bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Different Parts on the Chemical Composition, Silage Fermentation Profile, In Vitro and In Situ Digestibility of Paper Mulberry
Authors: Hao Yangyi , Huang Shuai , Liu Gaokun , Zhang Jun , Liu Gang , Cao Zhijun , Wang Yajing , Wang Wei , Li Shengli
Published: February 2021

Paper mulberry (Broussonetia papyrifera, PM) is high protein but unutilized as a feed source. The study explores the different parts (leaf, stem, and whole plant) of PM chemical composition, silage fermentation, and in vitro and in situ digestibility, aiming to give some guidelines to PM usage as feed. The result showed that the leaf had a higher fresh weight than the stem (p < 0.05). The dry matter contents of the three groups had no differences. The highest crude protein, ether extract, water-soluble carbohydrate, ash, calcium, phosphorus, amino acid contents, and butter capacity were observed in the leaf (p < 0.05). The stem had the highest (p < 0.05) neutral detergent fiber, acid detergent fiber, and lignin contents. After ensiling, the stem silage had the lowest pH value, ammonia nitrate (NH3-N), lactate, acetate, and propionate (p < 0.05). The leaf silage had the highest pH value (p < 0.05). The lactate, acetate, and propionate in the leaf and whole plant silage had no difference. The butyrate was not detected in all silage. The in vitro and in situ digestibility experiments showed the leaf had the highest digestibility (p < 0.05), which could produce more volatile fatty acids and have a higher effective digestibility. These results allow a greater understanding of PM to be used as a feedstuff.
Early Diagnosis of Canine Hip Laxity: Correlation between Clinical Orthopedic Examinations and the FCI Scoring Method in a Closed Cohort of Rottweilers
Authors: Vidoni Britta , Bauer Veronika , Bockstahler Barbara , Gumpenberger Michaela , Tichy Alexander , Aghapour Masoud
Published: February 2021

Canine hip dysplasia is a multifactorial disorder characterized by hip laxity and osteoarthritis. The early diagnosis of hip laxity is an important topic in small animal orthopedics. This study aimed to evaluate the correlation between clinical orthopedic examinations and the Fédération Cynologique Internationale (FCI) scoring method. Thirty purebred Rottweilers were examined at approximately four (20 ± 2 weeks), eight (35 ± 2 weeks), and twelve months of age (54 ± 1 weeks), respectively. The Ortolani, Barlow, and Bardens tests and reduction/subluxation angle measurements were performed at each time. FCI scoring was conducted at the third examination time. Positive correlations were recorded between the reduction angle and Ortolani test, reduction angle and FCI score, and Ortolani test and FCI score for the second and third examination dates. No correlation was observed between the subluxation angle and other methods. Despite previous studies reporting 16–20 weeks as the earliest age for diagnosing hip laxity in dogs, in our study, early diagnosis was possible from the age of 35 ± 2 weeks. This difference might originate from the small sample size, low number of the dogs with severe grades of laxity, and breed differences.
Typology Selection of Retaining Walls Based on Multicriteria Decision-Making Methods
Authors: Muñoz-Medina Belén , Ordóñez Javier , Romana Manuel G. , Lara-Galera Antonio
Published: February 2021

In civil engineering and construction, in the selection of the most adequate and sustainable alternative, all of the alternatives and selection criteria, such as the requirements of the construction process (which are often overlooked) and the preferences of designers, clients, or contractors, are not always taken into account. The purpose of this article is to suggest a methodology that may allow studying all of the possible alternatives to find the most ideal solution among all of the existing possibilities for the selection of retaining walls to be built in infrastructures in different environments. For this purpose, all typologies of retaining walls and selection criteria (external requirements, construction requirements, characteristics of the natural land and economic criteria) are first identified. Subsequently, a simple methodological method is proposed, allowing the relative importance of each criterion to be established and allowing us to select the most suitable solution for each situation by successively applying different multicriteria decision-making methods. Finally, the methodology developed is applied to two projects in different locations with different constraints. The results obtained provide a set of compromise solutions that remain as best-rank alternatives when the weights of the criteria change. Therefore, the methodology developed can be applied to the selection of typologies of other structures in future projects.
Weld Metal Microstructure Prediction in Laser Beam Welding of Austenitic Stainless Steel
Authors: Giudice Fabio , Sili Andrea
Published: February 2021

