bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclopropanation of Fluorinated Sulfur Ylides with 1‐Azadienes: Facile Synthesis of CF3‐Substituted Spiro Scaffolds
Authors: Chen Tao , Zhang Ye , Fu Zhenqian , Huang Wei
Published: November 2019

An efficient strategy for the synthesis of CF3‐substituted spiro scaffolds has been developed via cyclopropanation of fluorinated sulfur ylides with 1‐azadienes under mild conditions. A structurally diverse set of spiro benzofuranylidene cyclopropanes and spiro indenylidene cyclopropanes have been constructed in good to excellent yields with good to excellent diastereoselectivities.
Australian employment services: Help or hindrance in the achievement of mutual obligation?
Authors: O’Halloran David , Farnworth Louise , Thomacos Nikos
Published: November 2019

The concept of mutual obligation underpins Australian employment services. In return for receiving income support, there are three elements of mutual obligation: to actively seek work; to improve one’s competitiveness in the labour market; and to contribute to the community. Failing to undertake mutual obligation activities results in sanctions, usually unemployment benefit suspension or cancellation. In the year 2017/18, one mutual obligation activity, compulsory employment service provider appointments, accounted for more than 93 per cent of sanctions. The study reported here explores unemployed and recently employed workers’ experiences of appointments and their attitudes to the concept of mutual obligation. The findings are that unemployed workers say appointments have little utility for advancing elements of mutual obligation and are psychologically harmful. Non‐attendance may be a form of self‐protection although seeking a medical exemption or dropping out of the system altogether also appears to be a common self‐protection strategy. We also find that non‐attendance at appointments cannot be conflated with a negative attitude to mutual obligation and that unemployed workers want services that are effective and psychologically positive to help them to fulfil their mutual obligations.
A viable care migration programme for Australia's ageing population: Recruiting migrant personal care workers for Australian aged care
Authors: Morrison‐Dayan Rachel
Published: November 2019

Scholars and stakeholders alike have proposed the recruiting of migrant personal care workers as part of a strategy to respond to a prospective aged care deficit in Australia's ageing population. In recent years, there has been an increase in care migration to fulfil shortages among Australia's culturally and linguistically diverse and more remotely based populations. However, it is a difficult and resource‐intensive process to recruit migrant personal care workers under the labour agreement stream of the Temporary Skills Shortage visa. This article addresses the lacuna in existing literature dealing with the question of how Australia's migration framework ought to be structured to recruit migrant personal care workers as part of a strategy to prevent, or respond to, an aged care crisis. The article argues that the formation of an aged care industry labour agreement based on geographical and niche subsector labour market need is necessary to ensure the accessibility of the programme to aged care organisations. However, it is also argued that the introduction of a new low‐skill visa would better facilitate the recruitment of migrant personal care workers.
Treatment practices for aspirin‐exacerbated respiratory disease: analysis of a national insurance claims database
Authors: Roland Lauren T. , Nagy Celeste , Wang Heqiong , Moore Renee , Cahill Katherine N. , Laidlaw Tanya M. , Wise Sarah K. , DelGaudio John M. , Kuruvilla Merin , Levy Joshua M.
Published: November 2019

Background

Aspirin‐exacerbated respiratory disease (AERD) is the triad of asthma, nasal polyposis, and sensitivity to cyclooxygenase‐1 inhibitors. Treatment options include medical management, surgical intervention, and aspirin desensitization (AsaD).

Methods

AERD patients were identified using the MarketScan Database from 2009 to 2015. Patients were included using International Classification of Diseases, 9th edition (ICD‐9) codes for asthma, nasal polyposis, and drug allergy. Treatments were determined by Current Procedural Terminology (CPT) codes for drug desensitization and endonasal procedures. Geographic trends and timing of interventions between those exposed and not exposed to desensitization were explored.

Results

A total of 5628 patients met inclusion criteria for AERD, with mean age 46 years, 60% female; 395 (7%) underwent AsaD and 2171 (39%) underwent sinus surgery. Among patients who were desensitized, 229 (58%) underwent surgery, of whom 201 (88%) had surgery prior to AsaD (median [quartile 1, quartile 3]; 61 days [30, 208] prior to desensitization). For patients undergoing surgery following AsaD (n = 46), surgery was performed a median of 302 (163, 758) days after AsaD. Nineteen patients had multiple surgeries post‐AsaD with median time between surgeries being 734 days (312, 1484); 261 patients were not desensitized to aspirin but did undergo multiple surgeries, with the median of the median time between surgeries being 287 days (15, 617), which is shorter than for patients post‐AsaD (p < 0.001).

Conclusion

A very small percentage of AERD patients undergo AsaD. Patients who had AsaD underwent surgery approximately 2 months prior to AsaD. Patients who underwent AsaD experienced an increased time between surgeries compared to patients who did not undergo AsaD.
Prescription patterns and opioid usage in sinonasal surgery
Authors: Newberry Christopher I. , Casazza Geoffrey C. , Pruitt Liese C. , Meier Jeremy D. , Skarda David E. , Alt Jeremiah A.
Published: November 2019

Background

Excess opioid use after surgery contributes to opiate misuse and diversion. Understanding opioid prescribing and utilization patterns after sinonasal surgery is critical in designing effective practice protocols. In this study we aim to identify factors associated with variable opioid usage and further delineate optimal prescription patterns for sinonasal surgery.

Methods

All patients undergoing sinonasal surgery within a single health‐care system from March 2017 to August 2018 were sent electronic postoperative surveys. Data were collected on the amount of opioid required, pain control, presurgical opiate use, and narcotic disposal. Additional data collected from the electronic medical record included demographics, type of surgery performed, and total amount of opioid prescribed, including refills.

