bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermochromism from Ultrathin Colloidal Sb2Se3 Nanowires Undergoing Reversible Growth and Dissolution in an Amine–Thiol Mixture
Authors: Wu Wen‐Ya , Xu Yang , Ong Xuanwei , Bhatnagar Sumit , Chan Yinthai
Published: November 2018

Liquid‐based thermochromics can be incorporated into an arbitrarily shaped container and provide a visual map of the temperature changes within its volume. However, photochemical degradation, narrow temperature range of operation, and the need for stringent encapsulation processes are challenges that can limit their widespread use. Here, a unique solution‐based thermochromic comprising ultrathin colloidal Sb2Se3 nanowires in an amine–thiol mixture is introduced. The nanowires undergo reversible growth and dissolution with repeated cycles of heating and cooling between 20 and 160 °C, exhibiting intense and contrasting color changes during these processes. Furthermore, the transition temperature in which a change in color first appears can be continuously tuned over a range larger than 100 °C by introducing controlled amounts of Sn2+. The colloidal nanowire dispersion in the amine–thiol mixture retains its thermochromic properties over hundreds of temperature cycles, continuous heating at 80 °C over months, and shelf life of up to 2 years in an open container under ambient conditions. To illustrate its utility as a robust liquid thermochromic, the nanowire solution is coated onto standard filter paper and its uses as a rewritable surface by thermal scribing, as well as an inexpensive means of visualizing the temperature distribution of an anisotropically heated block are demonstrated.
Tin‐Catalyzed Synthesis of 5‐Substituted 1H‐Tetrazoles from Nitriles: Homogeneous and Heterogeneous Procedures
Authors: Chrétien Jean‐Mathieu , Kerric Gaelle , Zammattio Françoise , Galland Nicolas , Paris Michael , Quintard Jean‐Paul , Le Grognec Erwan
Published: November 2018

The preparation of 5‐substituted 1H‐tetrazoles was efficiently achieved by reaction of trimethylsilylazide with nitriles using a triorganotin alkoxide precatalyst. The reaction mechanism was first investigated using a homogeneous tributyltin derivative and was explored through experimental investigations and DFT calculations. A heterogeneous version was then developed using a polymer‐supported organotin alkoxide and afforded an efficient method for the preparation of tetrazoles in high yields with an easy work‐up and a residual tin concentration in the desired products compatible for pharmaceutical applications (less than 10 ppm).

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Understanding of Anion Transport in Polymer Electrolytes for Supercapacitors
Authors: Li Tong , Hu Jingzhi , Wei Bingqing
Published: November 2018

Polymer electrolytes are critical to solid‐state energy storage devices because of their electrical/mechanical/thermal stability. The energy storage mechanisms of supercapacitors call for a higher degree of anion transports in the polymer electrolytes. Therefore, the improvement of anions transport is critical to the performance of supercapacitors. However, the underlying transport mechanisms of different anions in the polymer electrolyte system has rarely been studied. In the present study, by molecular modeling, it is understood and demonstrated that different anions adapt to different transfer mechanisms in the polymer electrolytes during the charging/discharging process, allowing one to tune the anion transport by either adjusting the polymer structures or change the anion types. For the H2SO4‐poly(vinyl alcohol) (PVA)‐based system, the diffusion of anions is more significant, while the H3PO4‐PVA system relies on the alignment of anions to the electrical field. The fundamental understanding will guide polymer electrolyte design for the solid‐state energy storage devices.
Expert consensus on clinical assessment and intervention of vascular aging in China (2018)
Authors: Zhang Cuntai , Tao Jun ,   Cardiovascular Group, Society of Geriatrics, Chinese Medical Association
Published: November 2018

With the development of geriatric medicine, more and more reported research has found that as humans grow old, their blood vessels also age. Blood vessels are vital components of various organs. Vascular aging is an important physiological and pathological basis for the aging of organs and systems of the human body and is the common pathogenesis of various chronic diseases in the elderly. Early detection of vascular aging and the use of correct methods to delay and treat vascular aging are of great significance to prevent and control chronic diseases in the elderly and to deal with the increasingly serious problems of population aging. For this purpose, this consensus is formulated for use by geriatric doctors and related personnel.
Hypomethylating agents in combination with venetoclax for acute myeloid leukemia: Update on clinical trial data and practical considerations for use
Authors: Mei Matthew , Aldoss Ibrahim , Marcucci Guido , Pullarkat Vinod
Published: November 2018

One of the most promising developments in therapy for acute myeloid leukemia (AML) in recent years has been the combination of hypomethylating agents (HMA, either decitabine or 5‐azacytidine) with the Bcl‐2 inhibitor venetoclax (VEN). Although both classes of drugs have single‐agent activity in AML, the combination has resulted in high rates of complete remission (CR) both in the frontline and relapsed settings suggesting synergy between these two agents. Recent data have suggested that CR + CR with incomplete count recovery rate may exceed 70% for frontline VEN‐HMA. Moreover, this activity has been observed across various genetic subtypes of AML including those known to have very poor response to conventional chemotherapy. Although VEN has only recently obtained FDA approval for treatment of AML, there has been increasing on and off‐label use of this combination given its striking efficacy and excellent toxicity profile. In this article, we summarize the current available data on this combination and offer practical guidelines for management of patients receiving VEN‐HMA. Our recommendations are based on protocol guidelines, published data from clinical trials as well as from analysis of real world evidence from patients treated with this combination.
Body mass index trajectories during the first year of life and their determining factors
Authors: Liu Junxiu , Liu Jihong , Frongillo Edward A. , Boghossian Nansi S. , Cai Bo , Zhou Haiming , Hazlett Linda J.
Published: November 2018

Objective

The purpose of this study was to examine the trajectories of body mass index (BMI) in the first year of life and their determining factors.