In the present work an approach to weld metal microstructure prediction is proposed, based on an analytical method that allows the evaluation of the thermal fields generated during the laser beam travel on thick plates. Reference is made to AISI 304L austenitic steel as a base material, with the aim to predict the molten zone microstructure and verify the best condition to avoid hot cracking formation, which is a typical issue in austenitic steel welding. The “keyhole” full penetration welding mode, characteristic of high-power laser beam, was simulated considering the phenomenological laws of conduction by the superimposition of a line thermal source along the whole thickness and two point sources located, respectively, on the surface and at the position of the beam focus inside the joint. This model was fitted on the basis of the fusion zone profile, which was experimentally detected on a weld seam obtained by means of a CO2 laser beam, in a single pass on two squared edged AISI 304L plates, that were butt-positioned. Then the model was applied to evaluate the thermal fields and cooling rates, the fusion zone composition and the solidification mode.
Seg2pix: Few Shot Training Line Art Colorization with Segmented Image Data
Authors: Seo Chang Wook , Seo Yongduek
Published: February 2021

There are various challenging issues in automating line art colorization. In this paper, we propose a GAN approach incorporating semantic segmentation image data. Our GAN-based method, named Seg2pix, can automatically generate high quality colorized images, aiming at computerizing one of the most tedious and repetitive jobs performed by coloring workers in the webtoon industry. The network structure of Seg2pix is mostly a modification of the architecture of Pix2pix, which is a convolution-based generative adversarial network for image-to-image translation. Through this method, we can generate high quality colorized images of a particular character with only a few training data. Seg2pix is designed to reproduce a segmented image, which becomes the suggestion data for line art colorization. The segmented image is automatically generated through a generative network with a line art image and a segmentation ground truth. In the next step, this generative network creates a colorized image from the line art and segmented image, which is generated from the former step of the generative network. To summarize, only one line art image is required for testing the generative model, and an original colorized image and segmented image are additionally required as the ground truth for training the model. These generations of the segmented image and colorized image proceed by an end-to-end method sharing the same loss functions. By using this method, we produce better qualitative results for automatic colorization of a particular character’s line art. This improvement can also be measured by quantitative results with Learned Perceptual Image Patch Similarity (LPIPS) comparison. We believe this may help artists exercise their creative expertise mainly in the area where computerization is not yet capable.
Spotting Frozen Curd in PDO Buffalo Mozzarella Cheese Through Insights on Its Supramolecular Structure Acquired by 1H TD-NMR Relaxation Experiments
Authors: Mengucci Carlo , Rabiti Davide , Urbinati Eleonora , Picone Gianfranco , Romano Raffaele , Aiello Alessandra , Ferranti Pasquale , Capozzi Francesco
Published: February 2021

The addition of frozen curd (FC) during the production process of “Mozzarella di Bufala Campana”, an Italian cheese with Protected Designation of Origin (PDO), is a common fraud not involving modifications of the chemical composition in the final product. Its detection cannot thus be easily obtained by common analytical methods, which are targeted at changes in concentrations of diagnostic chemical species. In this work, the possibility of spotting this fraud by focusing on the modifications of the supramolecular structure of the food matrix, detected by time domain nuclear magnetic resonance (TD-NMR) experiments, was investigated. Cheese samples were manufactured in triplicate, according to the PDO disciplinary of production, except for using variable amounts of FC (i.e., 0, 15, 30, and 50% w/w). Relaxation data were analysed through different approaches: (i) Discrete multi-exponential fitting, (ii) continuous Laplace inverse fitting, and (iii) chemometrics approach. The strategy that lead to best detection results was the chemometrics analysis of raw Carr-Purcell-Meiboom-Gill (CPMG) decays, allowing to discriminate between compliant and adulterated samples, with as low as 15% of FC addition. The strategy is based on the use of machine learning for projection on latent structures of raw CPMG data and classification tasks for fraud detection, using quadratic discriminant analysis. By coupling TD-NMR raw decays with machine learning, this work opens the way to set up a system for detecting common food frauds modifying the matrix structure, for which no official authentication methods are yet available.
Painting Path Planning for a Painting Robot with a RealSense Depth Sensor
Authors: Tadic Vladimir , Odry Akos , Burkus Ervin , Kecskes Istvan , Kiraly Zoltan , Klincsik Mihaly , Sari Zoltan , Vizvari Zoltan , Toth Attila , Odry Peter
Published: February 2021

