bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of a Biocompatible Liquid Crystal Graphene Oxide–Gold Nanorods Electro‐ and Photoactive Interface for Cell Stimulation
Authors: Duc Daniela , Stoddart Paul R. , McArthur Sally L. , Kapsa Robert M. I. , Quigley Anita F. , Boyd‐Moss Mitchell , Moulton Simon E.
Published: March 2019

For decades, electrode–tissue interfaces are pursued to establish electrical stimulation as a reliable means to control neuronal cells behavior. However, spreading of electrical currents in tissues limits its spatial precision. Thus, optical cues, such as near‐infrared (NIR) light, are explored as alternatives. Presently, NIR stimulation requires higher energy input than electrical methods despite introduction of light absorbers, e.g., gold nanoparticles. As potential solution, NIR and electrical costimulation are proposed but with limited interfaces capable of sustaining this stimulation technique. Here, a novel electroactive nanocomposite with photoactive properties in the NIR range is constructed by N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride/N‐hydroxysulfosuccinimide sodium (EDC)/NHS conjugation of liquid crystal graphene oxide (LCGO) to protein‐coated gold nanorods (AuNR). The liquid crystal graphene oxide–gold nanorod nanocomposite (LCGO–AuNR) is fabricated into a hydrophilic electrode‐coating via drop‐casting, making it appropriate for versatile electrode–tissue interface fabrication. UV–vis spectrophotometry results demonstrate that LCGO–AuNR presents an absorbance peak at 798 nm (NIR range). Cyclic voltammetry measurements further confirm its electroactive capacitive properties. Furthermore, LCGO–AuNR coating supports cell adhesion, proliferation, and differentiation of NG108‐15 neuronal cells. This biocompatible interface is anticipated, with ideal electrical and optical properties for NIR and electrical costimulation, to enable further development of the technique for energy‐efficient and precise neuronal cell modulation.
Cell and Material‐Specific Phage Display Peptides Increase iPS‐MSC Mediated Bone and Vasculature Formation In Vivo
Authors: Ramaraju Harsha , Kohn David H.
Published: March 2019

Biomimetically designed materials matching the chemical and mechanical properties of tissue support higher mesenchymal stem cell (MSC) adhesion. However, directing cell‐specific attachment and ensuring uniform cell distribution within the interior of 3D biomaterials remain key challenges in healing critical sized defects. Previously, a phage display derived MSC‐specific peptide (DPIYALSWSGMA, DPI) was combined with a mineral binding sequence (VTKHLNQISQSY, VTK) to increase the magnitude and specificity of MSC attachment to calcium‐phosphate biomaterials in 2D. This study investigates how DPI‐VTK influences quantity and uniformity of iPS‐MSC mediated bone and vasculature formation in vivo. There is greater bone formation in vivo when iPS‐MSCs are transplanted on bone‐like mineral (BLM) constructs coated with DPI‐VTK compared to VTK (p < 0.002), uncoated BLM (p < 0.037), acellular BLM/DPI‐VTK (p < 0.003), and acellular BLM controls (p < 0.01). This study demonstrates, for the first time, the ability of non‐native phage‐display designed peptides to spatially control uniform cell distribution on 3D scaffolds and increase the magnitude and uniformity of bone and vasculature formation in vivo. Taken together, the study validates phage display as a novel technology platform to engineer non‐native peptides with the ability to drive cell specific attachment on biomaterials, direct bone regeneration, and engineer uniform vasculature in vivo.
Electrochemically Controlled Drug Release from a Conducting Polymer Hydrogel (PDMAAp/PEDOT) for Local Therapy and Bioelectronics
Authors: Kleber Carolin , Lienkamp Karen , Rühe Jürgen , Asplund Maria
Published: March 2019

In this study, the release of fluorescein from a photo‐crosslinked conducting polymer hydrogel made from a hydrogel precursor poly(dimethylacrylamide‐co‐4‐methacryloyloxy benzophenone (5%)‐co‐4‐styrenesulfonate (2.5%)) (PDMAAp) and the conducting polymer poly(3,4‐ethylenedioxythiophene) (PEDOT) is investigated. Fluorescein, here used as a model for a drug, is actively released through application of an electrical trigger signal. The detected quantity is more than six times higher in comparison to that released from a conventional PEDOT/polysterene sulfonate (PSS) system. Release profiles, drug dose, and timing can be tailored by the application of different trigger signals and pretreatments. To demonstrate that the novel drug release system can be used for a drug relevant for local delivery to a neural interface, experiments are furthermore performed with the anti‐inflammatory drug dexamethasone (Dex). The conducting polymer hydrogel facilitates the active release of Dex, in comparison to the previously used PEDOT/Dex. It is suggested that PEDOT/PDMAAp is an interesting alternative for conducting polymer based drug release systems, with the potential to offer more volume for storage, yet retaining the excellent electrochemical properties known for PEDOT electrodes.
Design, Formulation, and Evaluation of Novel Dissolving Microarray Patches Containing Rilpivirine for Intravaginal Delivery
Authors: Mc Crudden Maelíosa T. C. , Larrañeta Eneko , Clark Annie , Jarrahian Courtney , Rein‐Weston Annie , Creelman Benjamin , Moyo Yolanda , Lachau‐Durand Sophie , Niemeijer Nico , Williams Peter , McCarthy Helen O. , Zehrung Darin , Donnelly Ryan F.
Published: March 2019

