bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyvinyl alcohol modified polyvinylidene fluoride‐graphene oxide scaffold promotes osteogenic differentiation potential of human induced pluripotent stem cells
Authors: Azadian Esmaeel , Arjmand Bahar , Ardeshirylajimi Abdolreza , Hosseinzadeh Simzar , Omidi Meisam , Khojasteh Arash
Published: December 2019

Tissue engineering is fast becoming a key approach in bone medicine studies. Designing the ideally desirable combination of stem cells and scaffolds are at the hurt of efforts for producing implantable bone substitutes. Clinical application of stem cells could be associated with serious limitations, and engineering scaffolds that are able to imitate the important features of extracellular matrix is a major area of challenges within the field. In this study, electrospun scaffolds of polyvinylidene fluoride (PVDF), PVDF‐graphene oxide (GO), PVDF‐polyvinyl alcohol (PVA) and PVDF‐PVA‐GO were fabricated to study the osteogenic differentiation potential of human induced pluripotent stem cells (iPSCs) while cultured on fabricated scaffolds. Scanning electron microscopy study, viability assay, relative gene expression analysis, immunocytochemistry, alkaline phosphates activity, and calcium content assays confirmed that the osteogenesis rate of hiPSCs cultured on PVDF‐PVA‐Go is significantly higher than other scaffolds. Here, we showed that the biocompatible, nontoxic, flexible, piezoelectric, highly porous and interconnected three‐dimensional structure of electrospun PVDF‐PVA‐Go scaffold in combination with hiPSCs (as the stem cells with significant advantageous in comparison to other types) makes them a highly promising scaffold‐stem cell system for bone remodeling medicine. There was no evidence for the superiority of PVDF‐GO or PVDF‐PVA scaffold for osteogenesis, compared to each other; however both of them showed better potentials as to PVDF scaffold.
FFParam: Standalone package for CHARMM additive and Drude polarizable force field parametrization of small molecules
Authors: Kumar Anmol , Yoluk Ozge , MacKerell Alexander D.
Published: December 2019

Accurate force‐field (FF) parameters are key to reliable prediction of properties obtained from molecular modeling (MM) and molecular dynamics (MD) simulations. With ever‐widening applicability of MD simulations, robust parameters need to be generated for a wider range of chemical species. The CHARMM General Force Field program (CGenFF, https://cgenff.umaryland.edu/) is a tool for obtaining initial parameters for a given small molecule based on analogy with the available CGenFF parameters. However, improvement of these parameters is often required and performing their optimization remains tedious and time consuming. In addition, tools for optimization of small molecule parameters in the context of the Drude polarizable FF are not yet available. To overcome these issues, the FFParam package has been designed to facilitate the parametrization process. The package includes a graphical user interface (GUI) created using Qt libraries. FFParam supports Gaussian and Psi4 for performing quantum mechanical calculations and CHARMM and OpenMM for MM calculations. A Monte Carlo simulated annealing (MCSA) algorithm has been implemented for automated fitting of partial atomic charge, atomic polarizabilities and Thole scale parameters. The LSFITPAR program is called for automated fitting of bonded parameters. Accordingly, FFParam provides all the features required for generation and analysis of CHARMM and Drude FF parameters for small molecules. FFParam‐GUI includes a text editor, graph plotter, molecular visualization, and text to table converter to meet various requirements of the parametrization process. It is anticipated that FFParam will facilitate wider use of CGenFF as well as promote future use of the Drude polarizable FF.
Stress responses in the chemistry and mRNA abundance of the peripheral blood in the American alligator
Authors: Kohno Satomi , Zhu Jianguo , Guillette Louis J.
Published: December 2019

To monitor physiological and toxicological conditions in an endangered species, noninvasive to minimally invasive sampling methods are needed. We analyzed peripheral blood cells to determine if we could monitor some physiological responses of the American alligator following capture stress. Juvenile American alligators were restrained for 16 h to examine the stress response in plasma and blood cells. Plasma corticosterone concentrations were increased by restraint as were plasma concentrations of aspartate aminotransferase (AST), creatine kinase (CK), uric acid, and glucose; a sexually dimorphic response was seen in AST and CK concentrations. The lapse time of restraint was associated with altered messenger RNA (mRNA) levels of the glucocorticoid receptor (GCR) in red blood cells and JUN proto‐oncogene in both white and red blood cells. A two‐way cluster analysis revealed that two major clusters of factors were associated with the responses seen: (a) mRNA levels of GCR and heat‐shock proteins in both blood cells were associated with plasma corticosterone concentration, whereas (b) androgen receptors and JUN mRNA levels in both blood cells were associated with cloacal temperature and body composition. Blood cells appear to be an excellent source to examine the cellular stress response to steroid hormone signals in mRNA levels. We propose that this approach, using blood cells, could provide essential insights into the molecular responses associated with stress in reptiles as well as many other nontraditional model species, including endangered species.
Domino synthesis of pyrimido and imidazoquinazolinones
Authors: Fathalla Walid , Nofal Eman Y. , El‐Moneim Mohamed Abd
Published: December 2019

