bluuebunny/crossref_metadata_2025 huggingface dataset:
Geophagic Materials Characterization and Potential Impact on Human Health: The Case Study of Maputo City (Mozambique)
Authors: Bernardo Bernardino , Candeias Carla , Rocha Fernando
Published: May 2022

This study aims to characterize and estimate risk assessment associated with geophagic materials consumption in Maputo city (Mozambique). Samples were collected in extraction mines, unprepared and prepared ones, and in Maputo markets. Fractions < 2 mm (total consumed material) and <63 μm were analyzed to determine pH, EC, OM, chemical composition (XRF), and mineral phases present (XRD). The results revealed pH from slightly acidic to slightly alkaline, and electrical conductivity ranging from 13 to 47 μS/cm in mine unprepared and prepared samples, while 264–465 μS/cm in sampled sold in markets. Organic matter content was <2.76%, except in one sample (8.14%), suggesting a potential risk of containing bacteria. Textural analysis revealed that sand-size particles were more representative in all samples (57.2–93.02%). Mineralogical phases identified in the consumed sample were ranked quartz (>60%) > Fe oxides/hidroxides > phyllosilicates (micas and kaolinite) > feldspars, suggesting a risk of dental enamel damage and perforation of the sigmoid colon. The chemical concentration of some elements was higher than recommended daily dose, suggesting a potential risk. However, geophagic materials’ chemical composition does not pose a carcinogenic risk.
Assessment of Seasonal and Diurnal Variations of Alkaline Phosphatase Activity in Pasteurized Milk
Authors: Gerokomou Vaia , Rozos Georgios , Demertzis Panagiotis , Akrida-Demertzi Konstantoula
Published: May 2022

The present study was conducted to detect the concentration levels of ALP (alkaline phosphatase) in pasteurized milk and determine whether the pasteurization was successful or not, according to WHO Directives, which clearly state that the ALP (alkaline phosphatase) substance in pasteurized milk must be totally inactivated, by implementing a newly developed method. The study, additionally, focused on repeatability, stability of results, the effect of the environmental temperature, the effect of the different origins of the milk and convenience with respect to performance characteristics of three methods for the detection of ALP. The milk samples were collected from different areas of Greece during February 2016–February 2018 and May 2019–January 2020. The novel enzymatic biochemical method, named the “AP test”, showed superior characteristics for a diversity of materials such as milk, whey, cheese and butter in comparison to the other two methods that were used for screening and quantitative estimation of the concentration of ALP in samples.
Predictability and Clinical Stability of Barrier Membranes in Treatment of Periodontal Intrabony Defects: A Systematic Review and Meta-Analysis
Authors: Das Sharmistha , Panda Saurav , Nayak Rashmita , Mohanty Rinkee , Satpathy Anurag , Das Abhaya Chandra , Kumar Manoj , Lapinska Barbara
Published: May 2022

The adjunctive use of GTR membranes helps us to achieve predictable periodontal regeneration. The aim of this systematic review was to evaluate and compare the treatment efficacy of resorbable versus non-resorbable barrier membranes used in guided tissue regeneration in the treatment of intrabony defects in chronic periodontitis patients. The following databases were searched: Medline, the Cochrane Central Register of Controlled Trails (CENTRAL), SCOPUS, EMBASE. Randomized clinical trials (RCTs) published in English languages over the past 25 years were included. The primary outcomes assessed were: change of probing pocket depth (PD), change in clinical attachment level (CAL) and gingival recession coverage (GRC), and intrabony defect fill (IBDF). A total of eight RCTs were included for systematic review. The outcome of GR at a six-month interval revealed a significant difference in treatment effect with a mean difference of 0.42, 95% CI [0.02, 0.81]; Z = 2.09, (p = 0.04) favouring the resorbable membrane group. The intrabony defect depth fill at a 12-month interval revealed a significant difference in treatment effect with MD of 0.79, p = 0.00001; favoring the resorbable membrane group. The resorbable membrane showed a significant improvement in gingival recession coverage and intrabony defect fill, owing to its advantage of avoiding the second surgical intervention.
A Novel Framework for Online Remaining Useful Life Prediction of an Industrial Slurry Pump
Authors: Khan Muhammad Mohsin , Tse Peter W. , Yang Jinzhao
Published: May 2022

An efficient Remaining Useful Life (RUL) prediction method is one of the most important features of a condition-based maintenance system. A running machine’s RUL prognosis in its real-time is a challenging task, especially when there is no historic failure data available for that particular machine. In this paper, an online RUL of an in-operation industrial slurry pump having no historical failure data has been predicted. At first, the available raw vibration datasets were filtered out for valid datasets. The obtained valid datasets were utilized for constructing the Health Degradation Trends (HDTs) using principal component analysis and a moving average method. Then, a novel procedure for automatically selecting the HDT’s data points for initiating the iteration process of prediction was formulated. Afterward, a hybrid deep LSTM model embedded with a smart learning rate mechanism was developed for estimating the online RUL using the selected points of HDTs. The online RUL prediction results produced by the developed model were quite satisfactory when they were compared with other online RUL prediction methods.
Identification of Seasonal Honey Based on Quantitative Detection of Typical Pollen DNA
Authors: Truong A-Tai , Yoo Mi-Sun , Cho Yun Sang , Yoon Byoungsu
Published: May 2022