Results

Three‐hundred sixty four patients were included. A mean number of 25.3 tablets were prescribed per patient, yet the mean taken was just 11.8 tablets. Excess opioids were prescribed 84.9% of the time with a mean excess narcotic in oral morphine equivalents of 152.5. Among patients, 11.8% reported using no opioids, whereas 52.1% used <50% and 36.1% used >50% of their narcotic prescription. Patients used 9.3% of their full prescription and only 2.6% required a refill. The amount used was not associated with complexity of endoscopic sinus surgery, type of opiate prescribed, gender, distance living from hospital, or current opioid usage before surgery (p > 0.05). The addition of septoplasty and/or turbinoplasty was associated with variation in opioid usage (p < 0.001). A total of 76.1% of patients incorrectly discarded/stored excess opiates.

Conclusion

Opioids are overprescribed after sinonasal surgery. The amount of postoperative opiate prescribed should be greatly reduced and may be based on the specific procedures performed. Improved patient education regarding disposal of excess narcotics may help to curtail future opioid diversion.
Early treatment of progressive vertebral arteriovenous fistula caused by cervical penetrating injury
Authors: Murakami Mamoru , Maruyama Daisuke , Fujiwara Gaku , Komaru Yujiro , Murakami Nobukuni , Iiduka Ryoji
Published: November 2019

Background

Penetrating injury of the vertebral artery (VA) is uncommon because it lies deep in the neck and is surrounded by a bony foramen. Vertebral–venous fistula is a rare vascular condition in which there is direct aberrant communication among the extracranial vertebral artery, its radicular or muscular branches, and adjacent venous structures.

Case Presentation

We report an asymptomatic patient of fistula from the vertebral artery to the paravertebral veins secondary to a cervical stab wound that increased in size and flow, as observed on the angiogram 10 days later, which was successfully treated by endovascular surgery. The postoperative angiogram showed improved visualization of the bilateral posterior cerebral arteries.

Conclusion

Endovascular embolization at the early phase should be undertaken for traumatic high‐flow vertebral–venous fistula, even if the patient is asymptomatic, to prevent progressive posterior circulation insufficiency due to the rapid growth of the fistula, which can ultimately lead to the steal phenomenon.
Dual Illumination Enhances Transformation of an Engineered Green‐to‐Red Photoconvertible Fluorescent Protein
Authors: Krueger Taylor D. , Tang Longteng , Zhu Liangdong , Breen Isabella L. , Wachter Rebekka M. , Fang Chong
Published: November 2019

The molecular mechanisms for the photoconversion of fluorescent proteins remain elusive owing to the challenges of monitoring chromophore structural dynamics during the light‐induced processes. We implemented time‐resolved electronic and stimulated Raman spectroscopies to reveal two hidden species of an engineered ancestral GFP‐like protein LEA, involving semi‐trapped protonated and trapped deprotonated chromophores en route to photoconversion in pH 7.9 buffer. A new dual‐illumination approach was examined, using 400 and 505 nm light simultaneously to achieve faster conversion and higher color contrast. Substitution of UV irradiation with visible light benefits bioimaging, while the spectral benchmark of a trapped chromophore with characteristic ring twisting and bridge‐H bending motions enables rational design of functional proteins. With the improved H‐bonding network and structural motions, the photoexcited chromophore could increase the photoswitching‐aided photoconversion while reducing trapped species.
Structure Selectivity of Alkaline Periodate Oxidation on Lignocellulose for Facile Isolation of Cellulose Nanocrystals
Authors: Liu Peiwen , Pang Bo , Dechert Sebastian , Zhang Xizhou Cecily , Andreas Loren B , Fischer Steffen , Meyer Franc , Zhang Kai
Published: November 2019

Reported here for the first time is the alkaline periodate oxidation of lignocelluloses for the selective isolation of cellulose nanocrystals (CNCs). With the high concentrations as a potassium salt at pH 10, periodate ions predominantly exist as dimeric orthoperiodate ions (H2I2O104−). With reduced oxidizing activity in alkaline solutions, dimeric orthoperiodate ions preferentially oxidized non‐ordered cellulose regions. The alkaline surroundings promoted the degradation of these oxidized cellulose chains by β‐alkoxy fragmentation and generated CNCs. The obtained CNCs were uniform in size and generally contained carboxy groups. Furthermore, the reaction solution could be reused after regeneration of the periodate with ozone gas. This method allows direct production of CNCs from diverse sources, in particular lignocellulosic raw materials including sawdust (European beech and Scots pine), flax, and kenaf, in addition to microcrystalline cellulose and pulp.
Novel green synthesis of Hibiscus sabdariffa flower extract conjugated gold nanoparticles with excellent anti‐acute myeloid leukemia effect in comparison to daunorubicin in a leukemic rodent model
Authors: Zangeneh Mohammad Mahdi , Zangeneh Akram
Published: November 2019