A simple method for the synthesis of N‐alkyl‐2‐arylquinazolin‐4‐amines, methyl 4‐((2‐arylquinazolin‐4‐yl)amino) butanoates, 6‐aryl‐2,3‐dihydro‐4H‐pyrimido[1,2‐c]quinazolin‐4‐ones, and 5‐arylimidazo[1,2‐c]quinazolin‐3(2H)‐ones has been described. It involves a simple reaction of N‐(2‐cyanophenyl)‐substitutedbenzimidoyl chlorides with alkylamine, γ‐aminobutyric acid, β‐alanine, l‐alanine, and glycine methyl esters hydrochloride in acetonitrile to afford the desired compounds after a series of instantaneous reactions that include Dimroth rearrangement. The reaction involves reflux for 12 hours, simple addition of reagents to an in situ generated benzimidoyl chloride, and simple workup, to form 21 examples of pure compounds in high yields. The active intermediate N‐(2‐cyanophenyl)‐substitutedbenzimidoyl chlorides were formed by the reaction of N‐(2‐cyanophenyl)‐substitutedbenzamides with thionyl chloride in a one‐pot strategy. The alternative method described for this preparation deals with an exhausting multistep reactions starting from anthranilic acid.
Thiazolidine‐4‐one clubbed pyrazoles hybrids: Potent α‐amylase and α‐glucosidase inhibitors with NLO properties
Authors: Kumar Parvin , Duhan Meenakshi , Sindhu Jayant , Kadyan Kulbir , Saini Sangeeta , Panihar Neeraj
Published: December 2019

Molecular hybrids based on thiazolidin‐4‐one and pyrazolyl pharmacophore (THZP) as new antidiabetic agents were synthesized. Two sets of signals came into view in 1H NMR of THZP8‐THZP14 exhibited the presence of a configurational isomeric mixture of 2E,5Z (38.24%‐41.58%) and 2Z,5Z isomers (58.42%‐61.76%), which was further endorsed by density functional theory (DFT) studies. All the compounds exhibit promising nonlinear optical properties (NLO). Further, the biological potential of THZPs was explored in terms of α‐amylase and α‐glucosidase inhibition. DFT‐based descriptors were calculated to describe the reactivity, and a relationship was developed with biological activities. THZP9 and THZP14 showed remarkable inhibition of α‐amylase and α‐glucosidase with IC50 9.90μM and 4.84μM, respectively, as compared with standard drug acarbose.
Copulatory mechanics in the wolf spider Agalenocosa pirity reveals a hidden diversity of locking systems in Lycosidae (Araneae)
Authors: Poy Dante , Ramírez Martín J. , Michalik Peter , Piacentini Luis N.
Published: December 2019

Genital traits are among the fastest to evolve, and the processes that drive their evolution are intensively studied. Spiders are characterized by complex genitalia, but the functional role of the different structures during genital coupling is largely unknown. Members of one of the largest spider groups, the retrolateral tibial apophysis (RTA) clade, are characterized by a RTA on the male palp, which is thought to play a crucial role during genital coupling. However, the RTA was lost in several families including the species‐rich wolf spiders (Lycosidae) leading to the hypothesis that the genital coupling is achieved by alternative mechanisms. Here, we investigate the genital interactions during copulation in the wolf spider Agalenocosa pirity (Zoicinae) on cryofixed mating pairs using electron, optical and X‐ray microscopy and compare our findings with other lycosids and entelegyne spiders. We found an unprecedented coupling mechanism for lycosid spiders involving the palea and a membranous cuticle folding adjacent to the epigynal plate. Additionally, we show an uncommon coupling between the median apophysis and the contralateral genital opening, and confirmed that the terminal apophysis acts as functional conductor, as previously hypothesized for males of Zoicinae. Phylogenetic mapping of RTA indicated that the basal tibial process found in Agalenocosa is a secondary acquisition rather than a modified RTA.
Reconstructive and prosthodontic outcomes after multiple palatomaxillary reconstructions
Authors: Sharif Kayvon F. , Sims John R. , Yue Lauren E. , Baik Fred M. , Kiplagat Kimberly J. , Buchbinder Daniel , Okay Devin J. , Chai Raymond L. , Urken Mark L.
Published: December 2019

Objective

A subset of patients who undergo major palatomaxillary reconstruction do not initially achieve their intended oncologic and/or reconstructive goals and require additional surgery. We aim to detail the unique management considerations in this patient population.

Methods

We performed a retrospective review of patients who underwent palatomaxillary reconstruction by the senior author (m.l.u.) between 1998 and 2016.

Results

Twenty‐one patients required multiple reconstructions. The median time to second reconstruction was 17 months. The most common reason for a second reconstruction was for recurrent disease (10 of 21), followed by functional/aesthetic reasons (7 of 21) and osteoradionecrosis (4 of 21). Four patients went on to have a third reconstruction, and two underwent a fourth. A total of 27 reconstructions were performed, consisting of 20 soft tissue free flaps, four vascularized bone free flaps, and three locoregional flaps.

Conclusion

This patient cohort represents unique oncologic and reconstructive challenges. With long‐term follow‐up, multiple reconstructions may be required to optimize oncologic and functional/aesthetic outcomes. This is the first series of its kind that details the reasons for, as well as the outcomes of, patients who required multiple reconstructive procedures following initial palatomaxillary reconstruction.

Level of Evidence

2B Laryngoscope, 130:2349–2353, 2020
Successful Treatment of Cosmetic Oral Mucosal Tattoos Using QS 694‐nm Ruby Laser and 755‐nm Alexandrite Picosecond Laser
Authors: Feng Hao , Christman Mitalee P. , Muzumdar Sonal , Geronemus Roy G.
Published: December 2019

Background and Objectives

Q‐switched (QS) and picosecond lasers can effectively and safely remove unwanted tattoo pigments. Cosmetic mucosal tattoos are rare and there are only a handful of cases of successful laser tattoo removal, all with QS 1064‐nm neodymium‐doped yttrium aluminum garnet (Nd:YAG) laser.

