bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Stencil for Patterning and Modeling in a Quantitative Volume Using EWOD and DEP Devices for Microfluidics
Authors: Lin Yi-Wei , Ciou Ying-Jhen , Yao Da-Jeng
Published: September 2021

Applying microfluidic patterning, droplets were precisely generated on an electrowetting-on-dielectric (EWOD) chip considering these parameters: number of generating electrodes, number of cutting electrodes, voltage, frequency and gap between upper and lower plates of the electrode array on the EWOD chip. In a subsequent patterning experiment, an environment with three generating electrodes, one cutting electrode and a gap height 10 μm, we obtained a quantitative volume for patterning. Propylene carbonate liquid and a mixed colloid of polyphthalate carbonate (PPC) and photosensitive polymer material were manipulated into varied patterns. With support from a Z-axis lifting platform and a UV lamp, a cured 3D structure was stacked. Using an EWOD system, a multi-layer three-dimensional structure was produced for the patterning. A two-plate EWOD system patterned propylene carbonate in a quantitative volume at 140 Vpp/20 kHz with automatic patterning.
Genomic Analysis Illustrated a Single Introduction and Evolution of Israeli Bluetongue Serotype 8 Virus Population 2008–2019
Authors: Golender Natalia , Eldar Avi , Ehrlich Marcelo , Kenigswald Gabriel , Shlamovitz Ily , Even-Tov Boris , Zamir Lior , Klement Eyal , Bumbarov Velizar
Published: September 2021

Outbreaks of the European Bluetongue virus (BTV) serotype 8 (BTV-8), which are characterized by activity cycles separated by years of inactivity, may be influenced by genetic changes of the virus or by herd immunity. BTV activity in Israel is characterized by similar dynamics, but differs from European countries in its vector population, environmental conditions, and lack of cattle vaccination against this serotype. Comparison of these two geographical systems and characterization of their epidemiological connection is therefore of high interest in-order to better understand the factors influencing BTV-8 evolution. BTV-8, closely related to the European strain, was introduced to Israel in 2008. It was at the center of BT outbreaks in 2010 and 2015–2016 and thereafter was lastly isolated in Israel in 2019. We performed genetic analyses of twelve BTV-8 Israeli strains isolated between 2008 and 2019 and compared them with published sequences of BTV-8 isolated in other countries. The analysis revealed a single introduction of BTV-8 into Israel and thereafter extensive occurrence of genomic drifts and multiple reassortments with local BTV strains. Comparison of the Israeli and Cypriot BTV-8 from 2015 to 2016 suggests transmission of the virus between the two countries and a separate and parallel development from European or other Israeli BTV-8 strains. The parallel development of other BTV-8 strains was demonstrated by the identification of the Israeli BTV-8 ISR-1194/1/19 strain, which exhibited common origin with reassorted Israeli BTV-8 strains from 2010 and additional reassortment of seven segments. In order to reveal the source of BTV-8 introduction into Israel we performed BEAST analysis which showed that a probable common ancestor for both European and Israeli BTV-8 presumably existed in 2003–2004. In 2019, a possible new introduction occurred in Israel, where a novel BTV-8 strain was detected, sharing ~95% identity by segments 2 and 6 with Nigerian BTV-8NIG1982/07 and European–Middle Eastern strains. The results of the study indicate that Israel and neighboring countries consist a separate environmental and evolutionary system, distinct from European ones.
Unique Association of Sulphosalts from the Kľačianka Occurrence, Nízke Tatry Mts., Slovak Republic
Authors: Sejkora Jiří , Števko Martin , Pršek Jaroslav , Hovorič Róbert , Makovicky Emil , Chovan Martin
Published: September 2021

Unique association of sulphosalts was discovered at the Kľačianka occurrence, Nízke Tatry Mts., Slovak Republic. It is bound to thin hydrothermal veins with Sb mineralization hosted by the Variscan muscovite-biotite granodiorite and granite of Prašivá type. Ore mineralogy and crystal chemistry of ore minerals are studied here by ore microscopy, X-ray powder diffraction, electron microprobe analyses, and Raman spectroscopy. The early ore mineralization composed of pyrite and arsenopyrite is hosted in quartz gangue and is followed by abundant association of sulfosalts. Stibnite, zinkenite, robinsonite (including Cu-bearing variety), jamesonite, scainiite, dadsonite, disulfodadsonite, rouxelite, chovanite, semseyite, boulangerite, geocronite, tintinaite (with low Bi contents), tetrahedrite-(Fe), tetrahedrite-(Zn), bournonite, chalcostibite, bismuthinite, and gladite in association with sphalerite and rare galena and gold are identified here. The chlorine-rich character of the described sulphosalt association is its characteristic phenomenon. It is represented not only by the occurrence of Cl-sulphosalt and dadsonite, but increased Cl contents were detected in boulangerite, chovanite, disulfodadsonite, robinsonite, rouxelite, scainiite, or tintinaite. The presence of oxygen-containing sulphosalts, such as rouxelite, scainiite and chovanite, is also interesting. The crystallization of these rare chloro-, oxy- and oxy-chloro-sulphosalts at the Kľačianka occurrence required very specific conditions (elevated O2/S2 fugacity) and high chlorine activity in ore-forming fluids.
Study on the Stability Principle of Mechanical Structure of Roadway with Composite Roof
Authors: Yu Yang , Lu Jianfei , Chen Dingchao , Pan Yuxin , Zhao Xiangqian , Zhang Lianying
Published: September 2021