Nanobiotechnology is a capable technology that deals with nanomaterials in several scientific domains such as medicine, chemistry, nanotechnology, and biotechnology. In this scale, remarkable differences are seen in many properties of materials that are not observed on a larger scale. In this regard, pharmacologists have tried to synthesize many supplements and drugs from the nanoparticles. The present study confirms the ability of aqueous extract of Hibiscus sabdariffa grown under in vitro condition for the biosynthesis of gold nanoparticles (AuNPs). Also, in this study, we revealed the anti‐acute myeloid leukemia activity of AuNPs compared to daunorubicin in a leukemic rodent model. These nanoparticles were characterized by fourier‐transform infrared spectroscopy (FT‐IR) spectroscopy, ultraviolet–visible spectroscopy (UV–Vis.), X‐ray diffraction (XRD), field emission scanning electron microscopy (FE‐SEM), and transmission electron microscopy (TEM) analysis. TEM and FE‐SEM images exhibited a uniform spherical morphology and diameters of 15‐45 nm for the biosynthesized nanoparticles. In vivo design, induction of acute myeloid leukemia was done by 7,12‐Dimethylbenz[a]anthracene (DMBA) in 75 mice. Then, the animals were randomly divided into six subgroups, including HAuCl4, H. sabdariffa, AuNPs, daunorubicin, untreated, and control. AuNPs similar to daunorubicin, significantly (P ≤ .05) reduced the pro‐inflammatory cytokines (IL1, IL6, IL12, IL18, IFNY, and TNFα), and the total white blood cell (WBC), blast, monocyte, neutrophil, eosinophil, and basophil counts and enhanced the anti‐inflammatory cytokines (IL4, IL5, IL10, IL13, and IFNα) and the platelet, lymphocyte, and red blood cell (RBC) parameters as compared to the untreated mice. By quantitative real‐time polymerase chain reaction, sphingosine‐1‐phosphate receptor‐1 and sphingosine‐1‐phosphate receptor‐5 mRNA expression in lymphocytes were significantly (P ≤ .05) raised by treating the leukemic mice with the AuNPs and daunorubicin. In vitro design, 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) test revealed similar antioxidant potentials for daunorubicin and AuNPs. Besides, AuNPs similar to daunorubicin had low cell viability dose‐dependently against Murine C1498, Human HL‐60/vcr, and 32D‐FLT3‐ITD cell lines without any cytotoxicity on HUVEC cell line. In conclusion, the results of chemical characterization confirm that the H. sabdariffa flower can be used to produce gold nanoparticles with a remarkable amount of anti‐acute myeloid leukemia effect.
A combined experimental and modelling investigations on mixed bioligand complexes of divalent cobalt and copper in β‐cyclodextrin
Authors: Abdel‐Mottaleb M.S.A. , Ismail E.H.
Published: November 2019

The biologically active divalent metal complexes [Co(II)(GluArg)(H2O)2] (1) and [Cu(II)(GluArg)] (2) (where Co = cobalt and Cu = copper) of mixed glutamic (Glu) and l‐arginine (Arg) amino acids form a stable 1:1 inclusion complex with β‐cyclodextrin (β‐CD) in water. The preferred orientation of guest molecules into the host is simulated by quantum chemical computations. Geometry‐optimized results using ONIOM technique identified the structure and show that the glutamic acid chelate moiety of both metal ions complexes is encapsulated within the β‐CD cavity while the l‐arginine chelate is partially located outside the cavity. The calculated inclusion binding energy (ΔEB, kJ mol−1) and other thermodynamic parameters reveal the noticeable thermal stability of 2‐(β‐CD) over the 1‐(β‐CD) capsulate. A reverse trend is experimentally found from the determined association constant values (K, m−1). The chemical reactivity and reactive site selectivity of these complexes were elucidated via conceptual density functional theory and an electrostatic potential surface map. Global electronic molecular descriptors [such as chemical potential (μ), hardness (η) and electrophilicity (ω)] validated the experimental findings. The reactivity of the encapsulated complexes is altered vis‐à‐vis the free complexes. The obtained results and contradictions are discussed and rationalized.
Diglyceride production via noncatalyzed esterification of glycerol and oleic acid
Authors: Ting Racquel Ranchie , Agapay Ramelito , Angkawijaya Artik Elisa , Tran Nguyen Phuong Lan , Truong Chi Thanh , Ju Yi‐Hsu
Published: November 2019

Production of diglycerides (DG) plays an important role in food, pharmaceutical, and cosmetic industries. In this study, optimal conditions for DG synthesis via noncatalyzed esterification of oleic acid with glycerol were determined. The temperatures (150°C, 175°C, and 200°C), oleic acid to glycerol molar ratios (1:1, 2:1, 3:1, and 4:1), and initial water content were varied to determine DG selectivity and % conversion over an 8‐hr period in a nitrogen‐purged system. The results exhibited a similar trend to catalyzed studies wherein an increase in temperature and molar ratio leaned towards the production of triglycerides (TG). It was also noted that tested initial water contents had an insignificant effect on reaction rates and product selectivity. Addition of molecular sieves for removal of water also resulted in negligible effects within this temperature range. DG production is optimum at 175°C and 2:1 molar ratio at 4 hr resulting in a product containing 42.6 ± 0.92 wt.% DG and a process selectivity of 1.11 ± 0.06 g DG/g (monoglycerides + TG). Purification by silica gel column chromatography of the product with the highest selectivity resulted in an enriched mixture with a yield of 58.25% and purity of 86.95 wt.% DG. Compared with catalyzed reactions, this system would require less downstream processing as removal of catalysts is not required and saponification does not occur. Although this procedure involves higher reaction temperature compared with enzyme‐catalyzed reactions, the time required to obtain high conversion is much shorter.
Phosphor powders‐incorporated polylactic acid polymeric composite used as 3D printing filaments with green luminescence properties
Authors: Wan Meiling , Jiang Xiao , Nie Jianliang , Cao Qingyun , Zheng Wenxu , Dong Xianming , Fan Z. Hugh , Zhou Wuyi
Published: November 2019

