bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled Massive Encapsulation via Tandem Step Emulsification in Glass
Authors: Ofner Alessandro , Mattich Iacopo , Hagander Michael , Dutto Alessandro , Seybold Hansjörg , Rühs Patrick A. , Studart André R.
Published: December 2018

Controlled encapsulation is important in pharmaceutics, agriculture, food products, and in emerging materials applications. Microfluidics offers a compelling approach to create controlled emulsions and microcapsules for these applications, but upscaling of this technology for the robust encapsulation of chemically diverse active ingredients is not yet demonstrated. Here, it is shown that microfluidic step emulsification can be exploited in upscaled glass devices to robustly produce monodisperse double emulsions and functional microcapsules in tandem at high throughput rates. The effect of geometrical parameters of the devices and the operating flow rates on the morphology, dimensions, and structure of monodisperse double emulsions is investigated and quantified using simple quantitative models. Using such double emulsions as templates, mechanoresponsive microcapsules that can be embedded in a soft matrix to generate damage‐reporting polymer parts that change color in areas subjected to excessive mechanical loads are created. Thanks to the chemical versatility and mechanical robustness of glass, this platform should enable the high‐throughput encapsulation of a wide variety of chemicals while providing the exquisite control achievable through microfluidics.
Design‐to‐Device Approach Affords Panchromatic Co‐Sensitized Solar Cells
Authors: Cooper Christopher B. , Beard Edward J. , Vázquez‐Mayagoitia Álvaro , Stan Liliana , Stenning Gavin B. G. , Nye Daniel W. , Vigil Julian A. , Tomar Tina , Jia Jingwen , Bodedla Govardhana B. , Chen Song , Gallego Lucía , Franco Santiago , Carella Antonio , Thomas K. R. Justin , Xue Song , Zhu Xunjin , Cole Jacqueline M.
Published: December 2018

Data‐driven materials discovery has become increasingly important in identifying materials that exhibit specific, desirable properties from a vast chemical search space. Synergic prediction and experimental validation are needed to accelerate scientific advances related to critical societal applications. A design‐to‐device study that uses high‐throughput screens with algorithmic encodings of structure–property relationships is reported to identify new materials with panchromatic optical absorption, whose photovoltaic device applications are then experimentally verified. The data‐mining methods source 9431 dye candidates, which are auto‐generated from the literature using a custom text‐mining tool. These candidates are sifted via a data‐mining workflow that is tailored to identify optimal combinations of organic dyes that have complementary optical absorption properties such that they can harvest all available sunlight when acting as co‐sensitizers for dye‐sensitized solar cells (DSSCs). Six promising dye combinations are shortlisted for device testing, whereupon one dye combination yields co‐sensitized DSSCs with power conversion efficiencies comparable to those of the high‐performance, organometallic dye, N719. These results demonstrate how data‐driven molecular engineering can accelerate materials discovery for panchromatic photovoltaic or other applications.
Puffing Up Energetic Metal–Organic Frameworks to Large Carbon Networks with Hierarchical Porosity and Atomically Dispersed Metal Sites
Authors: Zhao Ruo , Liang Zibin , Gao Song , Yang Ce , Zhu Bingjun , Zhao Junliang , Qu Chong , Zou Ruqiang , Xu Qiang
Published: December 2018

Large carbon networks featuring hierarchical pores and atomically dispersed metal sites (ADMSs) are ideal materials for energy storage and conversion due to the spatially continuous conductive networks and highly active ADMSs. However, it is a challenge to synthesize such ADMS‐decorated carbon networks. Here, an innovative fusion‐foaming methodology is presented in which energetic metal–organic framework (EMOF) nanoparticles are puffed up to submillimeter‐scaled ADMS‐decorated carbon networks via a one‐step pyrolysis. Their extraordinary catalytic performance towards oxygen reduction reaction verifies the practicability of this synthetic approach. Moreover, this approach can be readily applicable to a wide range of unexplored EMOFs, expanding scopes for future materials design.
Gerichtete Evolution ermöglicht das Design von maßgeschneiderten Proteinen zur nachhaltigen Produktion von Chemikalien und Pharmazeutika
Authors: Bornscheuer Uwe T. , Hauer Bernhard , Jaeger Karl Erich , Schwaneberg Ulrich
Published: December 2018

Die gelenkte oder gerichtete Evolution (“directed evolution”) hat sich zu einem Standardverfahren entwickelt, um natürliche Proteine für eine breite Palette von Anwendungen maßzuschneidern. Es gelang über verschiedene Industriebereiche hinweg, eine hohe Wertschöpfung und einen hohen gesellschaftlichen Nutzen zu erzielen. Beispiele sind die enzymatische Herstellung von Chemikalien und Pharmazeutika sowie Anwendungen in Ernährung, Futtermittel und Waschmittel. Diese nachhaltigen Industrieverfahren sind essenziell für den Übergang von einer Erdöl‐basierten Wirtschaft hin zu einer Bioökonomie, die auf nachwachsenden Rohstoffe beruht. Ein vergleichbarer Durchbruch wurde durch die Technologie des Phagen‐Displays (“phage display”) erzielt, die es durch gerichtete Evolution ermöglicht, hochselektive Antikörper durch physikalische Kopplung des Phänotyps und des zugehörigen Genotyps zu finden, die für eine breite Palette von Anwendungen in Diagnostik und Therapie zur Verfügung stehen.
Scalable Enantioselective Total Synthesis of (−)‐Goniomitine
Authors: Bin Huai‐Yu , Wang Ke , Yang Dan , Yang Xiao‐Hui , Xie Jian‐Hua , Zhou Qi‐Lin
Published: December 2018