Antiretroviral (ARV) drugs have, for many years, been studied and administered in the prevention and treatment of human immunodeficiency virus (HIV). Intramuscular (IM) injection of long acting (LA) ARVs are in clinical development, but injectable formulations require regular access to healthcare facilities and disposal facilities for sharps. The development of a discrete, self‐administered, and self‐disabling vehicle to deliver ARVs could obviate these issues. This study describes the formulation, mechanical characterization, and in vivo evaluation of dissolving microarray patches (MAPs) containing a LA nanosuspension of the ARV, rilpivirine (RPV, RPV LA), for vaginal delivery. This is the first study to apply MAPs into vaginal tissue. The RPV LA MAPs penetrate ex vivo skin and a synthetic vaginal skin model and withstand the effects of potential dragging motion across synthetic vaginal epithelium. In in vivo studies, the mean plasma concentration of RPV in rats at the 56 day endpoint (116.5 ng mL−1) is comparable to that achieved in the IM control cohort (118.9 ng mL−1). RPV is detected systemically, in lymph and vaginal tissue, indicating the potential to deliver RPV LA to primary sites of viral challenge and replication. This innovative research has future potential for patients and healthcare workers, particularly in low‐resource settings.
Physical Structuring of Injectable Polymeric Systems to Controllably Deliver Nanosized Extracellular Vesicles
Authors: Nikravesh Niusha , Davies Owen G. , Azoidis Ioannis , Moakes Richard J. A. , Marani Lucia , Turner Mark , Kearney Cathal J. , Eisenstein Neil M. , Grover Liam M. , Cox Sophie C.
Published: March 2019

Extracellular vesicles (EVs) are emerging as a promising alternative approach to cell‐therapies. However, to realize the potential of these nanoparticles as new regenerative tools, healthcare materials that address the current limitations of systemic administration need to be developed. Here, two technologies for controlling the structure of alginate based microgel suspensions are used to develop sustained local release of EVs, in vitro. Microparticles formed using a shearing technique are compared to those manufactured using vibrational technology, resulting in either anisotropic sheet‐like or spheroid particles, respectively. EVs harvested from preosteoblasts are isolated using differential ultracentrifugation and successfully loaded into the two systems, while maintaining their structures. Promisingly, in addition to exhibiting even EV distribution and high stability, controlled release of vesicles from both structures is exhibited, in vitro, over the 12 days studied. Interestingly, a significantly greater number of EVs are released from the suspensions formed by shearing (69.9 ± 10.5%), compared to the spheroids (35.1 ± 7.6%). Ultimately, alterations to the hydrogel physical structures have shown to tailor nanoparticle release while simultaneously providing ideal material characteristics for clinical injection. Thus, the sustained release mechanisms achieved through manipulating the formation of such biomaterials provide a key to unlocking the therapeutic potential held within EVs.
3D Bioprinting of Functional Islets of Langerhans in an Alginate/Methylcellulose Hydrogel Blend
Authors: Duin Sarah , Schütz Kathleen , Ahlfeld Tilman , Lehmann Susann , Lode Anja , Ludwig Barbara , Gelinsky Michael
Published: March 2019

Transplantation of pancreatic islets is a promising strategy to alleviate the unstable blood‐glucose control that some patients with diabetes type 1 exhibit and has seen many advances over the years. Protection of transplanted islets from the immune system can be accomplished by encapsulation within a hydrogel, the most investigated of which is alginate. In this study, islet encapsulation is combined with 3D extrusion bioprinting, an additive manufacturing method which enables the fabrication of 3D structures with a precise geometry to produce macroporous hydrogel constructs with embedded islets. Using a plottable hydrogel blend consisting of clinically approved ultrapure alginate and methylcellulose (Alg/MC) enables encapsulating pancreatic islets in macroporous 3D hydrogel constructs of defined geometry while retaining their viability, morphology, and functionality. Diffusion of glucose and insulin in the Alg/MC hydrogel is comparable to diffusion in plain alginate; the embedded islets continuously produce insulin and glucagon throughout the observation and still react to glucose stimulation albeit to a lesser degree than control islets.
Support and Interface Effects in Water‐Splitting Electrocatalysts
Authors: Zhang Jian , Zhang Qiuyu , Feng Xinliang
Published: March 2019

Water‐splitting electrolyzers that can convert electricity into storable hydrogen are a fascinating and scalable energy conversion technology for the utilization of renewable energies. To speed up the sluggish hydrogen and oxygen evolution reactions (HER and OER), electrocatalysts are essential for reducing their kinetic energy barriers and eventually improving the energy conversion efficiency. As efficient strategies for modulating the binding ability of water‐splitting intermediates on electrocatalyst surface, the support effect and interface effect are drawing growing attention. Herein, some of the recent research progress on the support and interface effects in HER, OER, and overall water‐splitting electrocatalysts is highlighted. Specifically, the correlation between the electronic interaction of the constituent components and the electrocatalytic water‐splitting performance of electrocatalysts is profoundly discussed, with the aim of advancing the development of highly efficient water‐splitting electrocatalysts, which may eventually replace the noble‐metal‐based electrocatalysts and bring the practically widespread utilization of water‐splitting electrolyzers into a reality.
Micron‐Scale Patterning of High Quantum Yield Quantum Dot LEDs
Authors: Azzellino Giovanni , Freyria Francesca S. , Nasilowski Michel , Bawendi Moungi G. , Bulović Vladimir
Published: March 2019

