bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Clinical Characteristics of Community-Acquired Acute Pyelonephritis and Antimicrobial Resistance of Uropathogenic Escherichia coli in South Korea in the Past Decade
Authors: Kwon Ki Tae , Kim Bongyoung , Ryu Seong-yeol , Wie Seong-Heon , Kim Jieun , Jo Hyun-uk , Park Se Yoon , Hong Kyung-Wook , Kim Hye In , Kim Hyun ah , Kim Mi-Hee , Bae Mi Hyun , Sohn Yong-Hak , Kim Jieun , Lee Yangsoon , Pai Hyunjoo
Published: September 2020

This study examined changes in the clinical characteristics of community-acquired acute pyelonephritis (CA-APN) in South Korea between the period 2010–2011 and 2017–2018. We recruited all CA-APN patients aged ≥19 years who visited eight hospitals in South Korea from September 2017 to August 2018, prospectively. Data collected were compared with those from the previous study in 2010–2012, with the same design and participation from 11 hospitals. A total of 617 patients were enrolled and compared to 818 patients’ data collected in 2010–2011. Escherichia coli was the most common causative pathogen of CA-APN in both periods (87.3% vs. 86.5%, p = 0.680). E. coli isolates showed significantly higher antimicrobial resistance against fluoroquinolone (32.0% vs. 21.6%, p < 0.001), cefotaxime (33.6% vs. 8.3%, p < 0.001), and trimethoprim/sulfamethoxazole (37.5% vs. 29.2%, p = 0.013) in 2017–2018 than in 2010–2011. Total duration of antibiotic treatment increased from 16.55 ± 9.68 days in 2010–2011 to 19.12 ± 9.90 days in 2017–2018 (p < 0.001); the duration of carbapenem usage increased from 0.59 ± 2.87 days in 2010–2011 to 1.79 ± 4.89 days in 2010–2011 (p < 0.001). The median hospitalization was higher for patients in 2017–2018 than in 2010–2011 (9 vs. 7 days, p < 0.001). In conclusion, antimicrobial resistance of E. coli to almost all antibiotic classes, especially third generation cephalosporin, increased significantly in CA-APN in South Korea. Consequently, total duration of antibiotic treatment, including carbapenem usage, increased.
Antifungal Packaging Film to Maintain Quality and Control Postharvest Diseases in Strawberries
Authors: Trinetta Valentina , McDaniel Austin , G. Batziakas Konstantinos , Yucel Umut , Nwadike Londa , Pliakoni Eleni
Published: September 2020

Strawberries are a highly perishable crop with postharvest losses than reach up to 40%. Cost-effective and sustainable technologies in the form of active packing films can provide a solution. Antimicrobial packaging films were produced from pullulan polymer and Solid Lipid Nanoparticles (SLN) containing 1% w/w cinnamaldehyde. Strawberries were stored at 3 °C for 10 days and 12 °C for 6 days. Microbial and physical quality parameters were evaluated during storage. A reduction of approximately 2 Log CFU/g in yeast and mold population was observed for treated strawberries stored at 3 °C as compared to the control (p < 0.05). Yeast and molds counts were significantly lower on day 2 and 4 at 12 °C for treated samples. Strawberries packaged with the active films demonstrated lower respiration rates and the retention of bright red color at both storage temperatures. Active pullulan films were effective in maintaining the desired strawberry quality and reducing fungal decay during refrigerated storage.
Retinoprotective Effect of Wild Olive (Acebuche) Oil-Enriched Diet against Ocular Oxidative Stress Induced by Arterial Hypertension
Authors: Santana-Garrido Álvaro , Reyes-Goya Claudia , Pérez-Camino M. Carmen , André Helder , Mate Alfonso , Vázquez Carmen M.
Published: September 2020

Oxidative stress plays an important role in the pathogenesis of ocular diseases, including hypertensive eye diseases. The beneficial effects of olive oil on cardiovascular diseases might rely on minor constituents. Currently, very little is known about the chemical composition and/or therapeutic effects of the cultivated olive tree’s counterpart, wild olive (also known in Spain as acebuche—ACE). Here, we aimed to analyze the antioxidant and retinoprotective effects of ACE oil on the eye of hypertensive mice made hypertensive via administration of NG-nitro-L-arginine-methyl-ester (L-NAME), which were subjected to a dietary supplementation with either ACE oil or extra virgin olive oil (EVOO) for comparison purposes. Deep analyses of major and minor compounds present in both oils was accompanied by blood pressure monitoring, morphometric analyses, as well as different determinations of oxidative stress-related parameters in retinal layers. Aside from its antihypertensive effect, an ACE oil-enriched diet reduced NADPH (nicotinamide adenine dinucleotide phosphate) oxidase activity/gene/protein expression (with a major implication of NADPH oxidase (NOX)2 isoform) in the retinas of hypertensive mice. Supplementation with ACE oil in hypertensive animals also improved alterations in nitric oxide bioavailability and in antioxidant enzyme profile. Interestingly, our findings show that the use of ACE oil resulted in better outcomes, compared with reference EVOO, against hypertension-related oxidative retinal damage.
A Short Overview of Changes in Inflammatory Cytokines and Oxidative Stress in Response to Physical Activity and Antioxidant Supplementation
Authors: Taherkhani Shima , Suzuki Katsuhiko , Castell Lindy
Published: September 2020

