bluuebunny/crossref_metadata_2025 huggingface dataset:
Social threat attentional bias in childhood: Relations to aggression and hostile intent attributions
Authors: Miller Natalie V. , Johnston Charlotte
Published: January 2019

The goal of this study was to examine the ways attentional bias to social threat—measured across multiple attentional processes—is related to both child aggression and a well‐established cognitive correlate of aggression (namely, hostile intent attributions). A community sample of 211 children (51% male; 9–12 years; 55% Caucasian) participated in our cross‐sectional correlational design. Social threat attentional bias was measured through task performance on dot‐probe, attentional shifting, and temporal order judgment tasks; each task measured different attentional processes. Aggression was measured by parent‐ and child‐report. Hostile intent attributions were measured through child responses to vignettes involving peer conflict or rejection. Attentional bias to social threat within early phases of attentional processing (i.e., attentional prioritization; stimuli presented for <200 ms in temporal order judgment task) was significantly and positively related to both aggression and hostile intent attributions. Attentional bias to social threat within attentional orienting (stimuli presented for 500 ms in dot‐probe task) was positively and significantly related to hostile intent attributions. Attentional bias to social threat within attentional shifting (stimuli presented for multiple seconds) was not significantly related to aggression or hostile intent attributions. Higher levels of aggression and of hostile intent attributions were associated with an attentional bias to social threat within early, but not later, phases of attentional processing. These results suggest specificity in identifying dysfunctional attentional processes that may underlie aggression and aggression‐related cognitive biases.
Bias against agonist treatment for incarcerated people continues
Authors: Knopf Alison
Published: January 2019

When CommonWealth Magazine ran an article by Andrew Klein, Ph.D., on Jan. 4, our first question was “Why?” The main reason was to push back against an increasing demand for prisons and jails to offer agonists, Klein said. Despite the plethora of research showing agonists are effective treatment for opioid use disorder (OUD), including for incarcerated patients, Klein, a researcher, deviates from the mainstream of peer‐reviewed literature and seems to side more with the criminal justice system. So we talked to both Klein and a physician in charge of a jail‐based treatment system for this story.
House changes parties, Senate plans oversight of STR/SOR
Authors: Knopf Alison
Published: January 2019

So now that we have a Democratic House of Representatives, has the landscape changed for substance use disorders (SUDs) on Capitol Hill?
The protections of our privacy rights are under threat in Congress
Authors: Stauffer Bill
Published: January 2019

As the executive director of the Pennsylvania Recovery Organizations Alliance, the statewide recovery community organization of Pennsylvania, I am alarmed by ongoing efforts occurring in Congress to erode our substance use disorder patient record privacy rights. There are sweeping changes being considered in Congress that would fundamentally erode our rights.
New generation of harm‐reduction workers: Helton's concerns
Authors: Knopf Alison
Published: January 2019

Tracey Helton has been running peer programs for a decade, and involved with harm‐reduction work for two. Her “real” day job is working for San Francisco, a job that includes benefits and enables her to support her children. But it also allows her to run harm‐reduction services “from my closet,” as she puts it. We called her because we wanted to learn more about how she views the field.
Dearomative [4+2] Cycloaddition of Oxindole‐Embedded ortho‐Quinone Methides with 2,5‐Dialkylfurans
Authors: Shen Yao‐Bin , Li Shuai‐Shuai , Liu Xicheng , Yu Liping , Liu Qing , Xiao Jian
Published: January 2019

2,5‐Dialkylfurans were facilely converted to pharmaceutically significant spiro[chroman‐4,3′‐oxindole] scaffolds via an organocatalytic dearomative [4+2] cycloaddition with oxindole‐embedded ortho‐quinone methides. This method featured mild reaction conditions, simple operation, good yields, and excellent diastereoselectivities.

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Design and control of pressure‐swing distillation for separating ternary systems with three binary minimum azeotropes
Authors: Yang Ao , Shen Weifeng , Wei Shun'an , Dong Lichun , Li Jie , Gerbaud Vincent
Published: January 2019

The separation of ternary nonideal systems with multi‐azeotrope is very important because they are often found in the waste of chemical and pharmaceutical industries, which is much more difficult due to the formation of multi‐azeotrope and distillation boundary. We propose a systematic procedure for design and control of a triple‐column pressure‐swing distillation for separating ternary systems with three binary minimum azeotropes. This procedure involves thermodynamic insights, a two‐step optimization method, and effective control strategy. The separation of tetrahydrofuran (THF)/ethanol/water is used to illustrate the capability of the proposed procedure. It is found that the pressure limits in columns can be determined through the analysis of residue curve maps, distillation boundary, and isovolatility curves. The optimal triple‐column pressure‐swing distillation is generated with the minimum total annual cost (TAC) of $2.181 × 106 in sequence A. The operating conditions are well controlled approaching their desired specifications in an acceptable time when disturbances occur. © 2019 American Institute of Chemical Engineers AIChE J, 65: 1281–1293, 2019
Vestibular dysfunction is a manifestation of 22q11.2 deletion syndrome
Authors: Willaert Annelore , Van Eynde Charlotte , Verhaert Nicolas , Desloovere Christian , Vander Poorten Vincent , Devriendt Koenraad , Swillen Ann , Hens Greet
Published: January 2019

