bluuebunny/crossref_metadata_2025 huggingface dataset:
Multichannel Generations of Orbital Angular Momentum Modes with On‐Demand Characteristics on a Chip
Authors: Fu Pan , Ni Pei‐Nan , Wang Qiu‐Hua , Liu Yu‐Fei , Wu Bo , Chen Pei‐Pei , Kan Qiang , Wang Shuang‐Peng , Chen Hong‐Da , Xu Chen , Xie Yi‐Yang
Published: September 2021

The orthogonality among optical beams with different orbital angular momentum (OAM) modes presents a new perspective as independent data‐carrying channels for multiplexing and demultiplexing. In particular, the theoretically infinite topological charge of OAM beam promises the unbounded capacity in communication systems. As a key part for the advancement of OAM technologies, OAM source has attracted considerable interest and experienced a rapid development. Nevertheless, conventional approaches to create OAM modes mainly rely on the use of bulky optical devices and external laser source, preventing their implementation into a miniaturized system. As a contrast, on‐chip generation of OAM beams with a built‐in source stands out with several advantages, including small footprint, compactness, portability, and high‐power efficiency. In this work, a versatile approach to directly produce OAM modes with on‐demand characteristics on a chip is demonstrated. Featuring the judicious combination of the emerging dielectric metasurface with the standard vertical cavity surface‐emitting laser (VCSEL) platform, the approach represents a feasible solution to the wide implementation of wafer‐level OAM emitters for optoelectronic integrations. Prototype laser chips for the generation of both individual OAM beam and OAM array with novel functionalites, such as controllable directionality and spatially varying topological charge and distribution, are systematically presented.
Whispering Gallery‐Mode Microdroplet Tensiometry
Authors: Pirnat Gregor , Humar Matjaž
Published: September 2021

Droplets are ideally suited to support high‐Q‐factor whispering gallery modes (WGMs) due to their perfectly smooth surface. WGMs enable extremely precise measurements of the droplet properties such as size and shape. Herein, a simple, fast, and very precise technique to measure interfacial tension (IFT) between two immiscible liquids based on WGMs is demonstrated. A microdroplet is generated at the end of a glass microcapillary, submerged in a continuous liquid phase, and its size changes are monitored with nanometer precision via WGMs, while simultaneously applying finely tunable pressure through the microcapillary. IFT is determined from the size of the droplet and the pressure in the microcapillary at equilibrium. Droplets as small as 8 μm are used, thus requiring extremely small sample volume. The IFT measurements can be carried out also at nonequilibrium state when either the size of the droplet or the chemical composition of the continuous phase changes in time. Simultaneously, the WGMs enable very precise measurement of the refractive index of either the droplet or the continuous phase.
Trends in Workplace Wearable Technologies and Connected‐Worker Solutions for Next‐Generation Occupational Safety, Health, and Productivity
Authors: Patel Vishal , Chesmore Austin , Legner Christopher M. , Pandey Santosh
Published: September 2021

The workplace influences the safety, health, and productivity of workers at multiple levels. To protect and promote total worker health, smart hardware, and software tools have emerged for the identification, elimination, substitution, and control of occupational hazards. Wearable devices enable constant monitoring of individual workers and the environment, whereas connected worker solutions provide contextual information and decision support. Here, the recent trends in commercial workplace technologies to monitor and manage occupational risks, injuries, accidents, and diseases are reviewed. Workplace safety wearables for safe lifting, ergonomics, hazard identification, sleep monitoring, fatigue management, and heat and cold stress are discussed. Examples of workplace productivity wearables for asset tracking, augmented reality, gesture and motion control, brain wave sensing, and work stress management are given. Workplace health wearables designed for work‐related musculoskeletal disorders, functional movement disorders, respiratory hazards, cardiovascular health, outdoor sun exposure, and continuous glucose monitoring are shown. Connected worker platforms are discussed with information about the architecture, system modules, intelligent operations, and industry applications. Predictive analytics provide contextual information about occupational safety risks, resource allocation, equipment failure, and predictive maintenance. Altogether, these examples highlight the ground‐level benefits of real‐time visibility about frontline workers, work environment, distributed assets, workforce efficiency, and safety compliance.
The World Trade Center Health Program: Twenty years of health effects research
Authors: Daniels Robert D. , Kubale Travis L. , Reissman Dori B. , Howard John
Published: September 2021

It has been 20 years since the devastating terrorist attacks on September 11, 2001. Thousands were injured or killed during the attacks and many more are at risk of adverse health stemming from physical, psychological, and emotional stressors born out of the attacks. Private, federal, state, and local resources were gathered soon after the attacks to address impacts to the community, including the health and well‐being of both responders and survivors. Many of these efforts are now largely consolidated under the federally mandated World Trade Center (WTC) Health Program. This program provides medical monitoring and treatment of qualifying conditions among the 9/11‐exposed population and supports related physical and mental health research. In this commentary, we describe the WTC Health Program, with emphasis on the health‐effects research it has funded since inception in 2011. We describe sentinel research publications, and how science has impacted the program. We provide examples relating studies in this special issue to important roles in the WTC Health Program research agenda. Finally, we provide a perspective on future research needs.
Synthesis of 4‐Chalcogenylated Isoxazoles Mediated by PhICl2 and Diorganyl Disulfides/Diselenides
Authors: Yu Zhenyang , Zhang Dongke , Li Xiaoxian , Zhang Beibei , Yang Zhifang , Qian Yan , Du Yunfei
Published: September 2021