Micron‐scale resolution patterning of colloidal quantum dots (QDs) is demonstrated by adopting inkjet printing as a technique that is solvent and room temperature compatible, maintains optical and electronic properties of printed QD films, and results in minimal materials waste during the deposition process. With a combination of solvent engineering and substrate patterning single prints of PbS–CdS core–shell QDs (with peak photoluminescence emission at λ = 1270 nm wavelength) are deployed to form QD films of nanoscale‐thickness, with regular micron‐scale patterns. Inkjet printing of infrared QD films is chosen as a case study for manufacture of QD‐light emitting diodes (QD‐LEDs), and demonstrates devices with a record peak external quantum efficiency in excess of 2% that is finally comparable with state‐of‐the‐art spin‐coated prototypes.
Dynamic Metasurfaces Using Phase‐Change Chalcogenides
Authors: Ding Fei , Yang Yuanqing , Bozhevolnyi Sergey I.
Published: March 2019

Metasurfaces have attracted increasing attention and provide promising solutions for cost‐effective and highly efficient optics due to their unprecedented capabilities in light manipulation. In recent years, phase‐change materials (PCMs), especially phase‐change chalcogenides, are integrated into metasurfaces to explore innovative configurations exhibiting remarkable tunability and reconfigurability due to the dramatic optical contrasts available in PCMs along with their high chemical and long‐term stability and high switching speeds. In this review, the current achievements and ongoing developments in dynamic metasurfaces based on phase‐change chalcogenides, an emerging field in nanophotonics and optoelectronics, are outlined. Starting with the basic material properties of phase‐change chalcogenides, the structural transformations and dielectric functions of two main chalcogenides are described. This is followed by an overview of the main progress in typical dynamic metasurfaces based on phase‐change chalcogenides enabling global and local amplitude/phase modulation. The review ends with a short conclusion and outlook on possible future developments.
Biomimetic Superstructures Assembled from Au Nanostars and Nanospheres for Efficient Solar Evaporation
Authors: Song Guofen , Yuan Yang , Liu Jie , Liu Qinglei , Zhang Wang , Fang Jing , Gu Jiajun , Ma Dongling , Zhang Di
Published: March 2019

The control of the shapes and assembling structures of plasmonic nanoparticles is vital for the optical properties and photothermal conversion performance. Here, gold nanospheres and nanostars are assembled into ridges/disordered nanohole arrays architecture in nanoparticle colloids using light‐trapping Papilio Paris forewings (OPPs) as templates. In solar steam generation, water evaporation efficiency reaches 83.3% for nanostar assemblies (NSAs) and 68.6% for nanosphere assemblies (NSPAs) under 1‐sun (1 kW m−2) irradiation. Both the biomimetic superstructures exhibit significant enhancement of near‐infrared light absorption compared to OPPs, and NSAs show higher absorption than NSPAs in the range of 200–2500 nm. Finite element method simulations reveal such broadband absorption is ascribed to the hybridization of localized surface plasmon modes of continuous‐assembled Au nanoparticles in the biomimetic structures as well as the wing photonic structures with light‐transferring ridges with an inverted V shape and light‐trapping disordered nanohole arrays. It is revealed that optical properties of superstructures can be tuned not only by controlling their 3D structures but also by changing the shape of nanosized building blocks. It is hoped that this work will provide inspirations for the design and assembly of nanophotonic structures and devices for solar energy conversion.
A General Approach for Buckled Bulk Composites by Combined Biaxial Stretch and Layer‐by‐Layer Deposition and Their Electrical and Electromagnetic Applications
Authors: Liu Zhongsheng , Wan Fayu , Mou Linlin , Jung de Andrade Monica , Qian Dong , Wang Run , Yin Shougen , Li Kun , Chen Hong , An Baigang , Hu Zhizhi , Wang Hongzhi , Zhu Meifang , Fang Shaoli , Liu Zunfeng
Published: March 2019

Fabrication of high quality stretchable conductors that show bulk structure, high electrical conductivity, and stable conductance under large deformations is crucial for wearable electronics and soft robots. A key difficulty here is to introduce buckled structure into the conductive phase of the bulk conductors and overcome the lateral crack problem in the conductive phase during buckle formation. In this paper, a general approach is introduced for fabricating novel buckled bulk composite (BBC) stretchable conductors based on common conductive nanomaterial by using sequential biaxial stretch–release and layer‐by‐layer deposition to provide alternating buckled conductive layers and elastomer layers. This biaxial stretch is used to keep the width of elastomers unchanged before and after stretching, to avoid the lateral crack formation of the conductive layer. This method can be applied to common nanoparticles, such as silver nanoparticles, silver nanowires, single‐walled carbon nanotubes, and graphenes. The BBCs exhibit high conductance, uniform structure, and stable conductance during deformation and temperature change, which are demonstrated as applications in electrical interconnects, electrothermally driven artificial muscles, electromagnetic interference shielding materials, and reconfigurable antennas.
Stabilization of Precursor Solution and Perovskite Layer by Addition of Sulfur
Authors: Min Hanul , Kim Gwisu , Paik Min Jae , Lee Seungwoon , Yang Woon Seok , Jung Minsu , Seok Sang Il
Published: March 2019