The 22q11.2 deletion syndrome (22q11.2DS) is the second most common cause of developmental delay after Down syndrome. Impaired cognitive development is highly prevalent, but also motor abnormalities such as hypotonia and delays in achieving motor milestones are described. Instability is frequently detected in children, adolescents, and adults and is mostly attributed to their limited motor performance. Until now, vestibular function has not been investigated in these patients, despite the growing evidence that they often have inner ear malformations. The aim of this prospective study was to identify the presence and character of vestibular dysfunction in 22q11.2DS. We investigated 23 subjects with proven 22q11.2DS, older than the age of 12. We performed caloric testing and pendular rotation chair tests with videonystagmography, cervical vestibular‐evoked myogenic potential (c‐VEMP)‐testing, and posturography. Additional otoscopy and audiometry were performed on all subjects. We found a unilateral caloric hypofunction in 55% of patients, a certain absent c‐VEMP response in 15% of ears, an inconclusive c‐VEMP response in 33% of ears, and abnormal posturography in 68% of patients, of whom 42% displayed a typical vestibular pattern. Remarkably, 90% revealed uni‐ or bilateral weak caloric responses, independent of caloric symmetry. Vestibular dysfunction is frequent in subjects with 22q11.2DS. This knowledge should be taken into account when assessing motor performance in these patients. Additional larger studies are needed to determine whether this dysfunction implicates a therapeutic potential.
Informativeness of dental morphology in ancestry estimation in African Americans
Authors: Gross Jessica M. , Edgar Heather J. H.
Published: January 2019

Objectives

Our objective is to assess the informativeness of dental morphology in estimating biogeographic ancestry in African Americans.

Materials and methods

The data are 62 dental morphological traits scored as nondichotomized and dichotomized in 797 individuals, 992,601 SNPs from 271 individuals, and 645 STRs from 177 individuals. Each dataset consists of Africans, Europeans, and African Americans. For each dataset, we summed Fisher Information (FI), then used STRUCTURE to estimate ancestry.

Results

Total FI was highest for SNPs, followed by STRs, nondichotomized dental traits, and dichotomized dental traits. For both genetic datasets, Africans and Europeans fell into two distinctive clusters with low 90% credible regions for individual ancestry estimates. In African Americans, membership in the African cluster was 76.4% and 80.4% for SNPs and STRs, respectively. For the dental data, all Africans and Europeans had appreciable membership in both clusters and comparatively high 90% credible regions for individual ancestry estimates. Nonetheless, African Americans had consistently higher membership in the same cluster in which Africans had high membership. African American membership in this cluster was significantly higher for the nondichotomized form than for the dichotomized.

Discussion and conclusions

FI potentially provides a useful gauge of the effectiveness of dental and genetic data for ancestry estimation. The comparatively high FI of nondichotomized dental traits suggests data in this form may be better suited for studies of admixture than dichotomized data. Because of high error in individual ancestry estimates, dental morphological data may be unable to distinguish differences in ancestry among individuals within admixed populations.
Levels of training in critical care echocardiography in adults. Recommendations from the College of Intensive Care Medicine Ultrasound Special Interest Group
Authors: Nanjayya Vinodh B. , Orde Sam , Hilton Andrew , Yang Yang , Costello Cartan , Evans John , Nalos Marek , Yastrebov Konstantin
Published: January 2019

Critical care echocardiography (CCE) is commonly performed in many intensive care units across Australia and New Zealand (ANZ). The scope of practice ranges from Basic CCE through to Advanced CCE and includes the use of transthoracic echocardiography and transoesophageal echocardiography. Many training and qualification pathways exist with no standardisation of education goals. This document defines different levels of CCE expertise and recommends minimum training standards for each level of adult CCE in ANZ. Guidelines committee of College of Intensive Care Medicine's Ultrasound Special Interest Group held multiple face to face meetings, organised teleconferences, conducted a survey of the Fellows of the college and reviewed the international CCE training pathways prior to writing these guidelines.
SLC13A3 variants cause acute reversible leukoencephalopathy and α‐ketoglutarate accumulation
Authors: Dewulf Joseph P. , Wiame Elsa , Dorboz Imen , Elmaleh‐Bergès Monique , Imbard Apolline , Dumitriu Dana , Rak Malgorzata , Bourillon Agnès , Helaers Raphaël , Malla Alisha , Renaldo Florence , Boespflug‐Tanguy Odile , Vincent Marie‐Françoise , Benoist Jean‐François , Wevers Ron A. , Schlessinger Avner , Van Schaftingen Emile , Nassogne Marie‐Cécile , Schiff Manuel
Published: January 2019

Objective

SLC13A3 encodes the plasma membrane Na+/dicarboxylate cotransporter 3, which imports inside the cell 4 to 6 carbon dicarboxylates as well as N‐acetylaspartate (NAA). SLC13A3 is mainly expressed in kidney, in astrocytes, and in the choroid plexus. We describe two unrelated patients presenting with acute, reversible (and recurrent in one) neurological deterioration during a febrile illness. Both patients exhibited a reversible leukoencephalopathy and a urinary excretion of α‐ketoglutarate (αKG) that was markedly increased and persisted over time. In one patient, increased concentrations of cerebrospinal fluid NAA and dicarboxylates (including αKG) were observed. Extensive workup was unsuccessful, and a genetic cause was suspected.

Methods

Whole exome sequencing (WES) was performed. Our teams were connected through GeneMatcher.