Monofloral honey is produced from the nectar of a single predominant botanical species in a particular season and has certain unique properties. Valuable monofloral honey produced in a particular season with unique properties is often targeted for adulteration. Herein, a method for the identification of monofloral honey and determination of its production season was developed. Major nectar plants, including Prunus sp., Robinia pseudoacacia, Castanea sp., and Kalopanax sp., were selected to evaluate the honey produced between April and July in South Korea. Results showed that the highest amount of DNA from each plant was detected in the corresponding flowering season. The pollens tended to accumulate in the honeycomb after the flowering season. The accumulations result in an increase in the diversity of pollen detected in honey. Additionally, DNA quantity of each plant decreased in the samples as the number of plant DNA types increased from May to July. Moreover, the authenticity of the commercial monofloral honey samples showed only cherry blossom honey was found authentic, which exhibited the expected high amount of Prunus sp. DNA. This molecular tool is expected to be useful in verifying the origin of monofloral honey and its production season.
Fluoroquinolones as Tyrosinase Inhibitors; Enzyme Kinetics and Molecular Docking Studies to Explore Their Mechanism of Action
Authors: Alyami Bandar A. , Alqarni Ali O. , Alqahtani Yahya S. , Mahnashi Mater H. , Javed Qamar , Hassan Mubashir , Tahir Tehreem , Ali Anser , Kotwica-Mojzych Katarzyna , Mojzych Mariusz
Published: May 2022

The binding of fluoroquinolones, the most commonly prescribed antibiotics, with melanin is well explored. However, their binding patterns and exact mechanism of interaction with tyrosinase, a key enzyme in melanogenesis, are not explored yet. Thus, in the present study, seven fluoroquinolone drugs were selected to characterize their interactions with the tyrosinase enzyme: ciprofloxacin, enoxacin sesquihydrate, ofloxacin, levofloxacin, sparfloxacin, moxifloxacin and gemifloxacin. The results confirmed that all the drugs execute excellent enzyme activity, with an inhibition range from IC50 = 28 ± 4 to 50 ± 1.9 μM, outperforming the standard hydroquinone (IC50 = 170 μM). Later, kinetic studies revealed that all the drugs showed irreversible, but mixed-type, tyrosinase inhibition, with a preferentially competitive mode of action. Further, 2D and 3D docked complexes and binding analyses confirmed their significant interactions in the active region of the target enzyme, sufficient for the downstream signaling responsible for the observed tyrosinase inhibition. Thus, this is the first report demonstrating their mechanism of tyrosinase inhibition, critical for melanin-dependent responses, including toxicity.
Ultra-Scratch-Resistant, Hydrophobic and Transparent Organosilicon-Epoxy-Resin Coating with a Double Cross-Link Structure
Authors: Qiu Zeyu , Lin Haofeng , Zeng Longlong , Liang Yunfeng , Zeng Chunhong , Hong Ruijiang
Published: May 2022

In this paper, an ultra-scratch-resistant, hydrophobic and transparent coating was fabricated by the sol–gel method using (3-Glycidyloxypropyl) triethoxysilane (GPTES) and curing agents. When the silanol was condensated, the ring-opening reaction of the epoxy groups also took place, which formed a double-cross-linked network (Si–O–Si and R3N). This network structure restricted the molecule chains from being twisted or dislocated, resulting in a great improvement of the abrasion resistance of the coating. A pencil hardness grade up to 8H was obtained. The coating also showed excellent stability after being soaked in pH = 2 and pH = 12 solutions, seawater and acetone, respectively. In addition, a water contact angle of 121° was obtained by post-treatment with hexamethyldisilazane (HMDS). The average transmittance of the coating reached to 90% in the wavelength range of 400~800 nm, nearly identical to the glass substrate. With multiple desirable properties and a simple fabrication process, this low-cost coating shows great potential in many practical applications.
Effect of Jack Thrust Angle Change on Mechanical Characteristics of Shield Tunnel Segmental Linings Considering Additional Constrained Boundaries
Authors: He Lichao , Jiang Yu , Zhang Wenjun
Published: May 2022

With the attitude adjustment of shield machine, the jack thrust angle will change and may lead to great damage to segmental lining structures. In this paper, a three-dimensional refined finite element method is proposed to study the action mechanism and influence of jack thrust angle change on the mechanical characteristics of shield tunnel, considering additional constrained boundaries formed by various construction loads. Firstly, the finite element method is established and verified. Then, a series of analyses is carried out to investigate the mechanical performance of a certain tunnel lining with eleven rings under conditions of different jack thrust angles. An in-depth discussion is conducted on the obtained displacement, deformation, and stress distribution. A quantitative standard is finally gained for controlling the jack thrust angle. The results show that the maximum segment displacement occurs at the lower part of the arch waist of the second ring out of the shield tail, which has little relationship with the attitude adjustment. With the increase of the jack thrust angle, the maximum offset between the rings increases linearly, which is not conducive to the safety of the lining structures. The development direction of the tunnel displacement is opposite to that of the jack thrust deflection. The displacement of the tunnel is most affected by the jack thrust deflection when the shield machine is upward, which is also the most unfavorable situation for the segmental linings. The results in this paper provide novel insights into the effect of jack thrust on shield tunnel.
Analysis of Hydrogen Filling of 175 Liter Tank for Large-Sized Hydrogen Vehicle
Authors: Kim Moo-Sun , Jeon Hong-Kyu , Lee Kang-Won , Ryu Joon-Hyoung , Choi Sung-Woong
Published: May 2022