Excessive release of inflammatory cytokines and oxidative stress (OS) are triggering factors in the onset of chronic diseases. One of the factors that can ensure health in humans is regular physical activity. This type of activity can enhance immune function and dramatically prevent the spread of the cytokine response and OS. However, if physical activity is done intensely at irregular intervals, it is not only unhealthy but can also lead to muscle damage, OS, and inflammation. In this review, the response of cytokines and OS to exercise is described. In addition, it is focused predominantly on the role of reactive oxygen and nitrogen species (RONS) generated from muscle metabolism and damage during exercise and on the modulatory effects of antioxidant supplements. Furthermore, the influence of factors such as age, sex, and type of exercise protocol (volume, duration, and intensity of training) is analyzed. The effect of antioxidant supplements on improving OS and inflammatory cytokines is somewhat ambiguous. More research is needed to understand this issue, considering in greater detail factors such as level of training, health status, age, sex, disease, and type of exercise protocol.
Noise Impact Mitigation of Shopping Centres Located near Densely Populated Areas for a Better Quality of Life
Authors: Deaconu Marius , Cican Grigore , Cristea Laurentiu
Published: September 2020

The growth of the urban population and its activity in major cities has led to various public health challenges, including environmental pollution, which are reflected in a decrease in the well-being of societies. This paper presents a predictive tool used to mitigate the noise impact study of commercial centre noise on the surrounding houses, the study being conducted prior to its construction. Before the construction of the supermarket, the sound pressure levels from the façade of the surrounding building are measured to have a background noise level of the analysed area. The noise impact study is made using prediction software in which the houses and the shopping centre buildings are numerically modelled. The main noise sources of the commercial centre, defined in numerical predictions, are represented by the air conditioners, heat pumps situated on the roof and the noise generated by the activities from the supply ramp. The noise impact evaluation is performed at different heights and by determining the number of affected inhabitants. To reduce the number of exposed inhabitants to noise, four technical solutions are presented. The proposed noise solutions are based on technical and economic analyses and also on the urban landscape. The study presents the noise prediction for which the propagation calculus was made according to ISO 9613-2. The noise limits were evaluated according to the Romanian national legislation. The final part of this study presents the noise measurements performed after the construction of this shopping centre and the validation of the implemented noise reduction solution.
Bounded-Error-Pruned Sensor Data Compression for Energy-Efficient IoT of Environmental Intelligence
Authors: Chang Ray-I. , Chu Yu-Hsien , Wei Lien-Chen , Wang Chia-Hui
Published: September 2020

Emerging IoT (Internet of Things) technologies have enjoyed tremendous success in a variety of applications. Since sensors in IoT consume a lot of energy to transmit their data, data compression used to prolong system lifetime has become a hot research topic. In many real-world applications, such as IEI (IoT of environmental intelligence), the required sensing data usually have limited error tolerance according to the QoS2 (quality of sensor service) or QoD (quality of decision-making) required. However, the bounded-error-pruned sensor data can achieve higher data correlation for better compression without jeopardizing QoS2/QoD. Moreover, the sensing data in widely spread sensors usually have strong temporal and spatial correlations. We thus propose a BESDC (bounded-error-pruned sensor data compression) scheme to achieve better leverage between the bounded error and compression ratio for sensor data. In this paper, our experiments on a sensor network of two-tier tree architecture consider four different environmental datasets including PM 2.5, CO, temperature and seismic wave with different scales of bounded errors. With the bounded errors required by the given IEI applications, our BESDC can reduce the total size of data transmission to minimize both energy consumption in sensor-tier devices and storage of fog-tier servers. The experimental results demonstrate that our BESDC can reduce transmission data by over 55% and save 50% energy consumption when assigning 1% of error tolerance within QoS2/QoD requirement. To the best of our knowledge, the proposed BESDC scheme can help other energy-efficient IoT schemes applying network topologies and routing protocols to further enhance energy-efficient IoT services.
Optimization Design of RV Reducer Crankshaft Bearing
Authors: Huang Jian , Li Chaoyang , Chen Bingkui
Published: September 2020

The crankshaft bearing is the key component of a rotate vector (RV) reducer. However, owing to the harsh working load and restricted available space, the bearing often suffers from fatigue failure. Therefore, this study proposes a novel optimization method for RV reducer crankshaft bearings. A nonlinear constraint optimization model for the design of the bearing considering the crowned roller profile is formulated and is solved by using a crow search algorithm. The goal of the optimization is to maximize the fatigue life of the bearing. The design variables corresponding to the bearing geometry and crowned roller profile are considered. The load working conditions of the bearing and structure of the RV reducer are analyzed. Various constraints, including geometry, lubrication, strength of the bearing, and structure of the RV reducer, are established. Through the optimization design, the optimum crowned roller profile suitable for the working load of the bearing is obtained, and the stress concentration between the roller and raceway is eliminated. Taking the crankshaft bearing of RV-20E and RV-110E type reducers as examples, the bearings were optimized by the proposed method. After optimization, the bearing life of the RV-20E type reducer is increased by 196%, and the bearing life of the RV-110E type reducer is increased by 168%.
Recent Developments in Instrumentation of Functional Near-Infrared Spectroscopy Systems
Authors: Althobaiti Murad , Al-Naib Ibraheem
Published: September 2020