Efficient perovskite solar cells (PSCs) are mainly fabricated by a solution coating processes. However, the efficiency of such devices varies significantly with the aging time of the precursor solution used to fabricate them, which includes a mixture of perovskite components, especially methylammonium (MA), and formamidinium (FA) cations. Herein, how the inorganic–organic hybrid perovskite precursor solution of (FAPbI3)0.95(MAPbBr3)0.05 degrades over time and how such degradation can be effectively inhibited is reported on, and the associated mechanism of degradation is discussed. Such degradation of the precursor solution is closely related to the loss of MA cations dissolved in the FA solution through the deprotonation of MA to volatile methylamine (CH3NH2). Addition of elemental sulfur (S8) drastically stabilizes the precursor solution owing to amine–sulfur coordination, without compromising the power conversion efficiency (PCE) of the derived PSCs. Furthermore, sulfur introduced to stabilize the precursor solution results in improved PSC stability.
Patient with anomalous skin pigmentation expands the phenotype of ARID2 loss‐of‐function disorder, a SWI/SNF‐related intellectual disability
Authors: Khazanchi Rohan , Ronspies Carey A. , Smith Scott C. , Starr Lois J.
Published: March 2019

ARID2 loss‐of‐function is associated with a rare genetic disorder characterized in 14 reported patients to date. ARID2 encodes a member of the SWItch/sucrose non‐fermentable chromatin remodeling complex. Other genes encoding subunits of this complex, such as ARID1A, ARID1B, and SMARCA2, are mutated in association with Coffin‐Siris syndrome (CSS) and Nicolaides Baraitser syndrome (NCBRS) phenotypes. Previously reported ARID2 mutations manifested clinically with a CSS‐like phenotype including intellectual disability, coarsened facial features, fifth toenail hypoplasia, and other recognizable dysmorphisms. However, heterogeneity exists between previously reported patients with some patients showing more overlapping features with NCBRS. Herein, we present a patient with a novel disease‐causing ARID2 loss‐of‐function mutation. His clinical features included intellectual disability, coarse and dysmorphic facial features, toenail hypoplasia, ADHD, short stature, and delayed development consistent with prior reports. Our patient also presented with previously unreported clinical findings including ophthalmologic involvement, persistent fetal fingertip and toetip pads, and diffuse hyperpigmentary and hypopigmentary changes sparing his face, palms, and soles. The anomalous skin findings are particularly of interest given prior literature outlining the role of ARID2 in melanocyte homeostasis and melanoma. This clinical report and review of the literature is further affirming of the characteristic symptoms and expands the phenotype of this newly described and rare syndrome.
Neu–Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis
Authors: Bourque Danielle K. , Cloutier Mireille , Kernohan Kristin D. , Bareke Eric , Grynspan David , Michaud Jean ,   Care4Rare Canada Consortium, Boycott Kym M.
Published: March 2019

Neu–Laxova syndrome (NLS) is a lethal autosomal recessive microcephaly syndrome associated with intrauterine growth restriction (IUGR) and multiple congenital anomalies. Clinical features include central nervous system malformations, joint contractures, ichthyosis, edema, and dysmorphic facial features. Biallelic pathogenic variants in either the PHGDH or PSAT1 genes have been shown to cause NLS. Using exome sequencing, we aimed to identify the underlying genetic diagnosis in three fetuses (from one family) with prenatal skin edema, severe IUGR, micrognathia, renal anomalies, and arthrogryposis and identified a homozygous c.1A>C (p.Met1?, NM_006623.3) variant in the PHGDH gene. Loss of the translation start codon is a novel genetic mechanism for the development of NLS. Prenatal diagnosis of NLS is challenging and few reports describe the fetal pathology. Fetal neuropathologic examination revealed: delayed brain development, congenital agenesis of the corticospinal tracts, and hypoplasia of the hippocampus, cerebellum and brainstem. Each pregnancy also showed increased nuchal translucency (NT) or cystic hygroma. While NLS is rare, it may be a cause of recurrent increased NT/cystic hygroma. This finding provides further support that cystic hygroma has many different genetic causes and that exome sequencing may shed light on the underlying genetic diagnoses in this group of prenatal patients.
Neuronal apolipoprotein E4 increases cell death and phosphorylated tau release in alzheimer disease
Authors: Wadhwani Anil R. , Affaneh Amira , Van Gulden Stephanie , Kessler John A.
Published: March 2019

Objective

The apolipoprotein E (APOE) E4 isoform is the strongest genetic risk factor for sporadic Alzheimer disease (AD). Although APOE is predominantly expressed by astrocytes in the central nervous system, neuronal expression of APOE is of increasing interest in age‐related cognitive impairment, neurological injury, and neurodegeneration. Here, we show that endogenous expression of E4 in stem‐cell–derived neurons predisposes them to injury and promotes the release of phosphorylated tau.

Methods

Induced pluripotent stem cells from 2 unrelated AD patients carrying the E4 allele were corrected to the E3/E3 genotype with the CRISPR/Cas9 system and differentiated into pure cultures of forebrain excitatory neurons without contamination from other cells types.

Results

Compared to unedited E4 neurons, E3 neurons were less susceptible to ionomycin‐induced cytotoxicity. Biochemically, E4 cells exhibited increased tau phosphorylation and ERK1/2 phosphoactivation. Moreover, E4 neurons released increased amounts of phosphorylated tau extracellularly in an isoform‐dependent manner by a heparin sulfate proteoglycan–dependent mechanism.