Due to the low density of hydrogen gas under ambient temperature and atmospheric pressure conditions, the high-pressure gaseous hydrogen storage method is widely employed. With high-pressure characteristics of hydrogen storage, rigorous safety precautions are required, such as filling of compressed gas in a hydrogen tank to achieve reliable operational solutions. Especially for the large-sized tanks (above 150 L), safety operation of hydrogen storage should be considered. In the present study, the compressed hydrogen gas behavior in a large hydrogen tank of 175 L is investigated for its filling. To validate the numerical approach used in this study, numerical models for the adaptation of the gas and turbulence models are examined. Numerical parametric studies on hydrogen filling for the large hydrogen tank of 175 L are conducted to estimate the hydrogen gas behavior in the hydrogen tank under various conditions of state of charge of pressure and ambient temperature. From the parametric studies, the relationship between the initial SOC pressure condition and the maximum temperature rise of hydrogen gas was shown. That is, the maximum temperature rise increases as the ambient temperature decreases, and the rise increases as the SOC decreases.
Morphology of Meteorite Surfaces Ablated by High-Power Lasers: Review and Applications
Authors: Křivková Anna , Laitl Vojtěch , Chatzitheodoridis Elias , Petera Lukáš , Kubelík Petr , Knížek Antonín , Saeidfirozeh Homa , Drtinová Barbora , Čuba Václav , Páclík Dan , Mocek Tomáš , Brajer Jan , Kaufman Jan , Divoký Martin , Koukal Jakub , Dudžák Roman , Schmidt Nikola , Boháček Petr , Civiš Svatopluk , Lenža Libor , Krůs Miroslav , Ferus Martin
Published: May 2022

Under controlled laboratory conditions, lasers represent a source of energy with well-defined parameters suitable for mimicking phenomena such as ablation, disintegration, and plasma formation processes that take place during the hypervelocity atmospheric entry of meteoroids. Furthermore, lasers have also been proposed for employment in future space exploration and planetary defense in a wide range of potential applications. This highlights the importance of an experimental investigation of lasers’ interaction with real samples of interplanetary matter: meteorite specimens. We summarize the results of numerous meteorite laser ablation experiments performed by several laser sources—a femtosecond Ti:Sapphire laser, the multislab ceramic Yb:YAG Bivoj laser, and the iodine laser known as PALS (Prague Asterix Laser System). The differences in the ablation spots’ morphology and their dependence on the laser parameters are examined via optical microscopy, scanning electron microscopy, and profilometry in the context of the meteorite properties and the physical characteristics of laser-induced plasma.
Compression and Fungal Heat Production in Maize Bulk Considering Kernel Breakage
Authors: Liu Chaosai , Zhou Yang , Chen Guixiang , Zheng Deqian , Yue Longfei
Published: May 2022

Breakage in maize kernels and vertical pressure in grains lead to the uneven distribution of grain bulk density, which easily causes undesired problems in terms of grain storage. The objective of this study was, therefore, to determine the compression and heat production of the whole kernel (WK) and half kernel (HK) under two different loadings, i.e., 50 and 150 kPa, in maize bulk. An easy-to-use element testing system was developed by modification of an oedometer, and an empirical–analytical–numerical method was established to evaluate fungal heat production, considering kernel breakage and vertical pressure. Based on the experimental results, it was found that breakage induced larger compression; the compression of HK was 62% and 58% higher than that of WK at 50 kPa and 150 kPa, respectively. The creep model of the Hooke spring–Kelvin model in series can be used to accurately describe the creep behavior of maize bulk. Fungi and aerobic plate counting (APC) were affected significantly by the breakage and vertical pressure. APC in HK was 19 and 15 times that of WK under 150 and 50 kPa, respectively. The heat released by the development of fungi was found to be directly related to the APC results. The average temperatures of WK and HK under 150 and 50 kPa were 11.1%, 9.7%, 7.9%, and 7.6% higher than the room temperature, respectively. A numerical method was established to simulate the temperature increase due to fungi development. Based on the numerical results, heat production (Q) by fungi was estimated, and the results showed that the Q in HK was 1.29 and 1.32 times that of WK on average under 150 and 50 kPa. Additionally, the heat production results agreed very well with the APC results.
Influence of the Grid Resolutions on the Computer-Simulated Surface Air Pollution Concentrations in Bulgaria
Authors: Gadzhev Georgi , Ganev Kostadin , Mukhtarov Plamen
Published: May 2022