This report described that a series of 4‐chalcogenylated isoxazoles were readily synthesized from the one‐pot reaction of alkynone Z‐O‐methyloximes with (dichloroiodo)benzene (PhICl2) and diorganyl disulfides/diselenides under metal‐free conditions. The reaction process was enabled by the electrophilic organosulfenyl chloride (RSCl) or selenenyl chloride (RSeCl) species, which were generated in situ from the reaction of PhICl2 and diorganyl disulfides/diselenides. The striking feature of the approach is the in‐situ formation of the electrophilic RSCl or RSeCl species, thus markedly decreasing the total usage of electrophiles when compared with the existing methods. This method exhibited a good functional groups tolerance for both alkynone Z‐O‐methyloximes and diorganyl disulfides/diselenides and the reaction could proceed at room temperature under ambient atmosphere within a short time to afford a series of functionalized isoxazoles in moderate to excellent yields.
Preparing for effective, adaptive risk communication about per‐ and polyfluoroalkyl substances in drinking water
Authors: Harclerode Melissa , Baryluk Sarah , Lanza Heather , Frangos John
Published: September 2021

Drinking water contamination and the potential subsequent long‐term adverse health outcomes is an issue of high importance and personal interest to affected communities. Per‐ and polyfluoroalkyl substances (PFAS) further complicate these issues through their technical complexity; evolving scientific and public health data; and inconsistent, incomplete, and evolving governmental guidance on screening and mitigation. The use of a community‐specific adaptive risk communication strategy can allow municipalities to assess and mitigate PFAS while addressing community concerns. Utilizing demographics data and the qualitative observations of the community's concerns based on social media and news activity, the study team prepared two outreach strategies for PFAS assessment and mitigation. Overall, application of this strategy to two different case studies revealed that the framework is sufficiently flexible to meet specific community needs. Evaluation of the communities' risk perception factors showed that while there were some commonalities, sufficiently different risk perception factors existed, which necessitated a community‐specific strategy.

Article Impact Statement

Creation of a community‐specific outreach plan for drinking water per‐ and polyfluoroalkyl substances issues is necessary for effective risk communication and outreach.
Modified clays reduce leaching of per‐ and polyfluoroalkyl substances from AFFF‐contaminated soils
Authors: Wang Chenyang , Yan Bei , Munoz Gabriel , Sauvé Sébastien , Liu Jinxia
Published: September 2021

Technologies applicable at a field scale to mitigate soil and groundwater pollution by per‐ and polyfluoroalkyl substances (PFAS) due to the release of aqueous film‐forming foams are urgently needed. We demonstrate that modified bentonite clays as soil amendments can effectively reduce the leaching of PFAS from impacted soils. In batch experiments, the significant decrease (95%–99%) of leachable anionic PFAS, including perfluorooctane sulfonate, perfluorohexane sulfonate, and perfluorooctane carboxylate, was achieved in 1–4 days at a clay dosage as low as 0.5% w/w. A significant decline of leachable cationic and zwitterionic PFAS (70%–99%) was also observed. The clays performed the best in immobilizing PFAS anions, while granular activated carbon was effective in preventing PFAS cation leaching. Hardwood biochar had minor or negligible effects on any PFAS. The study provides strong evidence to support using modified clays as part of mitigation or remediation strategies to prevent PFAS from mobilizing on a field scale.

Article Impact Statement

The study demonstrated that modified bentonite clays effectively immobilize various PFAS in AFFF‐contaminated soils to prevent leaching.
Practical implications of perfluoroalkyl substances adsorption on bottle materials: Isotherms
Authors: Kleiner Eric J. , Sanan Toby , Smith Samantha J. , Pressman Jonathan G. , Abulikemu Gulizhaer , Crone Brian C. , Wahman David G.
Published: September 2021

To assess the practical implications of various bottle materials used in anion exchange (IX) or granular activated carbon (GAC) isotherm experiments, adsorption of seven per‐ and polyfluoroalkyl substances (PFAS) onto three common bottle materials (silanized glass, polypropylene, and high‐density polyethylene [HDPE]) were screened. Results were similar between bottle materials; therefore, only HDPE was used in a detailed bottle material isotherm study with 11 PFAS. For each PFAS, an HDPE bottle isotherm was generated with equilibrium liquid phase concentrations relevant to drinking water (<2000 ng/L). Percent PFAS recoveries between 90% and 103%, 85% and 114%, and 54% and 108% were determined for perfluoro‐2‐propoxypropanoic acid (GenX), five perfluoroalkyl carboxylic acids, and five perfluoroalkyl sulfonic acids (PFSA), respectively. These results indicated only the five PFSA adsorbed to the HDPE bottles in a concentration‐dependent manner. Furthermore, linear isomer versions of two PFSA exhibited greater adsorption. For each PFSA studied, a linear isotherm was generated and used to develop guidance for conducting future IX and GAC isotherm studies. Specifically, the minimum initial isotherm concentration was established such that a maximum 1% loss would be expected to the HDPE bottles, resulting in required initial concentrations of the five PFSA between 21 and 75 times that of the design isotherm liquid equilibrium concentration.