A new class of multifunctional nanocomposites holds strong potential in three‐dimensional (3D) printing. In this study, SrAl2O4:Eu2+,Dy3+ powders with fluorescence property were modified with SiO2 to improve its dispersibility and compatibility in the polylactic acid (PLA) matrix. The composite filaments with a diameter of 1.75 ± 0.05 mm containing 2 wt % of modified particles were prepared by a melt blending method. The fluorescent analysis reveals that the composite filaments can be excited by light with a broad band of wavelength from 345 to 455 nm with the highest excitation intensity at 426 nm and have a major emission peak at 487 nm. The morphological analysis and mechanical performance testing on the printed samples showed that modified particles were uniformly dispersed within the PLA matrix and improved the mechanical properties of the composite filaments. Moreover, the modified particles improved hydrophobic behavior and antibacterial properties in comparison with unmodified composite. Therefore, the composite material will have potential applications such as making prototypes for customized furniture and accessories by 3D printing technology. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48644.
Dual responsive wool fabric by cellulose nanowhisker reinforced shape memory polyurethane
Authors: Korkmaz Memiş Nazife , Kaplan Sibel
Published: November 2019

Shape memory wool fabrics having both temperature and moisture responsiveness were fabricated by a functional nanocomposite treatment comprising of shape memory polyurethane (SMPU) and cellulose nanowhisker (CNW). Water vapor permeability and sweat absorption properties were investigated under different temperature or relative humidity values to test smart comfort capabilities of the treated fabrics. Besides, felting shrinkage and weight loss of the fabrics after repeated washing cycles were investigated for end use performance. It was found out that the wool fabrics functionalized by nanocomposite treatments exhibited dynamic breathability and sweat absorption changing with temperature and relative humidity of body or environment. Moreover, nanocomposite application enhanced rigidity, tear strength, anti‐felting and weight loss performances of the wool fabric. 20 wt% CNW concentration can be suggested for thermal comfort, mechanical and end use performance enhancements to obtain smart garments having dynamic responsiveness to both body physiological and environmental changes. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48674.
“Inverted” Deep Eutectic Solvents Based on Host‐Guest Interactions
Authors: Yu Dongkun , Mou Hongyu , Fu Hui , Lan Xue , Wang Yingxiong , Mu Tiancheng
Published: November 2019

Herein, the concept of “inverted” (the mode “molecules mainly interact with cations”) deep eutectic solvents (DESs) is proposed. A strategy to form inverted DESs by host‐guest interactions was developed, and thus numerous DESs could be designed and formed by a combination of host and guest molecules. These liquids are expected to be used as nonaqueous electrolytes in potassium‐ion batteries or other fields for further exploration.
Close Encounters of the Viral Kind: Cross‐Kingdom Synergies at the Host–Pathogen Interface
Authors: Rowe Hannah M. , Rosch Jason W.
Published: November 2019

The synergies between viral and bacterial infections are well established. Most studies have been focused on the indirect mechanisms underlying this phenomenon, including immune modulation and alterations to the mucosal structures that promote pathogen outgrowth. A growing body of evidence implicates direct binding of virus to bacterial surfaces being an additional mechanism of synergy at the host–pathogen interface. These cross‐kingdom interactions enhance bacterial and viral adhesion and can alter tissue tropism. These bacterial–viral complexes play unique roles in pathogenesis and can alter virulence potential. The bacterial–viral complexes may also play important roles in pathogen transmission. Additionally, the complexes are recognized by the host immune system in a distinct manner, thus presenting novel routes for vaccine development. These synergies are active for multiple species in both the respiratory and gastrointestinal tract, indicating that direct interactions between bacteria and virus to modulate host interactions are used by a diverse array of species.
The implementation and adoptability of behavioral skills training in a university career center
Authors: Wirantana Vinthia , Stocco Corey S. , Kohn Carolynn S.
Published: November 2019

We evaluated the extent to which staff at a university career center (a) already used, (b) could be taught to use, and (c) might continue to use behavioral skills training (BST) when teaching interview answers to college students. We used a nonconcurrent multiple baseline design across three staff‐student dyads to assess the extent to which staff implemented BST and students provided appropriate answers before and after training. Results showed that interview training at the career center typically consisted of few BST steps, but staff could be taught on how to implement BST. All staff rated BST as an acceptable and effective form of interview training, but only one indicated that he or she was likely to adopt BST at the career center.
Evaluating the influence of time of day on activity engagement in persons with dementia
Authors: Boyden Darienne E. , Miltenberger Raymond G. , Novotny Marissa A.
Published: November 2019

Dementia is a serious disease affecting a growing number of people. With the onset of dementia comes a decline in social activity engagement that can negatively impact multiple aspects of a person's life. Research suggests that time of day may influence a person with dementia's behavior, including activity engagement, but such research is limited. The purpose of this study was to evaluate the influence of time of day on engagement in activities in persons diagnosed with dementia. An alternating treatments design was used with three participants to measure activity engagement during two times of day, morning and afternoon, and during two activities, a moderately preferred and a low preferred. Results showed no differentiation in engagement between morning and afternoon activities for all three participants, with high levels of engagement during both times of day. For two participants, results showed no differentiation in engagement between moderately preferred and low preferred activities. For one participant, levels of engagement were higher during moderately preferred activities than during low preferred activities.
Human elastin‐like polypeptides as a versatile platform for exploitation of ultrasensitive bilirubin detection by UnaG
Authors: Bandiera Antonella , Corich Lucia , Tommasi Silvia , De Bortoli Marco , Pelizzo Paola , Stebel Marco , Paladin Dino , Passamonti Sabina
Published: November 2019