A scalable enantioselective total synthesis of (−)‐goniomitine has been developed by using an iridium‐catalyzed asymmetric hydrogenation of an exocyclic enone ester to control the configuration of the molecule. The synthesis begins from commercially available starting materials, and proceeds through an integrated asymmetric ketone hydrogenation, Johnson–Claisen rearrangement, and one‐pot oxidation/deprotection/cyclization process. With this highly efficient and scalable strategy, (−)‐goniomitine was synthesized in eleven steps with 27 % overall yield, and formal enantioselective syntheses of (+)‐1,2‐dehydroaspidospermidine, (+)‐aspidospermidine, and (+)‐vincadifformine were also achieved.
Catalyst‐Controlled 1,2‐ and 1,1‐Arylboration of α‐Alkyl Alkenyl Arenes
Authors: Bergmann Allison M. , Dorn Stanna K. , Smith Kevin B. , Logan Kaitlyn M. , Brown M. Kevin
Published: December 2018

Two methods are reported for the 1,2‐ and 1,1‐arylboration of α‐methyl vinyl arenes. In the case of 1,2‐arylboration, the formation of a quaternary center occurred through a rare cross‐coupling reaction of a tertiary organometallic complex. 1,1‐Arylboration was enabled by catalyst optimization and occurred through a β‐hydride elimination/reinsertion cascade. Enantioselective variants of both processes are presented as well as mechanistic investigations.
Pharmacokinetics and metabolism of pemafibrate, a novel selective peroxisome proliferator‐activated receptor‐alpha modulator, in rats and monkeys
Authors: Ogawa Shin‐ichiro , Tsunenari Yoshihiko , Kawai Hiroyuki , Yamazaki Hiroshi
Published: December 2018

The metabolic profiles and pharmacokinetics of pemafibrate, a novel selective peroxisome proliferator activated receptor‐alpha modulator currently launched as an antidyslipidemic drug, were investigated in vitro using hepatocytes from rats, monkeys and humans and in vivo in rats and monkeys. Hepatocytes from rats, monkeys and humans all biotransformed pemafibrate to its demethylated form (M1). The bioavailabilities of pemafibrate in Sprague–Dawley rats and cynomolgus monkeys were 15% and 87%, respectively, after a single oral administration of pemafibrate (1 mg/kg). In rat plasma, unmetabolized pemafibrate was the major form, accounting for 29% of the area under the curve (AUC) of total radioactivity. In monkey plasma, in contrast, the major circulating metabolites were M2/3 (dearylated/dicarboxylic acid forms, 15%), M4 (N‐dealkylated form, 21%) and M5 (benzylic oxidative form, 9%), but pemafibrate was the notable minor form (3%). These results, in combination with the reported findings in humans, suggest that the metabolite profile of pemafibrate in plasma was different for rats and monkeys, and that monkeys could be a suitable animal model for further pharmacokinetic studies of pemafibrate in humans.
Stochastic search variable selection based on two mixture components and continuous‐scale weighting
Authors: Rinta‐aho Marko J. , Sillanpää Mikko J.
Published: December 2018

Stochastic search variable selection (SSVS) is a Bayesian variable selection method that employs covariate‐specific discrete indicator variables to select which covariates (e.g., molecular markers) are included in or excluded from the model. We present a new variant of SSVS where, instead of discrete indicator variables, we use continuous‐scale weighting variables (which take also values between zero and one) to select covariates into the model. The improved model performance is shown and compared to standard SSVS using simulated and real quantitative trait locus mapping datasets. The decision making to decide phenotype‐genotype associations in our SSVS variant is based on median of posterior distribution or using Bayes factors. We also show here that by using continuous‐scale weighting variables it is possible to improve mixing properties of Markov chain Monte Carlo sampling substantially compared to standard SSVS. Also, the separation of association signals and nonsignals (control of noise level) seems to be more efficient compared to the standard SSVS. Thus, the novel method provides efficient new framework for SSVS analysis that additionally provides whole posterior distribution for pseudo‐indicators which means more information and may help in decision making.
Metabolomics study on promoting blood circulation and ameliorating blood stasis: Investigating the mechanism of Angelica sinensis and its processed products
Authors: Yuan Ziwen , Zhong Lijia , Hua Yongli , Ji Peng , Yao Wanling , Ma Qi , Zhang Xiaosong , Wen Yanqiao , Yang Lihong , Wei Yanming
Published: December 2018

Angelica sinensis (Danggui, DG) parched with alcohol (Jiu Danggui, JDG) and charred DG are the main processed products of DG, which are used to treat blood stasis syndrome (BSS). However, their therapeutic effect and mechanisms are still unclear. Based on an acute rat BSS model, the intervention effects of DG and its processed products (DGPPs) were evaluated by the hemorheology and coagulation function parameters. Meanwhile, plasma and urine metabolites were detected and analyzed by liquid chromatography coupled to quadrupole time‐of‐flight mass spectrometry and multivariate statistical analysis method. The results of hemorheology, coagulation function parameters and metabolomics all showed that the BSS model was successfully established, DGPPs intervention could significantly relieve rats BSS and the therapeutic effect of JDG was best. Moreover, 23 differential metabolites (14 in plasma and nine in urine) were identified that were closely related to the BSS, involving seven potential target metabolic pathways. DGPP intervention showed different degrees of reverse effect on these metabolites. JDG was the most effective owing to extensive regulation effect on differential metabolites. This study provides a reference for understanding the pathological mechanism of BSS and the mechanism of DGPPs, which lays a theoretical foundation for the rational use of DGPPs in clinical practice.
The development of a core syllabus for teaching musculoskeletal anatomy of the vertebral column and limbs to medical students
Authors: Webb Alexandra L. , Green Rodney A. , Woodley Stephanie J.
Published: December 2018