In the last three decades, the development and steady improvement of various optical technologies at the near-infrared region of the electromagnetic spectrum has inspired a large number of scientists around the world to design and develop functional near-infrared spectroscopy (fNIRS) systems for various medical applications. This has been driven further by the availability of new sources and detectors that support very compact and wearable system designs. In this article, we review fNIRS systems from the instrumentation point of view, discussing the associated challenges and state-of-the-art approaches. In the beginning, the fundamentals of fNIRS systems as well as light-tissue interaction at NIR are briefly introduced. After that, we present the basics of NIR systems instrumentation. Next, the recent development of continuous-wave, frequency-domain, and time-domain fNIRS systems are discussed. Finally, we provide a summary of these three modalities and an outlook into the future of fNIRS technology.
A Robot Has a Mind of Its Own Because We Intuitively Share It
Authors: Sumitani Mizuho , Osumi Michihiro , Abe Hiroaki , Azuma Kenji , Tsuchida Rikuhei , Sumitani Masahiko
Published: September 2020

People perceive the mind in two dimensions: intellectual and affective. Advances in artificial intelligence enable people to perceive the intellectual mind of a robot through their semantic interactions. Conversely, it has been still controversial whether a robot has an affective mind of its own without any intellectual actions or semantic interactions. We investigated pain experiences when observing three different facial expressions of a virtual agent modeling affective minds (i.e., painful, unhappy, and neutral). The cold pain detection threshold of 19 healthy subjects was measured as they watched a black screen, then changes in their cold pain detection thresholds were evaluated as they watched the facial expressions. Subjects were asked to rate the pain intensity from the respective facial expressions. Changes of cold pain detection thresholds were compared and adjusted by the respective pain intensities. Only when watching the painful expression of a virtual agent did, the cold pain detection threshold increase significantly. By directly evaluating intuitive pain responses when observing facial expressions of a virtual agent, we found that we ‘share’ empathic neural responses, which can be intuitively emerge, according to observed pain intensity with a robot (a virtual agent).
Did ERA5 Improve Temperature and Precipitation Reanalysis over East Africa?
Authors: Gleixner Stephanie , Demissie Teferi , Diro Gulilat Tefera
Published: September 2020

Reanalysis products are often taken as an alternative solution to observational weather and climate data due to availability and accessibility problems, particularly in data-sparse regions such as Africa. Proper evaluation of their strengths and weaknesses, however, should not be overlooked. The aim of this study was to evaluate the performance of ERA5 reanalysis and to document the progress made compared to ERA-interim for the fields of near-surface temperature and precipitation over Africa. Results show that in ERA5 the climatological biases in temperature and precipitation are clearly reduced and the representation of inter-annual variability is improved over most of Africa. However, both reanalysis products performed less well in terms of capturing the observed long-term trends, despite a slightly better performance of ERA5 over ERA-interim. Further regional analysis over East Africa shows that the representation of the annual cycle of precipitation is substantially improved in ERA5 by reducing the wet bias during the rainy season. The spatial distribution of precipitation during extreme years is also better represented in ERA5. While ERA5 has improved much in comparison to its predecessor, there is still demand for improved products with even higher resolution and accuracy to satisfy impact-based studies, such as in agriculture and water resources.
Changes in Methane Emission and Community Composition of Methane-Cycling Microorganisms Along an Elevation Gradient in the Dongting Lake Floodplain, China
Authors: Ren Yijie , Zhu Lianlian , Deng Zhengmiao , Xie Yonghong , Zhang Chengyi , Xiao Fengjin , Chen Xinsheng , Li Feng , Zou Yeai , Sheng Rong , Zhang Xiaoyan , Chen Xian
Published: September 2020

Methane (CH4) emission and environmental controls of CH4-cycling microorganisms are unclear in inland floodplains. Here, we examined soil CH4 emissions and the community composition of CH4-cycling microorganisms under three vegetation types—mudflat (MF, no vegetation cover), Carex meadow (CM, mainly Carex brevicuspis), and reed land (RL, mainly Miscanthus sacchariflorus)—from water-adjacent areas to higher-elevation land in the Dongting Lake floodplain, China. The results showed that CH4 emission is the highest in CM, while significant absorption was observed in the RL site. The abundance ratio of methanogen/methanotroph was the highest in CM, intermediate in MF, and lowest in RL. The Methanosarcinaceae family represented the dominant methanogens in the three sampling sites (41.32–75.25%). The genus Methylocystis (60.85%, type II methanotrophs) was dominant in CM, while Methylobacter and Methylosarcina (type I methanotrophs) were the dominant genera in MF (51.00%) and RL (50.24%), respectively. Structural equation model analysis showed that methanogen and methanotroph abundance were affected by water table depth, soil water content, and pH indirectly through soil organic content, total nitrogen, microbial biomass carbon, and microbial biomass nitrogen. These results indicated that the Dongting Lake floodplain may change from a CH4 source to a CH4 sink with vegetation succession with an increase in elevation, and the methanogen/methanotroph ratio can be used as a proxy for CH4 emission in wetland soils. The continuous increase in reed area combined with the decrease in Carex meadow may mitigate CH4 emission and enhance the CH4 sink function during the non-flood season in the Dongting Lake floodplain.
Application of the Hidden Markov Bayesian Classifier and Propagation Concept for Probabilistic Assessment of Meteorological and Hydrological Droughts in South Korea
Authors: Sattar Muhammad Nouman , Jehanzaib Muhammad , Kim Ji Eun , Kwon Hyun-Han , Kim Tae-Woong
Published: September 2020