Study Design/Materials and Methods

A 19‐year‐old Fitzpatrick skin‐type II female presented for treatment of a 6‐month‐old, black tattoo on the mucosal surface of her lower lip. She underwent six treatment sessions with a QS 694‐nm ruby laser on months 0, 1, 3, 5, 7, and 12.

A 30‐year‐old Fitzpatrick skin‐type IV male presented for treatment of a 10‐year‐old black tattoo on his left buccal mucosa. He underwent one treatment with 755‐nm alexandrite picosecond lasers.

Results

One month after last treatment, both patients demonstrated marked improvement to the treatment area without scarring or dyspigmentation.

Conclusions

Given the excellent results seen in the patients presented here, the authors recommend that lasers should be the first‐line treatment for the removal of unwanted cosmetic mucosal tattoos, which are typically easier to remove than cutaneous tattoos and can be accomplished with various wavelengths in the picosecond and nanosecond domains. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Application of geographical information system (GIS) for the development of climatological air temperature vulnerability maps: An example from Morocco
Authors: Lagrini Khaoula , Ghafiri Abdessamad , Ouali Abdellah , Elrhaz Khalid , Feddoul Rhizlane , Elmoutaki Saida
Published: December 2019

Air temperature conditions affect various aspects of human life through diverse pathways, such as health, agriculture, labour productivity, infrastructure and building constructions, economic production, and so on. To address better efforts at resolving this issue, decision‐making tools need to be developed to identify and prioritize areas where appropriate actions are required. The present paper identifies vulnerable areas in Morocco with a focus on three different aspects: high temperatures, low temperatures and daily temperature amplitude. Maps were created using the National Oceanic and Atmospheric Administration (NOAA)‐developed Climate Forecast System Reanalysis (CFSR) 30 year‐long daily maximum and minimum temperature data set. Several indicators as well as vulnerability indexes were defined and calculated. Maps showing the spatial distribution of these indicators were created. The results show that 78% of Morocco is considered to be non‐vulnerable areas to areas with low vulnerability; and 19% is characterized by moderate vulnerability to the effects of temperature. The remaining areas are characterized by high to extreme vulnerability: the most vulnerable areas are located in the provinces of Figuig, Jerada and Boulemane in the eastern part of the country, as well as in the provinces of Khouribga, Fquih Ben Saleh and Settat in the central part. This implies, for example, that national‐level planners in the agriculture and transport/infrastructure sectors in the central part need to take into account temperature vulnerabilities as they develop sector strategies and plans.
Existence and multiplicity of normalized solutions for a class of Schrödinger‐Poisson equations with general nonlinearities
Authors: Xie Weihong , Chen Haibo , Shi Hongxia
Published: December 2019

In this paper, we study the existence and multiplicity of standing waves with prescribed
‐norm Schrödinger‐Poisson equations with general nonlinearities in
:

where
and
is superlinear and satisfies the monotonicity condition. To this end, we look for critical points of the following functional

constrained on the
‐spheres
, where
. We consider the case where
is unbounded from below on
and establish the existence of critical points of
on
for
sufficiently small and under some mild assumptions on
. In addition, we show that there are infinitely many radial critical points
of
on
when
is odd and present a convergence property of
as
. Our results generalize some recent results in the literature.
Accuracy investigation of equivalent dipole arrays for near‐field estimation in presence of shielding or dielectric structures
Authors: Kwak Kyungjin , Bae Tae‐il , Hong Kichul , Kim Hyungsoo , Kim Jingook
Published: December 2019

The accuracy of equivalent dipole arrays for source modeling of electromagnetic fields is affected by several factors. In the step for extracting equivalent dipole arrays for a given source, there are three factors that can affect accuracy: scanning height, source spacing, and scanning gap. In the evaluation step of reconstructed fields, there are two other factors that can also affect accuracy: evaluation height and additional structures. In this paper, simple guidelines are suggested considering the three factors in extracting equivalent dipole arrays. Also, the effects of the evaluation height on accuracy of reconstructed fields are demonstrated in the presence of shielding or dielectric structures. A feature selective validation process was utilized to evaluate similarities between actual and estimated fields.
Psychometric properties of the transaddiction craving triggers questionnaire in alcohol use disorder
Authors: von Hammerstein Cora , Cornil Aurélien , Rothen Stéphane , Romo Lucia , Khazaal Yasser , Benyamina Amine , Billieux Joël , Luquiens Amandine
Published: December 2019

Objectives

We aimed to develop the transaddiction craving triggers questionnaire (TCTQ), which assesses the propensity of specific situations and contexts to trigger craving and to test its psychometric properties in alcohol use disorder (AUD).

Methods

This study included a sample of 111 AUD outpatients. We performed exploratory factor analysis (EFA) and calculated item–dimension correlations. Internal consistency was measured with Cronbach's alpha coefficient. Construct validity was assessed through Spearman correlations with craving, emotional symptoms, impulsivity, mindfulness, and drinking characteristics.