Article Impact Statement

Assesses the practical implications of per‐ and polyfluoroalkyl substances adsorption to various bottle materials used in environmental sampling and isotherm experiments.
Elastic Organic Crystals Based on Barbituric Derivative: Multi‐faceted Bending and Flexible Optical Waveguide
Authors: Peng Jiang , Bai Jiakun , Cao Xiumian , He Jieting , Xu Weiqing , Jia Junhui
Published: September 2021

Elastic organic single crystals with light‐emitting and multi‐faceted bending properties are extremely rare. They have potential application in optical materials and have attracted the extensive attention of researchers. In this paper, we reported a structurally simple barbituric derivative DBDT, which was easily crystallized and gained long needle‐like crystals (centimeter‐scale) in DCM/CH3OH (v/v=2/8). Upon applying or removing the mechanical force, both the (100) and (040) faces of the needle‐like crystal showed reversible bending behaviour, showing the nature of multi‐faceted bending. The average hardness (H) and elastic modulus (E) were 0.28±0.01 GPa and 4.56±0.03 GPa for the (040) plane, respectively. Through the analysis of the single crystal data, it could be seen that the van der waals (C−H⋅⋅⋅π and C−H⋅⋅⋅C), H‐bond (C−H⋅⋅⋅O) and π⋅⋅⋅π interactions between molecules were responsible for the generation of the crystal elasticity. Interestingly, elastic crystals exhibited optical waveguide characteristics in straight or bent state. The optical loss coefficients measured at 627 nm were 0.7 dBmm−1 (straight state) and 0.9 dBmm−1 (bent state), while the optical loss coefficient (α) were 1.5 dBmm−1 (straight state) and 1.8 dBmm−1 (bent state) at 567 nm. Notably, the elastic organic molecular crystal based on barbituric derivative could be used as the candidate for flexible optical devices.
Variable selection in nonparametric functional concurrent regression
Authors: Ghosal Rahul , Maity Arnab
Published: September 2021

We develop a new method for variable selection in nonparametric functional concurrent regression. The commonly used functional linear concurrent model (FLCM) is far too restrictive in assuming linearity of the covariate effects, which is not necessarily true in many real‐world applications. The nonparametric functional concurrent model (NPFCM), on the other hand, is much more flexible and can capture complex dynamic relationships present between the response and the covariates. We extend the classically used variable selection methods, e.g., group LASSO, group SCAD and group MCP, to perform variable selection in NPFCM. We show via numerical simulations that the proposed variable selection method with the non‐convex penalties can identify the true functional predictors with minimal false‐positive rate and negligible false‐negative rate. The proposed method also provides better out‐of‐sample prediction accuracy compared to the FLCM in the presence of nonlinear effects of the functional predictors. The proposed method's application is demonstrated by identifying the influential predictor variables in two real data studies: a dietary calcium absorption study, and some bike‐sharing data.
IL‐27 mediates anti‐inflammatory effect in cigarette smoke induced emphysema by negatively regulating IFN‐γ producing cytotoxic CD8+T cells in mice
Authors: Qiu Shi‐lin , Sun Qi‐xiang , Zhou Jian‐peng , Tang Hai‐juan , Chen Yan‐qiong , Chen Fu‐shou , Feng Tao , He Zai‐qing , Qin Hua‐jiao , Duan Min‐chao
Published: September 2021

Chronic airway inflammation mediated by CD8+T lymphocytes contributes to the pathogenesis of Chronic obstructive pulmonary disease (COPD). Deciphering the fingerprint of the chronic inflammation orchestrated by CD8+T cells may allow the development of novel approaches to COPD management. Here, the expression of IL‐27 and IFN‐γ+CD8+Tc1 cells were evaluated in patients with COPD and in cigarette smoke‐exposed mice. The production of IL‐27 by marrow‐derived dendritic cells (mDCs) in response to cigarette smoke extract (CSE) was assessed. The role of IL‐27 in IFN‐γ+CD8+Tc1 cells was explored. We demonstrated that elevated IL‐27 was accompanied by an exaggerated IFN‐γ+CD8+Tc1 response in a smoking mouse model of emphysema. We noted that lung dendritic cells were one of the main sources of IL‐27 during chronic cigarette smoke exposure. Moreover, CSE directly induced the production of IL‐27 by mDCs in vitro. IL‐27 negatively regulated the differentiation of IFN‐γ+CD8+Tc1 cells isolated from cigarette smoke‐exposed mice in a STAT1‐ and STAT3‐independent manner. Systemic administration of recombinant IL‐27 attenuated IFN‐γ+CD8+Tc1 response in the late phase of cigarette smoke exposure. Our results uncovered that IL‐27 negatively regulates IFN‐γ+CD8+Tc1 response in the late stage of chronic cigarette smoke exposure, which may provide a new strategy for the anti‐inflammatory treatment of smoking‐related COPD/emphysema.
Formation of a colloidal band via pH‐dependent electrokinetics
Authors: Doan Viet Sang , Shin Sangwoo
Published: September 2021

Electroosmosis on nonuniformly charged surfaces often gives rise to intriguing flow behaviors, which can be utilized in applications such as mixing processes and designing micromotors. Here, we demonstrate nonuniform electroosmosis induced by electrochemical reactions. Water electrolysis creates pH gradients near the electrodes that cause a spatiotemporal change in the wall zeta potential, leading to nonuniform electroosmosis. Such nonuniform EOFs induce multiple vortices, which promote the continuous accumulation of particles that subsequently form a colloidal band. The band develops vertically into a “wall” of particles that spans from the bottom to the top surface of the chamber. Such a flow‐driven colloidal band can be potentially used in colloidal self‐assembly and separation processes irrespective of the particle surface properties. For instance, we demonstrate these vortices can promote rapid segregation of soft colloids such as oil droplets and fat globules.
Poly(Vinylidene Fluoride) Nanofiber Array Films with High Strength for Effective Impact Energy Harvesting
Authors: Bai Zikui , Song Yuxian , Peng Jiashun , Chen Dongzhi , Zhou Yingshan , Tao Yongzhen , Gu Shaojin , Xu Jie , Deng Zhongmin , Yin Xianze , Xu Weilin
Published: September 2021