Drought is one of the most destructive natural hazards and results in negative effects on the environment, agriculture, economics, and society. A meteorological drought originates from atmospheric components, while a hydrological drought is influenced by properties of the hydrological cycle and generally induced by a continuous meteorological drought. Several studies have attempted to explain the cross dependencies between meteorological and hydrological droughts. However, these previous studies did not consider the propagation of drought classes. Therefore, in this study, to consider the drought propagation concept and to probabilistically assess the meteorological and hydrological drought classes, characterized by the Standardized Precipitation Index (SPI) and Standardized Runoff Index (SRI), respectively, we employed the Markov Bayesian Classifier (MBC) model that combines the procedure of iteration of feature extraction, classification, and application for assessment of drought classes for both SPI and SRI. The classification results were compared using the observed SPI and SRI, as well as with previous findings, which demonstrated that the MBC was able to reasonably determine drought classes. The accuracy of the MBC model in predicting all the classes of meteorological drought varies from 36 to 76% and in predicting all the classes of hydrological drought varies from 33 to 70%. The advantage of the MBC-based classification is that it considers drought propagation, which is very useful for planning, monitoring, and mitigation of hydrological drought in areas having problems related to hydrological data availability.
Future Projections for Wind, Wind Shear and Helicity in the Iberian Peninsula
Authors: Martins Joana , Rocha Alfredo , Viceto Carolina , Pereira Susana Cardoso , Santos João A.
Published: September 2020

Wind is among the most important climatic elements. Its characteristics are determinant for a wide range of natural processes and human activities. However, ongoing climate change is modifying these characteristics, which may have important implications. Climatic changes on wind speed and direction, wind shear intensity, and helicity, over the 21st century and for 26 cities in the Iberian Peninsula, under the Representative Concentration Pathway (RCP) 8.5 anthropogenic forcing scenario, are assessed. For this purpose, the Weather Research and Forecasting (WRF) model was used, with initial and boundary conditions being obtained from simulations with the Max Planck Institute for Meteorology Earth System Model (MPI-ESM-LR) climate model and ERA-Interim reanalysis. Quantile-quantile bias correction was applied to the simulated data prior to subsequent analysis. Overall, the results hint at a reduction in the intensity of both near-surface and 850 hPa (approx. 5%) wind in the future. Nevertheless, for the 300 hPa level, a decrease in summertime wind speed is accompanied by a slight increase in the remaining months. Furthermore, significant increases in the number of occurrences of extreme wind events were also identified, mainly in northwestern Iberia. For wind shear, an intensity increase is projected throughout most of the year (approx. 5% in the upper quantiles), mainly in southwestern Iberia. Helicity is also projected to undergo a strengthening, mostly in summer months and over southwestern Iberia, with greater emphasis on events of longer duration and intensity. This study highlights some important projected changes in the wind structure and profile under future anthropogenic forcing. This knowledge may support decisions on climate change adaptation options and risk reduction of several major sectors, such as energy and aviation, thus deserving further research.
Review on the Computational Genome Annotation of Sequences Obtained by Next-Generation Sequencing
Authors: Ejigu Girum Fitihamlak , Jung Jaehee
Published: September 2020

Next-Generation Sequencing (NGS) has made it easier to obtain genome-wide sequence data and it has shifted the research focus into genome annotation. The challenging tasks involved in annotation rely on the currently available tools and techniques to decode the information contained in nucleotide sequences. This information will improve our understanding of general aspects of life and evolution and improve our ability to diagnose genetic disorders. Here, we present a summary of both structural and functional annotations, as well as the associated comparative annotation tools and pipelines. We highlight visualization tools that immensely aid the annotation process and the contributions of the scientific community to the annotation. Further, we discuss quality-control practices and the need for re-annotation, and highlight the future of annotation.
Natural Compounds Modulate Drug Transporter Mediated Oral Cancer Treatment
Authors: Yang Hsiang , Wei Yu-Ching , Li Wan-Chun , Chen Hsin-Yung , Lin Hung-Ying , Chiang Chun-Pin , Chen Hsin-Ming
Published: September 2020

Oral cancer (OC) is a serious health problem. Surgery is the best method to treat the disease but might reduce the quality of life of patients. Photodynamic therapy (PDT) may enhance quality of life but with some limitations. Therefore, the development of a new strategy to facilitate PDT effectiveness has become crucial. ATP-binding cassette G2 (ABCG2) is a membrane protein-associated drug resistance and stemness in cancers. Here, we examined whether ABCG2 plays an important role in regulating the treatment efficacy of PDT and whether ABCG2 inhibition by natural compounds can promote the effect of PDT in OC cells. Several head and neck cancer cells were utilized in this study. OECM1 and SAS cells were selected to investigate the relationship between ABCG2 expression and protoporphyrin IX (PpIX) accumulation. Western blot analysis, flow cytometry analysis, and survival probability were performed to determine PDT efficacy and cellular stemness upon treatment of different dietary compounds, including epigallocatechin gallate (EGCG) and curcumin. In this study, we found that ABCG2 expression varied in OC cells. Hypoglycemic culture for SAS cells enhanced ABCG2 expression as higher ABCG2 expression was associated with lower PpIX accumulation and cellular stemness in OC cells. In contrast, suppression of ABCG2 expression by curcumin and tea polyphenol EGCG led to greater PpIX accumulation and enhanced PDT treatment efficiency in OC cells. In conclusion, ABCG2 plays an important role in regulating the effect of PDT. Change in glucose concentration and treatment with natural compounds modulated ABCG2 expression, resulting in altered PDT efficacy for OC cells. These modulations raise a potential new treatment strategy for early-stage OCs.
The Cytokine IL-1β and Piperine Complex Surveyed by Experimental and Computational Molecular Biophysics
Authors: Zazeri Gabriel , Povinelli Ana Paula Ribeiro , de Freitas Lima Marcelo , Cornélio Marinônio Lopes
Published: September 2020

