bluuebunny/crossref_metadata_2025 huggingface dataset:
Acid‐Triggered Charge‐Convertible Graphene‐Based All‐in‐One Nanocomplex for Enhanced Genetic Phototherapy of Triple‐Negative Breast Cancer
Authors: Wu Chunhui , Tian Yuan , Zhang Yingxue , Xu Jiming , Wang Yikun , Guan Xiaotian , Li Tingting , Yang Hong , Li Shun , Qin Xiang , Liu Yiyao
Published: December 2019

Highly efficient and stimulus‐responsive nanomedicines for cancer treatment are currently receiving tremendous attention. In this study, an acid‐triggered charge‐reversible graphene‐based all‐in‐one nanocomplex is appropriately designed by surface modification with multilayer polymers and simultaneous co‐transportation of photosensitizer indocyanine green (ICG) and oligonucleotide inhibitor of miR‐21 (miR‐21i) to achieve highly efficient genetic phototherapy in a controlled manner. The nanocomplex (denoted as GPCP/miR‐21i/ICG) effectively protects miR‐21i from degradation and exhibits excellent photothermal/photochemical reactive oxygen species (ROS) generation as well as fluorescence imaging ability. The cargoes ICG and miR‐21i can significantly be released at acidic pH compared with normal physiological medium and escaped from endosomes/lysosomes due to the acid‐triggered charge reversal effect. Typically, the released miR‐21i downregulate the endogenous miR‐21 and result in the upregulation of the target proteins PTEN and Bax, thus increasing the phototherapeutic efficiency of ICG. High in vivo anticancer efficiency against the MDA‐MB‐231 triple‐negative breast cancer (TNBC) model is obtained due to the combination of genetic regulation of miR‐21i and the photokilling effect of ICG. This work highlights the great potential of this smart nanocomplex as an attractive modality of gene‐photo combined treatment of cancer, especially for intractable TNBC.
Developments of Diketopyrrolopyrrole‐Dye‐Based Organic Semiconductors for a Wide Range of Applications in Electronics
Authors: Liu Qian , Bottle Steven E. , Sonar Prashant
Published: December 2019

In recent times, fused aromatic diketopyrrolopyrrole (DPP)‐based functional semiconductors have attracted considerable attention in the developing field of organic electronics. Over the past few years, DPP‐based semiconductors have demonstrated remarkable improvements in the performance of both organic field‐effect transistor (OFET) and organic photovoltaic (OPV) devices due to the favorable features of the DPP unit, such as excellent planarity and better electron‐withdrawing ability. Driven by this success, DPP‐based materials are now being exploited in various other electronic devices including complementary circuits, memory devices, chemical sensors, photodetectors, perovskite solar cells, organic light‐emitting diodes, and more. Recent developments in the use of DPP‐based materials for a wide range of electronic devices are summarized, focusing on OFET, OPV, and newly developed devices with a discussion of device performance in terms of molecular engineering. Useful guidance for the design of future DPP‐based materials and the exploration of more advanced applications is provided.
High‐Efficiency White Organic Light‐Emitting Diodes Based on All Nondoped Thermally Activated Delayed Fluorescence Emitters
Authors: Zhang Guang‐Hui , Xie Feng‐Ming , Wu Kailong , Li Yan‐Qing , Xie Guohua , Zou Shi‐Jie , Shen Yang , Zhao Xin , Yang Chuluo , Tang Jian‐Xin
Published: December 2019

While phosphorescent white organic light‐emitting diodes (WOLEDs) have attracted great attention due to their high efficiencies, the complex device structure (e.g., host–dopant systems) and the adoption of novel metals (e.g., Ir or Pt) inevitably increase the fabrication complication and manufacturing cost. Herein, a simple and cost‐effective structure based on all thermally activated delayed fluorescence (TADF) emitters is proposed to achieve high‐performance WOLEDs. The key feature of the WOLED structure is to insert an orange‐red TADF ultrathin layer within the nondoped blue TADF emitter, which can significantly reduce the energetic loss and therefore the operating voltage during electron–photon conversion process. After optimizing the energy transfer and exciton formation region between two color‐complementary TADF emitters, the all‐fluorescence WOLEDs exhibit an extremely high external quantum efficiency of 24.2% with a turn‐on voltage of 2.5 V and a color rendering index of >80. It is anticipated that the results will pave the way to the realization of high‐efficiency and low‐cost WOLEDs that can outperform the typical phosphorescent devices.
Engineering the Tenogenic Niche In Vitro with Microenvironmental Tools
Authors: Ryan Christina N. M. , Zeugolis Dimitrios I.
Published: December 2019

Tendon injuries affect millions of people worldwide annually. Considering that traditional approaches (e.g., surgery, exercise, steroid injections) have failed to reinstate tendon function following injury, recent efforts have been directed toward the development of cell‐based tendon repair and regeneration therapies. However, tenocytes readily lose their phenotype in culture and implantation of naïve stem cells is often associated with ectopic bone formation. To this end, there has been a surge in efforts to engineer the optimal tenogenic niche in vitro that will either maintain the phenotype of tenocytes or direct other cell types toward tenogenic lineage. Mono‐domain biochemical (e.g., media supplements, substrate coatings, oxygen tension), biological (e.g., growth factors, co‐culture systems), or biophysical (topography, rigidity, mechanical stimulation, macromolecular crowding) cues that replicate the native tendon milieu have shown some level of success, but they have failed to provide a functional therapy. Considering the complexity of the native tissue microenvironment together with recent advances in chemistry, biology, and engineering, it is anticipated that in the years to come multifactorial approaches are likely to yield a functional cell‐based therapy for tendon repair and regeneration.
Suppression of Concentration Quenching in Ortho‐Substituted Thermally Activated Delayed Fluorescence Emitters
Authors: Abroshan Hadi , Cho Eunkyung , Coropceanu Veaceslav , Brédas Jean‐Luc
Published: December 2019