Interpretation

Our results demonstrate that endogenous expression of E4 by stem‐cell–derived forebrain excitatory neurons predisposes neurons to calcium dysregulation and ultimately cell death. This change is associated with increased cellular tau phosphorylation and markedly enhanced release of phosphorylated tau. Importantly, these effects are independent of glial APOE. These findings suggest that E4 accelerates spreading of tau pathology and neuron death in part by neuron‐specific, glia‐independent mechanisms. Ann Neurol 2019;85:726–739
Mechanistic Dichotomy of Magnesium‐ and Zinc‐Based Germanium Nucleophiles in the C(sp3)−Ge Cross‐Coupling with Alkyl Electrophiles
Authors: Xue Weichao , Mao Wenbin , Zhang Liangliang , Oestreich Martin
Published: March 2019

Robust procedures for two mechanistically distinct C(sp3)−Ge bond formations from alkyl electrophiles and germanium nucleophiles are reported. The germanium reagents were made available as bench‐stable solutions by lithium‐to‐magnesium and lithium‐to‐zinc transmetalation, respectively. The germanium Grignard reagent reacts with various primary and secondary alkyl electrophiles by an ionic nucleophilic displacement. Conversely, the coupling of the corresponding zinc reagent requires a nickel catalyst, which then engages in radical bond formations with primary, secondary, and even tertiary alkyl bromides. Both methods avoid the regioselectivity issue of alkene hydrogermylation and enable the synthesis of a wide range of functionalized alkyl‐substituted germanes.
The importance of adjusting for pupil background in school value‐added models: A study of Progress 8 and school accountability in England
Authors: Leckie George , Goldstein Harvey
Published: March 2019

In the UK, USA and elsewhere, school accountability systems increasingly compare schools using value‐added measures of school performance derived from pupil scores in high‐stakes standardised tests. Rather than naïvely comparing school average scores, which largely reflect school intake differences in prior attainment, these measures attempt to compare the average progress or improvement pupils make during a year or phase of schooling. Schools, however, also differ in terms of their pupil demographic and socioeconomic characteristics and these factors also predict why some schools subsequently score higher than others. Many therefore argue that value‐added measures unadjusted for pupil background are biased in favour of schools with more ‘educationally advantaged’ intakes. But others worry that adjusting for pupil background entrenches socioeconomic inequities and excuses low‐performing schools. In this article we explore these theoretical arguments and their practical importance in the context of the ‘Progress 8’ secondary school accountability system in England, which has chosen to ignore pupil background. We reveal how the reported low or high performance of many schools changes dramatically once adjustments are made for pupil background, and these changes also affect the reported differential performances of regions and of different school types. We conclude that accountability systems which choose to ignore pupil background are likely to reward and punish the wrong schools and this will likely have detrimental effects on pupil learning. These findings, especially when coupled with more general concerns surrounding high‐stakes testing and school value‐added models, raise serious doubts about their use in school accountability systems.
Short-term cost-effectiveness of one-stage implant-based breast reconstruction with an acellular dermal matrix versus two-stage expander-implant reconstruction from a multicentre randomized clinical trial
Authors: Negenborn V L , Smit J M , Dikmans R E G , Winters H A H , Twisk J W R , Ruhé P Q , Mureau M A M , Tuinder S , Eltahir Y , Posch N A S , van Steveninck-Barends J M , van der Hulst R R W J , Ritt M J P F , Bouman M-B , Mullender M G
Published: March 2019

Background

Implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure and its economic impact is significant. This study aimed to analyse whether a direct one-stage IBBR with use of an acellular dermal matrix (ADM) is more cost-effective than two-stage (expander-implant) breast reconstruction.

Methods

The BRIOS (Breast Reconstruction In One Stage) study was an open-label multicentre RCT in which women scheduled for skin-sparing mastectomy and immediate IBBR were randomized between one-stage IBBR with ADM or two-stage IBBR. Duration of surgery and hospital stay, and visits for the primary surgery, unplanned and cosmetic procedures were recorded. Costs were estimated at an institutional level. Health status was assessed by means of the EuroQol Five Dimensions 5L questionnaire.

Results

Fifty-nine patients (91 breasts) underwent one-stage IBBR with ADM and 62 patients (92 breasts) two-stage IBBR. The mean(s.d.) duration of surgery in the one-stage group was significantly longer than that for two-stage IBBR for unilateral (2·52(0·55) versus 2·02(0·35) h; P < 0·001) and bilateral (4·03(1·00) versus 3·25(0·58) h; P = 0·017) reconstructions. Costs were higher for one-stage compared with two-stage IBBR for both unilateral (€12 448 (95 per cent c.i. 10 722 to 14 387) versus €9871 (9373 to 10 445) respectively; P = 0·025) and bilateral (€16 939 (14 887 to 19 360) versus €13 383 (12 414 to 14 669); P = 0·002) reconstructions. This was partly related to the use of relatively expensive ADM. There was no difference in postoperative health status between the groups.

Conclusion

One-stage IBBR with ADM was associated with higher costs, but similar health status, compared with conventional two-stage IBBR. Registration number: NTR5446 (http://www.trialregister.nl).
Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study)
Authors: Karakatsanis A , Hersi A-F , Pistiolis L , Olofsson Bagge R , Lykoudis P M , Eriksson S , Wärnberg F , Nagy G , Mohammed I , Sundqvist M , Bergkvist L , Kwong A , Olofsson H , Stålberg P
Published: March 2019

Background

One-fifth of patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) have invasive breast cancer (IBC) on definitive histology. Sentinel lymph node dissection (SLND) is performed in almost half of women having surgery for DCIS in Sweden. The aim of the present study was to try to minimize unnecessary SLND by injecting superparamagnetic iron oxide (SPIO) nanoparticles at the time of primary breast surgery, enabling SLND to be performed later, if IBC is found in the primary specimen.