With the typical composite roof roadway and roof fall accidents in the Guizhou Province of China as the research background, the expression of damage parameters of composite roof was deduced according to Weibull statistical distribution, generalized Hooke’s law and Mises yield criterion, and the influence of shape and scale parameters of Weibull on damage characteristic was discussed. Based on the infinite slab theory, the expressions of deflection and layer separation of each layer of the composite roof were obtained, the critical load expression of each delamination was determined, and the influence of roadway width, overlying strata load, elastic modulus, shape parameters and scale parameters on the stability of composite roof was explored. The research shows that the bolt support can effectively reduce the layer separation between the composite roofs and enhance the stability of the composite roof. On this basis, it is proposed that for the surrounding rock control problem of roadways with composite roof, the active support technology with bolts as the core should be adopted.
Communication of Sensor Data in Underground Mining Environments: An Evaluation of Wireless Signal Quality over Distance
Authors: Ikeda Hajime , Kolade Oluwafemi , Mahboob Muhammad Ahsan , Cawood Frederick Thomas , Kawamura Youhei
Published: September 2021

The technologies of the fourth industrial revolution have the potential to make zero harm possible for the first time in the history of mining. In the journey toward zero harm, rock stress monitoring systems are important for the risk management process. Although communication systems for underground mining have improved significantly over the past two decades, it remains difficult to achieve reliable-all-the-time wireless communication in ultra-deep level underground mines. The aim of this study is to explore and test a smart phone network for communicating sensor data from the underground production environment to the surface. In this paper, the evaluation and performance over distance of a wireless communication system is performed in underground mining environments. The wireless system transmits the data collected from a sensor installed in a narrow reef stope, horizontal tunnel, and vertical shaft area of a mock underground mine. The evaluation was performed using the received signal strength of a mobile receiver over distance. The path loss coefficients of the underground mining environment were then derived for the measurement areas. The results show that a communication speed of 80 Mbps was achieved in a 60 m range, thus, indicating the potential for the support of applications requiring higher data rates.
Resveratrol, EGCG and Vitamins Modulate Activated T Lymphocytes
Authors: Schwager Joseph , Seifert Nicole , Bompard Albine , Raederstorff Daniel , Bendik Igor
Published: September 2021

Vitamins and bioactives, which are constituents of the food chain, modulate T lymphocyte proliferation and differentiation, antibody production, and prevent inflammation and autoimmunity. We investigated the effects of vitamins (vitamin A (VA), D (VD), E (VE)) and bioactives (i.e., resveratrol (Res), epigallocatechin-3-gallate (EGCG)) on the adaptive immune response, as well as their synergistic or antagonistic interactions. Freshly isolated T lymphocytes from healthy individuals were activated with anti-CD3/CD28 antibodies for 4–5 days in the presence of bioactives and were analyzed by cytofluorometry. Interleukins, cytokines, and chemokines were measured by multiple ELISA. Gene expression was measured by quantitative RT-PCR. Res and EGCG increased CD4 surface intensity. EGCG led to an increased proportion of CD8+ lymphocytes. Anti-CD3/CD28 activation induced exuberant secretion of interleukins and cytokines by T lymphocyte subsets. VD strongly enhanced Th2 cytokines (e.g., IL-5, IL-13), whereas Res and EGCG favored secretion of Th1 cytokines (e.g., IL-2, INF-γ). Res and VD mutually influenced cytokine production, but VD dominated the cytokine secretion pattern. The substances changed gene expression of interleukins and cytokines in a similar way as they did secretion. Collectively, VD strongly modulated cytokine and interleukin production and favored Th2 functions. Resveratrol and EGCG promoted the Th1 response. VA and VE had only a marginal effect, but they altered both Th1 and Th2 response. In vivo, bioactives might therefore interact with vitamins and support the outcome and extent of the adaptive immune response.
Inflammatory and Cytotoxic Activities of Abietane Terpenoids from Nepeta bracteata Benth.
Authors: Zhang Manli , Chen Meiying , Hou Yong , Fan Congzhao , Wei Hongyan , Shi Leiling , Ma Guoxu , Zhang Jing
Published: September 2021

Nepeta bracteata Benth. is used clinically to treat tracheal inflammation, coughs, asthma, colds, fevers, adverse urination, and other symptoms, along with functions in clearing heat and removing dampness. However, there have been few studies characterizing the material basis of its efficacy. Therefore, the aim of this study was to screen for compounds with anti-inflammatory activities in N. bracteata Benth. Using silica gel, ODS C18, and Sephadex LH-20 column chromatography, as well as semipreparative HPLC, 10 compounds were separated from N. bracteata Benth. extract, including four new diterpenoids (1–4), one amide alkaloid (5), and five known diterpenoids (6–10). The structures of all the isolates were elucidated by HR-ESI-MS, NMR, and CD analyses. Using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, we investigated the anti-inflammatory activities of compounds 1–10. It is worth noting that all were able to inhibit nitric oxide (NO) production with IC50 values < 50 μM and little effect on RAW 264.7 macrophage viability. Compounds 2 and 4 displayed remarkable inhibition with IC50 values of 19.2 and 18.8 μM, respectively. Meanwhile, screening on HCT-8 cells demonstrated that compounds 2 and 4 also had moderate cytotoxic activities with IC50 values of 36.3 and 41.4 μM, respectively, which is related to their anti-inflammatory effects.
An Electrochemical Sensor Based on Gold and Bismuth Bimetallic Nanoparticles Decorated L-Cysteine Functionalized Graphene Oxide Nanocomposites for Sensitive Detection of Iron Ions in Water Samples
Authors: Zhou Na , Li Jing , Wang Shaoxia , Zhuang Xuming , Ni Shouqing , Luan Feng , Wu Xuran , Yu Shunyang
Published: September 2021