Results

WES analysis revealed variants in SLC13A3. A homozygous missense mutation (p.Ala254Asp) was found in the first patient. The second patient was heterozygous for another missense mutation (p.Gly548Ser) and an intronic mutation affecting splicing as demonstrated by reverse transcriptase polymerase chain reaction performed in muscle tissue (c.1016 + 3A > G). Mutations and segregation were confirmed by Sanger sequencing. Functional studies performed on HEK293T cells transiently transfected with wild‐type and mutant SLC13A3 indicated that the missense mutations caused a marked reduction in the capacity to transport αKG, succinate, and NAA.

Interpretation

SLC13A3 deficiency causes acute and reversible leukoencephalopathy with marked accumulation of αKG. Urine organic acids (especially αKG and NAA) and SLC13A3 mutations should be screened in patients presenting with unexplained reversible leukoencephalopathy, for which SLC13A3 deficiency is a novel differential diagnosis. ANN NEUROL 2019;85:385–395.
Abundant glutamic acid decarboxylase (GAD)‐reactive B cells in gad‐antibody–associated neurological disorders
Authors: Thaler Franziska S. , Thaller Anna L. , Biljecki Michelle , Schuh Elisabeth , Winklmeier Stephan , Mahler Christoph F. , Gerhards Ramona , Völk Stefanie , Schnorfeil Frauke , Subklewe Marion , Hohlfeld Reinhard , Kümpfel Tania , Meinl Edgar
Published: January 2019

High levels of antibodies against glutamic acid decarboxylase (GAD) are observed in patients with different neurological disorders, but cells producing these autoantibodies are largely unexplored. We detect circulating GAD‐reactive B cells in peripheral blood that readily differentiate into antibody‐producing cells. These cells are highly elevated in most patients with GAD‐antibody–associated disorders (n = 15) compared to controls (n = 19). They mainly produce GAD65 antibodies of the IgG1 and IgG4 subclasses and are as abundant as B cells reactive for common recall antigens. Bone marrow cells represent an additional source of GAD antibodies. The identification of GAD‐antibody–producing cells has implications for the selection of cell‐specific biologics. ANN NEUROL 2019;85:448–454.
A proliferation‐inducing ligand–mediated anti‐inflammatory response of astrocytes in multiple sclerosis
Authors: Baert Laurie , Benkhoucha Mahdia , Popa Natalia , Ahmed Mashal C. , Manfroi Benoit , Boutonnat Jean , Sturm Nathalie , Raguenez Gilda , Tessier Marine , Casez Olivier , Marignier Romain , Ahmadi Mitra , Broisat Alexis , Ghezzi Catherine , Rivat Cyril , Sonrier Corinne , Hahne Michael , Baeten Dominique , Vives Romain R. , Lortat‐Jacob Hugues , Marche Patrice N. , Schneider Pascal , Lassmann Hans P. , Boucraut Jose , Lalive Patrice H. , Huard Bertrand
Published: January 2019

Objective

The two related tumor necrosis factor members a proliferation‐inducing ligand (APRIL) and B‐cell activation factor (BAFF) are currently targeted in autoimmune diseases as B‐cell regulators. In multiple sclerosis (MS), combined APRIL/BAFF blockade led to unexpected exacerbated inflammation in the central nervous system (CNS) of patients. Here, we investigate the role of the APRIL/BAFF axis in the CNS.

Methods

APRIL expression was analyzed in MS lesions by immunohistochemistry. The in vivo role of APRIL was assessed in the murine MS model, experimental autoimmune encephalitis (EAE). Functional in vitro studies were performed with human and mouse astrocytes.

Results

APRIL was expressed in lesions from EAE. In its absence, the disease was worst. Lesions from MS patients also showed APRIL expression upon infiltration of macrophages. Notably, all the APRIL secreted by these macrophages specifically targeted astrocytes. The upregulation of chondroitin sulfate proteoglycan, sometimes bearing chondroitin sulfate of type E sugar moieties, binding APRIL, in reactive astrocytes explained the latter selectivity. Astrocytes responded to APRIL by producing a sufficient amount of IL‐10 to dampen antigen‐specific T‐cell proliferation and pathogenic cytokine secretion. Finally, an intraspinal delivery of recombinant APRIL before disease onset, shortly reduced EAE symptoms. Repeated intravenous injections of recombinant APRIL before and even at disease onset also had an effect.

Interpretation

Our data show that APRIL mediates an anti‐inflammatory response from astrocytes in MS lesions. This protective activity is not shared with BAFF. ANN NEUROL 2019;85:406–420.
A Multicatalytic Approach to the Hydroaminomethylation of α‐Olefins
Authors: Hanna Steven , Holder Jeffrey C. , Hartwig John F.
Published: January 2019

We report an approach to conducting the hydroaminomethylation of diverse α‐olefins with a wide range of alkyl, aryl, and heteroarylamines at relatively low temperatures (70–80 °C) and pressures (1.0–3.4 bar) of synthesis gas. This approach is based on simultaneously using two distinct catalysts that are mutually compatible. The hydroformylation step is catalyzed by a rhodium diphosphine complex, and the reductive amination step, which is conducted as a transfer hydrogenation with aqueous, buffered sodium formate as the reducing agent, is catalyzed by a cyclometallated iridium complex. By adjusting the ratio of CO to H2, we conducted the reaction at one atmosphere of gas with little change in yield. A diverse array of olefins and amines, including hetreroarylamines that do not react under more conventional conditions with a single catalyst, underwent hydroaminomethylation with this new system, and the pharmaceutical ibutilide was prepared in higher yield and under milder conditions than with a single catalyst.
Heterostructures Composed of N‐Doped Carbon Nanotubes Encapsulating Cobalt and β‐Mo2C Nanoparticles as Bifunctional Electrodes for Water Splitting
Authors: Ouyang Ting , Ye Ya‐Qian , Wu Chun‐Yan , Xiao Kang , Liu Zhao‐Qing
Published: January 2019