Thermally activated delayed fluorescence (TADF) emitters are typically embedded at low concentrations in a host matrix to suppress emission quenching. However, recent studies indicate that TADF compounds such as the oBFCzTrz emitter (5‐(2‐(4,6‐diphenyl‐1,3,5‐triazin‐2‐yl)phenyl)‐5H‐benzofuro[3,2‐c]carbazole) display insignificant concentration quenching dependence. To understand the origin of this beneficial behavior, the morphology, dynamics, electronic properties, and charge transport and energy transfer in a neat film of the oBFCzTrz emitter are characterized via molecular dynamic simulations combined with density functional theory calculations. The emissive layer shows glassy behavior at room temperature with the twisted configurations of the emitter molecules allowing for intramolecular donor–acceptor interactions, but disfavoring intermolecular π–π stacking, which suppresses the formation of intermolecular aggregate states. As a result, the electronic structure and luminescence of oBFCzTrz are not significantly altered by intermolecular interactions. The calculated diffusion lengths of the singlet and triplet excitons are small enough that there occurs no substantial concentration quenching effect. Overall, the design of new TADF emitters with structural motifs similar to those of oBFCzTrz offers potential to develop efficient organic light‐emitting diode devices in which the emissive layers are entirely composed of TADF molecules without the need for a host component.
Biosynthesis and chemical characterization of polydopamine‐capped silver nanoparticles for the treatment of acute myeloid leukemia in comparison to doxorubicin in a leukemic mouse model
Authors: Hemmati Saba , Joshani Zeinab , Zangeneh Akram , Zangeneh Mohammad Mahdi
Published: December 2019

The recent study reveals the cytotoxicity, antioxidant, and anti‐acute myeloid leukemia properties of polydopamine (PDA)‐capped silver nanoparticles (AgNPs) compared to doxorubicin in a leukemic mouse model. The synthesized AgNPs were characterized using different techniques including ultraviolet–visible spectroscopy (UV–Vis.), Fourier‐transform infrared spectroscopy (FT‐IR) spectroscopy, X‐ray diffraction (XRD), energy Dispersive X‐ray Spectrometry (EDS), field emission‐scanning electron microscopy (FE‐SEM), and transmission electron microscopy (TEM). FE‐SEM and TEM images revealed a uniform spherical morphology and average diameters of 15–25 nm for the nanoparticles. Also, in XRD analysis, ~20 nm was measured for the crystal size of nanoparticles. The results of the biological experiments were fed into SPSS‐22 software and analyzed by one‐way ANOVA. In the biological in vitro part of this study, AgNPs similar to doxorubicin had low cell viability dose‐dependently against Human HL‐60/vcr, 32D‐FLT3‐ITD, and Murine C1498 cell lines without any cytotoxicity on HUVEC cell line. In this study, 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) test revealed similar antioxidant potentials for doxorubicin and AgNPs. In the biological in vivo part of this study, 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 control, untreated, doxorubicin, AgNPs, PDA, and AgNO3. AgNPs similar to doxorubicin, significantly (p ≤ 0.05) reduced the pro‐inflammatory cytokines, and the total white blood cell (WBC), blast, monocyte, neutrophil, eosinophil, and basophil counts and enhanced the anti‐inflammatory cytokines and the platelet, lymphocyte, and red blood cell (RBC) parameters as compared to the untreated mice. By quantitative real‐time polymerase chain reaction (PCR), sphingosine‐1‐phosphate receptor‐1 (S1PR1) and sphingosine‐1‐phosphate receptor‐5 (S1PR5) mRNA expression in lymphocytes were significantly (p ≤ 0.05) raised by treating the leukemic mice with the AgNPs and doxorubicin. Above results confirm the therapeutic effects of AgNPs on acute myeloid leukemia in the leukemic mice. Further clinical trials are necessary for confirmation these remedial properties of AgNPs in human.
Assessment of compatibilization role of nanoclay in immiscible polystyrene/ethylene–octene copolymer blends via wide‐angle X‐ray scattering, microstructure, rheological analyses, and mechanical properties
Authors: Kiani Fatemeh , Entezam Mehdi , Khonakdar Hossein Ali , Jafari Seyed Hassan , Callsen Christoph , Altstädt Volker
Published: December 2019

Polystyrene (PS)/ethylene–octene copolymer (EOC) blends with 80/20 wt % composition containing different amounts (0, 1.0, 2.5, 5.0 and 7.5 wt %) of an organically modified nanoclay were prepared by one‐step melt‐mixing method. Also, the EOC‐rich blends with 80 wt % EOC content loaded with 0 and 5.0 wt % of the nanoclay were prepared under the similar processing conditions. Presence of both PS and EOC chains in between clay layers localized at the interface of the blends could be deduced by X‐ray diffraction analysis, which suggested formation possibility of PS‐EOC physical structures at the blend interface. Transmission electron microscopy results confirmed that clay nanoparticles were mainly localized at the interface of the blends and also partly in the PS and EOC components of the systems. The localization of the nanoclay was also described by the linear viscoelastic melt rheological studies. It is also revealed that nanoclay had stronger interactions with PS than EOC. This is reflected in the higher tensile properties in the PS‐rich system. The analysis of morphology of the developed systems by emulsification curve revealed that the optimum amount of nanoclay to modify PS‐rich blend is 2.5 wt %. At this clay loading, the blend exhibited the highest impact resistance. According to the overall results, suitability of nanoclay was confirmed for compatibilization of the PS/EOC blends. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48748.
Solid‐state shear milling method to prepare PA12/boron nitride thermal conductive composite powders and their selective laser sintering 3D‐printing
Authors: Yang Lu , Wang Lequan , Chen Yinghong
Published: December 2019