In this work, gold and bismuth bimetallic nanoparticles decorated L-cysteine functionalized graphene oxide nanocomposites (Au-BiNPs/SH-GO) were prepared and applied to selective detection of Fe(III) in lake and seawater samples by modifying onto glassy carbon electrodes. Bimetallic nanoparticles have various excellent properties and better catalytic properties because of the unique synergistic effect between metals. The modified electrode was characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and Raman spectroscopy. Under optimized conditions, current peak intensity increased linearly with increasing Fe(III) concentration over the range of 0.2–50 μM and a detection limit of 0.07 μM (S/N = 3). The Au-BiNPs/SH-GO/GCE was used for the determination of Fe(III) in lake and seawater samples with recoveries ranged from 90 to 103%. Those satisfactory results revealed the potential application of the Au-BiNPs/SH-GO electrochemical sensor for heavy metals detection in environmental monitoring.
Regular Nanowire Formation on Fe-Based Metal Glass by Manipulation of Surface Waves
Authors: Zhao Zhen , Xia Chaoqun , Yang Jianjun
Published: September 2021

We report the formation of a sole long nanowire structure and the regular nanowire arrays inside a groove on the surface of Fe-based metallic glass upon irradiation of two temporally delayed femtosecond lasers with the identical linear polarization parallel and perpendicular to the groove, respectively. The regular structure formation can be well observed within the delay time of 20 ps for a given total laser fluence of F = 30 mJ/cm2 and within a total laser fluence range of F = 30–42 mJ/cm2 for a given delay time of 5 ps. The structural features, including the unit width and distribution period, are measured on a one-hundred nanometer scale, much less than the incident laser wavelength of 800 nm. The degree of structure regularity sharply contrasts with traditional observations. To comprehensively understand such phenomena, we propose a new physical model by considering the spin angular momentum of surface plasmon and its enhanced inhomogeneous magnetization for the ferromagnetic metal. Therefore, an intensive TE polarized magnetic surface wave is excited to result in the nanometer-scaled energy fringes and the ablative troughs. The theory is further verified by the observation of nanowire structure disappearance at the larger time delays of two laser pulses.
Mini-LEDs with Diffuse Reflection Cavity Arrays and Quantum Dot Film for Thin, Large-Area, High-Luminance Flat Light Source
Authors: Ye Zhi Ting , Cheng Yuan Heng , Liu Ku Huan , Yang Kai Shiang
Published: September 2021

Mini-light-emitting diodes (mini-LEDs) were combined with multiple three-dimensional (3D) diffuse reflection cavity arrays (DRCAs) to produce thin, large-area, high-brightness, flat light source modules. The curvature of the 3D free-form DRCA was optimized to control its light path; this increased the distance between light sources and reduced the number of light sources used. Experiments with a 12.3-inch prototype indicated that 216 mini-LEDs were required for a 6 mm optical mixing distance to achieve a thin, large-area surface with high brightness, uniformity, and color saturation of 23,044 cd/m2, 90.13%, and 119.2, respectively. This module can serve as the local dimming backlight in next generation automotive displays.
Investigation on Plastic Flow Behaviors of FCC Polycrystalline Aluminum under Pre-Cyclic Tension-Compression Loading: Experiments and Crystal Plasticity Modeling
Authors: Lu Damin , Zhang Keshi , Hu Guijuan
Published: September 2021

The plastic flow behaviors of FCC polycrystalline aluminum after pre-cyclic tension-compression deformation are mainly investigated in tension–torsion stress space by the physically based crystal plasticity model introducing a back-stress. A global finite element model (GFEM) constructed of sufficient grains was established to simulate the same-size thin-walled tube specimen constrained and loaded as the experiments of yield surfaces. The computational results showed that the shape of subsequent yield surfaces and the plastic flow directions directly depended on the given offset strain levels and the applied re-loading paths under different pre-cyclic deformations. The angle deviation between the plastic flow direction and the theoretical orthogonal direction further indicated that there was a large difference between them in the inverse pre-straining direction, but the difference was negligible in the pre-straining direction. From the influence of the anisotropic evolution of the subsequent yield surfaces on plastic flow, we found that the plastic normality rule followed the smooth yield locus; conversely, the significant non-associated flow was attributed to the distorted yield locus. Furthermore, it was also demonstrated that the anisotropic evolution and the plastic flow trend of the subsequent yield surfaces obtained by experiments can be better reproduced by the crystal plasticity model.
Acetone-Sensitive Thin Films Comprising Coal Fly Ash Na-X Zeolites and Sol–Gel Nb2O5 Matrix
Authors: Lazarova Katerina , Boycheva Silviya , Vasileva Marina , Zgureva-Filipova Denitza , Georgieva Biliana , Babeva Tsvetanka
Published: September 2021