Methods

We used data from the Infant Feeding Practices Survey II restricted to children with 2 or more time points of BMI data during follow‐up visits within the first year of life (n = 2320). Latent class growth analysis was used to identify distinct BMI trajectories. Using multinomial logistic regression, we examined the prenatal and early life determinants of the identified trajectories.

Results

Three BMI trajectories were identified during the first year of life: “low‐stable” (81.6%), “high‐stable” (15.6%), and “rising” (2.8%) trajectories. Boys, preterm infants, infants born to overweight mothers, Hispanic mothers, non‐Hispanic Black mothers, and mothers who smoked during pregnancy were significantly more likely to have high‐stable versus low‐stable trajectories. Infants born to non‐Hispanic Black mothers were more likely to have a rising versus a low‐stable trajectory. Household income ≥350% of the federal poverty level and full adherence to the guidelines of the American Academy of Pediatrics for both breastfeeding exclusivity and duration reduced the likelihood of infants being in the rising versus the low‐stable trajectory.

Conclusion

Distinct BMI trajectories were evident as early as infancy. The predictors of these trajectories offer information about high‐risk groups, and important and preventable prenatal and postnatal risk factors for future intervention programs.
Using deep neural networks on airborne laser scanning data: Results from a case study of semi‐automatic mapping of archaeological topography on Arran, Scotland
Authors: Trier Øivind Due , Cowley David C. , Waldeland Anders Ueland
Published: November 2018

This article presents results of a case study within a project that seeks to develop heavily automated analysis of digital topographic data to extract archaeological information and to expedite large area mapping. Drawing on developments in computer vision and machine learning, this has the potential to fundamentally recast the capacity of archaeological prospection to cover large areas and deal with mass data, breaking a dependency on human resource. Without such developments, the potential of the vast amount of archaeological information embedded in large topographic and image‐based datasets cannot be realized. The purpose of the case study reported on here is to assess existing developments in a Norwegian study against digital topographic data for the island of Arran, Scotland, examining the transferability of the approach and providing a proof of concept in a Scottish context. For Arran, three monument classes were assessed – prehistoric roundhouses, shieling huts of medieval or post‐medieval date, and small clearance cairns. These present different challenges to detection, with preliminary results ranging from a manageable mix of false positives and true identifications to the chaotic. The influence of variable morphology and the occurrence of other, largely natural, objects of confusion in the landscape is discussed, highlighting the potential improvements in automated detection routines offered by adding anthropogenic and natural false positives to additional confusion classes.
2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis
Authors: Singh Jasvinder A. , Guyatt Gordon , Ogdie Alexis , Gladman Dafna D. , Deal Chad , Deodhar Atul , Dubreuil Maureen , Dunham Jonathan , Husni M. Elaine , Kenny Sarah , Kwan‐Morley Jennifer , Lin Janice , Marchetta Paula , Mease Philip J. , Merola Joseph F. , Miner Julie , Ritchlin Christopher T. , Siaton Bernadette , Smith Benjamin J. , Van Voorhees Abby S. , Jonsson Anna Helena , Shah Amit Aakash , Sullivan Nancy , Turgunbaev Marat , Coates Laura C. , Gottlieb Alice , Magrey Marina , Nowell W. Benjamin , Orbai Ana‐Maria , Reddy Soumya M. , Scher Jose U. , Siegel Evan , Siegel Michael , Walsh Jessica A. , Turner Amy S. , Reston James
Published: November 2018

Objective

To develop an evidence‐based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF).

Methods

We identified critical outcomes in PsA and clinically relevantPICO(population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA.GRADE(Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations.

Results

The guideline covers the management of active PsA in patients who are treatment‐naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin‐12/23 inhibitors (IL‐12/23i),IL‐17 inhibitors,CTLA4‐Ig (abatacept), and aJAKinhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat‐to‐target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment.

Conclusion

The 2018ACR/NPFPsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.
The dominant factor of social tags for users’ decision behavior on e‐commerce websites: Color or text
Authors: Xu Chen , Zhang Qin
Published: November 2018

Colored Tags (abbr.Tag) as a unique type of social tags is used on e‐commerce websites (e.g., Taobao) to summarize the high‐frequency keywords extracted from users' online reviews about products they bought before. Tag is represented inked red or green according to users' personal experiences and judgments about purchased items: red for positive comments, green for negative ones. The valence of users' emotion induced by red or green is controversial. This study firstly discovers that colored tags inked in red incite users' positive emotion (evaluations) and colored tags inked in green incite negative emotion (evaluations) using an ERP experiment, which is manifested in ERP components (e.g., N170, N2c, and LPC). There are two main features of Tag: the text of Tag (abbr. Text) and the color of Tag (abbr.Color). Our study then proves that Color (red or green) is the dominant factor in users' decision behavior compared with Text under the high cognitive load condition, while users' decision behavior is influenced by Text (positive tags or negative tags) predominately rather than by Color under the low cognitive load condition with the help of Eye tracking instrument. Those findings can help to design colored tags for recommendation systems on e‐commerce websites and other online platforms.
Tritopic Triazatruxene Ligands for Multicomponent Metal‐Organic Frameworks
Authors: Alkaş Adil , Cornelio Joel , Telfer Shane G.
Published: November 2018