The selective laser sintering (SLS) is one of the most important 3D‐printing technologies. However, the challenges in SLS could be in the limited high material cost and single material performance. Development of high‐performance and multifunctional copowders suitable for SLS is of great importance. Here, polyamide 12 (PA12)/boron nitride (BN) thermal conductive copowders suitable for SLS were successfully prepared through solid state shear milling (S3M) technology in combination with cryogenic pulverization technology. The particle size, morphology, grafting reaction between PA12 and BN, rheology behavior, and coalescence behavior of the obtained PA12/BN copowders were carefully investigated. The optimal amount of silica flow additive (0.5 wt %) was determined to achieve the good powder flowability. Under the optimum 3D‐printing conditions, the fabrication of parts with high BN loading could be achieved. When BN content was at 40 wt %, the flexural strength could reach 10.6 MPa and the thermal conductivity could reach 0.55 W/m·k, 77% higher than that of pure PA12. After treated with phenolic epoxy resin, the tensile strength and flexural strength of the printed parts with 40 wt % BN loading could reach 14.2 and 25.6 MPa, which were 130 and 115% higher than those of the untreated 3D‐printed parts, respectively. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48766.
Organocatalyzed Synthesis of Functionalized Quinolines
Authors: Li Lian‐Hua , Niu Zhi‐Jie , Liang Yong‐Min
Published: December 2019

As one of the most widely investigated compound skeleton, quinolines possess important medicinal and biological activities. As such, a great number of literatures, including reviews, have reported various methodologies to construct quinolines. Recently, organocatalyzed reactions have attracted the attention of organic chemists due to its being “green” because the reactions avoid the use of toxic metals. In this review, various distinctive contributions are surveyed with specific emphasis on organocatalyzed reactions for quinoline core constructions.
Identification of Pediatric Autism Spectrum Disorder Cases Using Health Administrative Data
Authors: Bickford Celeste D. , Oberlander Tim F. , Lanphear Nancy E. , Weikum Whitney M. , Janssen Patricia A. , Ouellette‐Kuntz Helene , Hanley Gillian E.
Published: December 2019

Administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases in epidemiological studies. However, validation studies on this mode of case ascertainment have lacked access to high‐quality clinical diagnostic data and have not followed published reporting guidelines. We report on the diagnostic accuracy of using readily available health administrative data for pediatric ASD case ascertainment. The validation cohort included almost all the ASD‐positive children born in British Columbia, Canada from April 1, 2000 to December 31, 2009 and consisted of 8,670 children in total. 4,079 ASD‐positive and 2,787 ASD‐negative children were identified using Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview‐Revised (ADI‐R) assessments done through the British Columbia Autism Assessment Network (BCAAN). An additional 1,804 ADOS/ADI‐R assessed ASD‐positive children were identified using Ministry of Education records. This prospectively collected clinical data (the diagnostic gold standard) was then linked to each child's physician billing and hospital discharge data. The diagnostic accuracy of 11 algorithms that used the administrative data to assign ASD case status was assessed. For all algorithms, high positive predictive values (PPVs) were observed alongside low values for other measures of diagnostic accuracy illustrating that PPVs alone are not an adequate measure of diagnostic accuracy. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders. Utilizing these data may result in misclassification bias. Methodologically sound, region‐specific validation studies are needed to support the use of administrative data for ASD case ascertainment. Autism Res 2020, 13: 456–463. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Health administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases for research purposes. However, previous validation studies on this sort of case identification have lacked access to high‐quality clinical diagnostic data and have not followed published reporting guidelines. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders.
MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma
Authors: Mei Zi , Zhang Kai , Lam Alfred King‐Yin , Huang Junwen , Qiu Feng , Qiao Bin , Zhang Yi
Published: December 2019

The modification of chimeric antigen receptor (CAR) endowing T cells with tumor‐specific cytotoxicity induces antitumor immunity. However, the structural characteristics of solid tumors, the loss of specific antigens, and the strong immunosuppressive environment are challenges to treat solid tumors with CAR‐T therapy. The purpose of our study was to find and verify the potentials of CAR‐T therapies for patients with head and neck squamous cell carcinoma (HNSCC). First, we selected MUC1 as our research target and verified its differential expression in cancer tissues and adjacent non‐neoplastic tissues (ANNT). Next, we constructed a second‐generation CAR and validated the cytotoxic function in vitro. In our study, we found that exogenous addition human IL22 recombinant protein could increase the MUC1 expression and enhance the function of T cells. In addition, we constructed a fourth‐generation CAR that secretes IL22. Finally, we verified the antitumor function of two different CAR‐T cells in vitro and in vivo, respectively. CAR‐MUC1‐IL22 T cells were found to have a stronger and more effective cytotoxic function against MUC1 + HNSCC cells. Taken together, these results demonstrate the potential effectiveness of CAR‐T in the treatment of patients with HNSCC and provide evidence‐based of MUC1 + CAR‐T therapy.
Herpetic optic perineuritis presenting as classic abducens nerve palsy
Authors: Abid Muhammad Abbas , Mughal Mustafa , Capelli Peter , Abid Muhammad Bilal
Published: December 2019