In this study, thin composite films of a sol–gel Nb2O5 matrix doped with coal fly ash Na-X zeolites were deposited by the spin-coating method. Fly ash of lignite coal collected from the electrostatic precipitators of one of the biggest TPPs in Bulgaria was used as a raw material for obtaining zeolites. Zeolite Na-X was synthesized by ultrasonic-assisted double stage fusion-hydrothermal alkaline conversion of coal fly ash. In order to improve the optical quality and sensing properties of the deposited thin films, synthesized zeolites were wet-milled for 60, 120, and 540 s prior to film deposition. The surface morphology of zeolite powders was studied both by scanning electron microscopy and transmission electron microscopy, while their porosity was investigated by N2-physisorption. Refractive index, extinction coefficient, and thickness of the films were determined through fitting of their reflectance spectra. The sensing ability of thin films towards acetone vapors was tested by measuring the reflectance spectra prior to and during exposure to the analyte, and the change in the reflection coefficient ∆R of the films was calculated. The influence of milling time of zeolites on the sensing and optical properties of the films was assumed and confirmed.
Ionic Liquid-Based Materials for Biomedical Applications
Authors: Correia Daniela Maria , Fernandes Liliana Correia , Fernandes Margarida Macedo , Hermenegildo Bruno , Meira Rafaela Marques , Ribeiro Clarisse , Ribeiro Sylvie , Reguera Javier , Lanceros-Méndez Senentxu
Published: September 2021

Ionic liquids (ILs) have been extensively explored and implemented in different areas, ranging from sensors and actuators to the biomedical field. The increasing attention devoted to ILs centers on their unique properties and possible combination of different cations and anions, allowing the development of materials with specific functionalities and requirements for applications. Particularly for biomedical applications, ILs have been used for biomaterials preparation, improving dissolution and processability, and have been combined with natural and synthetic polymer matrixes to develop IL-polymer hybrid materials to be employed in different fields of the biomedical area. This review focus on recent advances concerning the role of ILs in the development of biomaterials and their combination with natural and synthetic polymers for different biomedical areas, including drug delivery, cancer therapy, tissue engineering, antimicrobial and antifungal agents, and biosensing.
Advanced Electron Microscopy of Nanophased Synthetic Polymers and Soft Complexes for Energy and Medicine Applications
Authors: Chen Jihua
Published: September 2021

After decades of developments, electron microscopy has become a powerful and irreplaceable tool in understanding the ionic, electrical, mechanical, chemical, and other functional performances of next-generation polymers and soft complexes. The recent progress in electron microscopy of nanostructured polymers and soft assemblies is important for applications in many different fields, including, but not limited to, mesoporous and nanoporous materials, absorbents, membranes, solid electrolytes, battery electrodes, ion- and electron-transporting materials, organic semiconductors, soft robotics, optoelectronic devices, biomass, soft magnetic materials, and pharmaceutical drug design. For synthetic polymers and soft complexes, there are four main characteristics that differentiate them from their inorganic or biomacromolecular counterparts in electron microscopy studies: (1) lower contrast, (2) abundance of light elements, (3) polydispersity or nanomorphological variations, and (4) large changes induced by electron beams. Since 2011, the Center for Nanophase Materials Sciences (CNMS) at Oak Ridge National Laboratory has been working with numerous facility users on nanostructured polymer composites, block copolymers, polymer brushes, conjugated molecules, organic–inorganic hybrid nanomaterials, organic–inorganic interfaces, organic crystals, and other soft complexes. This review crystalizes some of the essential challenges, successes, failures, and techniques during the process in the past ten years. It also presents some outlooks and future expectations on the basis of these works at the intersection of electron microscopy, soft matter, and artificial intelligence. Machine learning is expected to automate and facilitate image processing and information extraction of polymer and soft hybrid nanostructures in aspects such as dose-controlled imaging and structure analysis.
Nanomechanical and Nanotribological Properties of Nanostructured Coatings of Tantalum and Its Compounds on Steel Substrates
Authors: Melnikova Galina , Kuznetsova Tatyana , Lapitskaya Vasilina , Petrovskaya Agata , Chizhik Sergei , Zykova Anna , Safonov Vladimir , Aizikovich Sergei , Sadyrin Evgeniy , Sun Weifu , Yakovin Stanislav
Published: September 2021

The present paper addresses the problem of identification of microstructural, nanomechanical, and tribological properties of thin films of tantalum (Ta) and its compounds deposited on stainless steel substrates by direct current magnetron sputtering. The compositions of the obtained nanostructured films were determined by energy dispersive spectroscopy. Surface morphology was investigated using atomic force microscopy (AFM). The coatings were found to be homogeneous and have low roughness values (<10 nm). The values of microhardness and elastic modulus were obtained by means of nanoindentation. Elastic modulus values for all the coatings remained unchanged with different atomic percentage of tantalum in the films. The values of microhardness of the tantalum films were increased after incorporation of the oxygen and nitrogen atoms into the crystal lattice of the coatings. The coefficient of friction, CoF, was determined by the AFM method in the “sliding” and “plowing” modes. Deposition of the coatings on the substrates led to a decrease of CoF for the coating-substrate system compared to the substrates; thus, the final product utilizing such a coating will presumably have a longer service life. The tantalum nitride films were characterized by the smallest values of CoF and specific volumetric wear.
Systematic Identification and Functional Validation of New snoRNAs in Human Muscle Progenitors
Authors: Bogard Baptiste , Francastel Claire , Hubé Florent
Published: September 2021