The bioactive piperine, a compound found in some pepper species, has been widely studied because of its therapeutic properties that include the inhibition of an important inflammation pathway triggered by interleukin-1 beta (IL-1β). However, investigation into the molecular interactions between IL-1β and piperine is not reported in the literature. Here, we present for the first time the characterisation of the complex formed by IL-1β and piperine through experimental and computational molecular biophysical analyses. Fluorescence spectroscopy unveiled the presence of one binding site for piperine with an affinity constant of 14.3 × 104 M−1 at 298 K. The thermodynamic analysis indicated that the interaction with IL-1β was spontaneous (∆G = −25 kJ/mol) and, when split into enthalpic and entropic contributions, the latter was more significant. Circular dichroism spectroscopy showed that piperine did not affect IL-1β secondary structure (~2%) and therefore its stability. The set of experimental data parameterized the computational biophysical approach. Through molecular docking, the binding site micro-environment was revealed to be composed mostly by non-polar amino acids. Furthermore, molecular dynamics, along with umbrella sampling, are in agreement with the thermodynamic parameters obtained by fluorescence assays and showed that large protein movements are not present in IL-1β, corroborating the circular dichroism data.
Production of Aromatic Compounds by Catalytic Depolymerization of Technical and Downstream Biorefinery Lignins
Authors: Cornejo Alfonso , Bimbela Fernando , Moreira Rui , Hablich Karina , García-Yoldi Íñigo , Maisterra Maitane , Portugal António , Gandía Luis M. , Martínez-Merino Víctor
Published: September 2020

Lignocellulosic materials are promising alternatives to non-renewable fossil sources when producing aromatic compounds. Lignins from Populus salicaceae. Pinus radiata and Pinus pinaster from industrial wastes and biorefinery effluents were isolated and characterized. Lignin was depolymerized using homogenous (NaOH) and heterogeneous (Ni-, Cu- or Ni-Cu-hydrotalcites) base catalysis and catalytic hydrogenolysis using Ru/C. When homogeneous base catalyzed depolymerization (BCD) and Ru/C hydrogenolysis were combined on poplar lignin, the aromatics amount was ca. 11 wt.%. Monomer distributions changed depending on the feedstock and the reaction conditions. Aqueous NaOH produced cleavage of the alkyl side chain that was preserved when using modified hydrotalcite catalysts or Ru/C-catalyzed hydrogenolysis in ethanol. Depolymerization using hydrotalcite catalysts in ethanol produced monomers bearing carbonyl groups on the alkyl side chain. The analysis of the reaction mixtures was done by size exclusion chromatography (SEC) and diffusion ordered nuclear magnetic resonance spectroscopy (DOSY NMR). 31P NMR and heteronuclear single quantum coherence spectroscopy (HSQC) were also used in this study. The content in poly-(hydroxy)-aromatic ethers in the reaction mixtures decreased upon thermal treatments in ethanol. It was concluded that thermo-solvolysis is key in lignin depolymerization, and that the synergistic effect of Ni and Cu provided monomers with oxidized alkyl side chains.
Loss of the Mitochondrial Fission GTPase Drp1 Contributes to Neurodegeneration in a Drosophila Model of Hereditary Spastic Paraplegia
Authors: Fowler Philippa C. , Byrne Dwayne J. , Blackstone Craig , O'Sullivan Niamh C.
Published: September 2020

Mitochondrial morphology, distribution and function are maintained by the opposing forces of mitochondrial fission and fusion, the perturbation of which gives rise to several neurodegenerative disorders. The large guanosine triphosphate (GTP)ase dynamin-related protein 1 (Drp1) is a critical regulator of mitochondrial fission by mediating membrane scission, often at points of mitochondrial constriction at endoplasmic reticulum (ER)-mitochondrial contacts. Hereditary spastic paraplegia (HSP) subtype SPG61 is a rare neurodegenerative disorder caused by mutations in the ER-shaping protein Arl6IP1. We have previously reported defects in both the ER and mitochondrial networks in a Drosophila model of SPG61. In this study, we report that knockdown of Arl6IP1 lowers Drp1 protein levels, resulting in reduced ER–mitochondrial contacts and impaired mitochondrial load at the distal ends of long motor neurons. Increasing mitochondrial fission, by overexpression of wild-type Drp1 but not a dominant negative Drp1, increases ER–mitochondrial contacts, restores mitochondrial load within axons and partially rescues locomotor deficits. Arl6IP1 knockdown Drosophila also demonstrate impaired autophagic flux and an accumulation of ubiquitinated proteins, which occur independent of Drp1-mediated mitochondrial fission defects. Together, these findings provide evidence that impaired mitochondrial fission contributes to neurodegeneration in this in vivo model of HSP.
Gender Differences and Unfairness Processing during Economic and Moral Decision-Making: A fNIRS Study
Authors: Vanutelli Maria , Meroni Francesca , Fronda Giulia , Balconi Michela , Lucchiari Claudio
Published: September 2020