The study of human anatomy is fundamental to medical education globally. Knowledge of musculoskeletal anatomy is essential for safe and effective clinical practice, yet this topic often receives insufficient medical program time and perceptions differ regarding which knowledge is core. Given the lack of syllabuses specific to musculoskeletal anatomy, this article aims to provide a detailed syllabus for the vertebral column and limbs relevant to medical students. A Delphi panel comprising anatomists and clinicians rated 2,260 anatomical structures and concepts as “essential,” “important,” “acceptable,” or “not required,” with evaluations based around the core knowledge deemed acceptable for a competent medical student. Based on the percentage of panelist agreement for an item to be considered “essential,” each item was then classified as core (≥60%), recommended (30%–59%), not recommended (20%–29%), or not core (<20%). Items not classified as core or recommended but rated important by greater than 50% of the panel were highlighted for future consideration. A total of 252/389 musculoskeletal concept items were categorized as core or recommended. The number of core or recommended items for the vertebral column, upper limb, and lower limb were 220/438, 322/663, and 318/770, respectively. Ninety‐six items were recommended for future consideration. The results of this Delphi panel will be published on the International Federation of Associations of Anatomists website for continuing international consideration and deliberation by relevant stakeholders. The aim is to set an internationally recognized syllabus, that covers the minimum musculoskeletal content that is academically and clinically relevant. Clin. Anat. 32:974–1007, 2019. © 2019 Wiley Periodicals, Inc.
Mapping Aldehyde Dehydrogenase 1A1 Activity using an [18F]Substrate‐Based Approach
Authors: Pereira Raul , Gendron Thibault , Sanghera Chandan , Greenwood Hannah E. , Newcombe Joseph , McCormick Patrick N. , Sander Kerstin , Topf Maya , Årstad Erik , Witney Timothy H.
Published: December 2018

Aldehyde dehydrogenases (ALDHs) catalyze the oxidation of aldehydes to carboxylic acids. Elevated ALDH expression in human cancers is linked to metastases and poor overall survival. Despite ALDH being a poor prognostic factor, the non‐invasive assessment of ALDH activity in vivo has not been possible due to a lack of sensitive and translational imaging agents. Presented in this report are the synthesis and biological evaluation of ALDH1A1‐selective chemical probes composed of an aromatic aldehyde derived from N,N‐diethylamino benzaldehyde (DEAB) linked to a fluorinated pyridine ring either via an amide or amine linkage. Of the focused library of compounds evaluated, N‐ethyl‐6‐(fluoro)‐N‐(4‐formylbenzyl)nicotinamide 4 b was found to have excellent affinity and isozyme selectivity for ALDH1A1 in vitro. Following 18F‐fluorination, [18F]4 b was taken up by colorectal tumor cells and trapped through the conversion to its 18F‐labeled carboxylate product under the action of ALDH. In vivo positron emission tomography revealed high uptake of [18F]4 b in the lungs and liver, with radioactivity cleared through the urinary tract. Oxidation of [18F]4 b, however, was observed in vivo, which may limit the tissue penetration of this first‐in‐class radiotracer.
Phosphine Oxidation with Water and Ferrocenium(III) Cation induced by Visible‐Light Irradiation
Authors: Tanabe Yoshiaki , Nakajima Kazunari , Nishibayashi Yoshiaki
Published: December 2018

Invited for the cover of this issue is the group of Yoshiaki Nishibayashi at The University of Tokyo. Read the full text of the article at 10.1002/chem.201805129.
Development of novel method for quantitative determination of carbon chemical reactivity
Authors: Huang Xianai , Ng Ka Wing , Giroux Louis
Published: December 2018

The coke reactivity index (CRI) measurement determined with the ASTM standard is affected by both the chemical and physical properties of the coke. The contribution made by each of these factors to the measurement result cannot be easily distinguished and quantified. A new thermogravimetric analysis (TGA) technique was developed to provide further information about the chemical behaviour of the coke to facilitate an improved interpretation of the CRI measurement. The development of the technique takes into consideration the potential change in reaction rate controlling mechanism in TGA equipment. It makes use of the shrinking core model to identify the reaction rate control regime and to extract reaction rate parameters from experimental measurement. A rigorous data processing procedure was developed to ensure consistent interpretation of the measurement data while repeatability was established through measurement repetition. The sensitivity of common variable factors between different TGA apparatus on measurement results was also examined. It was demonstrated that the measurement results of this new technique are highly repeatable and reproducible.
Long‐range projections from sparse populations of GABAergic neurons in murine subplate
Authors: Boon Jacqueline , Clarke Emma , Kessaris Nicoletta , Goffinet André , Molnár Zoltán , Hoerder‐Suabedissen Anna
Published: December 2018

The murine subplate contains some of the earliest generated populations of neurons in the cerebral cortex, which play an important role in the maturation of cortical inhibition. Here we present multiple lines of evidence, that the subplate itself is only very sparsely populated with GABAergic neurons at postnatal day (P)8. We used three different transgenic mouse lines, each of which labels a subset of GABAergic, ganglionic eminence derived neurons. Dlx5/6‐eGFP labels the most neurons in cortex (on average 11% of NEUN+ cells across all layers at P8) whereas CGE‐derived Lhx6‐Cre::Dlx1‐Venusfl cells are the sparsest (2% of NEUN+ cells across all layers at P8). There is significant variability in the layer distribution of labeled interneurons, with Dlx5/6‐eGFP and Lhx6‐Cre::R26R‐YFP being expressed most abundantly in Layer 5, whereas CGE‐derived Lhx6‐Cre::Dlx1‐Venusfl cells are least abundant in that layer. All three lines label at most 3% of NEUN+ neurons in the subplate, in contrast to L5, in which up to 30% of neurons are GFP+ in Dlx5/6‐eGFP. We assessed all three GABAergic populations for expression of the subplate neuron marker connective tissue growth factor (CTGF). CTGF labels up to two‐thirds of NEUN+ cells in the subplate, but was never found to colocalize with labeled GABAergic neurons in any of the three transgenic strains. Despite the GABAergic neuronal population in the subplate being sparse, long‐distance axonal connection tracing with carbocyanine dyes revealed that some Gad65‐GFP+ subplate cells form long‐range axonal projections to the internal capsule or callosum.
What color do you feel? Color choices are driven by mood
Authors: Jonauskaite Domicele , Althaus Betty , Dael Nele , Dan‐Glauser Elise , Mohr Christine
Published: December 2018