Herein, we demonstrate the use of heterostructures comprised of Co/β‐Mo2C@N‐CNT hybrids for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in an alkaline electrolyte. The Co can not only create a well‐defined heterointerface with β‐Mo2C but also overcomes the poor OER activity of β‐Mo2C, thus leading to enhanced electrocatalytic activity for HER and OER. DFT calculations further proved that cooperation between the N‐CNTs, Co, and β‐Mo2C results in lower energy barriers of intermediates and thus greatly enhances the HER and OER performance. This study not only provides a simple strategy for the construction of heterostructures with nonprecious metals, but also provides in‐depth insight into the HER and OER mechanism in alkaline solution.
Alfa fiber/polypropylene composites: Influence of fiber extraction method and chemical treatments
Authors: Labidi Khaled , Cao Zhi , Zrida Montassar , Murphy Alan , Hamzaoui Ahmed Hichem , Devine Declan M.
Published: January 2019

Alfa fiber/polypropylene composites were manufactured using twin‐screw extrusion. Fibers were extracted using alkaline and steam explosion methods. Three chemical treatments were also applied to the alkaline‐extracted fibers: stearic acid (SA), and potassium permanganate dissolved in water (KW) and in acetone (KA). Finally, thermal annealing was applied to the composites. The results indicate that composites with steam‐exploded fibers had a significantly higher melt flow index than composites with alkaline‐extracted fibers. Moreover, the incorporation of fibers into the matrix increased the Young's modulus, where the optimum results were obtained utilizing the alkaline‐extracted fibers. Both extraction methods also significantly decreased the water uptake, especially the steam explosion. The three chemical treatments increased the melt flow index and conversely decreased the tensile strength and Young's modulus. In addition, KW treatment decreased the water uptake. Finally, thermal annealing increased the tensile strength and Young's modulus of composites with SA‐treated fibers. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47392.
Preparation and performance of poly(ethylene oxide)‐based composite solid electrolyte for all solid‐state lithium batteries
Authors: Li Xiaolong , Wang Xianyou , Shao Dingsheng , Liu Lei , Yang Li
Published: January 2019

Poly(ethylene oxide)‐based solid electrolyte is attractive for using in all solid‐state lithium batteries. However, the polymer has a certain degree of crystallization, which is adverse to the conduction of lithium ions. In order to overcome this drawback, a flexible composite polymer electrolyte (CPE) containing TiO2 nanoparticles is elaborately designed and synthesized by tape casting method. The effects of different molar ratios of EO: Li and mass fraction of TiO2 on the physical and electrochemical performances are carefully studied. The results show the CPE10 having 10 wt % TiO2 has the lowest degree of crystallinity of 9.04%, the lowest activation energy of 8.63 × 10−5 eV mol−1. Besides, the CPE10 shows a lower polarization and higher decomposition voltage. Thus, prepared all solid‐state battery LiFePO4/CPE10/Li shows a high initial capacity of 160 mAh g−1 at 0.1 C, 134 mAh g−1 at 0.5 C and higher capacity retention of 93.2% after 50 cycles at 0.5 C (1 C = 170 mAh g−1). © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47498.
Study on functional microcapsules containing catalysts for controlling the curing time and temperature of epoxy resin
Authors: Ha Jin Uk , Hwang Ye Jin , Jeoung Sun Kyoung , Lee Pyoung‐Chan , Kim Soo Young , Park Joo Kyung , Kim Jung Teag , Yeom Ji Hyun
Published: January 2019

In this study, functional microcapsules (FMs) were designed for controlling the curing time and temperature of epoxy through modifications to thermally expandable microcapsules. The FMs were prepared with a mixture of liquid hydrocarbons and N,N‐dimethylbenzylamine in the core, and acrylonitrile (AN)—methyl methacrylate copolymer or AN–methacrylate copolymer were used for the shell. Since the FMs were intentionally designed to have thermally vulnerable polymeric shells, the catalyst in the core could be released at the designated temperature. Therefore, FMs do not activate in epoxy at room temperature; rather, the FMs only become functional when the epoxy is cured under a heated atmosphere. Released catalyst at the higher temperature was confirmed by pyrolysis gas chromatography–mass spectrometry and optical microscopy. This study shows that the results will depend on the different compositions of liquid hydrocarbons and catalyst. Particle size of the capsules was changed with different ratio of catalyst and liquid hydrocarbon at the core and type of polymeric shell. Differential scanning calorimetry and rheometer results showed that higher catalyst loading resulted lower in crystalline and shear thickening temperature, respectively. Adhesion strength of epoxy containing FMs was analyzed by lap shear strength in order to detect the void effect due to released gas from the FM. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47499.
Fabrication and evaluation of structural film adhesive using oxazolidinone modified novolac epoxy resin
Authors: Pal Ranajit , Sudhi Suraj , Raghavan Rajeev
Published: January 2019