Optic perineuritis is a rare manifestation of herpes zoster ophthalmicus (HZO). Relative afferent pupillary defect (RAPD) is an important early clue to an impending nerve involvement, and robust clinical examination allows early detection of such rare metachronous manifestation of cutaneous HZ and institution of timely management for such sight‐threatening conditions.
The evaluation of oxidative stress in patients with psoriasis vulgaris and atopic dermatitis by measuring the urinary level of 8‐hydroxy‐2′‐deoxyguanosine
Authors: Shimamoto Junko , Kurokawa Teruo , Tanizaki Hideaki , Moriwaki Shinichi
Published: December 2019

Objectives

Recent studies have revealed the relationship of oxidative stress to various medical disorders, such as cancer and ischemic heart disease. Atopic dermatitis (AD) and psoriasis vulgaris (PV) are chronic inflammatory dermatoses, and oxidative stress is presumed to be involved in the development of these diseases as well as their becoming refractory.

Methods

In this study, we collected urine samples from 40 AD patients, 25 PV patients, and 39 healthy volunteers (HVs). The level of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) in each urine sample was measured and then compared among the groups. We also evaluated the relationship between the AD and PV severity and the urinary 8‐OHdG level.

Results

We found that the urinary 8‐OHdG level was significantly higher in the AD and PV groups than in the HV group. We did not, however, identify an association between the 8‐OHdG level and the age, disease duration, or disease severity in the AD or PV groups.

Conclusions

Our results demonstrated an association between urinary 8‐OHdG and the development of AD and PV, suggesting that both are oxidative stress‐related diseases. Treatments or lifestyle improvements focused on anti‐oxidation may therefore be vital for preventing these chronic dermatoses from developing and becoming refractory.
The role of end‐diastolic myocardial fibre stretch on infarct extension
Authors: Leong Chin Neng , Dokos Socrates , Andriyana Andri , Liew Yih Miin , Chan Bee Ting , Abdul Aziz Yang Faridah , Chee Kok‐Han , Sridhar Ganiga Srinivasaiah , Lim Einly
Published: December 2019

Myocardial infarct extension, a process involving the enlargement of infarct and border zone, leads to progressive degeneration of left ventricular (LV) function and eventually gives rise to heart failure. Despite carrying a high risk, the causation of infarct extension is still a subject of much speculation. In this study, patient‐specific LV models were developed to investigate the correlation between infarct extension and impaired regional mechanics. Subsequently, sensitivity analysis was performed to examine the causal factors responsible for the impaired regional mechanics observed in regions surrounding the infarct and border zone. From our simulations, fibre strain, fibre stress and fibre stress‐strain loop (FSSL) were the key biomechanical variables affected in these regions. Among these variables, only FSSL was correlated with infarct extension, as reflected in its work density dissipation (WDD) index value, with high WDD indices recorded at regions with infarct extension. Impaired FSSL is caused by inadequate contraction force generation during the isovolumic contraction and ejection phases. Our further analysis revealed that the inadequacy in contraction force generation is not necessarily due to impaired myocardial intrinsic contractility, but at least in part, due to inadequate muscle fibre stretch at end‐diastole, which depresses the ability of myocardium to generate adequate contraction force in the subsequent systole (according to the Frank‐Starling law). Moreover, an excessively stiff infarct may cause its neighbouring myocardium to be understretched at end‐diastole, subsequently depressing the systolic contractile force of the neighbouring myocardium, which was found to be correlated with infarct extension.
Mechanistic Investigation of a Hybrid Zn/V2O5 Rechargeable Battery with a Binary Li+/Zn2+ Aqueous Electrolyte
Authors: Batyrbekuly Dauren , Cajoly Sabrina , Laïk Barbara , Pereira‐Ramos Jean‐Pierre , Emery Nicolas , Bakenov Zhumabay , Baddour‐Hadjean Rita
Published: December 2019

Low‐cost, easily processable, and environmentally friendly rechargeable aqueous zinc batteries have great potential for large‐scale energy storage, which justifies their receiving extensive attention in recent years. An original concept based on the use of a binary Li+/Zn2+ aqueous electrolyte is described herein for the case of the Zn/V2O5 system. In this hybrid, the positive side involves mainly the Li+ insertion/deinsertion reaction of V2O5, whereas the negative electrode operates according to zinc dissolution–deposition cycles. The Zn//3 mol L−1 Li2SO4–4 mol L−1 ZnSO4///V2O5 cell worked in the narrow voltage range of 1.6–0.8 V with capacities of approximately 136–125 mA h g−1 at rates of C/20–C/5, respectively. At 1 C, the capacity of 80 mA h g−1 was outstandingly stable for more than 300 cycles with a capacity retention of 100 %. A detailed structural study by XRD and Raman spectroscopy allowed the peculiar response of the V2O5 layered host lattice on discharge–charge and cycling to be unraveled. Strong similarities with the well‐known structural changes reported in nonaqueous lithiated electrolytes were highlighted, although the emergence of the usual distorted δ‐LiV2O5 phase was not detected on discharge to 0.8 V. The pristine host structure was restored and maintained during cycling with mitigated structural changes leading to high capacity retention. The present electrochemical and structural findings reveal a reaction mechanism mainly based on Li+ intercalation, but co‐intercalation of a few Zn2+ ions between the oxide layers cannot be completely dismissed. The presence of zinc cations between the oxide layers is thought to relieve the structural stress induced in V2O5 under operation, and this resulted in a limited volume expansion of 4 %. This fundamental investigation of a reaction mechanism operating in an environmentally friendly aqueous medium has not been reported before.
Flow control with plasma‐based actuator in different velocity regimes: Momentum and heat transfer effects
Authors: Mehdipoor Mostafa , Sohbatzadeh Farshad , Zabihpoor Mahmood
Published: December 2019