Multicomponent metal‐organic frameworks (MOFs) are built up from multiple ligands that are geometrically distinct. These ligands occupy specific positions in the MOF lattice. Installing different functionalities at precise locations in the framework is an important step in making MOFs for specific applications. This can be achieved by designing functionalized ligands for multicomponent MOFs. Here, we report a simple synthetic procedure for a new tritopic triazatruxene based tricarboxylic acid, H3tat. We show that this ligand can be symmetrically derivatized with various substituents on its nitrogen centres. We report a new isoreticular series of well‐ordered quaternary MOFs based on these new triazatruxene ligands together with two linear carboxylate ligands and Zn4O clusters. These MOFs are isostructural to the previously reported MUF‐77 series and show similar high surface areas and large pore volumes. Furthermore, H‐bonding between the NH sites of the incorporated triazatruxene ligands and guest molecules is employed to modify their fluorescence behavior.
Techno‐economic assessment of the use of solvents in the scale‐up of microbial sesquiterpene production for fuels and fine chemicals
Authors: Cuesta Susana Pedraza‐de la , Knopper Loes , van der Wielen Luuk A.M. , Cuellar Maria C.
Published: November 2018

Sesquiterpenes are a group of versatile, 15‐carbon molecules with applications ranging from fuels to fine chemicals and pharmaceuticals. When produced by microbial fermentation at laboratory scale, solvents are often employed for reducing product evaporation and enhancing recovery. However, it is not clear whether this approach constitutes a favorable techno‐economic alternative at production scale. In this study empirical correlations, mass transfer and process flow sheeting models were used to perform a techno‐economic assessment of solvent‐based processes at scales typical for flavors and fragrances (25 MT year−1) and the fuel market (25 000 MT year−1). Different solvent‐based process options were compared to the current state of the art, which employs surfactants for product recovery. The use of solvents did reduce the sesquiterpene evaporation rate during fermentation and improved product recovery but it resulted in costs that were higher than, or similar to, the base case due to the additional equipment cost for solvent‐product separation. However, when selecting solvents compatible with the final product formulation (e.g. in a kerosene enrichment process), unit costs as low as $0.7 kg−1 can be achieved while decreasing environmental impact. © 2018 The Authors. Biofuels, Bioproducts and Biorefining published by Society of Chemical Industry and John Wiley & Sons, Ltd.
Childhood abuse, depressive vulnerability and gender dysphoria: Part 2
Authors: Firth Malcolm T.
Published: November 2018

Background

The recent reclassification of gender identity disorder as gender dysphoria (GD) in DSM‐5 identifies those seeking to pursue gender transition via specialist services as necessarily ‘distressed’ and therefore mentally disordered. Distress in gender variant clients may arise from a variety of stressors, external and intra‐psychic, many of which may have their roots in childhood experience [E. Bandini et al. (2011)].

Aims

(1) to review current thinking on gender variance and recognition and classification of GD (2) to detail the contribution of childhood adversity to distress in gender variant clients from an audit of 50 such clients (33 assigned/natal males and 17 assigned/natal females) of a mainstream NHS psychosexual service.

Methods

Current issues in classification and diagnosis of GD, and debate on the aetiology of gender variance, are reviewed briefly. Audit findings on health, treatment issues and support, and thematic analysis of childhood experiences, provide the basis for a case example of a post‐transition client experiencing some common difficulties associated with GD and childhood adversity.

Conclusions

Pragmatism of diagnosis and treatment of GD contrasts with the variety of theories of causation of gender variance itself. ‘Distress’ as a precondition of treatment may reflect childhood experience as much as GD‐specific symptoms, and may contribute more to persistent psychological vulnerability. While educational programmes in schools and a better knowledge base in counselling and related training curricula are indicated, gender dysphoric clients, pre‐ and post‐transition, experience common life problems for which generic forms of counselling and therapy are appropriate.
Practitioner‐based research and qualitative interviewing: Using therapeutic skills to enrich research in counselling and psychotherapy
Authors: McVey Lynn , Lees John , Nolan Greg
Published: November 2018

Background

The researcher's reflexive use of self forms part of a well‐established tradition in counselling and psychotherapy research. This paper reviews that tradition briefly, with particular reference to an approach known as ‘practitioner‐based research’ that has developed from it. In this approach, researcher‐practitioners use their therapeutic skills and judgement and thereby enrich their understanding of research participants, themselves and their relationship.

Aim

The paper aims to contribute to the practitioner‐based approach by showing how it can impact on data collection, using an example from a qualitative interview.