Small non-coding RNAs (sncRNAs) represent an important class of regulatory RNAs involved in the regulation of transcription, RNA splicing or translation. Among these sncRNAs, small nucleolar RNAs (snoRNAs) mostly originate from intron splicing in humans and are central to posttranscriptional regulation of gene expression. However, the characterization of the complete repertoire of sncRNAs in a given cellular context and the functional annotation of the human transcriptome are far from complete. Here, we report the large-scale identification of sncRNAs in the size range of 50 to 200 nucleotides without a priori on their biogenesis, structure and genomic origin in the context of normal human muscle cells. We provided a complete set of experimental validation of novel candidate snoRNAs by evaluating the prerequisites for their biogenesis and functionality, leading to their validation as genuine snoRNAs. Interestingly, we also found intergenic snoRNAs, which we showed are in fact integrated into candidate introns of unannotated transcripts or degraded by the Nonsense Mediated Decay pathway. Hence, intergenic snoRNAs represent a new type of landmark for the identification of new transcripts that have gone undetected because of low abundance or degradation after the release of the snoRNA.
Are Dietary Proteins the Key to Successful Body Weight Management? A Systematic Review and Meta-Analysis of Studies Assessing Body Weight Outcomes after Interventions with Increased Dietary Protein
Authors: Hansen Thea Toft , Astrup Arne , Sjödin Anders
Published: September 2021

The primary aim was to systematically review the current evidence investigating if dietary interventions rich in protein lead to improved body weight management in adults with excessive body weight. The secondary aim was to investigate potential modifying effects of phenotyping. A systematic literature search in PubMed, Web of Science, and Cochrane Library identified 375 randomized controlled trials with 43 unique trials meeting the inclusion criteria. The Cochrane collaboration tool was used for a thorough risk of bias assessment. Based on 37 studies evaluating effects of dietary protein on body weight, the participants with increased protein intake (ranging from 18–59 energy percentage [E%]) were found to reduce body weight by 1.6 (1.2; 2.0) kg (mean [95% confidence interval]) compared to controls (isocaloric interventions with energy reduction introduced in certain studies). Individuals with prediabetes were found to benefit more from a diet high in protein compared to individuals with normoglycemia, as did individuals without the obesity risk allele (AA genotype) compared to individuals with the obesity risk alleles (AG and GG genotypes). Thus, diets rich in protein would seem to have a moderate beneficial effect on body weight management.
A Pilot Randomized Controlled Trial of a Partial Meal Replacement Preconception Weight Loss Program for Women with Overweight and Obesity
Authors: Muirhead Roslyn , Kizirian Nathalie , Lal Ravin , Black Kirsten , Prys-Davies Ann , Nassar Natasha , Baur Louise , Sainsbury Amanda , Sweeting Arianne , Markovic Tania , Skilton Michael , Hyett Jon , de Vries Bradley , Tarnow-Mordi William , Brand-Miller Jennie , Gordon Adrienne
Published: September 2021

About half of Australian women have a body mass index in the overweight or obese range at the start of pregnancy, with serious consequences including preterm birth, gestational hypertension and diabetes, caesarean section, stillbirth, and childhood obesity. Trials to limit weight gain during pregnancy have had limited success and reducing weight before pregnancy has greater potential to improve outcomes. The PreBabe Pilot study was a randomised controlled pilot trial to assess the feasibility, acceptability and potential weight loss achieved using a commercial online partial meal replacement program, (MR) vs. telephone-based conventional dietary advice, (DA) for pre-conception weight-loss over a 10-week period. Women 18–40 years of age with a BMI ≥ 25 kg/m2 planning pregnancy within the next 6 to 12 months were included in the study. All participants had three clinic visits with a dietitian and one obstetric consultation. In total, 50 women were enrolled in the study between June 2018 and October 2019–26 in MR and 24 in DA. Study retention at the end of 10 week intervention 81% in the MR arm and 75% in the DA arm. In the-intention-to-treat analysis, women using meal replacements lost on average 5.4 ± 3.1% body weight compared to 2.3 ± 4.2% for women receiving conventional advice (p = 0.029). Over 80% of women in the MR arm rated the support received as excellent, compared to 39% in the DA arm (p < 0.001). Women assigned to the MR intervention were more likely to achieve pregnancy within 12 months of the 10 week intervention (57% (12 of 21) women assigned to MR intervention vs. 22% (4 of 18) assigned to the DA group (p = 0.049) became pregnant). The findings suggest that a weight loss intervention using meal replacements in the preconception period was acceptable and may result in greater weight loss than conventional dietary advice alone.
Ketogenic Diets in Pancreatic Cancer and Associated Cachexia: Cellular Mechanisms and Clinical Perspectives
Authors: Cortez Natalia E. , Mackenzie Gerardo G.
Published: September 2021