In this study, control of the airflow by the direct current (DC) electrical discharge with bare electrodes has been investigated in different velocity regimes. The discharge characteristics of the plasma model are obtained numerically. An induced electrohydrodynamic (EHD) force on neutral flow was characterized based on momentum transfer from charged particles. The change in the incident flow parameters was studied by applying Navier–Stokes (N‐S) equations, considering source terms arising from a weakly ionized plasma. The effect of the discharge on the low‐ and high‐speed flow was simulated in this study. It was concluded that the changes of the velocity profile, airflow pressure, and oblique shock wave could be attributed to the EHD force from a nonthermal plasma to the incoming airflow. It was seen that the incident airflow is accelerated also by the induced EHD force. Our results show that the most important mechanism in the plasma‐based flow control is the momentum transfer from the electrical discharge to the incident flow and that the gas heating has no significant role.
Simultaneous measurement of perillyl alcohol and its metabolite perillic acid in plasma and lung after inhalational administration in Wistar rats
Authors: de Lima Daniela Carneiro , Rodrigues Silvana Vianna , Boaventura Gilson Teles , Cho Hee‐Yeon , Chen Thomas C. , Schönthal Axel H. , Da Fonseca Clovis Orlando
Published: December 2019

The inhalational administration of drugs is a practical and non‐invasive approach with the potential to reduce side effects and with a quick onset of therapeutic activity. Perillyl alcohol (POH) is a monoterpene with antitumor activity that currently is undergoing clinical evaluation as an inhalational anticancer agent. A detection method was developed that will be applicable to pharmacokinetic studies of not only POH, but also its longer‐lived main metabolite, perillic acid (PA), in lung tissue and plasma after inhalational delivery. The anticancer activity of POH was investigated in vitro with the use of various lung cancer cell lines. Toxicity was established by a standard MTT assay, and apoptosis markers were analyzed by Western blot. For the detection of POH and PA in lungs and plasma, albino Wistar rats were used that were exposed to POH inhalation. Tissues were subjected to chromatographic separation on an Agilent Zorbax Eclipse XDB C18 column, followed by detection of absorption in the ultraviolet (UV) range. In vitro, POH exerted cytotoxic activity against six different lung tumor cell lines, and apoptotic cell death was indicated by induction of active caspase 3 and cleavage of poly (ADP‐ribose) polymerase 1 (PARP1). These results demonstrate that inhalational delivery of POH results in effective biodistribution and metabolism of POH in the systemic circulation. In addition, our study introduces a simple, rapid HPLC‐UV method with high accuracy for simultaneous detection of POH and its metabolite PA in plasma, and for sensitive detection of PA in lung tissue, which should prove useful for applications in clinical studies.
Less invasive ventricular reconstruction for ischaemic heart failure
Authors: Klein Patrick , Anker Stefan D. , Wechsler Andrew , Skalsky Ivo , Neuzil Petr , Annest Lon S. , Bifi Mauro , McDonagh Theresa , Frerker Christian , Schmidt Tobias , Sievert Horst , Demaria Anthony N. , Kelle Sebastian
Published: December 2019

Aims

Surgical ventricular reconstruction to remodel, reshape, and reduce ventricular volume is an effective therapy in selected patients with chronic heart failure (HF) of ischaemic aetiology. The BioVentrix Revivent TC System offers efficacy comparable to conventional surgical ventricular reconstruction and is less invasive utilizing micro‐anchor pairs to exclude scarred myocardium on the beating heart. Here, we present 12‐months follow‐up data of an international multicenter study.

Methods and results

Patients were considered eligible for the procedure when they presented with symptomatic HF [New York Heart Association (NYHA) class ≥II], left ventricular (LV) dilatation and dysfunction caused by myocardial infarction, and akinetic and/or dyskinetic transmural scarred myocardium located in the anteroseptal, anterolateral, and/or apical regions. A total of 89 patients were enrolled and 86 patients were successfully treated (97%). At 12 months, a significant improvement in LV ejection fraction (29 ± 8% vs. 34 ± 9%, P < 0.005) and a reduction of LV volumes was observed (LV end‐systolic and end‐diastolic volume index both decreased: 74 ± 28 mL/m2 vs. 54 ± 23 mL/m2, P < 0.001; and 106 ± 33 mL/m2 vs. 80 ± 26 mL/m2, respectively, P < 0.0001). Four patients (4.5%) died in hospital and survival at 12 months was 90.6%. At baseline, 59% of HF patients were in NYHA class III compared with 22% at 12‐month follow‐up. Improvements in quality of life measures (Minnesota Living with Heart Failure Questionnaire 39 vs. 26 points, P < 0.001) and 6‐min walking test distance (363 m vs. 416 m, P = <0.001) were also significant.