The utilization of stereo cameras in robotic applications is presented in this paper. The use of a stereo depth sensor is a principal step in robotics applications, since it is the first step in sequences of robotic actions where the intent is to detect and extract windows and obstacles that are not meant to be painted from the surrounding wall. A RealSense D435 stereo camera was used for surface recording via a real-time, appearance-based (RTAB) mapping procedure, as well as to navigate the painting robot. Later, wall detection and the obstacle avoidance processes were performed using statistical filtering and a random sample consensus model (RANSAC) algorithm.
Postoperative Clinical Outcomes of Thoracoscopic Surgery under Local Anesthesia in Patients with Primary Spontaneous Pneumothorax
Authors: Kim Eunji , Lee Chi-Seung , Cho Jeong Su , I Hoseok , Kim Yeong Dae , Kim Eunsoo , Ahn Hyo Yeong
Published: February 2021

(1) Background: since the technologies of anesthesia and surgery were advanced, video-assisted thoracic surgery (VATS) under local anesthesia (LA) has been widely carried out and is considered a robust surgical technique to prevent the recurrence of pneumothorax in patients with recurrent primary spontaneous pneumothorax (PSP). In this study, postoperative clinical outcomes were compared to evaluate the feasibility and efficacy of VATS under LA compared with general anesthesia (GA) in patients with PSP. (2) Methods: 255 patients underwent wedge resection underwent VATS for PSP in our hospital from January 2014 to June 2019. Of them, 30 patients underwent the operation under LA and the others underwent the operation under GA. Except for the anesthesia method, the same surgical technique was adopted for all patients. All medical records were retrospectively reviewed. (3) Results: the total operation time and total hospital days were relatively shorter, post-chest tube drainage was significantly shorter (0.04), and visual analog scale (VAS) scores in the outpatient clinic were significantly lower in the LA group than in the GA group (p = 0.01). The incidence of postoperative recurrence after discharge in the LA group (3.3%) was also lower than in the GA group (18.67%) (p = 0.001). In the LA group, there were no cases of conversion to intubation. (4) Conclusions: our results showed relatively better clinical outcomes in VATS under LA with sedation than under GA in the treatment of PSP. Hence, LA with sedation can be considered as a robust anesthetic technique for VATS and as applicable in the surgical treatment of PSP.
Postural Stability and Proprioception Abnormalities in Patients with Knee Osteoarthritis
Authors: Labanca Luciana , Barone Giuseppe , Zaffagnini Stefano , Bragonzoni Laura , Benedetti Maria Grazia
Published: February 2021

Knee osteoarthritis (OA) leads to the damage of all joint components, with consequent proprioceptive impairment leading to a decline in balance and an increase in the risk of falls. This study was aimed at assessing postural stability and proprioception in patients with knee OA, and the relation between the impairment in postural stability and proprioception with the severity of OA and functional performance. Thirty-eight patients with knee OA were recruited. OA severity was classified with the Kellgren–Lawrence score. Postural stability and proprioception were assessed in double- and single-limb stance, in open- and closed-eyes with an instrumented device. Functional performance was assessed using the Knee Score Society (KSS) and the Short Performance Physical Battery (SPPB). Relationships between variables were analyzed. Postural stability was reduced with respect to reference values in double-limb stance tests in all knee OA patients, while in single-stance only in females. Radiological OA severity, KSS-Functional score and SPPB were correlated with greater postural stability impairments in single-stance. Knee OA patients show decreased functional abilities and postural stability impairments. Proprioception seems to be impaired mostly in females. In conclusion, clinical management of patients with OA should include an ongoing assessment and training of proprioception and postural stability during rehabilitation.
Spatial Skills and Perceptions of Space: Representing 2D Drawings as 3D Drawings inside Immersive Virtual Reality
Authors: Gómez-Tone Hugo C. , Martin-Gutierrez Jorge , Bustamante-Escapa John , Bustamante-Escapa Paola
Published: February 2021