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and extremely therapy-resistant cancer. It is estimated that up to 80% of PDAC patients present with cachexia, a multifactorial disorder characterized by the involuntary and ongoing wasting of skeletal muscle that affects therapeutic response and survival. During the last decade, there has been an increased interest in exploring dietary interventions to complement the treatment of PDAC and associated cachexia. Ketogenic diets (KDs) have gained attention for their anti-tumor potential. Characterized by a very low carbohydrate, moderate protein, and high fat composition, this diet mimics the metabolic changes that occur in fasting. Numerous studies report that a KD reduces tumor growth and can act as an adjuvant therapy in various cancers, including pancreatic cancer. However, research on the effect and mechanisms of action of KDs on PDAC-associated cachexia is limited. In this narrative review, we summarize the evidence of the impact of KDs in PDAC treatment and cachexia mitigation. Furthermore, we discuss key cellular mechanisms that explain KDs’ potential anti-tumor and anti-cachexia effects, focusing primarily on reprogramming of cell metabolism, epigenome, and the gut microbiome. Finally, we provide a perspective on future research needed to advance KDs into clinical use.
Preoperative Nutrition Intervention in Patients Undergoing Resection for Upper Gastrointestinal Cancer: Results from the Multi-Centre NOURISH Point Prevalence Study
Authors: Deftereos Irene , Yeung Justin M.-C. , Arslan Janan , Carter Vanessa M. , Isenring Elizabeth , Kiss Nicole ,   on behalf of The Nourish Point Prevalence Study Group
Published: September 2021

Background: Preoperative nutrition intervention is recommended prior to upper gastrointestinal (UGI) cancer resection; however, there is limited understanding of interventions received in current clinical practice. This study investigated type and frequency of preoperative dietetics intervention and nutrition support received and clinical and demographic factors associated with receipt of intervention. Associations between intervention and preoperative weight loss, surgical length of stay (LOS), and complications were also investigated. Methods: The NOURISH Point Prevalence Study was conducted between September 2019 and May 2020 across 27 Australian tertiary centres. Subjective global assessment and weight were performed within 7 days of admission. Patients reported on preoperative dietetics and nutrition intervention, and surgical LOS and complications were recorded. Results: Two-hundred patients participated (59% male, mean (standard deviation) age 67 (10)). Sixty percent had seen a dietitian preoperatively, whilst 50% were receiving nutrition support (92% oral nutrition support (ONS)). Patients undergoing pancreatic surgery were less likely to receive dietetics intervention and nutrition support than oesophageal or gastric surgeries (p < 0.001 and p = 0.029, respectively). Neoadjuvant therapy (p = 0.003) and malnutrition (p = 0.046) remained independently associated with receiving dietetics intervention; however, 31.3% of malnourished patients had not seen a dietitian. Patients who received ≥3 dietetics appointments had lower mean (SD) percentage weight loss at the 1-month preoperative timeframe compared with patients who received 0–2 appointments (1.2 (2.0) vs. 3.1 (3.3), p = 0.001). Patients who received ONS for >2 weeks had lower mean (SD) percentage weight loss than those who did not (1.2 (1.8) vs. 2.9 (3.4), p = 0.001). In malnourished patients, total dietetics appointments ≥3 was independently associated with reduced surgical complications (odds ratio 0.2, 95% confidence interval (CI) 0.1, 0.9, p = 0.04), and ONS >2 weeks was associated with reduced LOS (regression coefficient −7.3, 95% CI −14.3, −0.3, p = 0.04). Conclusions: Despite recommendations, there are low rates of preoperative dietetics consultation and nutrition support in this population, which are associated with increased preoperative weight loss and risk of increased LOS and complications in malnourished patients. The results of this study provide insights into evidence–practice gaps for improvement and data to support further research regarding optimal methods of preoperative nutrition support.
Food Intolerance: The Role of Histamine
Authors: Shulpekova Yulia O. , Nechaev Vladimir M. , Popova Irina R. , Deeva Tatiana A. , Kopylov Arthur T. , Malsagova Kristina A. , Kaysheva Anna L. , Ivashkin Vladimir T.
Published: September 2021

Histamine is a natural amine derived from L-histidine. Although it seems that our knowledge about this molecule is wide and diverse, the importance of histamine in many regulatory processes is still enigmatic. The interplay between different types of histamine receptors and the compound may cause ample effects, including histamine intoxication and so-called histamine intolerance or non-allergic food intolerance, leading to disturbances in immune regulation, manifestation of gastroenterological symptoms, and neurological diseases. Most cases of clinical manifestations of histamine intolerance are non-specific due to tissue-specific distribution of different histamine receptors and the lack of reproducible and reliable diagnostic markers. The diagnosis of histamine intolerance is fraught with difficulties, in addition to challenges related to the selection of a proper treatment strategy, the regular course of recovery, and reduced amelioration of chronic symptoms due to inappropriate treatment prescription. Here, we reviewed a history of histamine uptake starting from the current knowledge about its degradation and the prevalence of histamine precursors in daily food, and continuing with the receptor interactions after entering and the impacts on the immune, central nervous, and gastrointestinal systems. The purpose of this review is to build an extraordinarily specific method of histamine cycle assessment in regard to non-allergic intolerance and its possible dire consequences that can be suffered.
The Effect of Dietary Interventions on Chronic Inflammatory Diseases in Relation to the Microbiome: A Systematic Review
Authors: Wagenaar Carlijn A. , van de Put Marieke , Bisschops Michelle , Walrabenstein Wendy , de Jonge Catharina S. , Herrema Hilde , van Schaardenburg Dirkjan
Published: September 2021

