were based on adherence to the recommended intake in each food group and summed into a Healthy Diet Score (HDS). Results showed low adherence to national dietary recommendations. A significantly higher proportion of non‐native Norwegian‐speaking women had a high HDS compared with native Norwegian‐speaking women. Participants with a normal prepregnancy weight were more likely to have a high HDS compared with overweight or obese participants. Participants showed low adherence to the recommendations for whole grains, vegetables, and fruits and berries, and a relatively low proportion adhered to the recommendations for intakes of fish, red/processed meat, and ready‐made meals. However, the food group intakes varied by country of birth. Given the increase in women with GDM and the emerging evidence that maternal diet is a modifiable risk factor for GDM, effective nutrition communication strategies in antenatal care are urgently needed.
Prognostic significance of MTOR expression in HPV positive and negative head and neck cancers treated by chemoradiation
Authors: Wilson Thomas G. , Hanna Alaa , Recknagel Johnathon , Pruetz Barbara L. , Baschnagel Andrew M. , Wilson George D.
Published: October 2019

Background

The mechanistic target of rapamycin (MTOR) plays a key role in regulating cell growth and metabolism and is commonly overexpressed in head and neck cancer (HNSCC). This study investigated the association of MTOR with clinical outcome in human papilloma virus (HPV) positive and negative HNSCC patients treated by chemoradiation.

Methods

A tissue microarray (TMA) consisting of cores from 109 HNSCC patients treated by definitive chemoradiation was constructed and stained with antibodies against p16 and MTOR and expression correlated with clinicopathological features and clinical outcome.

Results

MTOR varied widely between tumor cores and was not associated with HPV status or clinicopathological features. There was a positive correlation with pre‐treatment FDG uptake.

(P = .01). In HPV negative patients, MTOR predicted for shorter locoregional control (P = .02), diseases free survival (P = .02), and overall survival (P = .04). MTOR expression was not associated with outcome in HPV positive patients.

Conclusions

Prognostic significance of MTOR expression depends on HPV status.
The implications of childcare on grandparents' health self‐management in a Chinese elderly population
Authors: Wang Xiao‐lei , Cheng Jing , Guo Chan‐yuan , Xu Xian‐rong
Published: October 2019

Grandparents caring for grandchildren has become a common experience in China. However, the health implications of grandparenting, especially for health self‐management, remain unclear. A cross‐sectional study was conducted to investigate the effects of grandparenting on health self‐management in older adults in China. Information on socioeconomic characteristics, grandparenting, and health self‐management was collected through interviewer‐administered questionnaires.

Age less than 50, male gender, higher education level, being a local resident, having a chronic illness, and supporting themselves financially were all factors that were significantly positively associated with health self‐management (P < .05) in grandparents. Grandparenting characteristics, including caring for grandchildren at night, a caregiving burden of more than 50%, poorly behaved grandchildren, caring for grandchildren more than 6 hours per day, and caring for grandchildren less than 1 year in age were significantly negatively associated with health self‐management in grandparents (P < .05). Multiple regression analyses indicated that grandparent age, receiving financial support from children, being a local resident, education level, grandchild behavior and age, and being an urban resident were all statistically significant factors associated with health self‐management in grandparents involved in grandparenting.

Taken together, these results suggested that financial condition and caregiving burden might be the major factors affecting health self‐management in grandparents involved in grandparenting.
An approximation technique for solutions of singularly perturbed one‐dimensional convection‐diffusion problem
Authors: Yüzbaşı Şuayip , Karaçayır Murat
Published: October 2019