The present study aims to demonstrate the effects of horizontal grid resolution on the simulated pollution concentration fields over Bulgaria. The computer simulations are performed with a set of models used worldwide—the Weather Research and Forecasting Model (WRF)—the meteorological preprocessor, the Community Multiscale Air Quality Modeling System (CMAQ)—chemical transport model, Sparse Matrix Operator Kernel Emissions (SMOKE)—emission model. The large-scale (background) meteorological data used in the study were taken from the ‘NCEP Global Analysis Data’ with a horizontal resolution of 1° × 1°. Using the ‘nesting’ capabilities of the WRF and CMAQ models, a resolution of 9 km was achieved for the territory of Bulgaria by sequentially solving the task in several consecutive nested areas. Three cases are considered in this paper: Case 1: The computer simulations result from the domain with a horizontal resolution (both of the emission source description and the grid) of 27 km.; Case 2: The computer simulations result from the domain with a horizontal resolution (both of the emission source description and the grid) of 9 km.; Case 3: A hybrid case with the computer simulations performed with a grid resolution of 9 km, but with emissions such as in the 27 km × 27 km domain. The simulations were performed, for all the three cases, for the period 2007–2014 year, thus creating an ensemble large and comprehensive enough to reflect the most typical atmospheric conditions with their typical recurrence. The numerical experiments showed the significant impact of the grid resolution not only in the pollution concentration pattern but also in the demonstrated generalized characteristics. Averaged over a large territory (Bulgaria); however, the performances for cases one and two are quite similar. Bulgaria is a country with a complex topography and with several considerably large point sources. Thus, some of the conclusions made, though based on Bulgarian-specific experiments, may be of general interest.
Prediction of Emission Reduction Potential from Road Diesel Vehicles in the Beijing–Tianjin–Hebei (BTH) Region, China
Authors: Guo Xiurui , Liu Yao , Chen Dongsheng , Gong Xiaoqian
Published: May 2022

China has started to focus on the reduction in pollutants from diesel vehicles with high emission intensities in recent years. Therefore, it is essential and valuable to conduct a deep and detailed exploration of the reduction potential from diesel vehicles and compare the abatement effect from different control measures in upcoming decades. This study attempted to estimate the present emissions of four conventional pollutants from diesel vehicles by applying the Computer Program to Calculate Emissions from Road Transport (COPERT) model, and to predict the future emission trends under different scenarios during 2019–2030, taking the Beijing–Tianjin–Hebei (BTH) region as the case study area. In addition, we analyzed the emission reduction potential of diesel vehicles and compared the reduction effects from different control measures. The results showed that the CO and NOX emissions from diesel vehicles in this region could increase by 104.8% and 83.9%, respectively, given no any additional control measures adopted over the next decade. The largest emission reduction effect could be achieved under the comprehensive scenario, which means that vehicular diesel emissions in 2030 could decrease by 74.8–94.0% compared to values in 2018. The effect of emission reduction under the emission standards’ upgrade scenario could cause a gradual increase and achieve a 19.8–82.6% reduction for the four pollutants in 2030. Furthermore, the new energy vehicle promotion scenario could achieve a considerable reduction effect. It could also offer better emission reduction effects under the highway to railway scenario for Tianjin and Hebei provinces. The old vehicle elimination scenario could have a considerable reduction effect, but only in the short term. Furthermore, emission reductions could be mainly influenced by heavy diesel trucks. These results can provide scientific support to formulate effective reduction measures to diesel vehicles for policy makers.
Soil Enzyme Activity Regulates the Response of Soil C Fluxes to N Fertilization in a Temperate Cultivated Grassland
Authors: Yang Yan , Fang Huajun , Cheng Shulan , Xu Lijun , Lu Mingzhu , Guo Yifan , Li Yuna , Zhou Yi
Published: May 2022

Exogenous nitrogen (N) inputs greatly change the emission and uptake of carbon dioxide (CO2) and methane (CH4) from temperate grassland soils, thereby affecting the carbon (C) budget of regional terrestrial ecosystems. Relevant research focused on natural grassland, but the effects of N fertilization on C exchange fluxes from different forage soils and the driving mechanisms were poorly understood. Here, a three-year N addition experiment was conducted on cultivated grassland planted with alfalfa (Medicago sativa) and bromegrass (Bromus inermis) in Inner Mongolia. The fluxes of soil-atmospheric CO2 and CH4; the content of the total dissolved N (TDN); the dissolved organic N (DON); the dissolved organic C (DOC); NH4+–N and NO3−–N in soil; enzyme activity; and auxiliary variables (soil temperature and moisture) were simultaneously measured. The results showed that N fertilization (>75 kg N ha−1 year−1) caused more serious soil acidification for alfalfa planting than for brome planting. N fertilization stimulated P-acquiring hydrolase (AP) in soil for growing Bromus inermis but did not affect C- and N-acquiring hydrolases (AG, BG, CBH, BX, LAP, and NAG). The oxidase activities (PHO and PER) of soil for planting Bromus inermis were higher than soil for planting Medicago sativa, regardless of N, whether fertilization was applied or not. Forage species and N fertilization did not affect soil CO2 flux, whereas a high rate of N fertilization (150 kg N ha−1 year−1) significantly inhibited CH4 uptake in soil for planting Medicago sativa. A synergistic effect between CO2 emission and CH4 uptake in soil was found over the short term. Our findings highlight that forage species affect soil enzyme activity in response to N fertilization. Soil enzyme activity may be an important regulatory factor for C exchange from temperate artificial grassland soil in response to N fertilization.
Otoacoustic Emissions in Non-Mammals
Authors: Manley Geoffrey A.
Published: May 2022