A new, bifunctional recombinant protein was expressed as the fusion product of human elastin‐like polypeptide (HELP) and the bilirubin‐binding protein UnaG. The engineered product displays both the HELP‐specific property of forming a functional hydrogel matrix and the UnaG‐specific capacity of emitting green fluorescence upon ligand binding. The new fusion protein has been proven to be effective at detecting bilirubin in complex environments with high background noise. A cell culture model of the stress response, consisting of bilirubin released in the cell culture medium, was set up to assess the bilirubin‐sensing properties of the functional matrix obtained by cross‐linking the HELP moiety. Our engineered protein allowed us to monitor cell induction by the release of bilirubin in the culture medium on a nanomolar scale. This study shows that elastin‐like protein fusion represents a versatile platform for the development of novel and commercially viable analytical and biosensing devices.
Gelatin interpenetration in poly N‐isopropylacrylamide network reduces the compressive modulus of the scaffold: A property employed to mimic hepatic matrix stiffness
Authors: Sarkar Joyita , Kamble Swapnil C. , Patil Rajendra , Kumar Ashok , Gosavi Suresh W.
Published: November 2019

The progression of liver disease from normal to cirrhotic state is characterized by modulation of the stiffness of the extracellular matrix (ECM). Mimicking this modulation in vitro scaffold could provide a better insight into hepatic cell behavior. In this study, interpenetrating poly(N‐isopropylacrylamide‐co‐gelatin) cryogels were synthesized in 48 different compositions to yield scaffolds of different properties. It was observed that a high concentration of N‐isopropylacrylamide (NIPAAm) leads to the formation of small pores while gelatin interpenetration on poly‐NIPAAm framework renders porous structure. Swelling properties and porosity of the gels decreased with an increase in NIPAAm concentration owing to the increased compactness of the gels. Gelatin interpenetration relaxed the gels and enhanced these properties. An increase in gelatin concentration led to a reduction in compressive moduli indicating that gelatin interpenetration in the poly‐NIPAAm network softens the cryogel. With the increase in NIPAAm concentration, the effect of gelatin interpenetration in reducing the compressive moduli expanded. The cytocompatibility studies indicated that the gels are cell‐adherent and compatible with HepG2. Furthermore, biochemical and real‐time polymerase chain reaction studies revealed that HepG2 and Huh‐7 cells cultured on scaffolds mimicking the ECM stiffness of normal liver (1.5–2.5 kPa) exhibited optimum liver‐specific functionalities. Increasing the stiffness to fibrotic (4–9 kPa) and cirrhotic (10–20 kPa) ECM decreases the functionality.
A review of the bioanalytical methods for the quantitative determination of capecitabine and its metabolites in biological matrices
Authors: Knikman Jonathan E. , Rosing Hilde , Guchelaar Henk‐Jan , Cats A. , Beijnen Jos H.
Published: November 2019

The bioanalysis of the oral anticancer drug capecitabine and its metabolites has been investigated extensively over the past years. This paper reviews methods for the bioanalysis of capecitabine and its metabolites. The focus of this review will be on sample pre‐treatment, chromatography and detection. Furthermore, the choice of standards and analytical problems encountered during analysis of capecitabine and its metabolites in biological matrices will be discussed. The major challenges in the bioanalysis of capecitabine and its metabolites are the simultaneous extraction and analysis due to the differences in polarity of the analytes. Furthermore we evaluate currently described methods for the quantification of capecitabine and its metabolites. Future wishes and perspectives are stated that could serve as an inspiration for further development of assays for the quantification of capecitabine and its metabolites.
Quantitation of cytidine‐5′‐monophospho‐N‐acetylneuraminic acid in human leukocytes using LC–MS/MS: method development and validation
Authors: Fang Meng , Xu Xin , Zhang Michael , Shi Yifan , Gu Guodong , Liu Wanjing , Class Bradley , Ciccone Carla , Gahl William A. , Huizing Marjan , Carrillo Nuria , Wang Amy Q.
Published: November 2019

The biosynthesis of sialic acid (Neu5Ac) leads to the intracellular production of cytidine‐5′‐monophospho‐N‐acetylneuraminic acid (CMP‐Neu5Ac), the active sialic acid donor to nascent glycans (glycoproteins and glycolipids) in the Golgi. UDP‐N‐acetylglucosamine 2‐epimerase/N‐acetylmannosamine kinase myopathy is a rare autosomal recessive muscular disease characterized by progressive muscle weakness and atrophy. To quantify the intracellular levels of CMP‐Neu5Ac as well as N‐acetylmannosamine (ManNAc) and Neu5Ac in human leukocytes, we developed and validated robust liquid chromatography–tandem mass spectrometry methods. A fit‐for‐purpose approach was implemented for method validation. Hydrophilic interaction chromatography was used to retain three hydrophilic analytes. The human leukocyte pellets were lysed and extracted in a methanol–water mixture and the leukocyte extract was used for LC–MS/MS analysis. The lower limits of quantitation for ManNAc, Neu5Ac and CMP‐Neu5Ac were 25.0, 25.0 and 10.0 ng/ml, respectively. These validated methods were applied to a clinical study.
The Clitoris—An Appraisal of its Reproductive Function During the Fertile Years: Why Was It, and Still Is, Overlooked in Accounts of Female Sexual Arousal
Authors: Levin Roy J.
Published: November 2019