Results

The EFA suggested a 3‐factor solution: unpleasant affect, pleasant affect, and cues and related thoughts. Cronbach's coefficient alpha ranged from .80 to .95 for the three factors and the total score. Weak positive correlations were identified between the TCTQ and drinking outcomes, and moderate correlation were found between the TCTQ and craving strength, impulsivity, anxiety, depression, and impact of alcohol on quality of life.

Conclusions

The 3‐factor structure is congruent with the well‐established propensity of emotions and cues to trigger craving. Construct validity is supported by close relations between the TCTQ and psychological well‐being rather than between the TCTQ and drinking behaviors. Longitudinal validation is warranted to assess sensitivity to change of the TCTQ and to explore its psychometric properties in other addictive disorders.
Undrained lower bound solutions for end bearing capacity of shallow circular piles in non‐homogeneous and anisotropic clays
Authors: Ukritchon Boonchai , Keawsawasvong Suraparb
Published: December 2019

The undrained bearing capacity of shallow circular piles in non‐homogeneous and anisotropic clay is investigated by the lower bound (LB) finite element limit analysis (FELA) under two‐dimensional (2D) axisymmetric condition using second‐order cone programming, and the new solution of the problem is presented. Modified from the isotropic von Mises yield criterion, a cross‐anisotropic undrained strength criterion of clays under the axisymmetric state of stress requiring three input shear strengths in triaxial compression, direct simple shear, and triaxial extension is employed in the 2D axisymmetric LB FELA. Parametric studies on the effects of pile embedment ratio, dimensionless strength gradient, anisotropic strength ratio, and pile roughness are investigated extensively, while the predicted failure mechanisms associated with these parameters are discussed and compared. Numerical results of undrained end bearing capacity of shallow circular piles are summarized in the form of design tables that are useful for design practice and represent a new contribution to the field of pile capacity considering the combined effects of undrained strength non‐homogeneity and anisotropy.
On a magneto‐poro‐thermoelastic medium under the influence of the Seebeck effect
Authors: Abd‐Elaziz Elsayed M. , Othman Mohamed I.A.
Published: December 2019

In this study, the poro‐thermoelastic problem with the effect of the magnetic field and Seebeck parameter was investigated. Modified Ohm's law that includes effects of the temperature gradient (Seebeck effect) and charge density, as well as generalized Fourier's law with current density, is introduced. We applied normal mode analysis to solve the resulting nondimensional coupled equations and then investigated the effects that nondimensional displacements, temperature distribution, excess pore water pressure, stresses, and induced magnetic field exerted on the poro‐thermoelastic half‐space medium. Numerical analyses are given graphically on the square (2D) and cubic (3D) domains to illustrate the effects of the porosity parameter, magnetic field, and Seebeck parameter on the physical variables.
Biogeochemical evidence for residence, diet, and health of theWoman in the Iron Coffin(Queens, New York City)
Authors: Quinn Rhonda L. , Warnasch Scott C. , Watson Monet , Godfrey Linda , Setera Jacob B. , VanTongeren Jill , Mortlock Richard , Wright James
Published: December 2019

In 2011, the mummified body of a Black adult female was discovered in a mid‐19th‐century Fisk iron coffin buried in Queens, New York City. Archival research points to the identity of the woman as Martha Peterson, a domestic worker who lived in the home of William Raymond, the business partner and neighbour of Almond Fisk, the coffin inventor and manufacturer. Here, we apply biogeochemical methods to provide information about theWoman in the Iron Coffin's (WIC's) residence, diet, and health to complement the biological profile and test the archival‐based interpretation of identity. We conducted stable isotopic (δ13C, δ15N, δ18O,87Sr/86Sr, and206Pb/207Pb) and elemental (As, Sr, and Pb) concentration analyses of a second premolar and one strand of hair to characterize her lifeways during middle childhood and near the time of death. We interpret WIC's geographic location during the time of tooth formation as local to the New York region, compared with established δ18O and87Sr/86Sr isoscapes of the United States and206Pb/207Pb values of regional coal and ore. WIC's δ13C and δ15N values indicate a mixed diet similar to contemporaneous peoples from other Mid‐Atlantic States. Pb concentrations are potentially indicative of acute Pb‐caused health problems in a period of ~1 year during middle childhood. Our biogeochemical results bolster archival‐based interpretations of WIC's identity as a member of the Peterson's, a local free Black family, and provide a glimpse into the life of a Black woman in 19th‐century New York City.
Synthesis and properties of shape memory polymers of LLA, TMC, and ε‐CL terpolymers
Authors: Wen Shaohua , Li Yongfei
Published: December 2019

Biodegradable polylactide (PLA) and its copolymers with shape memory properties have attracted great interests because of their important application prospects in biomedical field. In this study, random poly(L‐lactide‐co‐trimethylene carbonate‐co‐ε‐caprolactone) (LTCL) terpolymers with different molar ratio were synthesized and characterized. Monomer ε‐caprolactone (ε‐CL) was used in this study instead of glycolide in preliminary study of LTG terpolymers to investigate the transition temperature and the shape memory performance. Characterization on crystallization, mechanical properties, shape fixing, and recovery ratios of the terpolymers was conducted to investigate the correlation between crystallization and shape memory performance of LTCL terpolymers. The results are consistent with the formation of crystallized LLA segments, which could act as crosslinks, strengthened the stationary phase within the polymer matrix, and significantly improved the shape memory performance of LTCL terpolymers. For example, LTCL801010 is a crystalline polymer with high shape fixity and shape recovery ratio; its shape recovery temperature is 39°C. LTCL terpolymers with high CL content do not show shape memory performance for the rubbery at room temperature. Based on this study, PLA materials with shape memory property can be designed through the selection of monomers or the adjustment of comonomer ratio. These polymers with recovery temperature close to 37°C are expected to be used in human body such as scaffolds in tissue engineering.
Threat appeals in public service announcements: Effects of message framing and relationship norms
Authors: Wang Fei , Wang Xiang , Wang Zuo‐Jun
Published: December 2019