Rapid freehand drawings are of great importance in the early years of university studies of architecture, because both the physical characteristics of spaces and their sensory characteristics can be communicated through them. In order to draw architectural spaces, it is necessary to have the ability to visualize and manipulate them mentally, which leads us to the concept of spatial skills; but it also requires a development of spatial perception to express them in the drawings. The purpose of this research is to analyze the improvement of spatial skills through the full-scale sketching of architectural spaces in virtual immersive environments and to analyze spatial perception in reference to the capture of spatial sensations in virtual immersive environments. Spatial skills training was created based on the freehand drawing of architectural spaces using Head Mounted Displays (HMD) and registered the spatial sensations experienced also using HMD, but only in previously modeled realistic spaces. It was found that the training significantly improved orientation, rotation and visualization, and that the sensory journey and experimentation of architectural spaces realistically modeled in immersive virtual reality environments allows for the same sensations that the designer initially sought to convey.
Nanoparticles and Nanocrystals by Supercritical CO2-Assisted Techniques for Pharmaceutical Applications: A Review
Authors: Franco Paola , De Marco Iolanda
Published: February 2021

Many active ingredients currently prescribed show limited therapeutic efficacy, mainly due to their dissolution rate inadequate to treat the pathology of interest. A large drug particle size creates an additional problem if a specific site of action in the human body has to be reached. For this reason, active ingredient size reduction using micronization/nanonization techniques is a valid approach to improve the efficacy of active compounds. Supercritical carbon-dioxide-assisted technologies enable the production of different morphologies of different sizes, including nanoparticles and nanocrystals, by modulating operating conditions. Supercritical fluid-based processes have numerous advantages over techniques conventionally employed to produce nanosized particles or crystals, such as reduced use of toxic solvents, which are completely removed from the final product, ensuring safety for patients. Active compounds can be processed alone by supercritical techniques, although polymeric carriers are often added as stabilizers, to control the drug release on the basis of the desired therapeutic effect, as well as to improve drug processability with the chosen technology. This updated review on the application of supercritical micronization/nanonization techniques in the pharmaceutical field aims at highlighting the most effective current results, operating conditions, advantages, and limitations, providing future perspectives.
Switched Low-Noise Amplifier Using Gyrator-Based Matching Network for TD-LTE/LTE-U/Mid-Band 5G and WLAN Applications
Authors: Tsai Ching-Han , Lin Chun-Yi , Liang Ching-Piao , Chung Shyh-Jong , Tarng Jenn-Hwan
Published: February 2021

This paper presents a triple-band low-noise amplifier (LNA) fabricated using a 0.18 μm Complementary Metal-Oxide-Semiconductor (CMOS) process. The LNA uses a double-peak load network with a switched component to accomplish the triple-band operation. Moreover, noise reduction using a substrate resistor to ameliorate the noise performance is presented. Noise reduction of 1.5 dB can be achieved at 2.5 GHz without additional dc power and extra manufacturing costs. An input matching technique is realized simultaneously using a gyrator-based feedback topology. The triple-band LNA can be realized by using a dual-band input network with a switched matching mechanism. The target frequencies of the triple-band LNA are 2.3–2.7 GHz, 3.4–3.8 GHz, and 5.1–5.9 GHz, covering the operating frequency bands of time-division long-term evolution (TD-LTE), mid-band Fifth-generation (5G), LTE-unlicensed (LTE-U) band, and Wireless LAN (WLAN) technology. The measured power gains and noise figures at 2.5, 3.5, and 5.2 GHz are 12.3, 15.3, and 13.1 dB and 2.3, 2.2, and 2.6 dB, respectively.
Functionalization Strategies and Fabrication of Solvent-Cast PLLA for Bioresorbable Stents
Authors: Schieber Romain , Raymond Yago , Caparrós Cristina , Bou Jordi , Herrero Acero Enrique , Guebitz Georg M. , Canal Cristina , Pegueroles Marta
Published: February 2021

Actual polymer bioresorbable stents (BRS) generate a risk of device thrombosis as a consequence of the incomplete endothelialization after stent implantation. The material-tissue interactions are not fully controlled and stent fabrication techniques do not allow personalized medical solutions. This work investigates the effect of different functionalization strategies onto solvent-cast poly(l-lactic acid) (PLLA) surfaces with the capacity to enhance surface endothelial adhesion and the fabrication of 3D printed BRS. PLLA films were obtained by solvent casting and treated thermally to increase mechanical properties. Surface functionalization was performed by oxygen plasma (OP), sodium hydroxide (SH) etching, or cutinase enzyme (ET) hydrolysis, generating hydroxyl and carboxyl groups. A higher amount of carboxyl and hydroxyl groups was determined on OP and ET compared to the SH surfaces, as determined by contact angle and X-ray photoelectron spectroscopy (XPS). Endothelial cells (ECs) adhesion and spreading was higher on OP and ET functionalized surfaces correlated with the increase of functional groups without affecting the degradation. To verify the feasibility of the approach proposed, 3D printed PLLA BRS stents were produced by the solvent-cast direct writing technique.
Contamination and Potential Risk Assessment of Polycyclic Aromatic Hydrocarbons (PAHs) and Heavy Metals in House Settled Dust Collected from Residences of Young Children
Authors: Stamatelopoulou A. , Dasopoulou M. , Bairachtari K. , Karavoltsos S. , Sakellari A. , Maggos T.
Published: February 2021