Stimulating the clitoris activates the brain to instigate changes in the female genital tract, namely, the enhancement of vaginal blood flow that increases vaginal luminal pO2, vaginal transudate (lubrication) facilitating painless penile penetration and partial neutralization of the basal luminal acidic pH, vaginal tenting, and ballooning delaying sperm transport and allowing semen de‐coagulation and capacitation (sperm activation) factors to act until arousal ends (often by orgasm induction). All these genital changes taken together are of major importance in facilitating the possibility of reproductive success (and thus gene propagation) no matter how or when the clitoris is stimulated—they reveal its overlooked reproductive function. Of course, also commensurate with these changes, is its activation of sexual pleasure. The clitoris thus has both procreative (reproductive) and recreative (pleasure) functions of equal importance. Clitoridectomy creates not only sexual disability but also a reproductive disability. Clin. Anat. 32:136–145, 2019. © 2019 Wiley Periodicals, Inc.
Real‐world efficacy and potential mechanism of resistance of icotinib in Asian advanced non‐small cell lung cancer with EGFR uncommon mutations: A multi‐center study
Authors: Lei Lei , Wang Wen‐xian , Zhu You‐cai , Li Jin‐luan , Fang Yong , Wang Hong , Zhuang Wu , Zhang Yin‐bin , Wang Li‐ping , Fang Mei‐yu , Xu Chun‐wei , Wang Xiao‐jia , Lv Tang‐feng , Song Yong
Published: November 2019

The response to icotinib in advanced non‐small cell lung cancers (NSCLC) with EGFR uncommon mutation (EGFRum) is unclear. Here we reported the efficacy and potential resistance mechanism of icotinib in Chinese EGFRum NSCLC patients. Between July 2013 and November 2016, 3117 NSCLC patients were screened for EGFRum in a multi‐center study in China. Circulating tumor DNA (ctDNA) was detected and analyzed using next‐generation sequencing (NGS) after progression from icotinib. The efficacy, safety and the potential resistance mechanism of icotinib were explored. After a median follow‐up of 6.2 months, 69 patients (70.41%) developed disease progression, the objective rate (ORR) and disease control rate (DCR) were 13.27% and 29.59% respectively, and the median progression‐free survival (PFS) was 5.5 months (95% CI: 1.2‐13.0 months). Both complex‐pattern with EGFR classical mutations (EGFRcm) and single‐pattern have better PFS than complex‐pattern without EGFRcm (median PFS was 7.2 (95% CI: 4.65‐9.75), 5.2 (95% CI: 3.24‐7.16) and 3.2 (95% CI: 2.97‐3.44) months, respectively, P < .05); patients harboring S768I mutation had the worst PFS than others (2.0 months, P < .05). Diarrhea was the most frequent side effect (42.9%). Forty‐eight (69.6%) patients developed drug resistance after 3.0 months and 81.2% of them acquired T790M mutation. Better response was observed in complex‐pattern with the EGFRcm group. S768I mutation carriers may not benefit from icotinib. Acquired T790M mutation was common in icotinib‐resistant EGFRum NSCLC patients.
The diagnostic value of the ultrasound gray scale ratio for different sizes of thyroid nodules
Authors: Chen Xiaoyu , Gao Ming , Hu Linfei , Zhu Jialin , Zhang Sheng , Wei Xi
Published: November 2019

At present, hypoechogenicity, as one of the clinically relevant features associated with suspicion of malignant thyroid disease, is affected by the variability of modules and the experience of sonographers, thus leading to unsatisfying results. We propose the ultrasound gray scale ratio (UGSR) to obtain an objective, numerical estimate of the echogenicity degree in different‐sized thyroid nodules, and we then evaluate its diagnostic efficacy in differentiating benign and malignant thyroid lesions. In total, 553 ultrasound images of thyroid nodules from one kind of ultrasonographic scanner were analyzed, among which 281 were papillary thyroid carcinomas (PTCs) and 272 were nodular goiters (NGs). The UGSR of the PTCs, NGs, and surrounding normal thyroid tissue was measured by image analysis software. The best cut‐off value for distinguishing various sizes of PTCs and NGs was determined by receiver operating characteristic (ROC) curve analysis. As the UGSR increased, the sensitivity of the diagnosing PTCs decreased, and the specificity increased. When the maximum Jordan index was 0.611, the best cut‐off value was 0.692, and the corresponding sensitivity and specificity of diagnosing PTCs were 87.9% and 73.2%, respectively. For the analysis of subgroups of different tumor sizes, as the size of thyroid nodules increased from 0.3 to 2 cm, the sensitivity of the diagnosis of PTCs decreased from 97.5% to 58.8%, and the specificity increased from 72.4% to 90.9%. These results strongly suggest that the UGSR is an appropriate objective, numerical method for estimating the echogenicity degree and has various diagnostic efficacies in different‐sized thyroid nodules. Thus, the UGSR can be used as an additional ultrasound parameter in the diagnosis of different‐sized PTCs and NGs.
Association between PSA values and surveillance quality after prostate cancer surgery
Authors: Chapman Christina Hunter , Caram Megan E. V. , Radhakrishnan Archana , Tsodikov Alexander , Deville Curtiland , Burns Jennifer , Zaslavsky Alexander , Chang Michael , Leppert John T. , Hofer Timothy , Sales Anne E. , Hawley Sarah T. , Hollenbeck Brent K. , Skolarus Ted A.
Published: November 2019

Background

Although prostate‐specific antigen (PSA) testing is used for prostate cancer detection and posttreatment surveillance, thresholds in these settings differ. The screening cutoff of 4.0 ng/mL may be inappropriately used during postsurgery surveillance, where 0.2 ng/mL is typically used, creating missed opportunities for effective salvage radiation treatment. We performed a study to determine whether guideline concordance with annual postoperative PSA surveillance increases when PSA values exceed 4 ng/mL, which represents a screening threshold that is not relevant after surgery.