Otoacoustic emissions (OAE) that were sound-induced, current-induced, or spontaneous have been measured in non-mammalian land vertebrates, including in amphibians, reptiles, and birds. There are no forms of emissions known from mammals that have not also been observed in non-mammals. In each group and species, the emission frequencies clearly lie in the range known to be processed by the hair cells of the respective hearing organs. With some notable exceptions, the patterns underlying the measured spectra, input-output functions, suppression threshold curves, etc., show strong similarities to OAE measured in mammals. These profound similarities are presumably traceable to the fact that emissions are produced by active hair-cell mechanisms that are themselves dependent upon comparable nonlinear cellular processes. The differences observed—for example, in the width of spontaneous emission peaks and delay times in interactions between peaks—should provide insights into how hair-cell activity is coupled within the organ and thus partially routed out into the middle ear.
An Experimental Investigation of Thermal Runaway and Gas Release of NMC Lithium-Ion Pouch Batteries Depending on the State of Charge Level
Authors: Amano Kofi Owusu Ansah , Hahn Sarah-K. , Tschirschwitz Rico , Rappsilber Tim , Krause Ulrich
Published: May 2022

In this study, 19 experiments were conducted with 25 pouch cells of NMC cathode to investigate thermal runaway and the release of gases from lithium-ion batteries (LIBs). Single cells, double cells, and a four-cell battery stack were forced to undergo thermal runaway inside an air-tight reactor vessel with a volume of 100 dm3. The study involved two series of tests with two types of ignition sources. In the Series 1 tests, a heating plug was used to initiate thermal runaway in LIBs in the ranges of 80–89% and 90–100% SOC. In the Series 2 tests, a heating plate was used to trigger thermal runaway in LIBs in the ranges of 30–50%, 80–89%, and 90–100% SOC. Thermal runaway started at an onset temperature of 344 ± 5 K and 345 K for the Series 1 tests and from 393 ± 36 K to 487 ± 10 K for the Series 2 tests. Peak reaction temperatures ranged between 642 K and 1184 K, while the maximum pressures observed were between 1.2 bar and 7.28 bar. Thermal runaway induced explosion of the cells and lead to a rate of temperature increase greater than 10 K/s. The amounts of gases released from the LIBs were calculated from pressures and temperatures measured in the reactor. Then, the gas composition was analyzed using a Fourier transform infrared (FTIR) spectrometer. The highest gaseous production was achieved at a range of 90–100% SOC and higher battery capacities 72 L, 1.8 L/Ah (Series 1, battery stack) and 103 L, 3.2 L/Ah (Series 2, 32 Ah cell)). Among the gases analyzed, the concentration of gaseous emissions such as C2H4, CH4, and C2H6 increased at a higher cell capacity in both series of tests. The study results revealed characteristic variations of thermal behavior with respect to the type of ignition source used.
Lab-Scale Cultivation of Cupriavidus necator on Explosive Gas Mixtures: Carbon Dioxide Fixation into Polyhydroxybutyrate
Authors: Lambauer Vera , Kratzer Regina
Published: May 2022

Aerobic, hydrogen oxidizing bacteria are capable of efficient, non-phototrophic CO2 assimilation, using H2 as a reducing agent. The presence of explosive gas mixtures requires strict safety measures for bioreactor and process design. Here, we report a simplified, reproducible, and safe cultivation method to produce Cupriavidus necator H16 on a gram scale. Conditions for long-term strain maintenance and mineral media composition were optimized. Cultivations on the gaseous substrates H2, O2, and CO2 were accomplished in an explosion-proof bioreactor situated in a strong, grounded fume hood. Cells grew under O2 control and H2 and CO2 excess. The starting gas mixture was H2:CO2:O2 in a ratio of 85:10:2 (partial pressure of O2 0.02 atm). Dissolved oxygen was measured online and was kept below 1.6 mg/L by a stepwise increase of the O2 supply. Use of gas compositions within the explosion limits of oxyhydrogen facilitated production of 13.1 ± 0.4 g/L total biomass (gram cell dry mass) with a content of 79 ± 2% poly-(R)-3-hydroxybutyrate in a simple cultivation set-up with dissolved oxygen as the single controlled parameter. Approximately 98% of the obtained PHB was formed from CO2.
The Birth of the Mammalian Sleep
Authors: Rial Rubén V. , Canellas Francesca , Akaârir Mourad , Rubiño José A. , Barceló Pere , Martín Aida , Gamundí Antoni , Nicolau M. Cristina
Published: May 2022

Mammals evolved from small-sized reptiles that developed endothermic metabolism. This allowed filling the nocturnal niche. They traded-off visual acuity for sensitivity but became defenseless against the dangerous daylight. To avoid such danger, they rested with closed eyes in lightproof burrows during light-time. This was the birth of the mammalian sleep, the main finding of this report. Improved audition and olfaction counterweighed the visual impairments and facilitated the cortical development. This process is called “The Nocturnal Evolutionary Bottleneck”. Pre-mammals were nocturnal until the Cretacic-Paleogene extinction of dinosaurs. Some early mammals returned to diurnal activity, and this allowed the high variability in sleeping patterns observed today. The traits of Waking Idleness are almost identical to those of behavioral sleep, including homeostatic regulation. This is another important finding of this report. In summary, behavioral sleep seems to be an upgrade of Waking Idleness Indeed, the trait that never fails to show is quiescence. We conclude that the main function of sleep consists in guaranteeing it during a part of the daily cycle.
Orthotopic Transplantation of Human Paediatric High-Grade Glioma in Zebrafish Larvae
Authors: Larsson Susanna , Kettunen Petronella , Carén Helena
Published: May 2022