Absorbing high mechanical impact energy and converting it into electrical energy is challenging due to the low efficiency and strength of the existing piezoelectric generators. Here, a new type of piezoelectric nanogenerator is reported that is a sandwich structure composed of upper and lower electrodes and a poly(vinylidene fluoride) (PVDF) nanofiber array film. The PVDF nanofiber array films with dense vertical alignment characteristics are successfully fabricated by a combination of electrospinning and cutting methods. Each nanofiber in the nanofiber array film becomes an independent nanogenerator with an equivalent piezoelectric response which greatly enhances the charges collection and energy conversion efficiency of the nanogenerator. The maximum instantaneous power density of 26.3 μW cm−2can be reached under the impact of the 9.1 g ball falling freely from a height of 20 cm. The nanofiber array structure endows the piezoelectric nanogenerator with high mechanical strength in the normal direction of the surface and excellent stability. Furthermore, the power output of two parallel‐connected nanogenerators (1.5 × 1.5 cm2each) can light up 12 LEDs without storage devices. The unique properties of the piezoelectric nanogenerator offer great potential for high mechanical impact energy harvesting and effective conversion.
Cesium Iodide Incorporation in Tin Oxide Electron Transport Layer for Defect Passivation and Efficiency Enhancement in Double Cation Absorber‐Based Planar Perovskite Solar Cells
Authors: Venu Rajendran Muthukumar , Ganesan Saraswathi , Sudhakaran Menon Vidya , Raman Rohith Kumar , Alagumalai Ananthan , Krishnamoorthy Ananthanarayanan
Published: September 2021

Fermi level tuning and defect passivation at the electron selective layer (ESL)/perovskite interface has a strong effect on the perovskite solar cell (PSC) device performance. Two strategies are commonly used for passivation, 1) bulk passivation—by adding dopants in the ESL and 2) surface passivation—to suppress the interface dangling bonds using ligands. Herein, a novel dual passivation (bulk and surface) strategy is presented by incorporating a simple molecule cesium iodide (CsI) in the SnO
x
ESL. Passivation effects using different CsI dopant concentrations (0–10 wt%) in SnO
x
solution were studied and its beneficial role of defect passivation is discussed in detail. A systematic study revealed that the addition of CsI in the SnO
x
ESL not only significantly influences the open‐circuit voltage (V
oc) and fill factor (FF), but also suppresses the recombination at the interface due to its improved built in surface potential. Lower trap‐filled limit voltage (V
TFL), trap density (n
t), and diode ideality factor (n
id) are observed for the CsI incorporated SnO
x
ESL as compared with the bare SnO
x
layer which leads to a power conversion efficiency improvement from 14.3% to 15.4%.
Halogen‐Free Polyphosphazene‐Based Flame Retardant Cathode Materials for Li–S Batteries
Authors: Yeşilot Serkan , Küçükköylü Sedat , Mutlu Tutku , Demir-Cakan Rezan
Published: September 2021

Novel, eco‐friendly, and halogen‐free polyphosphazene‐based flame retardant (FR) cathodes for Li–S batteries are prepared by the inverse vulcanization of elemental sulfur with polybis(2‐acrylamidoethoxy)phosphazene (poly(AAE)) resulting in the covalently bonded different wt% sulfur content polymers. Due to the polar amide groups, poly(AAE)‐xS (x refer to the wt% of sulfur) composites assist in anchoring intermediate lithium polysulfide species. The structural characterizations of the poly(AAE)‐xS polymers are conducted by elemental analysis, Fourier‐transform infrared spectroscopy, differential scanning calorimeter, thermogravimetric analysis, and scanning electron microscopy. Their FR properties are elevated by calculation of the limiting oxygen index values and burning tests. Later, lithium‐ion storage mechanism of poly(AAE)‐55S polymer is evaluated, including cyclic voltammetry, rate performance tests and electrochemical impedance spectroscopy measurements. To compare with the electrochemical performance of poly(AAE)‐55S, a noncovalent blend polymer mixture and bare sulfur are also tested. It is found that covalently bonded poly(AAE)‐55S obtained by the inverse vulcanization of elemental sulfur and poly(AAE) results much pronounced capacities. Herein, new insights into the design and development of alternative cathode materials for safer Li–S batteries, both providing FR properties and good lithium polysulfides adsorption capabilities, are offered.
Genetic diversity and antibiotic resistance of Shigella spp. isolates from food products
Authors: Pakbin Babak , Amani Zahra , Allahyari Samaneh , Mousavi Shaghayegh , Mahmoudi Razzagh , Brück Wolfram Manuel , Peymani Amir
Published: September 2021

The emergence of multidrug‐resistant Shigella is a significant threat to global public health. Limited studies have investigated the incidence, antimicrobial susceptibility, and genetic diversity of Shigella isolated from food products. Conventional culture‐based, serologic, molecular, disk diffusion, PCR, and RAPD‐PCR methods were used to determine the prevalence rate, phenotypic and genotypic antibiotic resistance profile, and genetic diversity of the Shigella isolates from food samples including vegetable salad, ground meat, and raw cow's milk (405 samples). The prevalence rate of Shigella in food samples was 4.44%. The incidence of S. sonnei (3.7%) was higher than that of S. flexneri (0.74%). S. dysenteriae and S. boydii were not detected in food samples examined. Also, no Shigella were recovered from raw cow's milk. This study showed that the Shigella isolates were resistant to sulfamethoxazole/trimethoprim (83.3%), amoxicillin (66.6%), streptomycin (66.6%), tetracycline (61.1%), ampicillin (50%), amoxicillin–clavulanic acid (50%), azithromycin (50%), and chloramphenicol (50%) and completely sensitive to cefoxitin, cefepime, amikacin, and gentamicin. All Shigella isolates were multidrug‐resistant. We detected blaSHV resistance gene in all isolates; however, no isolate harbored blaTEM gene. RAPD‐PCR categorized the Shigella isolates into five main clusters. The highest antibiotic resistance was observed in the isolates of cluster R4. The finding of this study also indicated an association between antimicrobial resistance profiles and genotyping properties of the isolates. Novel food monitoring systems, including surveillance of multidrug‐resistant foodborne pathogens, especially in developing countries, are required to control the foodborne diseases.
Late Triassic foreland basin and Early Palaeozoic basement in the eastern Yidun Micro‐block and its tectonic implications for the eastern Palaeo‐Tethys
Authors: Xu Xianbing , Xia Yuan , Chen Jiaju , Liang Chenghua , Xu Yadong
Published: September 2021