Methods

Women with DCIS at high risk for the presence of invasion undergoing breast conservation, and patients with DCIS undergoing mastectomy were included. The primary outcome was whether this technique could reduce SLND. Secondary outcomes were number of SLNDs avoided, detection rate and procedure-related costs.

Results

This was a preplanned interim analysis of 189 procedures. IBC was found in 47 and a secondary SLND was performed in 41 women. Thus, 78·3 per cent of patients avoided SLND (P < 0·001). At reoperation, SPIO plus blue dye outperformed isotope and blue dye in detection of the sentinel node (40 of 40 versus 26 of 40 women; P < 0·001). Costs were reduced by a mean of 24·5 per cent in women without IBC (€3990 versus 5286; P < 0·001).

Conclusion

Marking the sentinel node with SPIO in women having surgery for DCIS was effective at avoiding unnecessary SLND in this study. Registration number: ISRCTN18430240 (http://www.isrctn.com).
Application of case study to introduce medical students to molecular biology techniques used in HIV diagnostics
Authors: Kocemba‐Pilarczyk Kinga A. , Ostrowska Barbara , Dudzik Paulina , Markiewicz Michał J. , Sotirios Souza Pegos Débora , Lim Chaewon
Published: March 2019

Diagnostic molecular biology is a fast developing discipline of laboratory medicine widely used in numerous medical branches such as oncology, hematology, immunology, internal medicine, or infectious diseases, which will certainly have a major impact on clinical medicine in the near future. Nowadays, educational process is forced to face the quickly growing overflow of easily accessible data and properly guide the students not to be lead astray in the information chaos. Hence, in view of the foregoing, it appears obvious that modern medical education should put particular stress on selective acquiring, interpreting, and applying integrated multidisciplinary knowledge rather than on just absorbing and memorizing huge amount of scattered information. The presented case study aims at familiarizing the students with basic molecular biology techniques such as enzyme‐linked immunosorbent assay, Western blot, and quantitative reverse transcription‐polymerase chain reaction. Importantly, it is not limited only to discussing and learning the principles of the assays mentioned earlier, but it also shows their practical application in a particular diagnostic process and give the guidelines on how to explain and interpret exemplary results. In parallel, the way the case study is constructed allows a tutor to lead students into discussion on clinical aspects related to HIV infection what should eventually create complete picture of a HIV diagnostic process, thereby integrating basic knowledge of molecular biology laboratory techniques, HIV biology, and immunological response. © 2019 International Union of Biochemistry and Molecular Biology, 47(3):355–360, 2019.
Analytical methodologies for the determination of ticagrelor
Authors: Kelemen Hajnal , Hancu Gabriel , Papp Lajos Attila
Published: March 2019

Ticagrelor is an orally administered platelet aggregation inhibitor with a cyclopentyl‐triazolopyrimidine structure; it is a selective reversible P2Y12 receptor antagonist, which prevents P2Y12‐mediated and ADP‐mediated platelet activation and aggregation. It is used to reduce the rate of cardiovascular death, myocardial infarction and stroke in patients with acute coronary syndrome or history of myocardial infarction. Several analytical methods have been published for the determination of ticagrelor in pharmaceuticals and biological materials by spectrophotometry, high‐performance liquid chromatography with ultraviolet detection and liquid chromatography coupled with tandem mass spectrometry. The purpose of the current review is to provide a systematic survey of the analytical techniques used for the determination of ticagrelor since its introduction in therapy until today.
OralLactobacillus reuteriLR06 orBifidobacteriumBL5b supplement do not produce analgesic effects on neuropathic and inflammatory pain in rats
Authors: Huang Jiangju , Zhang Chuanlei , Wang Jian , Guo Qulian , Zou Wangyuan
Published: March 2019

Background

Previous studies have reported that certain bacteria exert visceral antinociceptive activity in visceral pain and may also help to relieve neuropathic and inflammatory pain. Objective: The aim of this study was to explore the analgesic effect ofLactobacillus reuteriLR06 (LR06) orBifidobacteriumBL5b (BL5b) in chronic pain in vivo.

Design

Rats were randomly assigned into four groups: sham, Chronic Constriction Injury (CCI)/Complete Freund's Adjuvant (CFA) + control, CCI/CFA + LR06, and CCI/CFA + BL5b. Rats from the probiotic groups were treated with 1 x 109cfu (LR06 or BL5b) daily through gavage for 14 days after a pain model was successfully established. Mechanical and thermal hyperalgesia were used to assess the analgesic effect of the probiotics. Iba1 was used to verify the microglial inflammatory reaction in the different groups.

Results

The results showed that probioticsL. reuteriLR06 orBifidobacteriumBL5b had no significant antinociception effects in chronic pain rats. The chronic pain‐induced activation of microglia (Iba1) was not relieved by probiotics in CCI/CFA‐induced neuropathic or inflammatory pain rats.