Popular opinion holds that color has specific affective meaning. Brighter, more chromatic, and warm colors were conceptually linked to positive stimuli and darker, less chromatic, and cool colors to negative stimuli. Whether such systematic color associations exist with actually mood felt remains to be tested. We experimentally induced four moods—joy, relaxation, fear, and sadness—in a between‐subject design (N = 96). Subsequently, we asked participants to select a color, from an unrestricted sample, best representing their current mood. Color choices differed between moods on hue, lightness, and chroma. Yellow hues were systematically associated with joy while yellow‐green hues with relaxation. Lighter colors were matched to joy and relaxation (positive moods) than fear and sadness (negative moods). Most chromatic colors were matched to joy, then relaxation, fear, and sadness. We conclude that color choices represent felt mood to some extent, after accounting for a relatively low specificity for color‐mood associations.
Dental iron precipitates in patients with Type 2 diabetes
Authors: Ortiz‐Arrambide Miguel Angel , Juarez‐Ibarra Karla Isabel , Malagón‐Santiago Guadalupe Ismael , Cruz‐Fierro Norma , De La Garza‐Ramos Myriam Angelica
Published: December 2018

Diabetes mellitus (DM) is a frequent worldwide disease. There are currently more than 46 million people who suffer this disease in North America and the Caribbean. The objective of this study was to determine if there is an association between DM and the presence of iron precipitates (Fe2+) in dental structure. The third molar was extracted for reasons that merit extraction from 40 individuals with and without DM to analyze dentin tissue. Horizontal and longitudinal slices of tooth samples were made and later stained with 10% potassium cyanoferrate. The samples were observed by optical microscope to identify basophilic elements. A nonparametric Spearman correlation was performed to find an association between the quantitative (gender, group, and dentinal tissue) and qualitative variables (gender). The Mann–Whitney U test was used to find differences in the means of the nonparametric variables in two different groups in relation to the P value (<0.05). Iron elements were found in the predentin and circumpulpal dentin areas, and the results obtained showed a statistically significant difference between dentin tissue from patients with diabetes and those without. Individuals with Type 2 DM are prone to present iron precipitates in predentin and circumpulpal dentin tissue. Few iron elements were found in dental organs of individuals without DM.
The role of BRCA1‐associated protein 1 in the diagnosis of malignant mesothelioma in effusion and fine‐needle aspiration cytology
Authors: Hatem Layla , McIntire Patrick J , He Bing , Gogineni Swarna , Ho Mai , Mathew Susan , Margolskee Elizabeth M. , Siddiqui Momin T. , Rao Rema A.
Published: December 2018

Background

Malignant mesothelioma (MM) is a diagnostically challenging entity in cytology specimens due to the lack of architectural context and a cytomorphologic overlap between malignant and reactive mesothelial cells (RMCs). A diagnostic marker with excellent specificity is not currently available in clinical practice. The newly appreciated BRCA1‐associated protein 1 (BAP1) antibody may help distinguish MM from RMC based on its immunohistochemical (IHC) staining pattern but its role in cytopathology is controversial.

Methods

Immunohistochemistry with BAP1 antibody was performed on cell blocks from 39 cytology specimens including 13 cases of RMC and 26 cases of effusion and fine‐needle aspiration specimens (FNAC) with tissue‐specimen‐proven MM. Cases were dichotomised into positive and negative cohorts. Positivity was defined as >50% loss of nuclear BAP1 IHC staining.

Results

Of the 26 MM cases, a slight majority (14/26, 54%) showed loss of BAP1 nuclear IHC staining, while all 13 RMC controls showed strong nuclear BAP1 IHC staining. MM was more likely to show loss of BAP1 than RMC (P < .001); and peritoneal MM was more likely to demonstrate loss of BAP1 than pleural MM (P = .04). There was perfect specificity at 1.0 and positive predictive value of 1.0 for loss of nuclear BAP1 IHC staining. However, only modest sensitivity at 0.52 and negative predictive value of 0.50 was seen.

Conclusion

These data confirm that absence of BAP1 nuclear staining identifies malignant mesothelial cells. On the other hand, positive BAP1 nuclear staining can occur in both benign and malignant pleural effusions.
Intensive versus standard multifactorial cardiovascular risk factor control in screen‐detected type 2 diabetes: 5‐year and longer‐term modelled outcomes of the ADDITION‐Leicester study
Authors: Webb David , Dales Jolyon , Zaccardi Francesco , Hill Sian , Moore Corran , Farooqi Azhar , Griffin Simon , Davies Melanie , Khunti Kamlesh
Published: December 2018

Aims

Diabetes treatment algorithms recommend intensive intervention in those with a shorter duration of disease. Screening provides opportunities for earlier multifactorial cardiovascular risk factor control. Using data from the ADDITION‐Leicester study (NCT00318032), we estimated the effects of this approach on modelled risk of diabetes‐related complications in screen‐detected patients.