Chronic inflammation plays a central role in the pathophysiology of various non-communicable diseases. Dietary interventions can reduce inflammation, in part due to their effect on the gut microbiome. This systematic review aims to determine the effect of dietary interventions, specifically fiber intake, on chronic inflammatory diseases and the microbiome. It aims to form hypotheses on the potential mediating effects of the microbiome on disease outcomes after dietary changes. Included were clinical trials which performed a dietary intervention with a whole diet change or fiber supplement (>5 g/day) and investigated the gut microbiome in patients diagnosed with chronic inflammatory diseases such as cardiovascular disease (CVD), type 2 diabetes (T2DM), and autoimmune diseases (e.g., rheumatoid arthritis (RA), inflammatory bowel disease (IBD)). The 30 articles which met the inclusion criteria had an overall moderate to high risk of bias and were too heterogeneous to perform a meta-analysis. Dietary interventions were stratified based on fiber intake: low fiber, high fiber, and supplemental fiber. Overall, but most pronounced in patients with T2DM, high-fiber plant-based dietary interventions were consistently more effective at reducing disease-specific outcomes and pathogenic bacteria, as well as increasing microbiome alpha diversity and short-chain fatty acid (SCFA)-producing bacteria, compared to other diets and fiber supplements.
Potential Role of Hepatozoon canis in a Fatal Systemic Disease in a Puppy
Authors: De Bonis Andrea , Colombo Mariasole , Terragni Rossella , Bacci Barbara , Morelli Simone , Grillini Marika , Vignoli Massimo
Published: September 2021

Canine hepatozoonosis caused by Hepatozoon canis is an emerging disease in Europe. Clinical pictures vary from subclinical to life-threatening and non-specific clinical signs are predominantly reported. A 2-month-old female puppy originating from Southern Italy was adopted and moved to Northern Italy. Then, the dog was brought to a local veterinary practice for gastrointestinal signs, migrating lameness and pruritic dermatitis, and then tested positive for Hepatozoon spp. gamonts at the blood smear. After treatment with imidocarb dipropionate and doxycycline, the dog showed an initial clinical improvement. However, gastrointestinal signs recurred, and diffuse superficial pyoderma appeared on the thoracolumbar region, along with fever, lethargy, and weight loss. Eight months from the first onset of clinical signs, the dog was referred to a veterinary clinic and subjected to complete blood count, urine and fecal analysis, along with abdominal ultrasonography, whole-body CT and gastroduodenal endoscopy. Skin biopsies and blood samples were subjected to a PCR-coupled sequencing protocol, which scored both positive for H. canis. Alterations were consistent with a pre-existing cholangiohepatitis and multiple acquired extrahepatic shunts secondary to portal hypertension. The dog was euthanatized due to a clinical worsening two months later. The potential role of H. canis in the systemic disease observed, clinic-pathological findings and epizootiological implications are discussed.
Incident Type 2 Diabetes Risk of Selective Estrogen Receptor Modulators in Female Patients with Breast Cancer
Authors: Choi Yeo-Jin , Bak Keunhyeong , Yeo Yoon , Choi Yongwon , Shin Sooyoung
Published: September 2021

Accumulating evidence indicates a link between diabetes and cancer. Selective estrogen receptor modulators (SERMs) may increase diabetes risk via antiestrogen effects. This study investigated incident diabetes risk of SERM treatment and its effects on metastatic cancer and death prevention in breast cancer survivors. This retrospective cohort study included female patients with early-stage breast cancer, treated with or without SERMs, between 2008 and 2020 in a tertiary care hospital in Korea. Four propensity score-matched comparison pairs were designed: SERM use versus non-use, long-term use (≥1500 days) versus non-use, tamoxifen use versus non-use, and toremifene use versus non-use; then, logistic regression analysis was performed for risk analysis. SERMs in general were not associated with an elevated risk of diabetes; however, when used for ≥1500 days, SERMs—especially toremifene—substantially increased diabetes risk in breast cancer patients (OR 1.63, p = 0.048). Meanwhile, long-term SERM treatment was effective at preventing metastatic cancer (OR 0.20, p < 0.001) and death (OR 0.13, p < 0.001). SERM treatment, albeit generally safe and effective, may increase diabetes risk with its long-term use in women with breast cancer. Further studies are required to verify the association between toremifene treatment and incident diabetes.
New Strategies for the Treatment of Atrial Fibrillation
Authors: Jost Norbert , Christ Torsten , Magyar János
Published: September 2021

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in the clinical practice. It significantly contributes to the morbidity and mortality of the elderly population. Over the past 25–30 years intense effort in basic research has advanced the understanding of the relationship between the pathophysiology of AF and atrial remodelling. Nowadays it is clear that the various forms of atrial remodelling (electrical, contractile and structural) play crucial role in initiating and maintaining the persistent and permanent types of AF. Unlike in ventricular fibrillation, in AF rapid ectopic firing originating from pulmonary veins and re-entry mechanism may induce and maintain (due to atrial remodelling) this complex cardiac arrhythmia. The present review presents and discusses in detail the latest knowledge on the role of remodelling in AF. Special attention is paid to novel concepts and pharmacological targets presumably relevant to the drug treatment of atrial fibrillation.
Polyelectrolyte Matrices in the Modulation of Intermolecular Electrostatic Interactions for Amorphous Solid Dispersions: A Comprehensive Review
Authors: Tsiaxerli Anastasia , Karagianni Anna , Ouranidis Andreas , Kachrimanis Kyriakos
Published: September 2021