Methodology

A moment of interaction between a participant and a therapy researcher in a qualitative interview is examined, framed within psychotherapeutic intersubjectivity theory. The researcher's reflexive awareness of micro‐aspects of the relationship with the participant is reviewed, captured in their language and the split‐second daydreams or reveries that arose as they interacted.

Findings

The authors argue that the approach enhanced this small‐scale study by intensifying the researcher's engagement with the participant and enriching her understanding of their relationship and the subject under investigation.

Implications

The paper highlights the unique value and contribution that this approach offers to therapy research and practice.
Therapeutic practice with refugee clients: A qualitative study of therapist experience
Authors: Schweitzer Robert , van Wyk Sierra , Murray Kate
Published: November 2018

Background

There is limited research on the subjective experience of therapists and their understanding of therapeutic process when working with people from refugee backgrounds.

Objective

This study provides a qualitative account of therapists’ conceptions of therapeutic practice and experiences of working therapeutically with refugee clients.

Method

Participants were 12 mental health workers who had worked therapeutically with people from refugee backgrounds, with an average of 7.6 years (range 1.5–16 years) of experience in this field. Participants completed a semi‐structured interview and completed a brief quantitative survey.

Findings

Thematic analysis revealed a number of superordinate themes. Four key themes are explored in this study: principles of therapeutic practice; therapy as a relational experience; the role of context in informing therapeutic work with refugee clients; and the impact of therapeutic work on the therapist.

Discussion

The results revealed the complexity and demands of working with people from refugee backgrounds. Further, the lack of research evidence for the methods of therapeutic practice described in this study highlights the distinction between naturalistic therapeutic practice and the current state of the evidence regarding therapeutic interventions for refugee clients. The findings have important implications for training and supporting therapists to work with people who have fled their countries of origin and who have often been exposed to highly traumatic events.
Effect of Organic Solvents on the Electrochemical Performance of Sodium‐Ion Hybrid Capacitors
Authors: Park Myung‐Soo , Veerasubramani Ganesh Kumar , Thangavel Ranjith , Lee Yun‐Sung , Kim Dong‐Won
Published: November 2018

A comparative study on the ionic conductivity of carbonate‐ and ether‐based electrolytes was performed, which showed that the ionic conductivity was strongly affected by the dielectric constant of the organic solvent. The relationship between the physicochemical properties of a liquid electrolyte and the cycling performance of sodium‐ion hybrid capacitors (SICs) was assessed by comparing the electrochemical characteristics of SICs assembled with a negative activated carbon electrode and a positive Na3V2(PO4)3 electrode. Cyclic voltammetry, leakage current measurements, and electrochemical impedance spectroscopy results demonstrated that the good cycling performance of SICs with carbonate‐based electrolytes can be ascribed to their superior electrochemical stability, large amounts of free ions, and favorable electrochemical reaction kinetics. An SIC employing an electrolyte consisting of 1.0 M NaClO4 in ethylene carbonate/propylene carbonate exhibited a good rate capability and delivered a high initial discharge capacity of 98.7 mAh g−1 with a capacity retention of 90.8 % after 1000 cycles at a constant current density of 500 mA g−1.
The Hexameric Resorcinarene Capsule at Work: Supramolecular Catalysis in Confined Spaces
Authors: Gaeta Carmine , Talotta Carmen , De Rosa Margherita , La Manna Pellegrino , Soriente Annunziata , Neri Placido
Published: November 2018

The hexameric resorcinarene capsule reported by Atwood in 1997 is able to act as a supramolecular catalyst. Its inner cavity provides a unique environment, in which organic reactions can be efficiently catalyzed, thanks to the confinement effect of the substrates. In addition, different stereo‐ and regiochemical outcomes can be observed with respect to reactions in the bulk solvent. The hexameric capsule shows some catalytic features reminiscent of natural enzymes. In particular, highlights of the capsule discussed herein include 1) its ability to recognize the substrates (substrate selectivity), 2) the possibility of stabilizing the transition states and intermediates through secondary interactions, 3) an inherent Brønsted acidity, and 4) its ability to act as a hydrogen‐bond catalyst. In addition, it is also shown how the catalytic activity of the hexameric capsule can be modulated in the presence of competitive alkylammonium guests, which show high affinities for its internal cavity. These aspects are discussed through a critical examination of data reported in the literature in recent years.
Characterization and gonadal hormone regulation of a sexually dimorphic corticotropin‐releasing factor receptor 1 cell group
Authors: Rosinger Zachary J. , Jacobskind Jason S. , Bulanchuk Nicole , Malone Margaret , Fico Danielle , Justice Nicholas J. , Zuloaga Damian G.
Published: November 2018