Conclusions

Treatment with the Revivent TC System in patients with symptomatic HF results in significant and sustained reduction of LV volumes and improvement of LV function, symptoms, and quality of life.
Clinical value of pre‐discharge bio‐adrenomedullin as a marker of residual congestion and high risk of heart failure hospital readmission
Authors: Pandhi Paloma , ter Maaten Jozine M. , Emmens Johanna E. , Struck Joachim , Bergmann Andreas , Cleland John G. , Givertz Michael M. , Metra Marco , O'Connor Christopher M. , Teerlink John R. , Ponikowski Piotr , Cotter Gad , Davison Beth , van Veldhuisen Dirk J. , Voors Adriaan A.
Published: December 2019

Aims

Recently, bio‐adrenomedullin (bio‐ADM) was proposed as a congestion marker in heart failure (HF). In the present study, we aimed to study whether bio‐ADM levels at discharge from a hospital admission for worsening HF could provide additional information on (residual) congestion status, diuretic dose titration and clinical outcomes.

Methods and results

Plasma bio‐ADM was measured in 1236 acute HF patients in the PROTECT trial at day 7 or discharge. Median discharge bio‐ADM was 33.7 [21.5–61.5] pg/mL. Patients with higher discharge bio‐ADM levels were hospitalised longer, had higher brain natriuretic peptide levels, and poorer diuretic response (all P < 0.001). Bio‐ADM was the strongest predictor of discharge residual congestion (clinical congestion score > 3) (odds ratio 4.35, 95% confidence interval 3.37–5.62; P < 0.001). Oedema at discharge was one of the strongest predictors of discharge bio‐ADM (β = 0.218; P < 0.001). Higher discharge loop diuretic doses were associated with a poorer diuretic response during hospitalisation (β = 0.187; P < 0.001) and higher bio‐ADM levels (β = 0.084; P = 0.020). High discharge bio‐ADM levels combined with higher use of loop diuretics were independently associated with a greater risk of 60‐day HF rehospitalisation (hazard ratio 4.02, 95% confidence interval 2.23–7.26; P < 0.001).

Conclusion

In hospitalised HF patients, elevated pre‐discharge bio‐ADM levels were associated with higher discharge loop diuretic doses and reflected residual congestion. Patients with combined higher bio‐ADM levels and higher loop diuretic use at discharge had an increased risk of rehospitalisation. Assessment of discharge bio‐ADM levels may be a readily applicable marker to identify patients with residual congestion at higher risk of early hospital readmission.
Consultation prevalence among children, adolescents and young adults with pain conditions: A description of age‐ and gender differences
Authors: Bondesson E. , Olofsson T. , Caverius U. , Schelin M. E. C. , Jöud A.
Published: December 2019

Background

Pain is a common complaint presented in healthcare, but most epidemiological pain research has focused either on single pain conditions or on the adult population. The aim of this study was to investigate the 2017 consultation prevalence of a wide range of pain conditions in the general population of young people.

Methods

We used the Skåne Healthcare Register, covering prospectively collected data on all healthcare delivered (primary and secondary care) to the population in the region of Skåne, southern Sweden (population 2017 n = 1,344,689). For individuals aged 1–24 in 2017 (n = 373,178), we calculated the consultation prevalence, stratified by sex and age, and the standardised morbidity ratio (SMR) to assess overall healthcare consultation.

Results

A total of 58,981 (15.8%) individuals consulted at least once for any of the predefined pain conditions. Of these, 13.5% (n = 7,996) consulted four or more times for pain. Abdominal pain, joint pain/myalgia, headache and back/neck pain were the most common complaints. Overall, females had higher consultation prevalence than males: 17.6% versus 14.1% (p < .0001). SMR was 1.82 (95% CI = 1.74–1.87) for females with pain and 1.51 (95% CI = 1.42–1.56) for males with pain. Consultation prevalence increased with age, but this pattern varied between sex and pain condition.

Conclusions

Among individuals under the age of 25, a significant proportion consult for pain already in early ages, and they also have high healthcare consultation rates for conditions other than pain. The even higher consultation rates among young females need additional attention, both in the clinic and in research.

Significance

We present comprehensive 1‐year healthcare consultation prevalence data covering all levels of care. A significant proportion of children, adolescents and young adults consult for different pain conditions at multiple occasions warranting greater clinical awareness.
Exploratory Multicriteria Decision Analysis of Utility‐Scale Battery Storage Technologies for Multiple Grid Services Based on Life‐Cycle Approaches
Authors: Baumann Manuel , Peters Jens , Weil Marcel
Published: December 2019

Herein, a multicriteria decision‐making analysis (MCDA) of eight different utility‐scale battery storage technologies for four different application areas, involving 72 relevant stakeholders from industry and academia for criteria selection and weighting, is presented. The assessment is conducted for economic, environmental, technological, and social criteria using a combination of the analytic hierarchy process and technique for order preference by similarity to ideal solution. It includes a full life‐cycle costing and life‐cycle assessment using current data. Indicative rankings show that most lithium‐ion batteries can be recommended for all application areas. Lead‐acid batteries achieve rather low scores depending on the viewed application, but including a recycling scenario for this technology might lead to significant changes in final scores and rankings. This is also true for the redox flow battery. Furthermore, the weights provided by the stakeholders are very dispersing, leading to a low consensus about the relevance of the used criteria. In particular, social criteria are not well differentiated in the current state and do not add significant distinguishing features between different battery technologies.
Role of ocular cytology in vernal keratoconjunctivitis
Authors: Bruschi Gaia , Ghiglioni Daniele G. , Osnaghi Silvia , Rosazza Chiara , Pires Marafon Denise , Landi Massimo , Marchisio Paola G.
Published: December 2019