Subduction polarity and collisional process are still controversial in the eastern Palaeo‐Tethys. On the basis of 1:50,000‐scale geological mapping at the Heni Township, zircon U–Pb geochronology and whole‐rock geochemistry were analysed for volcano‐sedimentary rocks in the eastern Yidun Micro‐block, Qinghai‐Tibet Plateau. Early Palaeozoic sequences were reported firstly in the eastern Yidun Micro‐block. Two populations of detrital zircon U–Pb ages (~525 Ma and 800–1,250 Ma) and deformation and metamorphic characteristics imply that the Early Palaeozoic sequences were deposited during the Cambrian to Silurian in the South China Block. The Early Palaeozoic sequences in the eastern Yidun Micro‐block were extruded by Cenozoic NW‐SE strike‐slip faults. Both the Late Triassic upper Tumugou and Lamaya formations yield four prominent peak ages of ~260 Ma, ~450 Ma, 750 ~ 780 Ma, and ~1,850 Ma. U–Pb ages of youngest detrital zircons (226.2 ± 1.0–224.7 ± 1.1 Ma), uppermost andestic tuff (216.1 ± 0.3 Ma) and intruded granitoids (~215 Ma) show that both the upper Tumugou and Lamaya formations were deposited during 225 ~ 216 Ma. Whole‐rock geochemistry indicates that all sandstone samples underwent moderate weathering and strong sorting and recycling. They were derived from felsic provenance, like volcano‐sedimentary rocks and granitoids in the western Yidun and Qiangtang micro‐blocks, indicative of pre‐Norian closure of the Jinshajiang Ocean. The closure gave rise to a foreland basin filled by the 225–216 Ma volcano‐sedimentary rocks in the eastern Yidun Micro‐block. The closure of the Jinshajiang Ocean also led to a scissor‐like closure of the Ganze‐Litang Ocean by clockwise rotation. Combining these with previous work, the Ganze‐Litang Ocean was a back‐arc basin resulted from eastward subduction of the Jinshajiang Ocean and had not undergone oceanic subduction.
Performance of DNA methylation analysis of ASCL1, LHX8, ST6GALNAC5, GHSR, ZIC1 and SST for the triage of HPV‐positive women: Results from a Dutch primary HPV‐based screening cohort
Authors: Verhoef Lisanne , Bleeker Maaike C. G. , Polman Nicole , Steenbergen Renske D. M. , Meijer Chris J. L. M. , Melchers Willem J. G. , Bekkers Ruud L. , Molijn Anco C. , Quint Wim G. , van Kemenade Folkert J. , Berkhof Johannes , Heideman Daniëlle A. M.
Published: September 2021

Methylation of host‐cell deoxyribonucleic acid (DNA) has been proposed as a promising biomarker for triage of high‐risk (hr) human papillomavirus (HPV) positive women at screening. Our study aims to validate recently identified host‐cell DNA methylation markers for triage in an hrHPV‐positive cohort derived from primary HPV‐based cervical screening in The Netherlands. Methylation markers ASCL1, LHX8, ST6GALNAC5, GHSR, ZIC1 and SST were evaluated relative to the ACTB reference gene by multiplex quantitative methylation‐specific PCR (qMSP) in clinician‐collected cervical samples (n = 715) from hrHPV‐positive women (age 29‐60 years), who were enrolled in the Dutch IMPROVE screening trial (NTR5078). Primary clinical end‐point was cervical intraepithelial neoplasia grade 3 (CIN3) or cancer (CIN3+). The single‐marker and bi‐marker methylation classifiers developed for CIN3 detection in a previous series of hrHPV‐positive clinician‐collected cervical samples were applied. The diagnostic accuracy was visualised using receiver operating characteristic (ROC) curves and assessed through area under the ROC curve (AUC). The performance of the methylation markers to detect CIN3+ was determined using the predefined threshold calibrated at 70% clinical specificity. Individual methylation makers showed good performance for CIN3+ detection, with highest AUC for ASCL1 (0.844) and LHX8 (0.830). Combined as a bi‐marker panel with predefined threshold, ASCL1/LHX8 yielded a CIN3+ sensitivity of 76.9% (70/91; 95% CI 68.3‐85.6%) at a specificity of 74.5% (465/624; 95% CI 71.1‐77.9%). In conclusion, our study shows that the individual host‐cell DNA methylation classifiers and the bi‐marker panel ASCL1/LHX8 have clinical utility for the detection of CIN3+ in hrHPV‐positive women invited for routine screening.
Mimicking human riboflavin responsive neuromuscular disorders by silencing flad‐1 gene in C. elegans: Alteration of vitamin transport and cholinergic transmission
Authors: Leone Piero , Tolomeo Maria , Piancone Elisabetta , Puzzovio Pier Giorgio , De Giorgi Carla , Indiveri Cesare , Di Schiavi Elia , Barile Maria
Published: September 2021