Corticotropin‐releasing factor binds with high affinity to CRF receptor 1 (CRFR1) and is implicated in stress‐related mood disorders such as anxiety and depression. Using a validated CRFR1‐green fluorescent protein (GFP) reporter mouse, our laboratory recently discovered a nucleus of CRFR1 expressing cells that is prominent in the female rostral anteroventral periventricular nucleus (AVPV/PeN), but largely absent in males. This sex difference is present in the early postnatal period and remains dimorphic into adulthood. The present investigation sought to characterize the chemical composition and gonadal hormone regulation of these sexually dimorphic CRFR1 cells using immunohistochemical procedures. We report that CRFR1‐GFP‐ir cells within the female AVPV/PeN are largely distinct from other dimorphic cell populations (kisspeptin, tyrosine hydroxylase). However, CRFR1‐GFP‐ir cells within the AVPV/PeN highly co‐express estrogen receptor alpha as well as glucocorticoid receptor. A single injection of testosterone propionate or estradiol benzoate on the day of birth completely eliminates the AVPV/PeN sex difference, whereas adult gonadectomy has no effect on CRFR1‐GFP cell number. These results indicate that the AVPV/PeN CRFR1 is regulated by perinatal but not adult gonadal hormones. Finally, female AVPV/PeN CRFR1‐GFP‐ir cells are activated following an acute 30‐min restraint stress, as assessed by co‐localization of CRFR1‐GFP cells with phosphorylated (p) CREB. CRFR1‐GFP/pCREB cells were largely absent in the male AVPV/PeN. Together, these data indicate a stress and gonadal hormone responsive nucleus that is unique to females and may contribute to sex‐specific stress responses.
Age‐dependent release of high‐mobility group box protein‐1 and cellular neuroinflammation after traumatic brain injury in mice
Authors: Webster Kyria M. , Sun Mujun , Crack Peter J. , O'Brien Terence J. , Shultz Sandy R. , Semple Bridgette D.
Published: November 2018

Accumulating research suggests that children may be more vulnerable to poor long‐term outcomes after traumatic brain injury (TBI) compared to adults. The neuroinflammatory response, known to contribute to neuropathology after TBI, appears to differ depending upon age‐at‐insult, although this response has not been well‐characterized. Elevated levels of a key initiator of inflammation, high‐mobility group box protein 1 (HMGB1), have been associated with worsened outcomes after TBI in young patients. This study therefore aimed to characterize the acute time course of key mediators of the inflammatory cascade, including HMGB1, after pediatric and adult TBI. Male C57Bl/6 mice were subjected to severe controlled cortical impact or a sham control surgery, at either early adulthood (8–10 weeks) or a pediatric age (3 weeks). Cortical tissue was collected for Western blot detection of astrocyte and microglial activation (GFAP and CD68) and HMGB1 at 2 hr, 6 hr, 24 hr, 3 days, and 7 days postinjury, and serum was collected for enzyme‐linked immunoassays to quantify peripheral HMGB1. An additional cohort of brains was harvested at 3 day postinjury for immunofluorescence staining. Results demonstrated a temporal profile of CD68, GFAP, and HMGB1 after TBI relative to sham, which differed between the adult and pediatric cohorts. An increase in peripheral HMGB1 was found in serum from pediatric TBI mice, which was not evident in adult serum. Together, these findings demonstrate that HMGB1 and the downstream cellular inflammatory response are influenced by age‐at‐insult, which may be an important consideration for treatment strategies aiming to ameliorate this response after TBI.
Pharmacokinetic Interaction Study Between Saxagliptin and Omeprazole, Famotidine, or Magnesium and Aluminum Hydroxides Plus Simethicone in Healthy Subjects: An Open‐Label Randomized Crossover Study
Authors: Ren Song , Boulton David W.
Published: November 2018

Saxagliptin is an orally administered, highly potent, and selective dipeptidyl peptidase‐4 inhibitor for the management of type 2 diabetes mellitus. This study was conducted to determine the effect of magnesium and aluminum hydroxides plus simethicone, famotidine, and omeprazole on the pharmacokinetics of saxagliptin and its active metabolite, 5‐hydroxy saxagliptin. This was an open‐label, randomized, 5‐treatment, 5‐period, 3‐way crossover study in 15 healthy subjects. Mean Cmax of saxagliptin was 26% lower, but AUC was almost unchanged when saxagliptin was coadministered with Maalox Max. Mean Cmax was 14% higher, but AUC was almost unchanged when saxagliptin was coadministered with famotidine. Changes in pharmacokinetics of 5‐hydroxy saxagliptin generally paralleled the changes in saxagliptin. These pharmacokinetic changes were unlikely to be clinically meaningful. Coadministration of omeprazole did not affect saxagliptin Cmax or AUC. Saxagliptin in combination with these medicines resulted in no unexpected safety or tolerability findings in these healthy subjects. No dose adjustment of saxagliptin or separation in the time of saxagliptin dosing is necessary with medicines that raise gastric pH when coadministered with saxagliptin.
Toward Dynamic Prescribing Information: Codevelopment of Companion Model‐Informed Precision Dosing Tools in Drug Development
Authors: Polasek Thomas M. , Rayner Craig R. , Peck Richard W. , Rowland Andrew , Kimko Holly , Rostami‐Hodjegan Amin
Published: November 2018