Brain tumours are the most common cause of death among children with solid tumours, and high-grade gliomas (HGG) are among the most devastating forms with very poor outcomes. In the search for more effective treatments for paediatric HGG, there is a need for better experimental models. To date, there are no xenograft zebrafish models developed for human paediatric HGG; existing models rely on adult cells. The use of paediatric models is of great importance since it is well known that the genetic and epigenetic mechanisms behind adult and paediatric disease differ greatly. In this study, we present a clinically relevant in vivo model based on paediatric primary glioma stem cell (GSC) cultures, which after orthotopic injection into the zebrafish larvae, can be monitored using confocal imaging over time. We show that cells invade the brain tissue and can be followed up to 8 days post-injection while they establish in the fore/mid brain. This model offers an in vivo system where tumour invasion can be monitored and drug treatments quickly be evaluated. The possibility to monitor patient-specific cells has the potential to contribute to a better understanding of cellular behaviour and personalised treatments in the future.
The Role of Cerebrospinal Fluid Biomarkers in Dementia and Other Related Neurodegenerative Disorders
Authors: Paraskevas George P.
Published: May 2022

Over the course of the last 20 years, cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD), including amyloid beta peptide with 42 amino acids (Aβ42), total tau protein (τT), and tau protein phosphorylated at a threonine residue at position 181 (τP-181), have become a useful tool for the recognition and diagnosis of AD, even in early or atypical clinical presentations and in the presymptomatic stage of the disease [...]
Modern Developments in Transcranial Magnetic Stimulation: The Editorial
Authors: Sollmann Nico , Julkunen Petro
Published: May 2022

Transcranial magnetic stimulation (TMS) is being increasingly applied in neuroscience and the clinical setup [...]
Elderly Gliobastoma Patients: The Impact of Surgery and Adjuvant Treatments on Survival: A Single Institution Experience
Authors: Bruno Francesco , Pellerino Alessia , Pronello Edoardo , Palmiero Rosa , Bertero Luca , Mantovani Cristina , Bianconi Andrea , Melcarne Antonio , Garbossa Diego , Rudà Roberta
Published: May 2022

Introduction. Elderly glioblastoma (GBM) patients often show limited response to treatment and poor outcome. Here, we provide a case series of elderly GBM patients from our Institution, in whom we assessed the clinical characteristics, feasibility of surgical resection, response to adjuvant treatments, and outcome, along with the impact of comorbidities and clinical status on survival. Patients and Methods. We included patients ≥ 65-year-old. We collected information about clinical and molecular features, extent of resection, adjuvant treatments, treatment-related complications, and outcome. Results. We included 135 patients. Median age was 71 years. In total, 127 patients (94.0%) had a Karnofsky Performance Status (KPS) ≥70 and 61/135 (45.2%) a Charlson Comorbidity Score (CCI) > 3. MGMTp methylation was found in 70/135 (51.9%). Subtotal resections (STRs), gross-total resections (GTRs), and biopsies were 102 (75.6%), 10 (7.4%) and 23 (17.0%), respectively. Median progression-free survival and overall survival (mOS) were 8.0 and 10.5 months for the whole cohort. Notably, GTR and radio-chemotherapy with temozolomide in patients with MGMTp methylation were associated with significantly longer mOS (32.8 and 44.8 months, respectively). In a multivariable analysis, risk of death was affected by STR vs. GTR (HR 2.8, p = 0.002), MGMTp methylation (HR 0.55, p = 0.007), and KPS at baseline ≥70 (HR 0.43, p = 0.031). Conversely, CCI and post-surgical complications were not significant. Conclusions. Elderly GBM patients often have a dismal prognosis. However, it is possible to identify a subgroup with favourable clinical and molecular features, who benefit from GTR and radio-chemotherapy with temozolomide. A comprehensive prognostic score is needed to guide treatment modality and predict the outcome.
Detailed Structural Characterization of Existing RC Buildings for Seismic Exposure Modelling of the Lisbon Area
Authors: Xavier Válter , Couto Rita , Monteiro Ricardo , Castro José Miguel , Bento Rita
Published: May 2022

As many European countries, the Portuguese territory is a region of moderate seismicity, and a large part of its building stock includes reinforced concrete (RC) buildings built before the introduction of modern seismic codes (<1983s). Currently, the Lisbon building stock is composed of 45% of RC buildings, of which 71% were built in such a construction period. Being designed to only sustain gravitational loads and without adequate lateral load resistance, these buildings are likely to be severely damaged during an earthquake. This highlights the need to propose reliable seismic risk assessment and earthquake loss models for such structures. In this context, the development of an exposure model which quantifies the building stock susceptible to be seismically damaged, in terms of structural characteristics, spatial location, and occupancy, is of major importance. The main purpose of this paper is to contribute the definition of a building exposure model for the city of Lisbon, focusing on a detailed structural characterization of these typologies. It starts with an extensive collection and analysis of design blueprints of existing buildings in two Lisbon’s neighborhoods: Alvalade and Benfica, which were found to be representative of the RC building stock in the city. Then, the information collected is scrutinized and statistically post-processed through probability distributions that provide a clear insight on the RC typologies and their structural characteristics. These results can be used in the future for the development of a numerical models and to derive fragility and vulnerability models, fundamental to conducting seismic risk analyses.
Selecting an Appropriate Configuration in a Construction Project Using a Hybrid Multiple Attribute Decision Making and Failure Analysis Methods
Authors: Beiki Ashkezari Ali , Zokaee Mahsa , Aghsami Amir , Jolai Fariborz , Yazdani Maziar
Published: May 2022