Epoxy film adhesives are of prime importance for the fabrication of lightweight honeycomb structures for aerospace industries. This work involves the synthesis of oxazolidinone modified epoxy novolac resin (EPN‐OXA) via the reaction of EPN and toluene diisocyanate. EPN‐OXA was characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, gel permeation chromatography, and epoxy equivalent weight. EPN‐OXA was blended with solid epoxy resin, polyethersulfone (PES) toughened liquid epoxy resin, dicyandiamide, and aluminum powder to fabricate a film adhesive curing at 170–180 °C. Effect of additives and curative on the adhesive property was studied to optimize the composition. Effect of PES on the optimized composition was studied in detail. The best composition exhibited lap shear strength of 370 ± 10 kgf cm−2 at 25 °C and the strength was retained to 75% at −196 °C and 52% at 120 °C. PES significantly enhanced the interfacial strength at different temperatures (~1.6‐fold at −196 and 25 °C and ~1.8‐fold at 120 °C). It also improved tensile strength and fracture toughness by 1.4‐ and 2‐fold, respectively. The toughening effect of PES was further confirmed by scanning electron microscopy images. PES marginally reduced the glass‐transition temperature and it exhibited no effect on thermal stability. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47520.
Building an Artificial Stem Cell Niche: Prerequisites for Future 3D‐Formation of Inner Ear Structures—Toward 3D Inner Ear Biotechnology
Authors: de Groot Simon C. , Sliedregt Karen , van Benthem Peter Paul G. , Rivolta Marcelo N. , Huisman Margriet A.
Published: January 2019

In recent years, there has been an increased interest in stem cells for the purpose of regenerative medicine to deliver a wide range of therapies to treat many diseases. However, two‐dimensional cultures of stem cells are of limited use when studying the mechanism of pathogenesis of diseases and the feasibility of a treatment. Therefore, research is focusing on the strengths of stem cells in the three‐dimensional (3D) structures mimicking organs, that is, organoids, or organ‐on‐chip, for modeling human biology and disease. As 3D technology advances, it is necessary to know which signals stem cells need to multiply and differentiate into complex structures. This holds especially true for the complex 3D structure of the inner ear. Recent work suggests that although other factors play a role, the extracellular matrix (ECM), including its topography, is crucial to mimic a stem cell niche in vitro and to drive stem cells toward the formation of the tissue of interest. Technological developments have led to the investigation of biomaterials that closely resemble the native ECM. In the fast forward moving research of organoids and organs‐on‐chip, the inner ear has hardly received attention. This review aims to provide an overview, by describing the general context in which cells, matrix and morphogens cooperate in order to build a tissue, to facilitate research in 3D inner ear technology. Anat Rec, 303:408–426, 2020. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.
Identification of specific UGT1A9‐mediated glucuronidation of licoricidin in human liver microsomes
Authors: Cho Pil Joung , Kim Ju‐Hyun , Lee Hye Suk , Kim Jeong Ah , Lee Sangkyu
Published: January 2019

Licoricidin is a major prenylated isoflavone of Glycyrrhiza uralensis Fisch. (Leguminosae), and its pharmacological effects have been reported frequently. Typically, flavonoids having multiple hydroxyl groups are unambiguous substrates for glucuronyl conjugation by UDP‐glucuronosyltransferases (UGTs). The pharmacological effects of flavonoids are derived from the conjugation of glucuronide to yield the bioactive metabolite. Here, the metabolism of licoricidin in pooled human liver microsomes (HLMs) was investigated using high‐resolution quadrupole‐orbitrap mass spectrometry. One metabolite (M1) was identified in HLMs after incubation with licoricidin in the presence of uridine 5′‐diphosphoglucuronic acid (UDPGA) and NADPH. The structure of M1 was determined as a monoglucuronyl licoricidin, which was selectively produced by UGT1A9. Licoricidin showed a higher metabolic ratio and rapid metabolism with the recombinant human UGT1A9 than mycophenolic acid, a well‐known UGT1A9 substrate. In conclusion, the selective formation of 7‐glucuronyl licoricidin by UGT1A9 in HLMs could serve as a new selective substrate to determine the activity of UGT1A9 in vitro.
Application of data mining approach to identify drug subclasses based on solubility and permeability
Authors: Gatarić Biljana , Parojčić Jelena
Published: January 2019

Solubility and permeability are recognized as key parameters governing drug intestinal absorption and represent the basis for biopharmaceutics drug classification. The Biopharmaceutics Classification System (BCS) is widely accepted and adopted by regulatory agencies. However, currently established low/high permeability and solubility boundaries are the subject of the ongoing scientific discussion. The aim of the present study was to apply data mining analysis on the selected drugs data set in order to develop a human permeability predictive model based on selected molecular descriptors, and to perform data clustering and classification to identify drug subclasses with respect to dose/solubility ratio (D/S) and effective permeability (Peff). The Peff values predicted for 30 model drugs for which experimental human permeability data are not available were in good agreement with the reported fraction of drug absorbed. The results of clustering and classification analysis indicate the predominant influence of Peff over D/S. Two Peff cut‐off values (1 × 10−4 and 2.7 × 10−4 cm/s) have been identified indicating the existence of an intermediate group of drugs with moderate permeability. Advanced computational analysis employed in the present study enabled the recognition of complex relationships and patterns within physicochemical and biopharmaceutical properties associated with drug bioperformance.
To Submit or Not to Submit Annual Director Compensation for Stockholder Vote?
Authors: Barychev Yelena M.
Published: January 2019