Methods

A total of 345 (41% South Asian) people with screen‐detected type 2 diabetes were cluster randomised to receive 5 years of (1) intensive multifactorial risk factor intervention or (2) standard treatment according to national guidance. Estimated 10 to 20‐year risk of ischaemic heart disease, stroke, congestive cardiac failure, and death was calculated using UK‐PDS risk equations.

Results

Compared with standard care, mean treatment differences for intensive management at 5 years were −11.7(95%CI: −15.0, −8.4) and −6.6(−8.8, −4.4) mmHg for systolic and diastolic blood pressure, respectively; −0.27 (−0.66, −0.26) % for HbA1c; and −0.46(−0.66; −0.26), −0.34 (−0.51; −0.18), and −0.19 (−0.28; −0.10) mmol/L for total cholesterol, LDL‐cholesterol, and triglycerides, respectively. There was no significant weight gain in the intensive group despite additional medication use. Modelled risks were consistently lower for intensively managed patients. Absolute risk reduction associated with intensive treatment at 10 and 20 years were 3.5% and 6.2% for ischaemic heart disease and 6.3% and 8.8% for stroke. Risk reduction for congestive heart failure plateaued after 15 years at 5.3%. No differences were observed for blindness and all‐cause death.

Conclusion

Intensive multifactorial intervention in a multi‐ethnic population with screen‐detected type 2 diabetes results in sustained improvements in modelled ischaemic heart disease, stroke, and congestive cardiac failure.
Family‐based treatment: Where are we and where should we be going to improve recovery in child and adolescent eating disorders
Authors: Lock James , Le Grange Daniel
Published: December 2018

Objective

Family therapy has long been advocated as an effective intervention for eating disorders. A specific form of family therapy, one that utilizes family resources, has proven especially effective for adolescents with anorexia or bulimia nervosa (AN and BN). First developed in London, a behaviorally focused adaptation, called family‐based treatment (FBT), has been manualized and systematically studied in six randomized clinical trials for adolescent AN and two for adolescent BN.

Method

This Commentary focuses on manualized FBT; what we know, what we do not know (yet), and what we hope for.

Results

We do know that efficacy data for FBT, especially adolescent AN, are quite robust, even though remission rates remain elusive for more than half of all cases. While preliminary, moderators of FBT for adolescent AN have been identified and could aid us in determining the most (or least) responsive patient groups. And weight gain (∼2.5kg) by week four has been confirmed as an early predictor of remission at end‐of‐treatment. What we do not know, yet, is whether specific adaptations to manualized FBT will confer improved remission rates.

Discussion

Finally, and in terms of what is hoped for, we highlight the promise of improved access, dissemination, and implementation of FBT.
An expanded molecular phylogeny of Plumbaginaceae, with emphasis on Limonium (sea lavenders): Taxonomic implications and biogeographic considerations
Authors: Koutroumpa Konstantina , Theodoridis Spyros , Warren Ben H. , Jiménez Ares , Celep Ferhat , Doğan Musa , Romeiras Maria M. , Santos‐Guerra Arnoldo , Fernández‐Palacios Jóse María , Caujapé‐Castells Juli , Moura Mónica , Menezes de Sequeira Miguel , Conti Elena
Published: December 2018

Plumbaginaceae is characterized by a history of multiple taxonomic rearrangements and lacks a broad molecular phylogenetic framework. Limonium is the most species‐rich genus of the family with ca. 600 species and cosmopolitan distribution. Its center of diversity is the Mediterranean region, where ca. 70% of all Limonium species are endemic. In this study, we sample 201 Limonium species covering all described infrageneric entities and spanning its wide geographic range, along with 64 species of other Plumbaginaceae genera, representing 23 out of 29 genera of the family. Additionally, 20 species of the sister family Polygonaceae were used as outgroup. Sequences of three chloroplast (trnL‐F, matK, and rbcL) and one nuclear (ITS) loci were used to infer the molecular phylogeny employing maximum likelihood and Bayesian analyses. According to our results, within Plumbaginoideae, Plumbago forms a non‐monophyletic assemblage, with Plumbago europaea sister to Plumbagella, while the other Plumbago species form a clade sister to Dyerophytum. Within Limonioideae, Ikonnikovia is nested in Goniolimon, rejecting its former segregation as genus distinct from Goniolimon. Limonium is divided into two major clades: Limonium subg. Pteroclados s.l., including L. sect. Pteroclados and L. anthericoides, and L. subg. Limonium. The latter is divided into three well‐supported subclades: the monospecific L. sect. Limoniodendron sister to a clade comprising a mostly non‐Mediterranean subclade and a Mediterranean subclade. Our results set the foundation for taxonomic proposals on sections and subsections of Limonium, namely: (a) the newly described L. sect. Tenuiramosum, created to assign L. anthericoides at the sectional rank; (b) the more restricted circumscriptions of L. sect. Limonium (= L. sect. Limonium subsect. Genuinae) and L. sect. Sarcophyllum (for the Sudano‐Zambezian/Saharo‐Arabian clade); (c) the more expanded circumscription of L. sect. Nephrophyllum (including species of the L. bellidifolium complex); and (d) the new combinations for L. sect. Pruinosum and L. sect. Pteroclados subsect. Odontolepideae and subsect. Nobiles.
Factors of local recurrence and organ preservation with transoral laser microsurgery in laryngeal carcinomas; CHAID decision‐tree analysis
Authors: Vilaseca Isabel , Nogués‐Sabaté Anna , Avilés‐Jurado Francesc Xavier , Berenguer Joan , Grau Juan José , Verger Eugenia , Nadal Alfons , Muxí Africa , Bernal‐Sprekelsen Manuel , Blanch José Luis
Published: December 2018

Background

Indications of transoral laser microsurgery (TLM) are conditioned by the risk of local relapse.