In this study, a weighted residual method is presented in order to numerically solve singularly perturbed one‐dimensional parabolic convection‐diffusion problem. Assuming an approximate polynomial solution of a prescribed degree N, the method uses the set of bivariate monomials whose degrees do not exceed N as the set of base functions. Then, following Galerkin's path, inner product with the base functions are applied to the residual of the approximate solution polynomial. Incorporation of the initial and boundary conditions are ensured by forcing the approximate solution to satisfy these conditions on equidistant collocation points. The solution of the resulting linear system then yields the approximate polynomial solution. Additionally, the technique of residual correction, which aims to increase the accuracy of the approximate solution by estimating its error, is discussed briefly. The Galerkin‐like scheme and the residual correction technique are illustrated with two examples. The obtained results are also compared with other methods presented in the literature.
Separation and determination of ciprofloxacin in seawater, human blood plasma and tablet samples using molecularly imprinted polymer pipette‐tip solid phase extraction and its optimization by response surface methodology
Authors: Hashemi Sayyed Hossein , Ziyaadini Morteza , Kaykhaii Massoud , Jamali Keikha Ahmad , Naruie Nasrin
Published: October 2019

By synthesizing a molecular imprinted polymer as an efficient adsorbent, ciprofloxacin was micro‐extracted from seawater, human blood plasma and tablet samples by pipette‐tip micro solid phase extraction and determined spectrophotometrically. Response surface methodology was applied with central composite design to build a model based on factors affecting on microextraction of ciprofloxacin; including volume of eluent solvent, number of extraction cycles, number of elution cycles, and pH of sample. Other factors that affect extraction efficiency, such as type of eluent solvent, volume of sample, type, and amount of salt were optimized with one‐variable‐at‐a‐time method. Under optimum extraction condition, pH of sample solution was 7.0, volume of eluent solvent (methanol) was 200 µL, volume of sample solution was 10 mL, and the number of extraction and elution cycles was five and seven, respectively, amount of Na2SO4 (as salt) and MIP (as sorbent) were optimized at 150 and 2 mg, respectively. The linear range of the suggested method under optimum extraction factors was 5–150 µg/L with a limit of detection of 1.50 µg/L for the analyte. Reproducibility of the method (as relative standard deviation) was better than 7%.
Ontogenic succession of thermokarst thaw ponds is linked to dissolved organic matter quality and microbial degradation potential
Authors: Peura Sari , Wauthy Maxime , Simone Domenico , Eiler Alexander , Einarsdóttir Karólína , Rautio Milla , Bertilsson Stefan
Published: October 2019

Warming climate is thawing the permafrost in arctic and subarctic regions, leading to formation of thermokarst ponds. During the formation and geomorphological succession of these ponds, carbon that has been trapped in frozen soils for thousands of years is hydrologically mobilized and returned to the active carbon cycle. We sampled 12 thermokarst ponds representing three different stages of pond succession to study the potential of microbial communities to metabolize the organic carbon in the water. We investigated the quality of the dissolved organic carbon (DOC) in the water column based on the spectrophotometric and fluorometric properties of the chromophoric dissolved organic matter combined with parallel factor analysis and the potential of the microbial community for degrading these carbon compounds based on genetic markers related to carbon degradation. Our analysis showed a clear difference in the DOC quality across the different developmental stages. In the younger ponds, organic matter quality suggested that it was originating from the degrading permafrost and in the metagenomes collected from these ponds, the normalized abundance of genes related to degradation of carbon compounds was higher. There was also a shift in the degradation potential in the water column of the ponds, with higher potential for organic matter degradation in deeper, anoxic layers. In conclusion, our results show that the DOC quality and the genetic potential of the microbial community for carbon cycling change across the pond ontogeny, suggesting a capacity of the microbial communities to adapt to changing environmental conditions.
Intraosseous microdialysis for bone free flap monitoring in head and neck reconstructive surgery: A prospective pilot study
Authors: Dakpé Stéphanie , Colin Emilien , Bettoni Jérémie , Davrou Julien , Diouf Momar , Devauchelle Bernard , Testelin Sylvie
Published: October 2019

Background

Although some researchers have positioned microdialysis catheters in the soft tissue surrounding bone, the results did not accurately reflect bone metabolism. The present study's objective was to establish the feasibility of microdialysis with a catheter positioned directly in bone.