Yelena M. Barychev, partner at the Philadelphia‐based law firm Blank Rome LLP, writes and speaks frequently on corporate governance and securities compliance matters. Here, she examines the often‐thorny subject of director compensation and the legal issues involved when the issue is put to stockholders.
Comprehensive mutation profiling and mRNA expression analysis in atypical chronic myeloid leukemia in comparison with chronic myelomonocytic leukemia
Authors: Faisal Muhammad , Stark Helge , Büsche Guntram , Schlue Jerome , Teiken Kristin , Kreipe Hans H. , Lehmann Ulrich , Bartels Stephan
Published: January 2019

Atypical chronic myeloid leukemia (aCML) and chronic myelomonocytic leukemia (CMML) represent two histologically and clinically overlapping myelodysplastic/myeloproliferative neoplasms. Also the mutational landscapes of both entities show congruencies. We analyzed and compared an aCML cohort (n = 26) and a CMML cohort (n = 59) by next‐generation sequencing of 25 genes and by an nCounter approach for differential expression in 107 genes. Significant differences were found with regard to the mutation frequency of TET2, SETBP1, and CSF3R. Blast content of the bone marrow revealed an inverse correlation with the mutation status of SETBP1 in aCML and TET2 in CMML, respectively. By linear discriminant analysis, a mutation‐based machine learning algorithm was generated which placed 19/26 aCML cases (73%) and 54/59 (92%) CMML cases into the correct category. After multiple correction, differential mRNA expression could be detected between both cohorts in a subset of genes (FLT3, CSF3R, and SETBP1 showed the strongest correlation). However, due to high variances in the mRNA expression, the potential utility for the clinic is limited. We conclude that a medium‐sized NGS panel provides a valuable assistance for the correct classification of aCML and CMML.
How Histone Deacetylase Inhibitors Alter the Secondary Metabolites of Botryosphaeria mamane, an Endophytic Fungus Isolated from Bixa orellana
Authors: Triastuti Asih , Vansteelandt Marieke , Barakat Fatima , Trinel Manon , Jargeat Patricia , Fabre Nicolas , Amasifuen Guerra Carlos A. , Mejia Kember , Valentin Alexis , Haddad Mohamed
Published: January 2019

Fungi are talented organisms able to produce several natural products with a wide range of structural and pharmacological activities. The conventional fungal cultivation used in laboratories is too poor to mimic the natural habitats of fungi, and this can partially explain why most of the genes responsible for the production of metabolites are transcriptionally silenced. The use of Histone Deacetylase inhibitors (HDACis) to perturb fungal secondary biosynthetic machinery has proven to be an effective approach for discovering new fungal natural products. The present study relates the effects of suberoylanilide hydroxamic acid (SAHA) and sodium valproate (VS) on the metabolome of Botryosphaeria mamane, an endophytic fungus isolated from Bixa orellana L. UHPLC/HR‐MS analysis, integrated with four metabolomics tools: MS‐DIAL, MS‐FINDER, MetaboAnalyst and GNPS molecular networking, was established. This study highlighted that SAHA and VS changed metabolites in B. mamane, causing upregulation and downregulation of metabolites production. In addition, twelve compounds were detected in the extracts as metabolites structurally correlated to SAHA, indicating its important reactivity in the medium or its metabolism by the fungus. An addition of SAHA induced the production of eight metabolites while VS induced only two metabolites undetected in the control strain. This result illustrates the importance of adding HDACis to a fungal culture in order to induce metabolite production.
Mild Hydrogenation of α‐Pinene Catalyzed by Ru Nanoparticles Loaded on Boron‐doped Amphiphilic Core‐Shell Mesoporous Molecular Sieves
Authors: Yu Fengli , Xie Lihua , Wu Fangzhu , Yuan Bing , Xie Congxia , Yu Shitao , Liu Xien , Wang Lei , Wang Dan
Published: January 2019

Highly dispersed and stable catalysts comprising Ru nanoparticles supported on boron‐doped amphiphilic core‐shell mesoporous molecular sieves (MMS−C@MMS−NH2/B/Ru) with alkyl‐modified hydrophobic silica core and NH2‐functionalized hydrophilic silica shell are successfully prepared for use in hydrogenation of α‐pinene for the first time. Dodecyl‐modified MMS−C12@MMS−NH2/B/Ru exhibits the best catalytic activity under mild hydrogenation conditions. The abundant −NH2 functional groups on the molecular sieve surface and their amphipathy allow the sieves to facilitate attachment of more Ru nanoparticles, and to simplify their dispersion in the water‐organic reaction medium. Moreover, B‐doped molecular sieves may adjust their acidity to meet the needs of α‐pinene hydrogenation. Under mild reaction conditions (25 °C, 1 MPa H2, and 1 h), α‐pinene can be completely converted with 99 % selectivity to cis‐pinane, because every nanocomposite is equivalent to a microreactor. The catalytic activity does not change much over 5 cycles, indicating that Ru nanoparticles are stably loaded on the molecular sieves.
The effect of sodium‐glucose cotransporter 2 inhibitors and glucagon‐like peptide 1 agonists on cardiovascular disease in patients with type 2 diabetes
Authors: Dey Amit K. , Groenendyk Jacob , Mehta Nehal N. , Gourgari Evgenia
Published: January 2019