Riboflavin (Rf), or vitamin B2, is the precursor of FMN and FAD, redox cofactors of several dehydrogenases involved in energy metabolism, redox balance and other cell regulatory processes. FAD synthase, coded by FLAD1 gene in humans, is the last enzyme in the pathway converting Rf into FAD. Mutations in FLAD1 gene are responsible for neuromuscular disorders, in some cases treatable with Rf. In order to mimic these disorders, the Caenorhabditis elegans (C. elegans) gene orthologue of FLAD1 (flad‐1) was silenced in a model strain hypersensitive to RNA interference in nervous system. Silencing flad‐1 resulted in a significant decrease in total flavin content, paralleled by a decrease in the level of the FAD‐dependent ETFDH protein and by a secondary transcriptional down‐regulation of the Rf transporter 1 (rft‐1) possibly responsible for the total flavin content decrease. Conversely an increased ETFDH mRNA content was found. These biochemical changes were accompanied by significant phenotypical changes, including impairments of fertility and locomotion due to altered cholinergic transmission, as indicated by the increased sensitivity to aldicarb. A proposal is made that neuronal acetylcholine production/release is affected by alteration of Rf homeostasis. Rf supplementation restored flavin content, increased rft‐1 transcript levels and eliminated locomotion defects. In this aspect, C. elegans could provide a low‐cost animal model to elucidate the molecular rationale for Rf therapy in human Rf responsive neuromuscular disorders and to screen other molecules with therapeutic potential.
Design cytotoxicity: The effect of silver nanoparticles stabilized by selected antioxidants on melanoma cells
Authors: Barbasz Anna , Czyżowska Agnieszka , Piergies Natalia , Oćwieja Magdalena
Published: September 2021

Silver nanoparticles (AgNPs) prepared and stabilized by diverse biologically active substances seem to be especially useful in diverse biological and medical applications. The combination of AgNPs with bioactive substances, such as antioxidants, can lead to the development of new systems of desired anticancer properties. In this research, AgNPs were prepared with the use of diverse antioxidant combinations including gallic acid (GA), (−)‐epicatechin‐3‐gallate (EGCG), and caffeine (CAF). The insightful physicochemical characteristic revealed that each type of AgNPs exhibited spherical shape, comparable size distribution and negative surface charge. Surface‐enhanced Raman spectroscopy (SERS) delivered the information about the chemistry of AgNP stabilizing layers, which turned out to be a crucial factor tuning toxicity of AgNPs toward murine B16 melanoma cells (B16‐F0) and human skin melanoma (COLO 679) cells. EGCGAgNPs were the most cytotoxic among all the investigated AgNPs. They strongly reduced the activity of mitochondria, damaged cell membrane integrity, and penetrated inside the cells causing DNA damage. In turn, the toxicity of GAAgNPs strongly manifested via the induction of oxidative stress in the cells. It was found that CAFGAAgNPs exhibited the lowest toxicity toward the melanoma cells, which proved that a proper combination of antioxidants enable to prepare AgNPs of differentiated toxicity. It was established that human skin melanoma cells were significantly more sensitive to AgNPs than the murine melanoma cells.
Styrene bioconversion by Pseudomonas putida utilizing a non‐aqueous phase for polyhydroxyalkanoate production
Authors: Alonso‐Campos Victor , Covarrubias‐García Itzel , Arriaga Sonia
Published: September 2021

BACKGROUND

Styrene is a volatile organic compound used extensively worldwide. It is known to cause serious adverse effects on human health and the environment. The main limitation in the biological treatment of styrene is its low solubility. An alternative is the use of partitioning bioreactors (TPPB) which can improve mass transfer of styrene by addition of a hydrophobic non‐aqueous phase (NAP). This study explored silicone oil and an ionic liquid as NAPs in a TPPB to degrade styrene vapors using Pseudomonas putida S12. Lastly, the production of polyhydroxyalkanoates (PHA) was evaluated.

RESULTS

The NAPs were characterized in terms of biodegradability, toxicity and styrene partition coefficient (H). Results showed that styrene was 7.5 times more absorbed by the ionic liquid/aqueous phase mixture (H = 0.0035) than by the silicone oil/aqueous phase mixture (H = 0.0179) at 28 °C. Silicone oil and ionic liquid were non‐biodegradable by P. putida S12. However, the ionic liquid was inhibitory and toxic for P. putida S12 in contrast to silicone oil. Thus, the selected phase for the TPPB process was silicone oil. Silicone oil assays reached a 98% styrene removal efficiency faster (4 h) than the control (8 h). This finding was reflected in a faster production of the same amount of PHA in the presence of silicone oil.

CONCLUSIONS

The production of PHA was enhanced by the addition of silicone oil at 5% (v/v) in a TPPB batch process treating styrene vapors. © 2021 Society of Chemical Industry (SCI).
The etiology of resilience to disadvantage
Authors: Vazquez Alexandra Y. , Shewark Elizabeth A. , Clark D. Angus , Klump Kelly L. , Hyde Luke W. , Burt S. Alexandra
Published: September 2021

Background

Although early life exposure to chronic disadvantage is associated with deleterious outcomes, 40%–60% of exposed youth continue to thrive. To date, little is known about the etiology of these resilient outcomes.

Methods

The current study examined child twin families living in disadvantaged contexts (N = 417 pairs) to elucidate the etiology of resilience. We evaluated maternal reports of the Child Behavior Checklist to examine three domains of resilience and general resilience.

Results

Genetic, shared, and nonshared environmental influences significantly contributed to social resilience (22%, 61%, 17%, respectively) and psychiatric resilience (40%, 28%, 32%, respectively), but academic resilience was influenced only by genetic and nonshared environmental influences (65% and 35%, respectively). These three domains loaded significantly onto a latent resilience factor, with factor loadings ranging from 0.60 to 0.34. A common pathway model revealed that the variance common to all three forms of resilience was predominantly explained by genetic and non‐shared environmental influences (50% and 35%, respectively).