Methods

Thirty‐four patients (19 males, 15 females; median age: 59) were included in a prospective, nonrandomized clinical trial in the Department of Maxillofacial Surgery at Amiens‐Picardie University Hospital (Amiens, France). Fibula or iliac crest free flaps were used in reconstructive head and neck surgery (for cancer, osteoradionecrosis, trauma, or ameloblastoma) and monitored with microdialysis catheters positioned in a hole drilled into the bone. Glucose, lactate, pyruvate, and glycerol concentrations were analyzed for 5 days.

Results

All catheters were positioned successfully, and thrombosis did not occur during the monitoring. In two patients, an increase in the lactate concentration and a glucose level close to 0 were associated with signs of flap necrosis, with removal on Days 9 and 50. In viable flaps, the mean glucose level was 2.02 mmol/L, the mean lactate level was 8.36 mmol/L, and the mean lactate/pyruvate ratio was 53. Forty percent of the glucose values were below 1 mmol/L, and 50% of the lactate/pyruvate ratio values were above 50—suggesting a specific metabolic pattern because these values would be considered as alert values in soft tissue.

Conclusion

Monitoring bone free flaps with intraosseous microdialysis is feasible. This technique specifically assesses bone viability, and further studies are now necessary to define the alert values in bone.
The Buckwheat Iminosugar d‐Fagomine Attenuates Sucrose‐Induced Steatosis and Hypertension in Rats
Authors: Ramos‐Romero Sara , Hereu Mercè , Atienza Lidia , Amézqueta Susana , Casas Josefina , Muñoz Silvia , Medina Isabel , Miralles‐Pérez Bernat , Romeu Marta , Torres Josep L.
Published: October 2019

Scope

This study examines the long‐term functional effects of d‐fagomine on sucrose‐induced factors of metabolic dysfunctions and explores possible molecular mechanisms behind its action.

Methods and results

Wistar Kyoto rats are fed a 35% sucrose solution with d‐fagomine (or not, for comparison) or mineral water (controls) for 24 weeks. The following are recorded: body weight; energy intake; glucose tolerance; plasma leptin concentration and lipid profile; populations of Bacteroidetes, Firmicutes, bacteroidales, clostridiales, enterobacteriales, and Escherichia coli in feces; blood pressure; urine uric acid and F2t isoprostanes (F2‐IsoPs); perigonadal fat deposition; and hepatic histology and diacylglycerols (DAGs) in liver and adipose tissue. d‐Fagomine reduces sucrose‐induced hypertension, urine uric acid and F2‐IsoPs (markers of oxidative stress), steatosis, and liver DAGs, without significantly affecting perigonadal fat deposition, and impaired glucose tolerance. It also promotes excretion of enterobacteriales generated by the dietary intervention.

Conclusion

d‐fagomine counteracts sucrose‐induced steatosis and hypertension, presumably by reducing the postprandial levels of fructose in the liver.
Expanding the spectrum of transthyretin amyloidosis
Authors: Koike Haruki , Katsuno Masahisa
Published: October 2019

See article on pages 95–100 in this issue.
Association of Obesity Phenotypes with Electrocardiographic Markers of Poor Outcomes in the General Population
Authors: Ahmad Muhammad Imtiaz , Mongraw‐Chaffin Morgana , Lewis Kristina H. , Chen Haiying , Ard Jamy D. , Soliman Elsayed Z.
Published: October 2019

Objective

This study aimed to investigate the association of metabolically healthy obesity (MHO) and other obesity phenotypes with electrocardiographic (ECG) markers to understand the pathophysiological basis of increased cardiovascular disease (CVD) risk associated with these phenotypes.