Threat appeals have been widely utilized in numerous types of public service announcements (PSAs), and previous research has focused on the impact of the inherent messages in these announcements. By examining the research on the effects of framing PSAs in terms of the threat of the message to oneself or others, we proposed a clear conceptualization of “threat‐target framing.” The first two studies addressed the direct effects of threat‐target framing and found that other‐oriented threat appeals can evoke more guilt than can self‐oriented threat appeals. Moreover, self‐oriented threat appeals can evoke more fear and immediately direct recipients' attention to the smoker than can other‐oriented threat appeals. Study 3 reported that a contextual factor—relationship norms—was introduced as a potential moderating factor. Results showed that relationship norms had the potential to moderate the effect of threat‐target framing on recipients' fear response, but not the effect on recipients' guilt and coping response. In sum, the results highlighted the importance of message framing of advertising copies and the placement context. Our findings may be useful in understanding the antecedents of the persuasiveness of PSAs.
Successful Long‐term Anticoagulation with Enoxaparin in a Patient with a Mechanical Heart Valve
Authors: Wang Xin , Mathew Carol , Korapati Sowmya , Bathini Venu G.
Published: December 2019

Thromboembolism related to a mechanical heart valve (MHV) is a major complication after surgical valve replacement. Warfarin remains as guideline‐endorsed thromboprophylaxis in patients with MHVs. Alternative anticoagulation therapy for patients who do not tolerate or who fail warfarin is not adequately covered in the current guidelines. We report a case of successful long‐term anticoagulation with enoxaparin in a patient with a mechanical aortic valve who had a contraindication to warfarin. The patient developed a left thigh hematoma requiring surgical evacuation 1 month after initiation of weight‐based dosing of enoxaparin. His dose was then titrated based on peak anti‐factor Xa levels (goal 0.6–1.0 IU/ml). He remained free of signs and symptoms of thromboembolic events, valve dysfunction, bleeding complications, or major adverse effects from long‐term enoxaparin use for the next 13 years. Our case provides promising evidence of the potential role of enoxaparin in patients with MHVs in whom warfarin thromboprophylaxis is not possible. Meticulous monitoring of anti‐factor Xa levels and dosage adjustments are crucial to treatment success.
Drug Interaction Between Febuxostat and Thiopurine Antimetabolites: A Review of the FDA Adverse Event Reporting System and Medical Literature
Authors: Logan Jill K. , Wickramaratne Senarath Yapa Shalini , Harinstein Lisa , Saluja Bhawana , Muñoz Monica , Sahajwalla Chandrahas , Neuner Rosemarie , Seymour Sally
Published: December 2019

Background

There is a known drug interaction (DI) between xanthine oxidase (XO) inhibitors and the thiopurine immunosuppressants, azathioprine (AZA) and mercaptopurine (6‐MP). Xanthine oxidase inhibition increases concentrations of AZA and 6‐MP active metabolites, possibly resulting in myelosuppression. When allopurinol is used with AZA or 6‐MP, dose reduction of AZA or 6‐MP is recommended. Febuxostat is a newer XO inhibitor approved for the treatment of gout.

Objective

To determine the clinical impact of the febuxostat‐thiopurine DI.

Design and Setting

Case series derived from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and published medical literature.

Patients

Nineteen patients who received concomitant febuxostat and either AZA or 6‐MP.

Measurements

Laboratory and clinical data.

Results

Nineteen cases reporting myelosuppressive events were identified in patients receiving febuxostat with AZA or 6‐MP. Eighteen cases were treated with the combination of AZA and febuxostat. A median of 1.6 months elapsed from initiation of the drug combination until discovery of the event. Sixteen cases required hospitalization; 15 reported administration of blood products. Thirteen cases reported resolution of the event with discontinuation of both drugs, two reported discontinuation of the thiopurine only, and one reported discontinuation of febuxostat only.

Limitations

Thiopurine monotherapy may cause myelosuppression. Complications of immunosuppression that may contribute to the real‐world morbidity and mortality associated with the febuxostat‐thiopurine DI were not examined. Finally, FAERS data are limited by the voluntary nature of reporting.