Objective

To evaluate prognostic factors of local relapse and local control with TLM (LC‐TLM).

Methods

Local relapse and LC‐TLM were evaluated in 1119 patients. Logistic regression and CHAID decision tree analysis were performed.

Results

Local relapse correlated to previous radiotherapy failure (8.45, CI 95%: 2.64‐27.03; P < .001), paraglottic involvement (2.42, CI: 1.41‐4.15; P = .001), anterior commissure involvement (2.12, CI: 1.43‐3.14; P < .001), grade of differentiation (1.74, CI: 1.18‐2.57; P = .005), and alcohol consumption (1.4, CI: 0.99‐1.98; P = .057). Local relapse tended to inversely correlate with experience (0.73, CI: 0.51‐1.03; P = .078). The most important factors for local relapse were previous radiotherapy failure and anterior commissure involvement.

LC‐TLM inversely correlated with previous radiotherapy failure (0.09, CI: 0.03‐0.28; P < .001), paraglottic involvement (0.25, CI: 0.14‐0.43; P < .001), anterior commissure involvement (0.49, CI: 0.32‐0.77; P = .007), margins (0.56, CI: 0.30‐1.04; P = .068), and differentiation (0.68, CI: 0.44‐1.05; P = .087). LC‐TLM correlated with experience (1.71, CI: 1.13‐2.55; P = .010). The most important factors for LC‐TLM were previous radiotherapy failure and paraglottic involvement.

Conclusion

Previous radiotherapy failure is the most important factor for local relapse and LC‐TLM. In primary treatments, anterior commissure involvement and paraglottic involvement are the most important factors for local relapse and LC‐TLM, respectively.
Impact of systemic and tumor lipid metabolism on everolimus efficacy in advanced pancreatic neuroendocrine tumors (pNETs)
Authors: Vernieri Claudio , Pusceddu Sara , Fucà Giovanni , Indelicato Pietro , Centonze Giovanni , Castagnoli Lorenzo , Ferrari Elisa , Ajazi Arta , Pupa Serenella , Casola Stefano , Foiani Marco , Mazzaferro Vincenzo , Pruneri Giancarlo , Milione Massimo , de Braud Filippo
Published: December 2018

The mTOR inhibitor everolimus is effective against advanced pancreatic neuroendocrine tumors (pNETs). However, it can cause metabolic adverse events, such as hyperglycemia, hypertriglyceridemia and hypercholesterolemia. In this work we aimed at evaluating the impact of systemic and tumor lipid metabolism on everolimus efficacy. We carried out a monocentric, retrospective study to correlate plasma triglyceride and cholesterol levels with the progression free survival (PFS) of advanced pNET patients treated with everolimus. In formalin fixed, paraffin embedded (FFPE) tumor specimens, we also assessed by mRNA quantification and immunohistochemistry the expression of acetyl‐CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN), two enzymes crucially involved in fatty acid biosynthesis, and we analyzed their impact on PFS. We evaluated 58 consecutive pNET patients who started everolimus between December 2006 and January 2015. Patients with higher plasma triglycerides during the first 3 months of treatment had an increased risk of disease progression (aHR 3.08, 95% CIs 1.15–8.21; p = 0.025). In 23 FFPE tumor specimens amenable for IHC evaluations, we found a positive correlation between ACC1 and FASN at both mRNA (r = 0.87, p = 0.00045) and protein (r = 0.68, p = 0.0004) level. Patients with higher ACC1 protein expression in metastatic lesions had significantly lower PFS when compared to patients with lower ACC1 levels (5.5 vs. 36 months; aHR 4.49, 95% CIs 1.08–18.72; p = 0.039). In conclusion, systemic and tumor lipid metabolism are associated with the PFS of everolimus‐treated patients with advanced pNETs; based on these findings, dietary and pharmacological interventions targeting lipid metabolism could improve everolimus efficacy in this patient population.
The association between markers of tumour cell metabolism, the tumour microenvironment and outcomes in patients with colorectal cancer
Authors: Roseweir Antonia K. , Clark Jennifer , McSorley Stephen T. , vanWyk Hester C. , Quinn Jean A. , Horgan Paul G. , McMillan Donald C. , Park James H. , Edwards Joanne
Published: December 2018

Tumour cell anaerobic metabolism has been reported to be a prognostic factor in colorectal cancer. The present study investigated the association between monocarboxylate transporter (MCT) 1, MCT 2, lactate dehydrogenase (LDH) 1 and LDH 5, the tumour microenvironment, and outcome in patients with colorectal cancer. A cohort of 150 patients with stage I‐III CRC were utilised to assess tumour cell expression of MCT‐1, MCT‐2, LDH‐1 and LDH‐5 by immunohistochemistry. Expression levels were dichotomised and associations with tumour factors, the tumour microenvironment and survival analysed. Nuclear LDH‐5 associates with poor prognosis (HR 1.68 95% CI 0.99–2.84, p = 0.050) and trends toward increased tumour stroma percentage (TSP, p = 0.125). Cytoplasmic MCT‐2 also trends toward increased TSP (p = 0.081). When combined into a single score; nuclear LDH‐5 + TSP significantly associated with decreased survival independent of stage (HR 2.61 95% CI 1.27–5.35, p = 0.009), increased tumour budding (p = 0.002) and decreased stromal T‐lymphocytes (p = 0.014). Similarly, cytoplasmic MCT‐2 + TSP significantly associated with decreased survival (HR 2.32 95% CI 1.31–4.11, p = 0.003), decreased necrosis (p = 0.039), and increased tumour budding (p = 0.004). The present study reports that the combination of TSP and nuclear LDH‐5 was significantly associated with survival, increased tumour budding, and decreased stromal T‐lymphocytes. This supports the hypothesis that increased stromal invasion promotes tumour progression via modulation of tumour metabolism. Moreover, MCT‐2 and LDH‐5 may provide promising therapeutic targets for patients with stromal‐rich CRC.
Effect of sex hormone–binding globulin polymorphisms on the outcome of in vitro fertilization‐embryo transfer for polycystic ovary syndrome patients: A case‐control study
Authors: Liu Yang , Zhao Xi‐Xi , Hu Xiang‐Juan , Yang Feng , Lin Ping , Cui Shi‐Chang , Zhao Wei , Cao Xiao‐Yun , Wang Yong‐Sheng
Published: December 2018