Conclusion

Our results suggested thatL. reuteriLR06 orBifidobacteriumBL5b had no antinociceptive effects on CCI‐induced neuropathic pain and CFA‐induced inflammatory pain in rats.
Expansion of retinal stem cells and their progeny using cell microcarriers in a bioreactor
Authors: Baakdhah Tahani , van der Kooy Derek
Published: March 2019

Blindness as a consequence of degenerative eye diseases (e.g., age‐related macular degeneration and retinitis pigmentosa) is a major health problem and numbers are expected to increase by up to 50% by 2020. Unfortunately, adult mouse and human retinal stem cells (RSCs), unlike fish and amphibians, are quiescent in vivo and do not regenerate following disease or injury. To replace lost cells, we used microcarriers (MCs) in a suspension stirring bioreactor to help achieve numbers suitable for differentiation and transplantation. We achieved a significant 10‐fold enrichment of RSC yield compared to conventional static culture techniques using a combination of FACTIII MCs and relative hypoxia (5%) inside the bioreactor. We found that hypoxia (5% O2) was associated with better RSC expansion across all platforms; and this can be attributed to hypoxia‐induced increases in survival and/or symmetric division of stem cells. In the future, we will target the differentiation of RSCs and their progeny toward rod and cone photoreceptor phenotypes using FACTIII MCs inside bioreactors to expand their populations in order to produce the large numbers of cells needed for transplantation.
Antifungal Effect of Essential Oils from Five Kinds of Rutaceae Plants – Avoiding Pesticide Residue and Resistance
Authors: Chen Chuan‐Jiao , Li Qing‐Qing , Ma Yu‐Nan , Wang Wei , Cheng Yong‐Xian , Xu Fu‐Rong , Dong Xian
Published: March 2019

Panax notoginseng root is a traditional Chinese herb, of which the yield and quality have been seriously affected by microorganisms, and is commonly used to treat various kinds of bleeding. In this experiment, the effects of the antifungal properties of essential oils (EOs) from five kinds of Rutaceae plants on the growth of three kinds of pathogens were studied to develop natural, environmentally friendly antifungal agents. Citrus medica EO was found to have stronger inhibitory effects on the growth of pathogenic fungi in vitro than other EOs with the Oxford cup method, of which the chemical composition was further investigated by GC/MS. The major components were d‐limonene (22.79 %) and γ‐terpinene (9.71 %). The antifungal activities were evaluated by MIC and FIC assays. In these assays, C. medica EO, d‐limonene and γ‐terpinene were effective against three pathogens of P. notoginseng with MIC values ranging from 0.12 to 12.05 mg/mL. The association between hymexazol and C. medica EO showed a high synergistic effect with lower FIC index values (FICi=0.31–2.00). Furthermore, C. medica EO was further assessed in P. notoginseng planted in a continuous cropping soil (CCS) and was found to reduce the disease incidence and disease severity compared with P. notoginseng planted in CCS only without EO addition. This finding suggested that C. medica EO has potential as a natural environmentally antifungal agent against pathogens of P. notoginseng, ensuring its safety.
Bone mesenchymal stem cell‐conditioned medium attenuates the effect of oxidative stress injury on NSCs by inhibiting the Notch1 signaling pathway
Authors: Niu Yang , Xia Xiang , Song PeiWen , Fang Huang , Dong FuLong , Tao Hui , Yang Chao , Shen CaiLiang
Published: March 2019

Numerous studies have demonstrated the therapeutic effect of bone mesenchymal stem cells on spinal cord injury (SCI), especially on neural stem cells (NSCs). However, the predominant mechanisms of bone mesenchymal stem cells (BMSCs) are unclear. Recently, some researchers have found that paracrine signaling plays a key role in the therapeutic capacity of BMSCs and emphasized that the protective effect of BMSCs may be due to paracrine factors. In this study, we aimed to investigate the potential mechanisms of BMSCs to protect NSCs. NSCs were identified by immunocytochemistry. The oxidative stress environment was simulated by H2O2 (50, 100, 200 μM) for 2 h. The apoptotic rate of the NSCs was detected via flow cytometry. Lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) activity were evaluated via corresponding assay kits. Western blot was used to detect the expressions of Notch1, HES1, caspase‐3, cleave caspase‐3, Bax, and Bcl‐2. We found that H2O2 could significantly induce the apoptosis of NSCs, increase LDH, MDA levels, and decrease SOD activity by activating the Notch1 signaling pathway. DAPT (the specific blocker of Notch1) and BMSC‐conditioned medium (BMSC‐CM) could significantly prevent the apoptotic effect and oxidative stress injury on NSCs that were treated with H2O2. We also revealed that BMSC‐CM could decrease the expression of Notch1, Hes1, cleave caspase‐3, Bax, and increases the expression of Bcl‐2 in NSCs, which was induced by H2O2. These results have revealed that BMSC‐CM can neutralize the effect against oxidative stress injury on the apoptosis of NSCs by inhibiting the Notch1 signaling pathway.
Drug‐coated balloon versus plain old balloon angioplasty in femoropopliteal disease: An updated meta‐analysis of randomized controlled trials
Authors: Anantha‐Narayanan Mahesh , Shah Samit M. , Jelani Qurat‐Ul‐Ain , Garcia Santiago , Ionescu Costin , Regan Christopher , Mena‐Hurtado Carlos
Published: March 2019

Background

Drug‐coated balloon (DCB) angioplasty has emerged as a mainstay of therapy for the treatment of peripheral arterial disease (PAD) involving the superficial femoral and popliteal arteries. We performed a meta‐analysis including all available randomized controlled trials (RCTs) to date which compare DCB to plain balloon angioplasty (POBA) in femoropopliteal disease (FPD).

Methods

Five databases were analyzed including EMBASE, PubMed, Cochrane, Scopus, and Web‐of‐Science from January 2000 to September 2018 for RCTs comparing DCB to POBA in patients with FPD. Heterogeneity was determined using Cochrane's Q‐statistics. Random effects model was used.