Decisional conflicts have been investigated with social decision-making tasks, which represent good models to elicit social and emotional dynamics, including fairness perception. To explore these issues, we created two modified versions of the UG framed within an economic vs. a moral context that included two kinds of unfair offers: advantageous (upside, U) or disadvantageous (downside, D) from the responder’s perspective, and vice-versa for the proponent. The hemodynamic activity of 36 participants, 20 females and 16 males, was continuously recorded with fNIRS to investigate the presence of general or specific circuits between the different experimental conditions. Results showed that disadvantageous offers (D) are associated with an increased widespread cortical activation. Furthermore, we found that advantageous moral choices at the expense of others (U) were related to the activation of the right prefrontal cortex. Finally, we found gender-related differences in brain activations in the different frameworks. In particular, the DLPFC was recruited by females during the economic task, and by males during the moral frame. In conclusion, the present study confirmed and expanded previous data about the role of the prefrontal cortices in decision-making, suggesting the need for further studies to understand better the different prefrontal networks serving moral and economic decisions also considering gender-related differences.
Tele-Assisted Behavioral Intervention for Families with Children with Autism Spectrum Disorders: A Randomized Control Trial
Authors: Marino Flavia , Chilà Paola , Failla Chiara , Crimi Ilaria , Minutoli Roberta , Puglisi Alfio , Arnao Antonino Andrea , Tartarisco Gennaro , Ruta Liliana , Vagni David , Pioggia Giovanni
Published: September 2020

Background: Telehealth is useful for both autism spectrum disorder (ASD) diagnosis and treatment, but studies with a direct comparison between teletherapy and traditional in-person therapy are limited. Methods: This randomized control trial—ISRCTN (International Standard Randomised Controlled Trial Number) primary clinical trial registry ID ISRCTN15312724—was aimed at comparing the effect of a tele-assisted and in-person intervention based on a behavioral intervention protocol for families with children affected by ASDs. Forty-two parents with children with autism (30 months to 10 years old) were randomly assigned to 12 sessions of an applied behavioral analysis (ABA) intervention implemented in an individual and group setting, either with or without the inclusion of tele-assistance. Pre- and postintervention assessments were conducted using the Home Situation Questionnaire (HSQ-ASD) and the Parental Stress Index (PSI/SF). Results: Substantial improvements in the perception and management of children’s behavior by parents, as well as in the influence of a reduction in parent stress levels on said children’s behavior through the use of a tele-assisted intervention, were obtained. Conclusions: This randomized controlled trial demonstrates the evidence-based potential for telehealth to improve treatment of ASDs.
A Time-Lagged Examination of the Greenhaus and Allen Work-Family Balance Model
Authors: Landolfi Alfonso , Barattucci Massimiliano , Lo Presti Alessandro
Published: September 2020

The work-family interface is a compelling topic that calls into question labor market dynamics and work processes, together with important social and family composition changes. The present study aimed at examining the antecedents of Work-Family Balance (WFB) in Italy consistent with Greenhaus and Allen’s (2011) conceptual model in which the characteristics of work and family roles have an indirect impact on work-family balance through Work-Family Conflict (WFC) and Work-Family Enrichment (WFE), and where job and family satisfaction are considered as predictors of WFB. A total of 568 workers participated in a time-lagged correlational study, filling a questionnaire. The theoretical model was tested by assessing the mediating role of job and family satisfaction as well as related antecedents, conflict, and enrichment between the family and work contexts, through Structural Equation Modeling (SEM). The results partially confirmed the theoretical model: work-to-family enrichment and work-to-family conflict predicted family satisfaction, which also mediated their association with WFB. The results in the family-to-work direction did not support the initial research hypotheses. The hypotheses about associations between demands and resources, conflict and enrichment in both directions, and of the moderating role of core self-evaluations were partially confirmed. The results highlighted that organizations need to carry out periodic assessments of WFC and WFE, in order to provide benefits and resources, to reduce conflict, and increase enrichment, through proper interventions (training activities, professional development, mentoring, and forms of flexibility).
Preparation of Synthesis Gas from CO2 for Fischer–Tropsch Synthesis—Comparison of Alternative Process Configurations
Authors: Hannula Ilkka , Kaisalo Noora , Simell Pekka
Published: September 2020

We compare different approaches for the preparation of carbon monoxide-rich synthesis gas (syngas) for Fischer–Tropsch (FT) synthesis from carbon dioxide (CO2) using a self-consistent design and process simulation framework. Three alternative methods for suppling heat to the syngas preparation step are investigated, namely: allothermal from combustion (COMB), autothermal from partial oxidation (POX) and autothermal from electric resistance (ER) heating. In addition, two alternative design approaches for the syngas preparation step are investigated, namely: once-through (OT) and recycle (RC). The combination of these alternatives gives six basic configurations, each characterized by distinctive plant designs that have been individually modelled and analyzed. Carbon efficiencies (from CO2 to FT syncrude) are 50–55% for the OT designs and 65–89% for the RC designs, depending on the heat supply method. Thermal efficiencies (from electricity to FT syncrude) are 33–41% for configurations when using low temperature electrolyzer, and 48–59% when using high temperature electrolyzer. Of the RC designs, both the highest carbon efficiency and thermal efficiency was observed for the ER configuration, followed by POX and COMB configurations.
Analysis of Bone Scans in Various Tumor Entities Using a Deep-Learning-Based Artificial Neural Network Algorithm—Evaluation of Diagnostic Performance
Authors: Wuestemann Jan , Hupfeld Sebastian , Kupitz Dennis , Genseke Philipp , Schenke Simone , Pech Maciej , Kreissl Michael C. , Grosser Oliver S.
Published: September 2020