Conclusions

These results support recent conceptualizations of resilience as a multifaceted construct influenced by both genetic and environmental influences, only some of which overlap across the various domains of resilience.
LncRNA CDKN2B‐AS1 contributes to glioma development by regulating the miR‐199a‐5p/DDR1 axis
Authors: Lu Jiachao , Chen Yuanjun , Wen Liangbao , Zhou Quan , Yan Sheng
Published: September 2021

Background

Although cyclin‐dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B‐AS1) is upregulated in glioma, its function and potential mechanism in glioma remain unclear.

Methods

CDKN2B‐AS1 level in glioma tissues and cell lines LN229, U251, and U87 was measured by qRT‐PCR. Loss‐of‐function assays using short hairpin RNA for CDKN2B‐AS1 (sh‐CDKN2B‐AS1) were performed to evaluate the effect of CDKN2B‐AS1 on cell invasion, migration, proliferation, and apoptosis. The relationship among CDKN2B‐AS1, miR‐199a‐5p, and DDR1 was determined by bioinformatics analysis and luciferase reporter assay. Rescue experiments were conducted to explore the function of CDKN2B‐AS1 and miR‐199a‐5p in glioma. An in vivo animal model of lentivirally transduced U87 glioma xenografts in mice was established to confirm the role of CDKN2B‐AS1.

Results

CDKN2B‐AS1 is significantly upregulated in glioma tissues and cell lines. CDKN2B‐AS1 knockdown significantly inhibits cell proliferation, invasion, and migration, while promoting apoptosis of glioma cell lines U251 and U87. Further, a miR‐199a‐5p inhibitor attenuates the inhibitory effects of sh‐CDKN2B‐AS1 on these cell phenotypes. CDKN2B‐AS1 positively regulates DDR1 expression by directly sponging miR‐199a‐5p. Moreover, CDKN2B‐AS1 knockdown efficiently inhibits U87 tumor xenograft growth in mice.

Conclusion

Our study reveals that CDKN2B‐AS1 promotes glioma development by regulating the miR‐199a‐5p/DDR1 axis, suggesting that this lncRNA might be a potential therapeutic target.
Enhanced oral bioavailability and anti‐hyperuricemic activity of liquiritin via a self‐nanoemulsifying drug delivery system
Authors: Wei Chunmei , Wang Qilong , Weng Wen , Adu‐Frimpong Michael , Toreniyazov Elmurat , Ji Hao , Xu Ximing , Yu Jiangnan
Published: September 2021

BACKGROUND

This study focused on the development of a self‐nanoemulsifying drug delivery system (SNEDDS) to improve, potentially, the solubility and oral bioavailability of liquiritin (LQ).

METHODS

The solubility of LQ in different types of excipient, namely oils (OLs), emulsifiers (EMs), and co‐emulsifiers (CO‐EMs), was evaluated, and a pseudo‐ternary phase diagram (PTPD) and the formulation optimization were established. The prepared self‐nanoemulsifying drug delivery system of liquiritin (LQ‐SNEDDS) was assessed using droplet size (DS), zeta potential (ZP), polydispersity index (PDI), droplet morphology, drug release in vitro, and oral bioavailability.

RESULTS

After the dilution of the LQ‐SNEDDS, a transparent nanoemulsion was obtained with an acceptable DS (24.70 ± 0.73 nm), ZP (−18.69 ± 1.44 mV), and PDI (0.122 ± 0.006). The LQ‐SNEDDS that was developed had a better release rate in vitro than the free LQ suspension. Pharmacokinetic evaluation showed that the relative oral bioavailability of LQ‐SNEDDS was increased by 5.53 times, and LQ‐SNEDDS exhibited a delayed half life and longer retention time in comparison with those of free LQ. Similarly, LQ‐SNEDDS had a better urate lowering effect and provided better organ protection than free LQ at the same dose (P < 0.05).

CONCLUSIONS

The incorporation of LQ into SNEDDS could serve as a promising approach to improve the solubility, oral bioavailability, and anti‐hyperuricemic effect of LQ. © 2021 Society of Chemical Industry.
An alternative route for the preparation of phenol: Decomposition of cyclohexylbenzene‐1‐hydroperoxide
Authors: Yang Yufei , Zhang Yadong
Published: September 2021

In this work, a HPW/ZSM‐5 catalyst was prepared by impregnating phosphotungstic acid (HPW) with carrier ZSM‐5 zeolite and characterized by XRD, SEM, N2 adsorption/desorption isotherm, NH3‐TPD, and FT‐IR techniques. The catalytic performance of HPW/ZSM‐5 was investigated by using the decomposition reaction of cyclohexylbenzene‐1‐hydroperoxide (CHBHP) to phenol and cyclohexanone. The conversion rate of CHBHP was up to 97.28%. In addition, the reusability test exhibited that the high durability HPW/ZSM‐5 as the conversion rate of CHBHP only decreased by 3.11% after five runs. The kinetic study of the decomposition reaction indicated it was a primary reaction. The apparent activation energy of the decomposition reaction was 102.39 kJ·mol–1 in the temperature range of 45–60℃. All results indicate that the HPW/ZSM‐5 catalyst has good performance and promising applications in acid catalyzed organic chemistry.
Bioprinting of Human Liver‐Derived Epithelial Organoids for Toxicity Studies
Authors: Bouwmeester Manon C. , Bernal Paulina N. , Oosterhoff Loes A. , van Wolferen Monique E. , Lehmann Vivian , Vermaas Monique , Buchholz Maj‐Britt , Peiffer Quentin C. , Malda Jos , van der Laan Luc J. W. , Kramer Nynke I. , Schneeberger Kerstin , Levato Riccardo , Spee Bart
Published: September 2021