Methods

We used US Veterans Health Administration data to perform a retrospective longitudinal cohort study of men diagnosed with nonmetastatic prostate cancer from 2005 to 2008 who underwent radical prostatectomy. We used logistic regression to examine the association between postoperative PSA levels and receipt of an annual PSA test.

Results

Among 10 400 men and 38 901 person‐years of follow‐up, annual guideline concordance decreased from 95% in year 1 to 79% in year 7. After adjustment, guideline concordance was lower for the youngest and oldest men, Black, and unmarried men. Guideline concordance significantly increased as PSA exceeded 4 ng/mL (adjusted odds ratio 2.20 PSA > 4‐6 ng/mL vs PSA > 1‐4 ng/mL, 95% confidence interval 1.20‐4.03;P = .01).

Conclusions

Guideline concordance with prostate cancer surveillance increased when PSA values exceeded 4 ng/mL, suggesting a screening threshold not relevant after prostate cancer surgery, where 0.2 ng/mL is considered treatment failure, is impacting cancer surveillance quality. Clarification of PSA thresholds for early detection vs cancer surveillance, as well as emphasizing adherence for younger and Black men, appears warranted.
Efficacy of plaque debulking for bifurcated or ostial lesions by directional coronary atherectomy prior to second‐generation drug eluting stenting
Authors: Habara Maoto , Tsuchikane Etsuo , Nasu Kenya , Kinoshita Yoshihisa , Murata Akira , Suzuki Yoriyasu , Kawase Yoshiaki , Okubo Munenori , Matsuo Hitoshi , Suzuki Takahiko
Published: November 2019

Objectives

We sought to evaluate the efficacy of plaque debulking by directional coronary atherectomy (DCA) prior to second‐generation drug‐eluting stent (DES) implantation for bifurcated coronary lesions.

Background

Percutaneous coronary intervention (PCI) for bifurcated lesions still remains complex and challenging in terms of restenosis or stent thrombosis regardless of whether simple or complex stenting is used.

Methods

Patients with bifurcated lesions were enrolled in this prospective multicenter registry. Pre‐second‐generation DES plaque debulking with a novel DCA catheter (ATHEROCUT®, Nipro Co., Osaka, Japan) was conducted. All patients were scheduled to perform a follow up angiography (9–12 month coronary angiography or coronary computed tomography). The primary end point was target vessel failure (TVF) at follow up. Secondary end points were procedure‐related events and major adverse cardiac events at 1 year.

Results

A total of 77 patients with bifurcated lesions were enrolled. PCI with DCA was performed successfully in all cases without any major procedure‐related event and only one case required complex stenting. The TVF rate at 9–12 month follow up was 3.9% (3 of 77) and those were all associated with revascularization of the target vessel. Restenosis was only observed at the ostium of the main‐branch in three cases. No death, coronary artery bypass grafting, or myocardial infarction were reported for any patients within the first year.

Conclusion

DCA before second‐generation DES implantation can possibly avoid complex stenting and provide a good mid‐term outcome in patients with bifurcated lesions.
A hidden face of migration: Diabetic ketoacidosis in a severely malnourished refugee
Authors: Sap Suzanne , Wandji Nzebia Yanelle , Dohvoma Andin Viola , Hagbe Paule Yvette , Mbono Ritha , Fotang Tangmoh Irene , Koki Paul Olivier
Published: November 2019

Besides violence, the risk of under nutrition and infection, migrant children with noncommunicable chronic diseases face serious challenges in the management of their conditions. Management of diabetic ketoacidosis in a severely malnourished patient includes careful hydration, therapeutic feeding, and monitoring.
Progressive edemas and generalized telangiectasia: A presentation of Intravascular B‐cell Lymphoma
Authors: Vásquez Johanna , Romero Vicente , Vilas Pedro , Serra-Rexach José Antonio , Vidán María T.
Published: November 2019

Intravascular B‐cell Lymphoma is a rare lymphoproliferative disorder with a none specific clinical presentation. The association of cutaneous telangiectasia‐like lesions and elevated inflammatory markers should be guaranteed a skin biopsy.
Poroma: A case report of pulsatile papule visualized on dermoscopy
Authors: Eksomtramage Thanadon , Aiempanakit Kumpol
Published: November 2019

Poroma, a benign sweat tumor, commonly presents with a nontender papule on the extremities. It can appear with a blinking light appearance on dermoscopy in real time.
Nonpuerperal uterine inversion due to adenomyosis: A case report and a literature review
Authors: Merviel Philippe , Guilbert Sandrine , Abou Hassan Coline , Thomas‐Kergastel Isabelle , Conan‐Charlet Virginie , Marcorelles Pascale , Dupré Pierre‐François
Published: November 2019

Nonpuerperal uterine inversion is a very rare event. We reported on the first ever case of nonpuerperal uterine inversion due to adenomyosis. Magnetic resonance imaging is recommended in cases with an unusual vaginal mass, so that this possible uterine etiology can be taken into consideration.
Regeneration and expansion of autologous full‐thickness skin through a self‐propagating autologous skin graft technology
Authors: Patterson Charles W. , Stark Matthew , Sharma Silpa , Mundinger Gerhard S.
Published: November 2019