Conclusion

Current febuxostat labeling contraindicates concomitant administration of febuxostat with either AZA or 6‐MP. This case series demonstrates that the DI can result in clinically significant adverse events and is supportive of current febuxostat labeling.
LCAT protects against Lipoprotein‐X formation in a murine model of drug‐induced intrahepatic cholestasis
Authors: Amar Marcelo J. A. , Freeman Lita A. , Nishida Takafumi , Sampson Maureen L. , Pryor Milton , Vaisman Boris L. , Neufeld Edward B. , Karathanasis Sotirios K. , Remaley Alan T.
Published: December 2019

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare genetic disease characterized by low HDL‐C levels, low plasma cholesterol esterification, and the formation of Lipoprotein‐X (Lp‐X), an abnormal cholesterol‐rich lipoprotein particle. LCAT deficiency causes corneal opacities, normochromic normocytic anemia, and progressive renal disease due to Lp‐X deposition in the glomeruli. Recombinant LCAT is being investigated as a potential therapy for this disorder. Several hepatic disorders, namely primary biliary cirrhosis, primary sclerosing cholangitis, cholestatic liver disease, and chronic alcoholism also develop Lp‐X, which may contribute to the complications of these disorders. We aimed to test the hypothesis that an increase in plasma LCAT could prevent the formation of Lp‐X in other diseases besides FLD. We generated a murine model of intrahepatic cholestasis in LCAT‐deficient (KO), wild type (WT), and LCAT‐transgenic (Tg) mice by gavaging mice with alpha‐naphthylisothiocyanate (ANIT), a drug well known to induce intrahepatic cholestasis. Three days after the treatment, all mice developed hyperbilirubinemia and elevated liver function markers (ALT, AST, Alkaline Phosphatase). The presence of high levels of LCAT in the LCAT‐Tg mice, however, prevented the formation of Lp‐X and other plasma lipid abnormalities in WT and LCAT‐KO mice. In addition, we demonstrated that multiple injections of recombinant human LCAT can prevent significant accumulation of Lp‐X after ANIT treatment in WT mice. In summary, LCAT can protect against the formation of Lp‐X in a murine model of cholestasis and thus recombinant LCAT could be a potential therapy to prevent the formation of Lp‐X in other diseases besides FLD.
A flexible multi‐domain test with adaptive weights and its application to clinical trials
Authors: Zhao Yang , Yu Qifeng , Lake Stephen L.
Published: December 2019

The design of a clinical trial is often complicated by the multi‐systemic nature of the disease; a single endpoint often cannot capture the spectrum of potential therapeutic benefits. Multi‐domain outcomes which take into account patient heterogeneity of disease presentation through measurements of multiple symptom/functional domains are an attractive alternative to a single endpoint. A multi‐domain test with adaptive weights is proposed to synthesize the evidence of treatment efficacy over numerous disease domains. The test is a weighted sum of domain‐specific test statistics with weights selected adaptively via a data‐driven algorithm. The null distribution of the test statistic is constructed empirically through resampling and does not require estimation of the covariance structure of domain‐specific test statistics. Simulations show that the proposed test controls the type I error rate, and has increased power over other methods such as the O'Brien and Wei‐Lachin tests in scenarios reflective of clinical trial settings. Data from a clinical trial in a rare lysosomal storage disorder were used to illustrate the properties of the proposed test. As a strategy of combining marginal test statistics, the proposed test is flexible and readily applicable to a variety of clinical trial scenarios.
Characterization of microstructures and reaction mechanisms of Tröger's base polymers of intrinsic microporosity
Authors: Gies Anthony P. , Hefner Robert E. , Rau Nathan J. , Mukhopadhyay Sukrit , Reyes Jeremy Chris P. , Herceg Eldad
Published: December 2019

Rationale

Tröger's base polymers of intrinsic microporosity (PIMs) are receiving increasing attention for applications such as polymer molecular sieve membranes. Development of novel membrane materials requires microstructure analysis in order to overcome processing and applications challenges. This study aims to address these challenges and overcome some of the solubility/aggregation issues that hinder the analysis of these materials.

Methods

A combination of matrix‐assisted laser desorption/ionization mass spectrometry and collision‐induced dissociation was used to examine the reaction products of unfunctionalized Tröger's base PIMs.

Results

Enhanced data mining, using ultrahigh‐resolution mass spectrometry and statistical analysis, yielded a wealth of information on the molecular mass, chemical connectivity, and end groups of species generated during synthesis. Modifications of interest include N‐methyl, N‐methanimine, N‐formyl, and N‐methylol end‐capping moieties, as well as incomplete backbone methanodiazocine rings with missing bridging methylene linkages. Most importantly, a general fragmentation mechanism, supported by computational modeling, was developed to assist in the rapid identification of main‐chain and end‐group modifications in Tröger's base PIMs.

Conclusions

Unfunctionalized Tröger's base polymers were selected as a model system, to thoroughly study their end‐group modification chemistry. This model system could then be used to gain insights into complex hydroxy‐functional PIM materials.
Systematic identification of compounds in Macleaya microcarpa by high‐performance liquid chromatography/quadrupole time‐of‐flight tandem mass spectrometry combined with mass spectral fragmentation behavior of Macleaya alkaloids
Authors: Lin Li , Li Xiao‐Ying , Liu Sha‐Sha , Qing Zhi‐Xing , Liu Xiu‐Bin , Zeng Jian‐Guo , Liu Zhao‐Ying
Published: December 2019

Rationale

Macleaya microcarpa (Maxim.) Fedde belongs to the genus Macleaya of the Papaveraceae family. Benzylisoquinoline alkaloids (BIAs) are considered the main bioactive constituents of M. microcarpa.

Methods

Using high‐performance liquid chromatography/quadrupole time‐of‐flight tandem mass spectrometry (HPLC/QTOFMS/MS) we identified BIAs in the aerial parts of M. microcarpa in the early flowering stage. Target profiling and identification of BIAs in the extracted samples from the fresh aerial parts of M. microcarpa were exclusively based on a personal, accurate, mass database of known compounds and the mass spectral fragmentation behavior of Macleaya alkaloids.