Methods

A total of 3,700 participants (58.7 ± 13.6 years, 52% women) without CVD from the third National Health and Nutrition Examination Survey (NHANES III) were included. Logistic regression was used to examine the cross‐sectional association between obesity phenotypes (metabolically healthy without obesity [MHNO; reference], metabolically unhealthy without obesity, MHO, and metabolically unhealthy obesity) with ECG markers (PR interval, P‐wave duration, QRS duration, and QT interval).

Results

Higher odds of prolonged PR interval, P‐wave duration, and QRS duration were observed among all phenotypes compared with MHNO, with the highest in participants with obesity with or without metabolic syndrome. However, for QT interval, the trend of association with obesity phenotypes was as follows, from the strongest to the least strong: metabolically unhealthy obesity, metabolically healthy without obesity, and then MHO, compared with MHNO.

Conclusions

An association of obesity phenotypes with ECG abnormalities further raises doubt about the concept of MHO as a healthy state. Variations in associations with ECG markers may suggest that metabolic syndrome and obesity have a different relationship with different CVD outcomes and may explain some of the inconsistent CVD estimates for MHO.
Quantized event‐triggered H∞ control of linear networked systems with time‐varying delays and packet losses
Authors: Soltaninejad Moein , Ghiasi Amir Rikhtehgar , Ghaemi Sehraneh , Bagheri Peyman
Published: October 2019

This paper studies the event‐triggered (ET) H∞ control of linear networked systems based on static output‐feedback. An emulation‐based stabilization of the networked system is investigated under the constraints such as (i) quantizations, (ii) network‐induced delays, (iii) external disturbances, and (iv) packet losses. In particular, output measurement and control input quantizations, lower and upper bounds of the network‐induced delays, bounded external disturbances, and packet losses are carefully taken into account. The process of stability analysis has three steps. In the first step, a quantized ET control is defined, and then three sector‐bound methods for logarithmic quantization are formulated. In the second step, the ET‐mechanism is described with an input delay model. Based on the model, for two approaches, namely, switching‐ET and periodic‐ET, the criteria for the exponential stability and L2‐gain analysis of perturbed networked system are established, respectively. In the third step, a constraint for packet loss effect is provided. In summary, the stability analysis is based on linear matrix inequalities (LMIs) through a Lyapunov‐Krasovskii functional method. Finally, the simulation results are given to evaluate the validation of the analysis using two benchmark examples.
A structural equation model relating unemployment stress, spiritual intelligence, and mental health components: Mediators of coping mechanism
Authors: Arnout Boshra A.
Published: October 2019

This study aimed to evaluate a hypothesized structural model that reflects the relationship between unemployment stress, spiritual intelligence and mental health components. The sample of the study consisted of (761) unemployed adults (412 males and 349 females), their ages ranged between 30 to 48 year. They were divided into two samples: the first consisted of (352) unemployed adults to test the validity and reliability of the scales used in this study. And the second sample consisted of (409) unemployed adults to evaluate the hypothesized structural model. Researcher prepared the unemployment stress scale, and used the spiritual intelligence scale‐27, as well as prepared the short version of the mental health components scale based on the mental health scale‐50. In order to find how unemployment stress and spiritual intelligence predict the mental health components, the hypothesized model was examined using structural equation modeling. The results of test the proposed structural model concluded that the independent variable: unemployment stress contributed statistically significant directly to predict of the five dimensions of mental health components: mental mindfulness, flexibility, self‐efficiency, social support and happiness as dependent variables. At the same time, the independent variable: unemployment stress contributed statistically significant indirectly and proportionally to the prediction of the five dimensions of mental health as dependent variables through the dimensions of spiritual intelligence: spiritual mindfulness, spiritual abilities, spiritual presence as median variables. The proposed model of unemployment stress, spiritual intelligence and mental health components has a good fitness with the data were collected, and able to predict mental health among unemployed adults.
Numerical study of the effect of torsional fatigue loading on the energy absorption of composite tubes
Authors: Khomejani‐Farahani Soheil , Haghighi‐Yazdi Mojtaba , Safarabadi Majid
Published: October 2019