The bone scan index (BSI), initially introduced for metastatic prostate cancer, quantifies the osseous tumor load from planar bone scans. Following the basic idea of radiomics, this method incorporates specific deep-learning techniques (artificial neural network) in its development to provide automatic calculation, feature extraction, and diagnostic support. As its performance in tumor entities, not including prostate cancer, remains unclear, our aim was to obtain more data about this aspect. The results of BSI evaluation of bone scans from 951 consecutive patients with different tumors were retrospectively compared to clinical reports (bone metastases, yes/no). Statistical analysis included entity-specific receiver operating characteristics to determine optimized BSI cut-off values. In addition to prostate cancer (cut-off = 0.27%, sensitivity (SN) = 87%, specificity (SP) = 99%), the algorithm used provided comparable results for breast cancer (cut-off 0.18%, SN = 83%, SP = 87%) and colorectal cancer (cut-off = 0.10%, SN = 100%, SP = 90%). Worse performance was observed for lung cancer (cut-off = 0.06%, SN = 63%, SP = 70%) and renal cell carcinoma (cut-off = 0.30%, SN = 75%, SP = 84%). The algorithm did not perform satisfactorily in melanoma (SN = 60%). For most entities, a high negative predictive value (NPV ≥ 87.5%, melanoma 80%) was determined, whereas positive predictive value (PPV) was clinically not applicable. Automatically determined BSI showed good sensitivity and specificity in prostate cancer and various other entities. Particularly, the high NPV encourages applying BSI as a tool for computer-aided diagnostic in various tumor entities.
FUCCI Real-Time Cell-Cycle Imaging as a Guide for Designing Improved Cancer Therapy: A Review of Innovative Strategies to Target Quiescent Chemo-Resistant Cancer Cells
Authors: Yano Shuya , Tazawa Hiroshi , Kagawa Shunsuke , Fujiwara Toshiyoshi , Hoffman Robert M.
Published: September 2020

Progress in chemotherapy of solid cancer has been tragically slow due, in large part, to the chemoresistance of quiescent cancer cells in tumors. The fluorescence ubiquitination cell-cycle indicator (FUCCI) was developed in 2008 by Miyawaki et al., which color-codes the phases of the cell cycle in real-time. FUCCI utilizes genes linked to different color fluorescent reporters that are only expressed in specific phases of the cell cycle and can, thereby, image the phases of the cell cycle in real-time. Intravital real-time FUCCI imaging within tumors has demonstrated that an established tumor comprises a majority of quiescent cancer cells and a minor population of cycling cancer cells located at the tumor surface or in proximity to tumor blood vessels. In contrast to most cycling cancer cells, quiescent cancer cells are resistant to cytotoxic chemotherapy, most of which target cells in S/G2/M phases. The quiescent cancer cells can re-enter the cell cycle after surviving treatment, which suggests the reason why most cytotoxic chemotherapy is often ineffective for solid cancers. Thus, quiescent cancer cells are a major impediment to effective cancer therapy. FUCCI imaging can be used to effectively target quiescent cancer cells within tumors. For example, we review how FUCCI imaging can help to identify cell-cycle-specific therapeutics that comprise decoy of quiescent cancer cells from G1 phase to cycling phases, trapping the cancer cells in S/G2 phase where cancer cells are mostly sensitive to cytotoxic chemotherapy and eradicating the cancer cells with cytotoxic chemotherapy most active against S/G2 phase cells. FUCCI can readily image cell-cycle dynamics at the single cell level in real-time in vitro and in vivo. Therefore, visualizing cell cycle dynamics within tumors with FUCCI can provide a guide for many strategies to improve cell-cycle targeting therapy for solid cancers.
Does Pemetrexed Work in Targetable, Nonsquamous Non-Small-Cell Lung Cancer? A Narrative Review
Authors: Shih Jin-Yuan , Inoue Akira , Cheng Rebecca , Varea Rocio , Kim Sang-We
Published: September 2020

Pemetrexed is currently mainly considered for the treatment of advanced nonsquamous non-small-cell lung cancer (NSCLC) negative for gene mutations/rearrangements (wild-type disease (WTD)). This narrative review aimed to highlight the role of pemetrexed in the treatment of onco-driven nonsquamous advanced NSCLC by reviewing published clinical studies. For epidermal growth factor receptor (EGFR) mutations, patient survival following first-line pemetrexed–platinum was longer than for WTD. Later-line pemetrexed-based treatment after tyrosine kinase inhibitor (TKI) failure provided greater benefits than non-pemetrexed regimens. First- and later-line pemetrexed-based therapy also provided survival benefits in patients with anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 (ROS1) rearrangements. In patients with rearranged during transfection (RET) proto-oncogene rearrangements, survival with pemetrexed was similar to that in ALK- and ROS1-positive patients and longer than that in patients with Kirsten rat sarcoma (KRAS) virus proto-oncogene mutations or WTD, although the available studies were limited. For Erb-b2 receptor tyrosine kinase 2 (ERRB2) mutations, first-line pemetrexed showed outcomes similar to those for EGFR and KRAS alterations. Data on pemetrexed in patients with KRAS mutations or MNNG HOS-transforming (MET) expression were limited. Pemetrexed could be an option for first- and second-line treatment for TKI failure in nonsquamous advanced NSCLC with select targetable driver mutations.
Inflammatory Blood Markers as Prognostic and Predictive Factors in Early Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Authors: Corbeau Ileana , Thezenas Simon , Maran-Gonzalez Aurelie , Colombo Pierre-Emmanuel , Jacot William , Guiu Severine
Published: September 2020