New autologous skin regeneration technology yielded full‐thickness skin as evidenced by clinical observation and skin biopsy 5 months after surgery, providing relief for debilitating split‐thickness skin graft contracture in a pediatric burn case.
Post‐synthetic Modification of DUT‐5‐based Metal Organic Frameworks for the Generation of Single‐site Catalysts and their Application in Selective Epoxidation Reactions
Authors: Yildiz Ceylan , Kutonova Ksenia , Oßwald Simon , Titze‐Alonso Alba , Bitzer Johannes , Bräse Stefan , Kleist Wolfgang
Published: November 2019

New single‐site catalysts based on mixed‐linker metal‐organic frameworks with DUT‐5 structure, which contain immobilized Co2+, Mn2+ and Mn3+ complexes, have successfully been synthesized via post‐synthetic modification. 2,2’‐Bipyridine‐5,5’‐dicarboxylate linkers were directly metalated, while 2‐amino‐4,4’‐biphenyldicarboxylate linkers were post‐synthetically modified by their conversion to Schiff‐base ligands and a subsequent immobilization of the metal complexes. The resulting materials were used as catalysts in the selective epoxidation of trans‐stilbene and the activities and selectivities of the different catalysts were compared. The influence of various reaction parameters on conversion, yield and selectivity were investigated. Very low catalyst amounts of 0.02 mol % were sufficient to obtain a high conversion of trans‐stilbene using molecular oxygen from air as the oxidant. For cobalt‐containing MOF catalysts, conversions up to 90 % were observed and, thus, they were more active than their manganese‐containing counterparts. Recycling experiments and hot filtration tests proved that the reactions were mainly catalyzed via heterogeneous pathways.
Sulfonated Hyper‐cross‐linked Porous Polyacetylene Networks as Versatile Heterogeneous Acid Catalysts
Authors: Sekerová Lada , Březinová Pavlína , Do Thuy Tran , Vyskočilová Eliška , Krupka Jiří , Červený Libor , Havelková Lucie , Bashta Bogdana , Sedláček Jan
Published: November 2019

Two highly sulfonated micro/mesoporous polymers, P(1,3‐DEB)‐SO3H and P(1,4‐DEB)‐SO3H, with permanent porosity, the specific surface area about 550 m2 ⋅ g−1 and the content of SO3H groups of 2.7 mmol ⋅ g−1 were prepared as new acid Porous Polymer Catalysts, PPCs. The PPCs were achieved by easy sulfonation of parent hyper‐cross‐linked micro/mesoporous polyacetylene‐type networks resulting from a chain‐growth homopolymerization of 1,3‐ and 1,4‐diethynylbenzenes. New PPCs are reported as highly active and reusable heterogeneous catalysts of esterification of fatty acids with methanol and ethanol, Prins cyclization of aldehydes with isoprenol and intramolecular Prins cyclization of citronellal to isopulegol. The catalytic activity of the micro/mesoporous PPCs (TON values up to 522 mol ⋅ mol−1) was higher than that of commercial polymer‐based heterogeneous catalyst Amberlyst 15 possessing gel texture without permanent pores and that of p‐toluenesulfonic acid applied as a homogeneous catalyst.
Tailoring the Photoelectrochemical Activity of TiO2 Electrodes by Multilayer Screen‐Printing
Authors: Günnemann Carsten , Curti Mariano , Gerrit Eckert J. , Schneider Jenny , Bahnemann Detlef W.
Published: November 2019

Screen‐printing is a commonly used method for the preparation of photoelectrodes. Although previous studies have explored the effect of the number of printed layers on the efficiency of dye‐sensitized solar cells, its interplay with the photoelectrocatalytic properties of the electrodes has rarely been examined. This study focuses on this issue by studying the photoelectrocatalytic oxidation of methanol over TiO2 electrodes. Incident photon‐to‐current efficiencies reached 87 % at the optimal conditions of monochromatic (338 nm) irradiation of one‐layer films at 0.2 V vs NHE. However, the irradiation wavelength and applied bias strongly influenced the relative behavior of the films. For instance, at 0.5 V and 327 nm irradiation, the one‐layer electrode was 6 times more efficient than the four‐layer one, while at 385 nm the four‐layer electrode was 3.5 times more efficient. The results were explained on the basis of differing light absorption properties and charge carrier lifetimes. Modelling and quantification of the electron diffusion length (5.7 μm) helped to explain why the two‐layer electrode (4.89 μm thick) showed the most consistent efficiencies across all conditions. Complementarily, transient absorption spectroscopy was used to correlate the thicknesses with charge carrier lifetimes. Electron transfer to FTO was apparent only for the thinner electrode. Our work shows that the optimization of photoelectrocatalytic processes should include the number of layers as a key variable.
Metallopolymers as Nanostructured Solid‐State Platforms for Electrochemiluminescence Applications
Authors: Carrara Serena , Mauro Matteo , Hogan Conor F.
Published: November 2019

Electrochemiluminescence (ECL) is the process of light emission arising from an electrochemically generated excited state. ECL has been demonstrated to be a powerful tool for bioanalysis, in particular when phosphorescent transition metal complexes (TMCs) are used as emitters. Apart from molecular luminophores, there has been increasing interest in the use of both non‐conjugated and π‐conjugated metallopolymers over the last decade. Research efforts in this direction are driven by the appealing possibility to synergistically combine typical features of polymers, such as processability, with the enhanced photophysical and redox properties of several classes of TMCs. Indeed, solid‐state arrangements of ECL‐active metallopolymers enable their straightforward use as sensors with enhanced response. This concept article focuses on ECL‐active metallopolymers and their use in solid‐state platforms, providing a survey with relevant examples together with properties, mechanisms and proposed applications. Finally, the outlook for future applications across different research fields for these materials as well as their limitations for will be discussed.