Background

Children with vernal keratoconjunctivitis (VKC) present symptoms that are similar to other ocular allergies, but more pronounced, and are controlled using topical steroids. To avoid excessive and prolonged use of topical steroid eye drops, over the past 20 years galenic eye drops of cyclosporine with a concentration of 1% to 2% and tacrolimus with a concentration of 0.1% have been introduced as a treatment for the severe and unresponsive forms. The main symptoms of VKC occur most frequently during the spring and tend to get worse during the summer, meaning that affected children tend to avoid exposure to sunlight. The aim of this study was to assess the most common cell types present in the conjunctiva of children with VKC, how ocular treatment can influence them, and whether affected children express a typical conjunctival pattern, which could be useful as a pathognomonic pattern of VKC, allowing us to study this rare eye disease.

Method

This was a cohort study of 56 children, of whom 17 were not receiving any treatment at the time of testing, 14 were using steroid eye drops or had taken them in the previous 10 days, and 25 were treated with cyclosporine eye drops or tacrolimus eye drops 0.1%.

Result

Children in group 1 (no topical therapy) express more epithelial cells, neutrophils, mast cells, eosinophils, and lymphocytes than the other two groups.

Conclusion

Given the ease of performance, when conducting further longitudinal studies, the conjunctival cytology examination could be used, on the one hand, to diagnose VKC, especially when the clinical diagnosis is uncertain, and, on the other, to follow disease evolution and monitor the response to topical treatment.
The 6‐minute walk test is a good predictor of cardiorespiratory fitness in childhood cancer survivors when access to comprehensive testing is limited
Authors: Mizrahi David , Fardell Joanna E. , Cohn Richard J. , Partin Robyn E. , Howell Carrie R. , Hudson Melissa M. , Robison Leslie L. , Ness Kirsten K. , McBride Jamie , Field Penelope , Wakefield Claire E. , Simar David
Published: December 2019

Cardiovascular disease is up to 10 times more likely among childhood cancer survivors compared to siblings. Low cardiorespiratory fitness is a modifiable risk‐factor for cardiovascular diseases. Yet, cardiorespiratory fitness is not routinely screened in pediatric oncology, and healthy VO2max cut‐points are unavailable. We aimed to predict cardiorespiratory fitness by developing a simple algorithm and establish cut‐points identifying survivors’ cardiovascular fitness health‐risk zones. We recruited 262 childhood cancer survivors (8–18 years old, ≥1‐year posttreatment). Participants completed gold‐standard cardiorespiratory fitness assessment (Cardiopulmonary Exercise Test [CPET; VO2max]) and 6‐minute walk test (6MWT). Associations with VO2max were included in a linear regression algorithm to predict VO2max, which was then cross‐validated. We used Bland–Altman's limits of agreement and Receiver Operating Characteristic curves using FITNESSGRAM's “Healthy Fitness Zones” to identify cut‐points for adequate cardiorespiratory fitness. A total of 199 participants (aged 13.7 ± 2.7 years, 8.5 ± 3.5 years posttreatment) were included. We found a strong positive correlation between VO2max and 6MWT distance (r = 0.61, r2 = 0.37, p < 0.001). Our regression algorithm included 6MWT distance, waist‐to‐height ratio, age and sex to predict VO2max (r = 0.79, r2 = 0.62, p < 0.001). Forty percentages of predicted VO2max values were within ±3 ml/kg/min of measured VO2max. The cut‐point for FITNESSGRAM's “health‐risk” fitness zone was 39.8 ml/kg/min (males: AUC = 0.88), and 33.5 ml/kg/min (females: AUC = 0.82). We present an algorithm to reasonably predict cardiorespiratory fitness for childhood cancer survivors, using inexpensive measures. This algorithm has useful clinical application, particularly when CPET is unavailable. Our algorithm has the potential to assist clinicians to identify survivors below the cut‐points with increased cardiovascular disease‐risk, to monitor and refer for tailored interventions with exercise specialists.
Identifying rate limitation and a guide to design of fast‐charging Li‐ion battery
Authors: Zhang Sheng S.
Published: December 2019

Fast‐charging is highly demanded for applications requiring short charging time. However, fast‐charging triggers serious problems, leading to decline in charge acceptance and energy efficiency, accelerated capacity degradation, and safety risk. In this work, a three‐electrode coin cell with a Li metal reference electrode is designed to individually record the potential of two electrodes, and measure the impedance of each electrode by using a power‐optimized graphite‐LiNi0.80Co0.15Al0.05O2 electrode couple. It is shown that regardless of the state‐of‐charge the Li‐ion cell's impedance is contributed predominantly by the cathode, and that the cathode's impedance is dominated by the charge‐transfer resistance. In consistence with the impedance results, polarization of the Li‐ion cell is dominated by the cathode. It is surprised to find that no Li plating occurs on the graphite anode even if the charging rate is increased to 10 C (1 C = 1.30 mA cm−2). The results of this work indicate that low overall impedance with a high cathode‐to‐anode impedance ratio is the key to enabling safe fast‐charging, and that fast‐charging Li‐ion batteries without Li plating on the graphite anode is possible if the cathode and graphite anode are optimistically engineered.