Model‐informed precision dosing (MIPD) is biosimulation in healthcare to predict the drug dose for a given patient based on their individual characteristics that is most likely to improve efficacy and/or lower toxicity compared with traditional dosing. Despite widespread use of biosimulation in drug development, MIPD has not been adopted beyond academic‐hospital centers. A reason for this is that MIPD requires more supporting evidence in the language that everyday doctors understand—evidence‐based medicine. In this commentary, codevelopment of companion MIPD tools during drug development is advocated as a way to accelerate the generation of the evidence required for broader clinical implementation of MIPD. Such tools have the potential to evolve into “dynamic” prescribing information that could guide dose selection for complex patients.
The number of remaining teeth as a risk indicator of cognitive impairment: A cross‐sectional clinical study in Sado Island
Authors: Kuroki Ayumi , Sugita Noriko , Komatsu Shigeki , Wakasugi Minako , Yokoseki Akio , Yoshihara Akihiro , Kobayashi Tetsuo , Nakamura Kazutoshi , Momotsu Takeshi , Endo Naoto , Sato Kenji , Narita Ichiei , Yoshie Hiromasa
Published: November 2018

Most studies that have demonstrated an association between number of remaining teeth and cognitive impairment have treated teeth as a continuous variable, although the relationship is nonlinear. The aim of this cross‐sectional study was to determine the critical number of remaining teeth in hospital outpatients at which the association with cognitive impairment becomes apparent. Japanese adults living on Sado Island who visited Sado General Hospital were invited to participate in Project in Sado for Total Health. In total, 2,530 adults were interviewed and had their teeth counted; 1,476 of these individuals also completed the Mini‐Mental State Examination (MMSE) and underwent measurement of their serum high‐sensitivity C‐reactive protein (hsCRP) levels. Patients on dialysis and those with hsCRP ≥ 10 mg/L were excluded. The final study group consisted of 565 adults (290 men and 275 women) of mean age 69.8 (range 29–91) years. An MMSE score < 24 was considered to indicate cognitive impairment. The subjects were categorized according to whether they had an edentulous jaw or one to 10, 11–20, 21–27, or ≥28 remaining teeth. One hundred twenty‐eight of the 565 study participants were diagnosed to have cognitive impairment. Multiple logistic regression analysis revealed associations of cognitive impairment with older age, ischemic heart disease, smoking, and alcohol consumption. After adjustment for covariates, having one to 10 remaining teeth was significantly associated with cognitive impairment. There is a significant association between having only one to 10 remaining teeth and cognitive impairment in hospital outpatients.
Comparison of large‐scale citizen science data and long‐term study data for phenology modeling
Authors: Taylor Shawn D. , Meiners Joan M. , Riemer Kristina , Orr Michael C. , White Ethan P.
Published: November 2018

Large‐scale observational data from citizen science efforts are becoming increasingly common in ecology, and researchers often choose between these and data from intensive local‐scale studies for their analyses. This choice has potential trade‐offs related to spatial scale, observer variance, and interannual variability. Here we explored this issue with phenology by comparing models built using data from the large‐scale, citizen science USA National Phenology Network (USA‐NPN) effort with models built using data from more intensive studies at Long Term Ecological Research (LTER) sites. We built statistical and process based phenology models for species common to each data set. From these models, we compared parameter estimates, estimates of phenological events, and out‐of‐sample errors between models derived from both USA‐NPN and LTER data. We found that model parameter estimates for the same species were most similar between the two data sets when using simple models, but parameter estimates varied widely as model complexity increased. Despite this, estimates for the date of phenological events and out‐of‐sample errors were similar, regardless of the model chosen. Predictions for USA‐NPN data had the lowest error when using models built from the USA‐NPN data, while LTER predictions were best made using LTER‐derived models, confirming that models perform best when applied at the same scale they were built. This difference in the cross‐scale model comparison is likely due to variation in phenological requirements within species. Models using the USA‐NPN data set can integrate parameters over a large spatial scale while those using an LTER data set can only estimate parameters for a single location. Accordingly, the choice of data set depends on the research question. Inferences about species‐specific phenological requirements are best made with LTER data, and if USA‐NPN or similar data are all that is available, then analyses should be limited to simple models. Large‐scale predictive modeling is best done with the larger‐scale USA‐NPN data, which has high spatial representation and a large regional species pool. LTER data sets, on the other hand, have high site fidelity and thus characterize inter‐annual variability extremely well. Future research aimed at forecasting phenology events for particular species over larger scales should develop models that integrate the strengths of both data sets.
The big two dictionaries: Capturing agency and communion in natural language
Authors: Pietraszkiewicz Agnieszka , Formanowicz Magdalena , Gustafsson Sendén Marie , Boyd Ryan L. , Sikström Sverker , Sczesny Sabine
Published: November 2018

Four studies developed and validated two dictionaries to capture agentic and communal expressions in natural language. Their development followed the Linguistic Inquiry and Word Count (LIWC) approach (Study 1) and we tested their validity with frequency‐based analyses and semantic similarity measures. The newly developed Agency and Communion dictionaries were aligned with LIWC categories related to agency and communion (Study 2), and corresponded with subjective ratings (Study 3), confirming their convergent validity. Very low or absent correspondence between proposed dictionaries and unrelated LIWC categories demonstrated their discriminant validity (Study 2). Finally, we applied both dictionaries to language used in advertisements. In correspondence to gender stereotypes, male‐dominated jobs were advertised with more agentic than communal words, and female‐dominated jobs with more communal than agentic words (Study 4). Both dictionaries represent reliable tools for quantifying agentic and communal content in natural language, and will improve and facilitate future research on agency and communion.
Inhibition of astrocyte FAK–JNK signaling promotes subventricular zone neurogenesis through CNTF
Authors: Jia Cuihong , Keasey Matthew P. , Lovins Chiharu , Hagg Theo
Published: November 2018