Polycystic ovary syndrome (PCOS), known as a common endocrine disorder among females, plagues many PCOS patients. The current study aimed to explore the correlations of sex hormone–binding globulin (SHBG) polymorphisms with the outcome of in vitro fertilization‐embryo transfer (IVF‐ET) in PCOS patients. PCOS patients who underwent IVF‐ET and patients with non–PCOS‐related infertility were selected in the study. Correlations of SHBG rs6259 and rs727428 with the risk factors in PCOS were analyzed, followed by the evaluation of the effect of SHBG polymorphisms on the outcome of IVF‐ET in PCOS patients. At last, unconditional logistic regression analysis was performed to study the risk factors for IVF‐ET treatment outcome. Compared with SHBG rs6259 GG carriers, the incidence of PCOS was found to be elevated in SHBG rs6259 GA+AA carriers which indicated that the A allele was a risk factor for PCOS. Compared with SHBG rs6259 TT carriers, the number of retrieved oocytes and embryo as well as the fertility rate in SHBG rs6259 GA+AA carriers was found to be decreased, while the abortion rate, incidence of ovarian hyperstimulation syndrome, transplant rejection rate, estradiol, and testosterone in serum, as well as testosterone in follicular fluid were elevated. The luteal hormone, serum testosterone, and progesterone and GA+AA genotype of rs6259 were the risk factors for IVF‐ET treatment outcome. Taken together, the study showed that SHBG rs6259 polymorphisms might be correlated with the risk of PCOS and the outcome of IVF‐ET treatment.
Molecular design of all nitrogen pentazole‐based high energy density compounds with oxygen balance equal to zero
Authors: Wu Xiaowei , Liu Zhichao , Zhu Weihua
Published: December 2018

We designed a new family of pentazole‐based high energy density compounds with oxygen balance equal to zero by introducing −NH2, −NO2, −N3, −CF2NF2, and −C[NO2]3, and the properties including density, heats of formation, detonation performances, and impact sensitivity were investigated using density functional theory. The results show that half of these new energetic molecules exhibit higher densities than RDX (1.82 g/cm3), in which H5 gives the highest density of 2.09 g/cm3. Among all the 54 designed molecules, 22 compounds have higher D and P than RDX and eleven compounds have higher D and P than HMX, indicating that designing the pentazole‐based derivatives with oxygen balance equal to zero is a very effective way to obtain potential energetic compounds with outstanding detonation properties. Taking both the detonation performance and stability into consideration, nine compounds may be recognized as potential candidates of high energy density compounds. It is expected that our results will contribute to the theoretical design of new‐generation energetic explosives.
Beginning an Engineer's Journey: A Narrative Examination of How, When, and Why Students Choose the Engineering Major
Authors: Cruz Joshua , Kellam Nadia
Published: December 2018

Background

While recent engineering education research has focused on the pathways that students take as they transition into engineering programs in higher education, little has explicitly focused on developing an understanding of students as they select and transfer into engineering from other majors.

Purpose

The purpose of this paper is to gain a better understanding of how engineering students enter the engineering field by comparing commonalities across their experiences. Given recent literature that describes student dissatisfaction toward, misinformation about, and attrition in engineering programs, we explore the lived experiences of students entering the engineering field, with a particular focus on students changing their majors to engineering.

Methods

This paper synthesizes the stories of 21 undergraduate engineering students from a southeastern research university, 15 of whom began their undergraduate program in other majors and transferred into engineering. We employ a unique narrative structuralizing scheme based on Campbell's hero's journey and use the metaphor of the beginning of the journey to understand student trajectories that locate students in engineering studies.

Conclusions

With this information, we can better understand student conceptions of the engineering field when they enter; who enters the engineering field and why; how students’ expectations are met or not in engineering programs; and what are the factors that ultimately contribute to first‐year retention in engineering programs. In general, students entering engineering tend to have a limited understanding of what is entailed in an engineering program and benefit from interactions with advisors, teachers, and peers in the field. Such interactions may help students to more clearly decide what aspects of engineering are appropriate for them to pursue and help them to persist as they begin coursework.
Assembly of a miRNA‐modified QCM sensor for miRNA recognition through response patterns
Authors: Li Xue , Ma Ding , Zheng Sheng‐Run , Fan Jun , Wang Tai , Dai Zong , Zou Xiao‐Yong , Teng Shao‐Hua , Zhang Wei‐Guang
Published: December 2018

In this paper, a miRNA‐based quartz crystal microbalance (QCM) biosensor was fabricated and used to the rapid and effective sensing of miRNA. The specific hybridization between probe miRNA and different selected miRNAs (miR‐27a, miR‐27b, and Let‐7a) cause a different interaction mode, thus display different frequency change and response patterns in the QCM sensor, which were used to detect miR‐27a and miR‐27b. The selective sensing of miR‐27a in mixed miRNA solution was also achieved. This miRNA‐based QCM biosensor has the advantages of real‐time, label‐free, and short cycle detection.
Global drought trends under 1.5 and 2 °C warming
Authors: Xu Lei , Chen Nengcheng , Zhang Xiang
Published: December 2018