Polyelectrolyte polymers have been widely used in the pharmaceutical field as excipients to facilitate various drug delivery systems. Polyelectrolytes have been used to modulate the electrostatic environment and enhance favorable interactions between the drug and the polymer in amorphous solid dispersions (ASDs) prepared mainly by hot-melt extrusion. Polyelectrolytes have been used alone, or in combination with nonionic polymers as interpolyelectrolyte complexes, or after the addition of small molecular additives. They were found to enhance physical stability by favoring stabilizing intermolecular interactions, as well as to exert an antiplasticizing effect. Moreover, they not only enhance drug dissolution, but they have also been used for maintaining supersaturation, especially in the case of weakly basic drugs that tend to precipitate in the intestine. Additional uses include controlled and/or targeted drug release with enhanced physical stability and ease of preparation via novel continuous processes. Polyelectrolyte matrices, used along with scalable manufacturing methods in accordance with green chemistry principles, emerge as an attractive viable alternative for the preparation of ASDs with improved physical stability and biopharmaceutic performance.
mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation
Authors: Gómez-Aguado Itziar , Rodríguez-Castejón Julen , Beraza-Millor Marina , Vicente-Pascual Mónica , Rodríguez-Gascón Alicia , Garelli Sara , Battaglia Luigi , del Pozo-Rodríguez Ana , Solinís María
Published: September 2021

The anti-inflammatory cytokine Interleukin-10 (IL-10) is considered an efficient treatment for corneal inflammation, in spite of its short half-life and poor eye bioavailability. In the present work, mRNA-based nanomedicinal products based on solid lipid nanoparticles (SLNs) were developed in order to produce IL-10 to treat corneal inflammation. mRNA encoding green fluorescent protein (GFP) or human IL-10 was complexed with different SLNs and ligands. After, physicochemical characterization, transfection efficacy, intracellular disposition, cellular uptake and IL-10 expression of the nanosystems were evaluated in vitro in human corneal epithelial (HCE-2) cells. Energy-dependent mechanisms favoured HCE-2 transfection, whereas protein production was influenced by energy-independent uptake mechanisms. Nanovectors with a mean particle size between 94 and 348 nm and a positive superficial charge were formulated as eye drops containing 1% (w/v) of polyvinyl alcohol (PVA) with 7.1–7.5 pH. After three days of topical administration to mice, all formulations produced GFP in the corneal epithelium of mice. SLNs allowed the obtaining of a higher transfection efficiency than naked mRNA. All formulations produce IL-10, and the interleukin was even observed in the deeper layers of the epithelium of mice depending on the formulation. This work shows the potential application of mRNA-SLN-based nanosystems to address corneal inflammation by gene augmentation therapy.
Modulation of Conductivity of Alginate Hydrogels Containing Reduced Graphene Oxide through the Addition of Proteins
Authors: Raslan Ahmed , Ciriza Jesús , Ochoa de Retana Ana María , Sanjuán María Luisa , Toprak Muhammet S. , Galvez-Martin Patricia , Saenz-del-Burgo Laura , Pedraz Jose Luis
Published: September 2021

Modifying hydrogels in order to enhance their conductivity is an exciting field with applications in cardio and neuro-regenerative medicine. Therefore, we have designed hybrid alginate hydrogels containing uncoated and protein-coated reduced graphene oxide (rGO). We specifically studied the adsorption of three different proteins, BSA, elastin, and collagen, and the outcomes when these protein-coated rGO nanocomposites are embedded within the hydrogels. Our results demonstrate that BSA, elastin, and collagen are adsorbed onto the rGO surface, through a non-spontaneous phenomenon that fits Langmuir and pseudo-second-order adsorption models. Protein-coated rGOs are able to preclude further adsorption of erythropoietin, but not insulin. Collagen showed better adsorption capacity than BSA and elastin due to its hydrophobic nature, although requiring more energy. Moreover, collagen-coated rGO hybrid alginate hydrogels showed an enhancement in conductivity, showing that it could be a promising conductive scaffold for regenerative medicine.
A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies
Authors: Noorani Behnam , Bhalerao Aditya , Raut Snehal , Nozohouri Ehsan , Bickel Ulrich , Cucullo Luca
Published: September 2021

Microfluidics-based organ-on-a-chip technology allows for developing a new class of in-vitro blood-brain barrier (BBB) models that recapitulate many hemodynamic and architectural features of the brain microvasculature not attainable with conventional two-dimensional platforms. Herein, we describe and validate a novel microfluidic BBB model that closely mimics the one in situ. Induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) were juxtaposed with primary human pericytes and astrocytes in a co-culture to enable BBB-specific characteristics, such as low paracellular permeability, efflux activity, and osmotic responses. The permeability coefficients of [13C12] sucrose and [13C6] mannitol were assessed using a highly sensitive LC-MS/MS procedure. The resulting BBB displayed continuous tight-junction patterns, low permeability to mannitol and sucrose, and quasi-physiological responses to hyperosmolar opening and p-glycoprotein inhibitor treatment, as demonstrated by decreased BBB integrity and increased permeability of rhodamine 123, respectively. Astrocytes and pericytes on the abluminal side of the vascular channel provided the environmental cues necessary to form a tight barrier and extend the model’s long-term viability for time-course studies. In conclusion, our novel multi-culture microfluidic platform showcased the ability to replicate a quasi-physiological brain microvascular, thus enabling the development of a highly predictive and translationally relevant BBB model.