Results

A total of 97 alkaloids, comprising 7 benzyltetrahydroisoquinolines, 1aporphine, 9 tetraprotoberberines, 3 protoberberines, 2 N‐methyltetrahydroprotoberberines, 4 protopines, 47 dihydrobenzophenanthridines, and 24 benzophenanthridines, were identified from the fresh aerial parts of M. microcarpa, and 77 of these were detected for the first time in M. microcarpa. In addition, some of the screened alkaloids were related to the biosynthetic pathways of sanguinarine and chelerythrine.

Conclusions

The integrated method is sensitive and reliable for screening and identifying trace or ultra‐trace isoquinoline alkaloids and has contributed to a better understanding of BIAs in the fresh aerial parts of M. microcarpa.
In‐Plane Direct‐Write Assembly of Iridescent Colloidal Crystals
Authors: Tan Alvin T. L. , Nagelberg Sara , Chang‐Davidson Elizabeth , Tan Joel , Yang Joel K. W. , Kolle Mathias , Hart A. John
Published: December 2019

Materials made by directed self‐assembly of colloids can exhibit a rich spectrum of optical phenomena, including photonic bandgaps, coherent scattering, collective plasmonic resonance, and wave guiding. The assembly of colloidal particles with spatial selectivity is critical for studying these phenomena and for practical device fabrication. While there are well‐established techniques for patterning colloidal crystals, these often require multiple steps including the fabrication of a physical template for masking, etching, stamping, or directing dewetting. Here, the direct‐writing of colloidal suspensions is presented as a technique for fabrication of iridescent colloidal crystals in arbitrary 2D patterns. Leveraging the principles of convective assembly, the process can be optimized for high writing speeds (≈600 µm s−1) at mild process temperature (30 °C) while maintaining long‐range (cm‐scale) order in the colloidal crystals. The crystals exhibit structural color by grating diffraction, and analysis of diffraction allows particle size, relative grain size, and grain orientation to be deduced. The effect of write trajectory on particle ordering is discussed and insights for developing 3D printing techniques for colloidal crystals via layer‐wise printing and sintering are provided.
Missing Link between Helical Nano‐ and Microfilaments in B4 Phase Bent‐Core Liquid Crystals, and Deciphering which Chiral Center Controls the Filament Handedness
Authors: Shadpour Sasan , Nemati Ahlam , Salamończyk Mirosław , Prévôt Marianne E. , Liu Jiao , Boyd Nicola J. , Wilson Mark R. , Zhu Chenhui , Hegmann Elda , Jákli Antal I. , Hegmann Torsten
Published: December 2019

The range of possible morphologies for bent‐core B4 phase liquid crystals has recently expanded from helical nanofilaments (HNFs) and modulated HNFs to dual modulated HNFs, helical microfilaments, and heliconical‐layered nanocylinders. These new morphologies are observed when one or both aliphatic side chains contain a chiral center. Here, the following questions are addressed: which of these two chiral centers controls the handedness (helicity) and which morphology of the nanofilaments is formed by bent‐core liquid crystals with tris‐biphenyl diester core flanked by two chiral 2‐octyloxy side chains? The combined results reveal that the longer arm of these nonsymmetric bent‐core liquid crystals controls the handedness of the resulting dual modulated HNFs. These derivatives with opposite configuration of the two chiral side chains now feature twice as large dimensions compared to the homochiral derivatives with identical configuration. These results are supported by density functional theory calculations and stochastic dynamic atomistic simulations, which reveal that the relative difference between the para‐ and meta‐sides of the described series of compounds drives the variation in morphology. Finally, X‐ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) data also uncover the new morphology for B4 phases featuring p2/m symmetry within the filaments and less pronounced crystalline character.
Mapping undergraduate chemistry students' epistemic ideas about models and modeling
Authors: Lazenby Katherine , Stricker Avery , Brandriet Alexandra , Rupp Charlie A. , Mauger‐Sonnek Kathryn , Becker Nicole M.
Published: December 2019

Developing and using scientific models is an important scientific practice for science students. Undergraduate chemistry curricula are often centered on established disciplinary models, and assessments typically provide students with opportunities to use these models to predict and explain chemical phenomena. However, traditional curricula generally provide few opportunities for students to consider the epistemic nature of models and the process of modeling. To gain a sense of how introductory chemistry students understand model changeability, model multiplicity, the evaluation of models, and the process of modeling, we use a construct‐mapping approach to characterize the sophistication of students' epistemic knowledge of models and modeling. We present a set of four related construct maps that we developed based on the work of other scholars and empirically validated in an undergraduate introductory chemistry setting. We use the construct maps to identify themes in students' responses to an open‐ended survey instrument, the models in chemistry survey, and discuss the implications for teaching.
Using macro cross‐border trade data to better understand micro‐level country of origin effects
Authors: Kandogan Yener
Published: December 2019

The article adapts an estimation methodology from the border effects literature to reveal consumer ethnocentrism versus cosmopolitanism in each country, and animosity versus nostalgia between country pairs. The measurements rely on actual macro cross‐border trade data rather than individual purchase intentions typically used in the international marketing literature. The results from early 2010s suggest that purchasing intentions against imports found in this literature do not necessarily translate into actual consumption behavior in international trade. It is quite possible that the consumers are unable to assess country of origin of production despite growing ethnocentrism, and base their actual purchases on perceived origin of product brands. Specifically, it is found that most countries are cosmopolitan rather than ethnocentric, particularly developed countries, favoring any foreign product over domestic products. Most countries also have nostalgic purchasing behavior from specific trade partners with historical linkages. Outside the specific traditional animosities between a country pair, a developed country is relatively less open to imports from another developed trade partner, while an emerging country welcomes it more especially from another emerging trade partner.
Why Educators Should Care About Social and Emotional Learning?
Authors: Lubit Roy , Lubit Rina
Published: December 2019