Global drought extremes are projected to increase under future warming scenarios. However, global drought risk and pattern remain to be revealed below 1.5 and 2 °C warming levels. Here we used multi‐model simulations to estimate global drought trend based on multiple drought indicators. The frequency and duration of meteorological drought may increase much faster than surface soil moisture drought and root zone soil moisture drought under anthropogenic warming, with a probable ~36% (62%) increase in frequency and a ~15% (20%) increase in duration at 1.5 °C (2 °C) level relative to the reference period over the globe. A 5% (14%) increase of drought frequency is expected at 1.5 °C (2 °C) warming in the surface soil moisture, and a 5% (2%) increase of duration is also likely in the 0–10 cm soil layer. Unprecedented increased drought risk is anticipated at 2 °C level, with potential drought hot spots in North America, South America, southern Africa, Australia and Europe. Drought condition under future warming may be much worse in local areas. The drought frequency in the drylands is much less (>34%) than the humid areas, but the duration is much higher (>40%). The 2 °C relative to 1.5 °C warming is expected to bring higher drought risk than the 1.5 °C relative to 1 °C period with regard to the frequency.
Posttraumatic Stress Disorder and Cancer Risk: A Nested Case‐Control Study
Authors: Cohn Elana , Lurie Ido , Yang Yu‐Xiao , Bilker Warren B. , Haynes Kevin , Mamtani Ronac , Shacham‐Shmueli Einat , Margalit Ofer , Boursi Ben
Published: December 2018

Data regarding cancer risk for individuals who were exposed to traumatic and stressful life events are conflicting. We sought to evaluate the association between posttraumatic stress disorder (PTSD) and the risk of the four most common solid tumors: lung, breast, prostate, and colorectal cancers. We conducted four nested case‐control studies using a large UK population‐based database. Cases were defined as individuals with any medical code for the specific malignancy. For every case, we used incidence‐density sampling to match four controls by age, sex, practice site, and both duration and calendar time of follow‐up. Exposure of interest was any diagnosis of PTSD prior to cancer diagnosis. The odds ratios (ORs) and 95% confidence intervals (CIs) for cancer risk associated with PTSD were estimated using multivariable conditional logistic regression and were adjusted for smoking status, obesity, and antidepressant use. The study population included four case groups according to cancer type. There were 19,143 cases with lung cancer (74,473 matched controls), 22,163 cases with colorectal cancer (86,538 matched controls), 31,352 cases with breast cancer (123,285 matched controls), and 27,212 cases with prostate cancer (105,940 matched controls). There was no statistically significant association between PTSD and cancer risk among any of the cancer types: lung, OR = 0.73, 95% CI [0.43, 1.23]; breast, OR = 0.73, 95% CI [0.52, 1.01]; prostate, OR = 1.24, 95% CI [0.87, 1.77]; and colorectal, OR = 1.05, 95% CI [0.68, 1.62]. Our findings indicated that participants in our study with PTSD were not at increased risk of lung, breast, prostate, and colorectal cancers.
A novel method for the determination of field output factors and output correction factors for small static fields for six diodes and a microdiamond detector in megavoltage photon beams
Authors: Casar Božidar , Gershkevitsh Eduard , Mendez Ignasi , Jurković Slaven , Huq M. Saiful
Published: December 2018

Purpose

The goal of this work is to provide a large and consistent set of data for detector‐specific output correction factors, , for small static fields for seven solid‐state detectors and to determine field output factors, , using EBT3 radiochromic films and W1 plastic scintillator as reference detectors on two different linear accelerators and four megavoltage photon beams. Consistent measurement conditions and recommendations given in the International Code of Practice TRS‐483 for small‐field dosimetry were followed throughout the study.

Methods

were determined on two linacs, Elekta Versa HD and Varian TrueBeam, for 6 and 10 MV beams with and without flattening filter and for nine fields ranging from 0.5 × 0.5 cm2 to 10 × 10 cm2. Signal readings obtained with EBT3 radiochromic films and W1 plastic scintillator were fitted by an analytical function. Volume averaging correction factors, determined from two‐dimensional (2D) dose matrices obtained with EBT3 films and fitted to bivariate Gaussian function, were used to correct measured signals. were determined empirically for six diodes, IBA SFD, IBA Razor, PTW 60008 P, PTW 60012 E, PTW 60018 SRS, and SN EDGE, and a PTW 60019 microDiamond detector.

Results

Field output factors and detector‐specific are presented in the form of analytical functions as well as in the form of discrete values. It is found that in general, for a given linac, small‐field output factors need to be determined for every combination of beam energy and filtration (WFF or FFF) and field size as the differences between them can be statistically significant (P < 0.05). For different beam energies, the present data for are found to differ significantly (P < 0.05) from the corresponding data published in TRS‐483 mostly for the smallest fields (<1.5 cm). For the PTW microDiamond detector, statistically significant differences (P < 0.05) between values were found for all investigated beams on an Elekta Versa HD linac for field sizes 0.5 × 0.5 cm2 and 0.8 × 0.8 cm2. Significant differences in between beams of a given energy but with and without flattening filters are found for measurements made in small fields (<1.5 cm) at a given linac. Differences in are also found when measurements are made at different linacs using the same beam energy filtration combination; for the PTW microDiamond detector, these differences were found to be around 6% and were considered as significant.

Conclusions

Selection of two reference detectors, EBT3 films and W1 plastic scintillator, and use of an analytical function, is a novel approach for the determination of for small static fields in megavoltage photon beams. Large set of data for seven solid‐state detectors and four beam energies determined on two linacs by a single group of researchers can be considered a valuable supplement to the literature and the TRS‐483 dataset.