To successfully complete a project, selecting the most appropriate construction method and configuration is critical. There are, however, plenty of challenges associated with these complex decision-making processes. Clients require projects with the desired cost, time, and quality, so contractors should trade-off project goals through project configuration. To address this problem, in this study, an integrated FTA-DFMEA approach is proposed that implements the integrated AHP-TOPSIS method to improve construction project configuration. The proposed approach applies quality management techniques and MADM methods concurrently for the first time to improve construction project configuration considering project risks, costs and quality. At first, the Client’s requirements and market feedback are considered to identify potential failures in fulfilling project goals, and an integrated AHP-TOPSIS is used to select the most critical potential failure. Then fault tree analysis is used to indicate minimal paths. An inverse search in the operational model is performed to determine relevant tasks and identify defective project tasks based on WBS. Afterward, failure modes and effect analysis are applied to identify failure modes, and an integrated AHP-TOPSIS is used to rank failure modes and select the most critical one. Then Corrective actions are carried out for failure modes based on their priority, and project configuration is improved. This study considers construction resource suppliers with different policies, delivery lead times, warranty costs, and purchasing costs. Moreover, redundancy allocation and different configuration systems such as series and parallel are taken into account based on the arrangement and precedence of tasks. Finally, a case study of a building construction project is presented to test the viability of the proposed approach. The results indicate that the proposed approach is applicable as a time-efficient and powerful tool in the improvement of construction project configuration, which provides the optimal output by considering various criteria with respect to the client’s requirements and contractor’s obligations. Moreover, the algorithm provides various options for the contractor to improve the implementation of construction projects and better respond to challenges when fulfilling project goals.
Therapeutic Management of Advanced Hepatocellular Carcinoma: An Updated Review
Authors: Falette Puisieux Manon , Pellat Anna , Assaf Antoine , Ginestet Claire , Brezault Catherine , Dhooge Marion , Soyer Philippe , Coriat Romain
Published: May 2022

Hepatocellular carcinoma (HCC) usually occurs in the setting of liver cirrhosis and more rarely in a healthy liver. Its incidence has increased in the past years, especially in western countries with the rising prevalence of non-alcoholic fatty liver disease. The prognosis of advanced HCC is low. In the first-line setting of advanced HCC, sorafenib, a tyrosine kinase inhibitor, was the only validated treatment for many years. In 2020, the combination of atezolizumab, an immune checkpoint inhibitor, and bevacizumab showed superiority to sorafenib alone in survival, making it the first-line recommended treatment. Regorafenib and lenvatinib, other multikinase inhibitors, were also validated in the second and first-line settings, respectively. Transarterial chemoembolization can be an alternative treatment for patients with intermediate-stage HCC and preserved liver function, including unresectable multinodular HCC without extrahepatic spread. The current challenge in advanced HCC lies in the selection of a patient for the optimal treatment, taking into account the underlying liver disease and liver function. Indeed, all trial patients present with a Child–Pugh score of A, and the optimal approach for other patients is still unclear. Furthermore, the combination of atezolizumab and bevacizumab should be considered in the absence of medical contraindication. Many trials testing immune checkpoint inhibitors in association with anti-angiogenic agents are ongoing, and primary results are promising. The landscape in advanced HCC management is undergoing profound change, and many challenges remain for optimal patient management in the years to come. This review aimed to provide an overview of current systemic treatment options for patients with advanced unresectable HCC who are not candidates for liver-directed therapy.
Effects of COVID-19 Lockdown on Melanoma Diagnosis in Switzerland: Increased Tumor Thickness in Elderly Females and Shift towards Stage IV Melanoma during Lockdown
Authors: Kostner Lisa , Cerminara Sara Elisa , Pamplona Gustavo Santo Pedro , Maul Julia-Tatjana , Dummer Reinhard , Ramelyte Egle , Mangana Johanna , Wagner Nikolaus Benjamin , Cozzio Antonio , Kreiter Saskia , Kogler Angelika , Streit Markus , Wysocki Anja , Zippelius Alfred , Läubli Heinz , Navarini Alexander Andreas , Maul Lara Valeska
Published: May 2022