Results

Twenty‐two RCTs, including five trials of in‐stent restenosis (ISR) intervention, with 3,217 patients were included in the analysis. Mean follow‐up was approximately 21.6 ± 14.4 months. Overall, DCB use was associated with a 51% reduction in target vessel revascularization (TLR) when compared to POBA at follow‐up (relative risk [RR]: 0.49, 95% confidence interval [CI]: 0.40–0.61, P < 0.0001). Rates of TLR were 45% lower in the DCB group when compared to POBA in patients with ISR (RR: 0.55, 95% CI: 0.37–0.81, P = 0.002). DCB was associated with lower rates of binary stenosis, late lumen loss and higher primary safety endpoints. Major amputation and mortality were not different between DCB and POBA.

Conclusions

Use of DCBs is associated with improved vessel patency and a lower risk of TLR when compared to POBA in patients with FPD, especially in the setting of ISR. There was no difference in mortality between DCB and POBA in our meta‐analysis. Extended follow‐up of the available RCT data will be essential to analyze long‐term device‐related mortality.
In vitro test–retest repeatability of invasive physiological indices to assess coronary flow
Authors: Picard Fabien , Alansari Omar , Mogi Satoshi , van't Veer Marcel , Varenne Olivier , Adjedj Julien
Published: March 2019

Aims

Several invasive techniques are available in clinical practice to assess coronary flow. Nevertheless, the test–retest repeatability of these techniques in a controlled setting has not been reported. Therefore, we sought to evaluate fractional flow reserve (FFR), coronary flow reserve (CFR), index of microvascular resistance (IMR), and absolute coronary blood flow (ABF) with absolute microvascular resistance (AMR) test–retest repeatability using a coronary flow simulator.

Methods and Results

Using a coronary flow simulator (FFR WetLab version 2.0; Abbott Vascular, Santa Clara, CA), we created stenoses ranging from 0% to 70%, with 10% increments. Three different flows were established with their hyperemic phases, and two consecutive measurements were obtained, evaluating the following indices: FFR, CFR, IMR, ABF, and AMR, using a pressure/temperature wire and an infusion catheter. One hundred and thirty‐eight pairs of measurements were performed. Test–retest reliability was compared in 48 FFR, 18 CFR, 24 IMR, 24 ABF, and 24 AMR. Test–retest repeatability showed excellent reproducibility for FFR, ABF, and AMR; respectively 0.98 (0.97–0.99), 0.92 (0.81–0.97) and 0.91 (0.79–0.96) (P < 0.0001 for all). However, test–retest repeatability was weaker for IMR and poor for CFR; respectively 0.53 (0.16–0.77) (P = 0.006) and 0.27 (−0.26–0.67) (P = 0.30).

Conclusions

Using a coronary flow simulator, FFR and ABF with AMR had excellent test–retest reliability. IMR and CFR demonstrated weaker test–retest reliability.
Environmental Applications of Boron‐Doped Diamond Electrodes: 1. Applications in Water and Wastewater Treatment
Authors: Nidheesh P. V. , Divyapriya G. , Oturan Nihal , Trellu Clément , Oturan Mehmet A.
Published: March 2019

Over the past few decades, environmental applications of the boron‐doped diamond (BDD) electrode are reported to be vast and versatile. Applications of BDD electrodes in the field of electrochemical advanced oxidation processes (EAOPs) for the abatement of toxic persistent organic pollutants are significant, owing to the easy and effective way of treatment. This article focuses on highlighting and summarizing the applications of the BDD electrode for the treatment of different synthetic and real wastewaters, such as those involved in pharmaceuticals and personal care products, pesticides/herbicides, dyes, etc. We also review the processes and methodologies involving the synthesis of BDD electrodes and summarize the desirable characteristic features required for the application of EAOPs. Applications of BDD electrodes for the treatment of wastewater through different EAOPs, including anodic oxidation, electro‐Fenton, coupling processes such as electro‐Fenton pyrite, bioelectro‐Fenton, and their recent advancements are also discussed in detail. It envisages the greater potential for complete treatment of different toxic wastewater effluents. This Review shows that the application of BDD electrodes in the field of wastewater treatment is tremendous and proves to be a promising material for future perspectives.
Environmental Applications of Boron‐Doped Diamond Electrodes: 2. Soil Remediation and Sensing Applications
Authors: Trellu Clément , Chakraborty Shampa , Nidheesh P. V. , Oturan Mehmet A.
Published: March 2019

The chemical stability and electrocatalytic properties of boron‐doped diamond (BDD) electrodes give rise to various applications. While wastewater treatment is the most widely studied field, the use of BDD for soil remediation and environmental sensing is currently investigated more and more. With regards to soil remediation, promising results have been reported for the treatment of soil washing solutions. Anodic oxidation using BDD at high current density allows high mineralization rates of biorefractory soil pollutants and extracting agents to be reached. At low current density, selective degradation of target pollutants has been achieved, thus allowing the reuse of extracting agents for further soil washing steps. BDD‐based electrochemical sensors have been studied for chemical oxygen demand determination, pesticide/pharmaceutical detection as well as other applications such as pH, O2 and analysis of various organic and inorganic compounds. Low detection limits, wide linear ranges and low standard deviations have been achieved. The main reasons behind the superiority of BDD sensors are the chemical stability, wide applicability and resistance of BDD towards biofouling. The beauty of BDD sensing is that it can work for a variety of organic and inorganic compounds under many physicochemical parameters.