Background: Inflammatory blood markers, such as neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), have been reported as putative prognostic factors for survival and predictive factors for pathological complete response and toxicity in cancers, however with conflicting results. Methods: We retrospectively analyzed data of 280 patients with early breast cancer receiving neo-adjuvant chemotherapy between 2005 and 2013 in our center. Neutrophil count, lymphocyte count and platelet count before treatment were collected as well as data on pathological complete response, toxicity, recurrence and survival. Results: In multivariate analysis, high PLR was an independent prognostic factor for relapse-free survival (hazard ratio [HR] = 1.91; 95%CI = 1.15–3.16; p = 0.012) and for shorter overall survival (HR = 1.83; 95%CI = 1.03–3.24; p = 0.039). NLR was an independent predictive factor for febrile neutropenia (HR = 0.28; 95%CI = 0.13–0.58; p = 0.001). In triple negative breast cancer molecular subtype, low white blood cell count (<6.75 G/L) was predictive for a higher pathological complete response rate (odds ratio [OR] = 0.29; 95%CI = 0.14–0.61; p < 0.01). Conclusion: In the present study, PLR was found as an independent prognostic factor for survival, while NLR was an independent predictive factor for febrile neutropenia.
A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing
Authors: Saltsman James A. , Hammond William J. , Narayan Nicole J. C. , Requena David , Gehart Helmuth , Lalazar Gadi , LaQuaglia Michael P. , Clevers Hans , Simon Sanford
Published: September 2020

Hepatoblastoma is the most common childhood liver cancer. Although survival has improved significantly over the past few decades, there remains a group of children with aggressive disease who do not respond to current treatment regimens. There is a critical need for novel models to study aggressive hepatoblastoma as research to find new treatments is hampered by the small number of laboratory models of the disease. Organoids have emerged as robust models for many diseases, including cancer. We have generated and characterized a novel organoid model of aggressive hepatoblastoma directly from freshly resected patient tumors as a proof of concept for this approach. Hepatoblastoma tumor organoids recapitulate the key elements of patient tumors, including tumor architecture, mutational profile, gene expression patterns, and features of Wnt/β-catenin signaling that are hallmarks of hepatoblastoma pathophysiology. Tumor organoids were successfully used alongside non-tumor liver organoids from the same patient to perform a drug screen using twelve candidate compounds. One drug, JQ1, demonstrated increased destruction of liver organoids from hepatoblastoma tumor tissue relative to organoids from the adjacent non-tumor liver. Our findings suggest that hepatoblastoma organoids could be used for a variety of applications and have the potential to improve treatment options for the subset of hepatoblastoma patients who do not respond to existing treatments.
How Relevant Are Bone Marrow-Derived Mast Cells (BMMCs) as Models for Tissue Mast Cells? A Comparative Transcriptome Analysis of BMMCs and Peritoneal Mast Cells
Authors: Akula Srinivas , Paivandy Aida , Fu Zhirong , Thorpe Michael , Pejler Gunnar , Hellman Lars
Published: September 2020

Bone marrow-derived mast cells (BMMCs) are often used as a model system for studies of the role of MCs in health and disease. These cells are relatively easy to obtain from total bone marrow cells by culturing under the influence of IL-3 or stem cell factor (SCF). After 3 to 4 weeks in culture, a nearly homogenous cell population of toluidine blue-positive cells are often obtained. However, the question is how relevant equivalents these cells are to normal tissue MCs. By comparing the total transcriptome of purified peritoneal MCs with BMMCs, here we obtained a comparative view of these cells. We found several important transcripts that were expressed at very high levels in peritoneal MCs, but were almost totally absent from the BMMCs, including the major chymotryptic granule protease Mcpt4, the neurotrophin receptor Gfra2, the substance P receptor Mrgprb2, the metalloprotease Adamts9 and the complement factor 2 (C2). In addition, there were a number of other molecules that were expressed at much higher levels in peritoneal MCs than in BMMCs, including the transcription factors Myb and Meis2, the MilR1 (Allergin), Hdc (Histidine decarboxylase), Tarm1 and the IL-3 receptor alpha chain. We also found many transcripts that were highly expressed in BMMCs but were absent or expressed at low levels in the peritoneal MCs. However, there were also numerous MC-related transcripts that were expressed at similar levels in the two populations of cells, but almost absent in peritoneal macrophages and B cells. These results reveal that the transcriptome of BMMCs shows many similarities, but also many differences to that of tissue MCs. BMMCs can thereby serve as suitable models in many settings concerning the biology of MCs, but our findings also emphasize that great care should be taken when extrapolating findings from BMMCs to the in vivo function of tissue-resident MCs.