There is a need for long‐lived hepatic in vitro models to better predict drug induced liver injury (DILI). Human liver‐derived epithelial organoids are a promising cell source for advanced in vitro models. Here, organoid technology is combined with biofabrication techniques, which holds great potential for the design of in vitro models with complex and customizable architectures. Here, porous constructs with human hepatocyte‐like cells derived from organoids are generated using extrusion‐based printing technology. Cell viability of bioprinted organoids remains stable for up to ten days (88–107% cell viability compared to the day of printing). The expression of hepatic markers, transporters, and phase I enzymes increased compared to undifferentiated controls, and is comparable to non‐printed controls. Exposure to acetaminophen, a well‐known hepatotoxic compound, decreases cell viability of bioprinted liver organoids to 21–51% (p < 0.05) compared to the start of exposure, and elevated levels of damage marker miR‐122 are observed in the culture medium, indicating the potential use of the bioprinted constructs for toxicity testing. In conclusion, human liver‐derived epithelial organoids can be combined with a biofabrication approach, thereby paving the way to create perfusable, complex constructs which can be used as toxicology‐ and disease‐models.
Prognostic factors for patients with relapsed central nervous system nongerminomatous germ cell tumors
Authors: Abu‐Arja Mohammad H. , Osorio Diana S. , Lassaletta Alvaro , Graham Richard T. , Coven Scott L. , Stanek Joseph R. , Bouffet Eric , Finlay Jonathan L. , Abdelbaki Mohamed S.
Published: September 2021

We aimed toidentify prognostic factors that may help better understand the behavior of relapsed central nervous system nongerminomatous germ cell tumors. We identified nine studies, including 101 patients; 33 patients (33%) were alive 12 months post‐initial relapse. Sixty percent of patients with serum/cerebrospinal fluid (CSF) alpha‐fetoprotein (AFP) level ≤25 ng/mL at initial diagnosis were survivors compared with 28% among patients with serum/CSF AFP level >25 ng/mL (P = 0.01). Seventy‐one percent of patients who achieved complete response/continued complete response (CR/CCR) by the end of therapy at relapse were survivors compared with 7% among patients who had less than CR/CCR (P < 0.0001). Forty‐eight percent of patients who received marrow‐ablative chemotherapy followed by autologous hematopoietic cell rescue (HDCx/AuHCR) following relapse were survivors compared with 12% among patients who did not receive HDCx/AuHCR (P = 0.0001). Local relapse site, gross total surgical resection, and radiotherapy at relapse were not associated with improved outcomes.
Physician adjudication of angioedema diagnosis codes in a population of patients with heart failure prescribed angiotensin‐converting enzyme inhibitor therapy
Authors: Mansi Elizabeth T. , Johnson Eric S. , Thorp Micah L. , Go Alan S. , Lee Ming‐Sum , Shen Albert Yuh‐Jer , Park Ken J. , Budzynska Katarzyna , Markin Abraham , Sung Sue Hee , Thompson Jamie H. , Slaughter Matthew T. , Luong Tiffany Q. , An Jaejin , Reynolds Kristi , Roblin Douglas W. , Cassidy‐Bushrow Andrea E. , Kuntz Jennifer L. , Schlienger Raymond G. , Behr Sigrid , Smith David H.
Published: September 2021

Purpose

Our objective was to calculate the positive predictive value (PPV) of the ICD‐9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter‐rater reliability of physician adjudication.

Methods

Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin‐converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician‐adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD‐9‐CM code 995.1) meeting the inclusion criteria. The inter‐rater reliability of physician teams, or kappa statistic, was also calculated.

Results

There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient‐years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter‐rater reliability was 0.65 (95% CI: 0.47, 0.82).

Conclusions

ICD‐9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI.
Surfactant protein D concentration in a pediatric population with suspected sleep disorder
Authors: Ribot Caterina , Morell‐Garcia Daniel , Piérola Javier , Peña‐Zarza José A. , Sanchís Pilar , Muñiz Jesús , de la Peña Mónica , Alonso‐Fernández Alberto , Barceló Antonia
Published: September 2021

Obstructive sleep apnea (OSA) affects between 2% and 4% in children and there is a search for new biomarkers that can be useful both in the diagnosis and in the evolution of the disease. The surfactant protein D (SP‐D) is a collection that is part of the innate immune system exerting an anti‐inflammatory and antimicrobial effect. Thus, the objective of this study was to evaluate the concentration of SP‐D in the suspect OSA pediatric population. A total of 178 children were recruited in this prospective study. Blood samples, sleep parameters, feeding habits, anthropometric, sociodemographic, and family data were collected. Specific biochemical determinations were made, and the plasmatic concentrations of SP‐D were measured by enzyme‐linked immunosorbent assay. We found no statistical correlation between the SP‐D concentration and the apnea‐hypopnea index (AHI) from the data. Nevertheless, the changes in SP‐D levels could be correlated to a large extent by the arousals that often go along with hypopneas (r = −0.258, p = 0.011 unadjusted; r = −0.258, p = 0.014 adjusted by age and body mass inded [BMI] Z‐score). Intermittent hypoxia was correlated with C‐reactive protein levels (r = 0.547, p < 0.001 unadjusted; r = 0.542, p < 0.001 adjusted by age and BMI Z‐score). Although AHI and SP‐D did not appear to correlate, a secondary analysis suggests that sleep fragmentation, which is produced by arousals, may do, and further research is needed to determine the mechanisms by which changes in SP‐D occur in OSA.