Astrocyte‐derived ciliary neurotrophic factor (CNTF) promotes adult subventricular zone (SVZ) neurogenesis. We found that focal adhesion kinase (FAK) and JNK, but not ERK or P38, repress CNTF in vitro. Here, we defined the FAK–JNK pathway and its regulation of CNTF in mice, and the related leukemia inhibitory factor (LIF) and interleukin‐6 (IL‐6), which promote stem cell renewal at the expense of neurogenesis. Intrastriatal injection of FAK inhibitor, FAK14, in adult male C57BL/6 mice reduced pJNK and increased CNTF expression in the SVZ‐containing periventricular region. Injection of a JNK inhibitor increased CNTF without affecting LIF and IL‐6, and increased SVZ proliferation and neuroblast formation. The JNK inhibitor had no effect in CNTF−/− mice, suggesting that JNK inhibits SVZ neurogenesis by repressing CNTF. Inducible deletion of FAK in astrocytes increased SVZ CNTF and neurogenesis, but not LIF and IL‐6. Intrastriatal injection of inhibitors suggested that P38 reduces LIF and IL‐6 expression, whereas ERK induces CNTF and LIF. Intrastriatal FAK inhibition increased LIF, possibly through ERK, and IL‐6 through another pathway that does not involve P38. Systemic injection of FAK14 also inhibited JNK while increasing CNTF, but did not affect P38 and ERK activation, or LIF and IL‐6 expression. Importantly, systemic FAK14 increased SVZ neurogenesis in wild‐type C57BL/6 and CNTF+/+ mice, but not in CNTF−/− littermates, indicating that it acts by upregulating CNTF. These data show a surprising differential regulation of related cytokines and identify the FAK–JNK–CNTF pathway as a specific target in astrocytes to promote neurogenesis and possibly neuroprotection in neurological disorders.
Genotype 5 Hepatitis E Virus Produced by a Reverse Genetics System Has the Potential for Zoonotic Infection
Authors: Li Tian‐Cheng , Bai Huimin , Yoshizaki Sayaka , Ami Yasushi , Suzaki Yuriko , Doan Yen Hai , Takahashi Kazuaki , Mishiro Shunji , Takeda Naokazu , Wakita Takaji
Published: November 2018

Neither an animal model nor a cell culture system has been established for the genotype 5 hepatitis E virus (G5 HEV), and the pathogenicity, epidemiology, and replication mechanism of the virus remain unclear. In this study, we used a reverse genetics system to generate G5 HEV and examined the possibility of zoonotic infection. Capped and uncapped genomic G5 HEV RNAs generated by in vitro transcription were transfected into PLC/PRF/5 cells. Infectious G5 HEV was recovered from the capped G5 HEV RNA–transfected PLC/PRF/5 cells and the subsequently passaged cells. G5 HEV was also recovered from uncapped G5 HEV–transfected PLC/PRF/5 cells after a longer lag phase, suggesting that the 5′‐cap structure is not essential but affected the efficiency of G5 HEV replication. G5 HEV infection was neutralized not only by anti‐G5 HEV‐like particles (HEV‐LPs) antibody, but also by anti‐G1, anti‐G3, anti‐G4, and anti‐G7 HEV‐LPs antibodies. G5 HEV was capable of infecting cynomolgus monkeys negative for anti‐HEV antibody but not animals positive for anti‐G7 HEV immunoglobulin G (IgG), indicating that cynomolgus monkeys were susceptible to G5 HEV, and the serotype of G5 HEV was identical to that of G7 HEV and human HEVs. Moreover, G5 HEV replication was efficiently inhibited by ribavirin and partially inhibited by sofosbuvir. Conclusion: Infectious G5 HEV was produced using a reverse genetics system, and the antigenicity was identical to that of human HEVs and G7 HEV. Transmission of G5 HEV to primates was confirmed by an experimental infection, providing evidence of the possibility of zoonotic infection by G5 HEV.
Functional and structural characterization of a novel catechol‐O‐methyltransferase from Schizosaccharomyces pombe
Authors: Wang Qing , Teng Maikun , Li Xu
Published: November 2018

Catechol‐O‐methyltransferase (COMT1) catalyzes the transfer of a methyl group from S‐adenosylmethionine (SAM) to various catechol substrates. COMTs play vital roles in physiological processes in animals, plants, and fungi, as well as bacteria, and have essential application values in industry. spCOMT is a probable COMT from Schizosaccharomyces pombe. It has an extraordinary intracellular distribution different from other homologs and would thus be predicted to perform a distinct physiological function. In this report, recombinant spCOMT was purified and kinetically characterized for the first time. The enzymology assays indicate that spCOMT is a metal‐dependent enzyme and belongs to class I OMTs. In addition, the crystal structures of apo‐spCOMT and SAM‐complexed spCOMT were also presented, revealing that spCOMT possesses a conserved SAM‐binding site and Mg2+ pocket, but a distinct substrate pocket was not present in homologs. The mutagenesis ITC analysis revealed the SAM recognition characteristics of spCOMT. Based on all of the above findings, we speculated about the putative substrates’ characteristics and the substrate recognition mechanisms of spCOMT. This work will help in elucidating the physiological functions of spCOMT in S. pombe. © 2018 IUBMB Life, 71(3):330–339, 2019
Comparison of task interspersal ratios on efficiency of learning and problem behavior for children with autism spectrum disorder
Authors: Knutson Sophie C. , Kodak Tiffany , Costello Dayna R. , Cliett Terra
Published: November 2018