At the early stages of the COVID-19 outbreak in 2020, Switzerland was among the countries with the highest number of SARS-CoV2-infections per capita in the world. Lockdowns had a remarkable impact on primary care access and resulted in postponed cancer screenings. The aim of this study was to investigate the effects of the COVID-19 lockdown on the diagnosis of melanomas and stage of melanomas at diagnosis. In this retrospective, exploratory cohort study, 1240 patients with a new diagnosis of melanoma were analyzed at five tertiary care hospitals in German-speaking Switzerland over a period of two years and three months. We compared the pre-lockdown (01/FEB/19–15/MAR/20, n = 655) with the lockdown (16/MAR/20–22/JUN/20, n = 148) and post-lockdown period (23/JUN/20–30/APR/21, n = 437) by evaluating patients’ demographics and prognostic features using Breslow thickness, ulceration, subtype, and stages. We observed a short-term, two-week rise in melanoma diagnoses after the major lift of social lockdown restrictions. The difference of mean Breslow thicknesses was significantly greater in older females during the lockdown compared to the pre-lockdown (1.9 ± 1.3 mm, p = 0.03) and post-lockdown period (1.9 ± 1.3 mm, p = 0.048). Thickness increase was driven by nodular melanomas (2.9 ± 1.3 mm, p = 0.0021; resp. 2.6 ± 1.3 mm, p = 0.008). A proportional rise of advanced melanomas was observed during lockdown (p = 0.047). The findings provide clinically relevant insights into lockdown-related gender- and age-dependent effects on melanoma diagnosis. Our data highlight a stable course in new melanomas with a lower-than-expected increase in the post-lockdown period. The lockdown period led to a greater thickness in elderly women driven by nodular melanomas and a proportional shift towards stage IV melanoma. We intend to raise awareness for individual cancer care in future pandemic management strategies.
Multiphoton Microscopy Reveals DAPK1-Dependent Extracellular Matrix Remodeling in a Chorioallantoic Membrane (CAM) Model
Authors: Kunze Philipp , Kreiss Lucas , Novosadová Vendula , Roehe Adriana V. , Steinmann Sara , Prochazka Jan , Geppert Carol I. , Hartmann Arndt , Schürmann Sebastian , Friedrich Oliver , Schneider-Stock Regine
Published: May 2022

Cancer cells facilitate tumor growth by creating favorable tumor micro-environments (TME), altering homeostasis and immune response in the extracellular matrix (ECM) of surrounding tissue. A potential factor that contributes to TME generation and ECM remodeling is the cytoskeleton-associated human death-associated protein kinase 1 (DAPK1). Increased tumor cell motility and de-adhesion (thus, promoting metastasis), as well as upregulated plasminogen-signaling, are shown when functionally analyzing the DAPK1 ko-related proteome. However, the systematic investigation of how tumor cells actively modulate the ECM at the tissue level is experimentally challenging since animal models do not allow direct experimental access while artificial in vitro scaffolds cannot simulate the entire complexity of tissue systems. Here, we used the chorioallantoic membrane (CAM) assay as a natural, collagen-rich tissue model in combination with all-optical experimental access by multiphoton microscopy (MPM) to study the ECM remodeling potential of colorectal tumor cells with and without DAPK1 in situ and even in vivo. This approach demonstrates the suitability of the CAM assay in combination with multiphoton microscopy for studying collagen remodeling during tumor growth. Our results indicate the high ECM remodeling potential of DAPK1 ko tumor cells at the tissue level and support our findings from proteomics.
Is Gross Extrathyroidal Extension to Strap Muscles (T3b) Only a Risk Factor for Recurrence in Papillary Thyroid Carcinoma? A Propensity Score Matching Study
Authors: Kim Yongseon , Kim Yong-Seok , Bae Ja Seong , Kim Jeong Soo , Kim Kwangsoon
Published: May 2022

The presence of extrathyroidal extension (ETE) is associated with locoregional recurrence and distant metastases in papillary thyroid carcinoma (PTC). This study was designed to compare the recurrence risk between minimal ETE (mETE) and gross ETE (gETE) in patients with PTC using propensity score matching. In this study, 4452 patients with PTC who underwent thyroid surgery in a single center were retrospectively analyzed, and clinicopathological characteristics were compared according to the ETE status. Disease-free survival (DFS) and recurrence risk were compared between mETE and gETE after propensity score matching. The mean follow-up duration was 122.7 ± 22.5 months. In multivariate analysis, both mETE and gETE were not associated with recurrence risk before propensity score matching (p = 0.154 and p = 0.072, respectively). After propensity score matching, no significant difference in recurrence rates was observed between the two groups (p = 0.668). DFS of the gETE group did not significantly differ from that of the mETE group (log-rank p = 0.531). This study revealed that both mETE and gETE are not independent risk factors for the risk of recurrence in PTC. Our findings suggest that gETE invading strap muscles only might not be associated with worse oncological outcomes in PTC.
MAPK Signaling Pathway Is Essential for Female Reproductive Regulation in the Cabbage Beetle, Colaphellus bowringi
Authors: Huang Zijie , Tian Zhong , Zhao Yulian , Zhu Fen , Liu Wen , Wang Xiaoping
Published: May 2022

The mitogen-activated protein kinase (MAPK) signaling pathway is a well-conserved intracellular signal transduction pathway, and has important roles in mammalian reproduction. However, it is unknown whether MAPK also regulates insect reproductive mechanisms. Therefore, we investigated the role of the MAPK signaling pathway in ovarian growth and oviposition in the cabbage beetle Colaphellus bowringi, an economically important pest of Cruciferous vegetables. As an initial step, 14 genes from the extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK (P38) cascades were knocked down using RNA interference (RNAi). The results revealed that RNAi knockdown of MAPK-ERK kinase (MEK), ERK, Kinase suppressor of RAS 2 (KSR2), and P38 induced ovarian development stagnation, low fecundity, and decreased longevity, which indicate that ERK and P38 signaling pathways are important for female C. bowringi survival and reproduction. The potential regulatory role of ERK and P38 pathways in the female reproductive process was investigated using quantitative real-time PCR. We found that ERK pathway possibly regulated ecdysone biosynthesis and P38 pathway possibly involved in the germline stem cell (GSC) development and differentiation. Our findings demonstrated the importance of the MAPK signaling pathway in the female reproduction of insects, and further enhanced the molecular mechanism of female reproductive regulation in insects.