A three‐dimensional finite element model is developed to predict the effect of torsional fatigue loading on the energy absorption of unidirectional carbon/epoxy (AS4/3501‐6) composite tubes. Progressive fatigue damage model for fatigue loading and progressive failure model for axial velocity impact are implemented separately in the Abaqus software through user subroutine VUMAT. Each model is validated by the experimental data available in literature and good agreement is observed between the simulation results and experimental data. Then, these two models are sequentially applied to the composite tube with three different layups. The tube is first placed under torsional fatigue loading and a number of predefined loading cycles is applied. During this loading, the mechanical properties of the material are degraded based on sudden and gradual material properties degradation rules. Next, the fatigued tube is placed under axial impact loading. The results show that by increasing the number of fatigue cycles, the tube's ability to absorb energy is first reduced uniformly but in a particular cycle, due to the sudden drop in the shear mechanical properties of the material, the amount of energy absorption drops sharply and the tube loses its ability to absorb energy before it's catastrophic fatigue failure.
Effect of diabetes mellitus on voice: a systematic review
Authors: Ravi Rohit , Gunjawate Dhanshree R
Published: October 2019

A systematic review of literature was conducted to identify the influence of diabetes mellitus on voice. The search was carried out on PubMed, Scopus, CINAHL and Cochrane databases. Articles that discussed the effect of diabetes mellitus on voice were included in the review. Five studies were found to be suitable for inclusion. There is limited literature available on the effect of diabetes mellitus on voice. The studies pointed to a higher prevalence (12.5%) of voice problems among individuals with diabetes mellitus as compared to the general population, and higher gastro‐oesophageal reflux disorder related symptoms. Further, higher reflux symptom index and voice handicap index scores have been reported in these individuals. The other voice related changes reported across the studies include the presence of laryngeal involvement, hoarseness, and increased strained voice. Even though there is limited literature available, it points towards the presence of voice changes among people with diabetes. This information would help professionals to better counsel and refer patients with diabetes to laryngologists or voice therapists if they complain of voice changes. Copyright © 2019 John Wiley & Sons. Practical Diabetes 2019; 36(5): 177–180
Monitoring drug safety: is the Yellow Card Scheme struggling?
Authors: Chaplin Steve
Published: October 2019

In 2018, the Yellow Card Scheme reported a decline in the number of reported suspected adverse drug reactions, particularly among doctors and pharmacists. This article discusses the possible reasons for this and the action the MHRA is taking to improve reporting rates.
Effect of Cryogenic Dry Etching on Minority Charge Carrier Lifetime in Silicon
Authors: Kudryashov Dmitry A. , Gudovskikh Alexander S. , Baranov Artem I. , Morozov Ivan A. , Monastyrenko Anatoly O.
Published: October 2019

Micro‐ and nanostructured silicon surface application is a promising way of photovoltaic development. An enhancement of optical absorption in solar cells can be achieved, for example, using vertically aligned silicon nanostructures with high aspect ratios. Cryogenic plasma etching is a suitable method for such structures' formation; however, there is still lack of data describing an effect of cryogenic inductively coupled plasma (ICP) etching on defect formation in silicon (Si). The defects may act as recombination centers, leading to solar cell characteristics degradation. Herein, the cryogenic dry etching effects on defect formation in float‐zone (FZ) n‐type silicon substrates and on the photovoltaic properties of solar cells made of plasma‐etched silicon substrate are presented. The decrease in low‐injection minority carrier lifetime in silicon from 0.85 to 0.55 ms is observed by photoluminescence decay after the ICP dry etching at −140 °C. This leads to an open‐circuit voltage drop for the (p)a‐Si:H/(n)c‐Si/(n)a‐Si:H heterojunction structure from 680 to 630 mV. A detailed study of the defect properties by deep‐level transient spectroscopy (DLTS), numerical simulation, and its behavior after wet etching and thermal annealing is presented.