Exploring what is known about social and emotional learning as it applies to the educational landscape.
XAFS spectra from X‐ray fluorescence Kβ line using conventional energy‐discriminating detector
Authors: Okajima Toshihiro , Setoyama Hiroyuki , Brancewicz Marek , Kawamoto Masahide , Sakurai Yoshiharu
Published: December 2019

X‐ray fluorescence spectra of copper (Cu) metal, copper monoxide (CuO), and potassium chromate (K2CrO4) were recorded as a function of incident X‐ray energy near the Cu K‐edge and chromium (Cr) K‐edge, respectively, using a conventional silicon drift detector. The spectra contained components due to elastic, inelastic, and multiple scattering, in addition to the Kα and Kβ lines. Cu and Cr K‐edge X‐ray absorption fine structure (XAFS) spectra of Cu, CuO, and K2CrO4 were obtained by an intensity analysis of the Kα and Kβ lines. The intensity of the Kβ line for the different incident photon energies was obtained by numerically removing the additional scattering components using the MUSCAT program. These spectra exhibited a jump near the K absorption edges, which reproduced the spectral features obtained in transmission mode for both Cu, CuO, and K2CrO4. A chemical shift was also clearly identified in the X‐ray absorption near edges structure using the X‐ray fluorescence Kβ line. In addition, the Cr K‐edge extended XAFS spectrum of K2CrO4 was clearly observed using the Cr Kβ fluorescent line. The XAFS measurements on the Kα and Kβ lines are possible, and they carry equally valuable information.
Off-label use of bevacizumab for wet age-related macular degeneration in Europe
Authors: Bro Tomas , Derebecka Magdalena , Jørstad Øystein Kalsnes , Grzybowski Andrzej
Published: December 2019

Purpose

To analyse current off-label use of bevacizumab for wet age-related macular degeneration (AMD) in Europe.

Methods

The study was conducted as a combined survey and literature review. It included the 22 most populous countries in Europe. In each country, ophthalmologists with particular knowledge about off-label treatment responded to a questionnaire.

Results

Answers were obtained from twenty European countries. The off-label use of bevacizumab for wet AMD greatly differed between nations; the bevacizumab proportion varied from non-existent (0%) to very high (97%). There were also large disparities within single countries (e.g. 0–80%), which were attributable to differences in regional decision-making. Both governmental institutions and national ophthalmological societies expressed highly diverging opinions on the use of off-label treatment. Intravitreal administration of bevacizumab had been a matter of legal dispute in several countries. The question about responsibility for off-label therapy mainly remained unanswered.

Conclusions

There was a highly varying utilization of bevacizumab between European countries. Despite an intention of a consistent approach to medical regulations, Europe has not yet reached a professional or political consensus on the ophthalmic off-label use of bevacizumab.
Ultrastable and High-Performance Silk Energy Harvesting Textiles
Authors: Ye Chao , Dong Shaojun , Ren Jing , Ling Shengjie
Published: December 2019

Energy harvesting textiles (EHTs) have attracted much attention in wearable electronics and the internet-of-things for real-time mechanical energy harvesting associated with human activities. However, to satisfy practical application requirements, especially the demand for long-term use, it is challenging to construct an energy harvesting textile with elegant trade-off between mechanical and triboelectric performance. In this study, an energy harvesting textile was constructed using natural silk inspired hierarchical structural designs combined with rational material screening; this design strategy provides multiscale opportunities to optimize the mechanical and triboelectric performance of the final textile system. The resulting EHTs with traditional advantages of textiles showed good mechanical properties (tensile strength of 237 ± 13 MPa and toughness of 4.5 ± 0.4 MJ m−3 for single yarns), high power output (3.5 mW m−2), and excellent structural stability (99% conductivity maintained after 2.3 million multi-type cyclic deformations without severe change in appearance), exhibiting broad application prospects in integrated intelligent clothing, energy harvesting, and human-interactive interfaces.
Quantitative analysis of cryptocurrencies transaction graph
Authors: Motamed Amir Pasha , Bahrak Behnam
Published: December 2019

Cryptocurrencies as a new way of transferring assets and securing financial transactions have gained popularity in recent years. Transactions in cryptocurrencies are publicly available, hence, statistical studies on different aspects of these currencies are possible. However, previous statistical analysis on cryptocurrencies transactions have been very limited and mostly devoted to Bitcoin, with no comprehensive comparison between these currencies. In this study, we intend to compare the transaction graph of Bitcoin, Ethereum, Litecoin, Dash, and Z-Cash, with respect to the dynamics of their transaction graphs over time, and discuss their properties. In particular, we observed that the growth rate of the nodes and edges of the transaction graphs, and the density of these graphs, are closely related to the price of these currencies. We also found that the transaction graph of these currencies is non-assortative, i.e. addresses do not tend for transact with a particular type of addresses of higher or lower degree, and the degree sequence of their transaction graph follows the power law distribution.