Patients with type 2 diabetes have a significantly increased risk of cardiovascular disease (CVD) compared to the general population—with CVD accounting for two out of every three deaths in patients with diabetes. In 2008, the FDA suggested that CVD risk should be evaluated for any new antidiabetic therapy, leading to a multitude of large CVD outcome trials to assess CVD risk from these medications. Interestingly, several of these outcome trials with new novel antidiabetic therapies have demonstrated a clear and definite CVD advantage at mid‐term follow up in high‐risk patients with T2DM. In this review, we discuss two relatively new classes of diabetic drugs, sodium‐glucose cotransporter 2 inhibitors and glucagon‐like peptide 1 agonists, and their efficacy in improving cardiovascular outcomes.
Automatic navigation system for the mouse brain
Authors: Tappan Susan J. , Eastwood Brian S. , O'Connor Nathan , Wang Quanxin , Ng Lydia , Feng David , Hooks Bryan M. , Gerfen Charles R. , Hof Patrick R. , Schmitz Christoph , Glaser Jack R.
Published: January 2019

Identification and delineation of brain regions in histologic mouse brain sections is especially pivotal for many neurogenomics, transcriptomics, proteomics, and connectomics studies, yet this process is prone to observer error and bias. Here we present a novel brain navigation system, named NeuroInfo, whose general principle is similar to that of a global positioning system (GPS) in a car. NeuroInfo automatically navigates an investigator through the complex microscopic anatomy of histologic sections of mouse brains (thereafter: “experimental mouse brain sections”). This is achieved by automatically registering a digital image of an experimental mouse brain section with a three‐dimensional (3D) digital mouse brain atlas that is essentially based on the third version of the Allen Mouse Brain Common Coordinate Framework (CCF v3), retrieving graphical region delineations and annotations from the 3D digital mouse brain atlas, and superimposing this information onto the digital image of the experimental mouse brain section on a computer screen. By doing so, NeuroInfo helps in solving the long‐standing problem faced by researchers investigating experimental mouse brain sections under a light microscope—that of correctly identifying the distinct brain regions contained within the experimental mouse brain sections. Specifically, NeuroInfo provides an intuitive, readily‐available computer microscopy tool to enhance researchers' ability to correctly identify specific brain regions in experimental mouse brain sections. Extensive validation studies of NeuroInfo demonstrated that this novel technology performs remarkably well in accurately delineating regions that are large and/or located in the dorsal parts of mouse brains, independent on whether the sections were imaged with fluorescence or bright‐field microscopy. This novel navigation system provides a highly efficient way for registering a digital image of an experimental mouse brain section with the 3D digital mouse brain atlas in a minute and accurate delineation of the image in real‐time.
Correlations of Through‐Plane Cell Voltage Losses, Imbalance of Electrolytes, and Energy Storage Efficiency of a Vanadium Redox Flow Battery
Authors: Lim Hyebin , Yi Jung S. , Lee Doohwan
Published: January 2019

Correlations of the through‐plane voltage losses in the vanadium redox flow battery (VRFB), changes in the posolyte (positive electrolyte) and negolyte (negative electrolyte) conditions, energy storage capacity, and coulomb efficiency were investigated under an operando charge–discharge process. Collective and quantitative in situ studies with Ag/AgCl reference‐electrodes inserted into a VRFB single‐cell and the state of charge measuring external open‐circuit voltage half‐cells revealed that the overall performance of a VRFB is predominantly governed by (i) relatively high internal resistance of the anode half‐cell and (ii) conditions of the negolyte as the limiting electrolyte. The studies showed that the round‐trip coulomb efficiency, which is commonly used for VRFB performance analysis, has limitations in expressing the energy storage efficiency and capacity decay phenomena under a consecutive charge–discharge process. In situ and concurrent analysis of the internal cell overpotential and the electrolytes condition can provide quantitative information on the relative contributions of the coulombic round‐trip loss, concentration loss, vanadium crossover, and charge imbalance between the posolyte and negolyte for the overall efficiency and capacity decay phenomena. This operando analysis approach is highly effective for gaining an in‐depth and collective understanding of the complex phenomena taking place in the VRFB system.
High‐intensity breastfeeding improves insulin sensitivity during early post‐partum period in obese women with gestational diabetes
Authors: Yasuhi Ichiro , Yamashita Hiroshi , Maeda Kazuhisa , Nomiyama Makoto , Mizunoe Tomoya , Tada Katsuhiko , Yorozu Moe , Ogawa Masanobu , Kodama Takashi , Yamaguchi Ken , Okura Naofumi , Kawakami Kosuke , Maekawa Yuka , Hayashi Kimikazu
Published: January 2019

Aim

To investigate whether high‐intensity breastfeeding (HIB) reduces insulin resistance during early post‐partum period in women with gestational diabetes (GDM), independent of post‐partum weight change (PWC).

Materials and methods

In this multicentre prospective study, we included Japanese women with GDM who underwent a 75‐g oral glucose tolerance test (OGTT) during early post‐partum. We measured plasma insulin during OGTT to obtain a homeostasis model of assessment of insulin resistance (HOMA‐IR). We defined the condition in which infants were fed by breastfeeding alone or greater than or equal to 80% of the volume as HIB, and other statuses, including partial and nonbreastfeeding, as non‐HIB. We investigated the association between post‐partum HOMA‐IR and the breastfeeding status after adjusting for confounders including PWC.