The current study extends the literature on task interspersal (TI) by comparing the effects of four different TI ratios on the efficiency of skill acquisition and on levels of problem behavior in children with autism spectrum disorder and related disorders. The four ratios of TI were 3:1, 1:1, 1:3, and 0:1 mastered‐to‐acquisition tasks. An adapted alternating treatments design was implemented to compare the cumulative number of stimuli mastered, mean training time to mastery, rate of acquisition, and the level of problem behavior. The results showed that the 0:1 condition was the most efficient intervention procedure for all four participants. In addition, TI did not lead to a greater reduction in levels of problem behavior.
Muscle oxygenation dynamics in response to electrical stimulation as measured with near‐infrared spectroscopy: A pilot study
Authors: Huang Yi‐Hua , Chuang Ming‐Lung , Wang Pay‐Zen , Chen Yueh‐Chi , Chen Chung‐Ming , Sun Chia‐Wei
Published: November 2018

Neuromuscular electrical stimulation (NMES) is used for preventing muscle atrophy and improving muscle strength in patients and healthy people. However, the current intensity of NMES is usually set at a level that causes the stimulated muscles to contract. This typically causes pain. Quantifying the instantaneous changes in muscle microcirculation and metabolism during NMES before muscle contraction occurs is crucial, because it enables the current intensity to be optimally tuned, thereby reducing the NMES‐induced muscle pain and fatigue. We applied near‐infrared spectroscopy (NIRS) to measure instantaneous tissue oxygenation and deoxygenation changes in 43 healthy young adults during NMES at 10, 15, 20, 25, 30, and 35 mA. Having been stabilized at the NIRS signal baseline, the tissue oxygenation and total hemoglobin concentration increased immediately after stimulation in a dose‐dependent manner (P < 0.05) until stimulation was stopped at the level causing muscle contraction without pain. Tissue deoxygenation appeared relatively unchanged during NMES. We conclude that NIRS can be used to determine the optimal NMES current intensity by monitoring oxygenation changes.
Probing the mechanism of simultaneous bioenergy production and biodegradation process of Congo red in microbial fuel cells
Authors: Gomaa Ola M , Fapetu Segun , Kyazze Godfrey , Keshavarz Tajalli
Published: November 2018

BACKGROUND

Many approaches have been employed to increase the understanding and consequently the performance of microbial fuel cells to obtain simultaneous power production and biodegradation. This study uses recombinant Escherichia coli K‐12 with MtrA, MtrC and MtrCAB inserts previously prepared using synthetic biology to evaluate the involvement of each of these genes in bioenergy production and biodegradation of Congo red using a double chamber microbial fuel cell.

RESULTS

MtrC was the key gene required for energy production corresponding to an average voltage of 360 mV (external resistance 1 kΩ) and power density of 59 mW m‐2, while E. coli with MtrCAB insert showed the highest decolourisation which reached 80% in 36 h under microbial fuel cell conditions. Coulombic efficiency was 1.2% for E. coli with MtrCAB compared with 2.5% and 2.3% for MtrC and MtrA inserts, respectively. Riboflavin seems to be involved in the electron transferring, its concentration was highest for E. coli with MtrA insert despite its poor performance for both bioenergy production and dye degradation.

CONCLUSION

This study suggests that electrons are mutually exclusive between electricity production, dye degradation and other cellular activities. This study helps to improve our understanding of the dual bioenergy/decolourisation process taking place in MFCs in order to maximize the outcome. © 2018 Society of Chemical Industry
Natural selection for killer receptors and their MHC class I ligands: In pursuit of gene pairs that fit well in tandem
Authors: Brown Michael G , Gamache Awndre , Nash William T , Cronk John
Published: November 2018

Our understanding of the genetic basis of host resistance to viral infection and disease has progressed significantly over the last century. Numerous genes coding for modifiers of immune functions have been identified, which impact a variety of critical cellular processes, including signaling via lymphocyte receptors and their ligands, signal transduction, cytokine signaling, production and release of cytotoxic effectors, transcriptional regulation, and proliferation. Genome-wide association studies implicate an important role for both highly polymorphic NK cell receptors and their MHC class I ligands in modifying host resistance. These findings indicate NK cells are critical mediators of viral control with considerable potential to affect morbidity and mortality outcomes. They further suggest that both stimulatory and inhibitory NK receptor polymorphisms alter NK cell sensing of MHC I ligands on viral targets, which influences how NK cells respond to infection. In many cases, however, the underlying causes associated with host outcomes remain elusive. Herein, we discuss several modes of NK cell sensing of MHC I and MHC I-like molecules on viral targets, and the role of genetic diversity in this evolutionarily dynamic process. We further suggest that natural selection for paired NK receptors with opposing function, but shared MHC I ligands may give rise to rare, but highly effective MHC I-dependent modes of NK cell sensing of viral targets.