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Percolation‐Based Metrics to Quantify the Resilience of Communication Systems
Authors: Benipayo Caesar S.
Published: December 2019

Resilience theory plays a critical part in the practical design of modern engineered resilient systems that comprise of cyber‐physical systems and components having interdependencies intended to make the whole system robust. In this paper, the percolation‐based metric is utilized to quantify the communication systems' resilience. Because there is no consistent and reliable way to measure resilience, the percolation‐based metric framework is developed to model the component or system failure by removing fractions of the nodes or links, causing the network to transition from functional to non‐functional. The efficacy of the percolation‐based metric model is demonstrated by using the power grid and maritime platform systems (legacy and future design versions) as case studies. The results from the analysis of the maritime communication and power grid systems are presented. The results indicate that percolation‐based metric may be a useful approach for system engineers and designers to gain improved insight into the quantification of communication system resilience.
Approaching The Indian Bullet Train Project Through System Thinking
Authors: Tattikota V Jagadeeswar Rao , Alukal Paul , Nayal Kirti , Das Seema , Rajput Dinesh , Mukundan R
Published: December 2019

We analyze a complex techno‐economic project of the Indian Bullet Train system, under construction via the High‐speed Rail lines in India, with an estimated speed of the train in 350 kmph and covering a distance of 500Km, the project is in collaboration with Japan and estimated cost is to be at Rs.1080 Billions. The groundwork for the Bullet Train Project started in December 2017 and the project dead line is set as August 2023 with land acquisition dead line to be completed by December 2018. The land requirement is 1400 Hectares which is divided into 7000 plots in 195 villages in Gujarat and 104 villages in Maharashtra.

Despite location of bullet train project being in India's most economically and industrially developed states, the land acquisition got delayed. In this paper, we develop a systemigram to depict the whole problem. Based on the data available, CLD (Causal loop diagram) is created indicating cause and effect relation and feedback loops. On the application of system thinking approach, this study can be further explored for identifying archetypes.

It was identified that the land acquisition process is more influenced by the coordination and interaction between policy makers and locals. It can be said that, if these two are on the same page with regards to the various terms and conditions such as conditions of compensation, then land acquisition will be done on time.
A System and Method for improving the Model Based Systems Engineering Environment capability
Authors: Prasanna Kumar R N , Patil Shailesh
Published: December 2019

As the evolution of new technologies such as IOT and Cloud Computational Analysis continue, the Systems have become more and more complex and it is grown much in size. Unfortunately the present day SE Environments, Modeling languages and the related tool sets are not sufficient enough to represent the multiple streams problem at hand in one integrated modeling environment which makes all of the Stakeholders and Engineers & Non‐engineers understand the problem scenarios. This lack of integrated modelling environment and a methodology for an additional representation of multiple problem domains limits off the analysis capabilities, timely communication of the technical and project risks to various stakeholders for decision making. It happens due to the inherent capability & limitations of each modeling languages followed so far by the Model Based System Engineering (MBSE) community & to bridge across them. This research paper focuses on improving the SE modeling environment capability from at least three distinct directions. First, it proposes a way to strengthen the SysML semantics with concrete guidelines which helps to reduce the incompleteness & ambiguous nature of the SysML elements especially in the Non Functional Requirements modeling. Then it explores the possibility of integrating the ontology aspects offered in evolving Life‐cycle Modeling Language (LML) specification to an extended SysML profile to complement its constructs to facilitate communication with non‐system engineers as well. Finally, this paper draws parallel between the LML architectural modeling concepts with the Architecture Analysis & Design Language (AADL) constructs and realizes them in an extended SysML profile. This will facilitate the seamless flow of models at various abstraction levels & translation of architectural model information from LML to AADL analytical environment. A case study implemented using an extended SysML profile & a methodology will be presented to measure its effectiveness.
FGE‐sulfatase‐based bacterial biosensor with single copy evolved sensing cassette for arsenic detection
Authors: Sangkaew Watsawan , Sallabhan Ratiboot , Ritcharoon Benjarat , Mongkolsuk Skorn , Loprasert Suvit
Published: December 2019

BACKGROUND

Arsenic (As) is classified as a Group 1 human carcinogen, and the maximum arsenic contamination level allowed in drinking water is10 μg L−1. In this study, a genetic‐based whole‐cell biosensor for arsenic detection was constructed and engineered for rapid and more efficient arsenic detection.

RESULTS

The promoter and repressor responsive to arsenic (ArsBR) were newly isolated from Bacillus cereus ATCC14579. The reporter gene was atsBA carrying formylglycine‐generating enzyme (FGE) and sulfatase, which provided a fluorescent product after reacting with 4‐methylumbelliferyl sulfate (4‐MUS). To improve the performance of the arsenic biosensor, firstly, more efficient Escherichia coli host strains were constructed, including the disruption of the arsenic efflux pump, multidrug efflux pump and arsenical‐resistant genes; secondly, a repressor (ArsBR) was engineered by an error‐prone polymerase chain reaction (PCR) technique, aiming to lower the detection limit; lastly, a single copy biosensor cassette in an E. coli chromosome was constructed.

CONCLUSION

The stable and sensitive biosensor was able to detect As(III) at 5 μg L−1 and As(V) at 50 μg L−1 in 3.5 h with a very low fluorescent background. Moreover, the roles of all seven cysteine residues of the repressor were also investigated. Interestingly, the six cysteine residues Cys 28, 34, 36, 89, 90 and 100 are functionally involved in arsenic sensing, but not Cys 101. © 2019 Society of Chemical Industry