Results

Among 222 women with GDM who underwent the OGTT at 7.9 ± 2.3 weeks post‐partum with a PWC of −7.8 ± 3.4 kg, although the rate of abnormal glucose tolerance (prediabetes and diabetes) did not differ between the groups (33% vs 32%), the HOMA‐IR in the HIB women (n = 166) was significantly lower than that in the non‐HIB women (n = 56) (1.12 ± 0.85 vs 1.72 ± 1.43, P = 0.0002). The effect of the HIB was independently associated with lower HOMA‐IR after adjusting for confounders including PMC. However, the subgroup analysis according to their pre‐pregnancy obesity states showed that the effect was seen only in the obese subjects (BMI ≥ 25).

Conclusions

In obese Japanese women with GDM, HIB has a significant effect in reducing insulin resistance during early post‐partum, independent of the post‐partum weight loss.
Confident body, confident child: Evaluation of a universal parenting resource promoting healthy body image and eating patterns in early childhood—6‐ and 12‐month outcomes from a randomized controlled trial
Authors: Hart Laura M. , Damiano Stephanie R. , Li‐Wai‐Suen Connie S. N. , Paxton Susan J.
Published: January 2019

Objective

To evaluate Confident Body, Confident Child (CBCC), a universal parenting resource designed to promote positive body image and healthy eating patterns in children aged 2–6 years, at 6‐ and 12‐months follow‐up.

Method

A four‐arm randomized controlled trial with 345 parents was conducted. Group (A) received the CBCC resource pack + workshop, (B) received the CBCC resource pack only, (C) received a nutrition booklet and (D) received no interventions until all questionnaires were completed (i.e., waitlist control). Measures of parenting variables relevant to child body image and eating patterns, and parent‐report of child weight, were administered at baseline, 6‐weeks post‐intervention (results reported previously), and 6‐ and 12‐months follow‐up.

Results

Mixed effects modeling comparing group averages over time revealed that significant group differences on measures of knowledge, parenting intentions and the parental feeding practice of weight restriction were still present at 12‐months follow‐up, though the remaining measures showed no significant differences between groups over time. The two CBCC groups reported more positive and less negative outcomes than the nutrition booklet active control.

Discussion

The CBCC program achieved sustained improvements in some parenting variables at 12‐months, suggesting its value as an effective parenting intervention. Changes to the intervention design, such as the addition of a follow‐up parent workshop, however, would likely increase its efficacy.
Portal hypertension in prolonged anorexia nervosa with laxative abuse: A case report of three patients
Authors: Koga Aiko , Toda Kenta , Tatsushima Keita , Matsuubayashi Sunao , Tamura Naho , Imamura Masatoshi , Kawai Keisuke
Published: January 2019

Objective

There has been no report on portal hypertension related to anorexia nervosa (AN).

Method

We describe three cases of portal hypertension manifesting with collateral circulation represented by gastroesophageal varices in prolonged AN with laxative abuse and self‐vomiting. These women, in their 20s to 50s, were diagnosed as having AN binging and purging type (AN‐BP) that included self‐induced vomiting and abuse of irritating laxatives (more than 100 tablets daily).

Results

Case 1 showed prominent ascites and a gastro‐renal shunt on computed tomography scanning. Case 2 showed gastroesophageal varices on endoscopic examination. Case 3 showed gastroesophageal varices on computed tomography scanning and endoscopic examination. We performed liver biopsies in all patients and found only slight pericellular fibrosis. Our patients showed typical symptoms of portal hypertension, although liver cirrhosis was not present.

Discussion

We speculated that abnormal eating and purging behaviors were involved in the development of portal hypertension. We hypothesized that long‐term laxative abuse, dehydration, and abnormal eating behavior are involved in the development of portal hypertension, considering these were common features in our patients. Portal hypertension and gastroesophageal varices should be considered as one of the potentially existing complications in prolonged AN‐BP with self‐induced vomiting and abuse of irritating laxatives.
Characteristics of outpatients diagnosed with the selective/neophobic presentation of avoidant/restrictive food intake disorder
Authors: Zickgraf Hana F. , Murray Helen B. , Kratz Hilary E. , Franklin Martin E.
Published: January 2019

Objective

Although Avoidant/Restrictive Food Intake Disorder (ARFID) has existed since the publication of DSM‐5 in 2013, research on the descriptive psychopathology of treatment‐seeking patients with formal ARFID diagnoses is sparse, and limited to tertiary eating disorder‐focused treatment settings where most patients present with weight loss/malnutrition. In these settings, the selective/neophobic symptom presentation is rare compared to other primary eating restrictions. We aimed provide initial descriptive psychopathology of ARFID primary selective/neophobic symptom presentation in an outpatient setting, and to explore the prevalence of the core ARFID symptoms and clinical differences among patients meeting criteria based on weight/nutritional symptoms versus psychosocial impairment only.

Method

We reviewed the charts of 22 consecutive outpatients diagnosed with ARFID caused by selective/neophobic eating, and describe symptoms, impairment, illness trajectory, and demographic features. Patients who met ARFID criteria because of weight loss/nutritional problems were compared to those who met for psychosocial impairment only on demographic and clinical characteristics.

Results

Patients were predominantly male (81.8%) and school‐aged (4–11 years). 81.8% had no weight/nutritional symptoms documented by a medical provider. All met criteria for significant psychosocial impairment. There were few differences between patients who did versus did not meet weight loss/nutritional criteria for ARFID; they differed only in age and in the presence of appetite disturbances consistent with another proposed presentation of ARFID.

Discussion

These results provide novel data on the clinical characteristics of individuals who present with a primary presentation of selective/neophobic ARFID, including support for psychosocial impairment as sufficient for fulfilling ARFID criterion A.