House settled dust (HSD) contains various hazardous materials, including polycyclic aromatic hydrocarbons (PAHs) and metals. Exposure to toxicants contained in HSD is of paramount concern especially in the case of young children, due to their particular behavioral characteristics. In this context, extracts of sieved vacuum cleaner dust from 20 residences with young children were examined for the presence of PAHs and trace metals, in Athens, Greece. The results indicated that PAHs and metals were ubiquitous in the studied residences. The calculated enrichment factors (EF) of trace metals indicated that Cu, Se, Zn, Hg, Cd, and Pb were mainly of anthropogenic. According to the PCA analysis, the main sources of household dust were: smoking inside the houses, combustion processes, resuspension of soil dust, and vehicle traffic. In general, the cancer risk due to PAHs exposure was found lower than the threshold value. The ingestion of house dust was the most important route of exposure to metals. The dose of almost all elements for the children was found 1–2 orders of magnitude lower than the corresponding reference values. Both the carcinogenic and noncarcinogenic risks of exposure were within the safety limits.
Selective Transfer of Si Thin-Film Microchips by SiO2 Terraces on Host Chips for Fluidic Self-Assembly
Authors: Fujita Yutaka , Ishihara Shoji , Nakashima Yuki , Nishigaya Kosuke , Tanabe Katsuaki
Published: February 2021

Fluidic self-assembly is a versatile on-chip integration method. In this scheme, a large number of semiconductor microchips are spontaneously deposited onto a host chip. The host chip typically comprises a Si substrate with an array of pockets at the designated microchip placement sites. In this study, we installed an SiO2 layer on the terrace region between the pockets of the host chip, to reduce the attraction with the Si microchips. By the SiO2-topped terrace scheme, we demonstrated a significant enhancement in the deposition selectivity of the Si microchips to the pocket sites, relative to the case of the conventional Si-only host chip. We theoretically explained the deposition selectivity enhancement in terms of the van der Waals interaction. Furthermore, our quantitative analysis implicated a potential applicability of the commonly used interlayer dielectrics, such as HfO2, silsesquioxanes, and allyl ethers, directly as the terrace component.
Lady of the House: Augustina Meza (ca. 1758–1819), Print Publishing, and the Women of Mexican Late Colonial Art
Authors: Donahue-Wallace Kelly
Published: February 2021

Using archival records of the Sagrario Metropolitano and material analysis of extant prints, the paper presents the life and work of the only known woman printmaker in viceregal New Spain, María Augustina Meza. It traces Meza and her work through two marriages to fellow engravers and a 50-year career as owner of an independent print publishing shop in Mexico City. In doing so, the paper places Meza’s print publishing business and its practices within the context of artists’ shops run by women in the mid- to late-eighteenth century. The article simultaneously extends the recognized role of women in printing and broadens our understanding of women within the business of both printmaking and painting in late colonial Mexico City. It furthermore joins the scholarship demonstrating with new empirical research that the lived realities of women in viceregal New Spain were more complex than traditional, stereotypical visions of women’s lives have previously allowed.
Retrieval of Metop-A/IASI N2O Profiles and Validation with NDACC FTIR Data
Authors: Barret Brice , Gouzenes Yvan , Le Flochmoen Eric , Ferrant Sylvain
Published: February 2021

This paper reports atmospheric profiles of N2O retrieved from Metop/IASI with the Software for the Retrieval of IASI Data (SOFRID) for the 2008–2018 period and their validation with FTIR data from 12 stations of the Network for the Detection of Atmospheric Composition Changes (NDACC). SOFRID retrievals performed in the 2160–2218 cm−1 spectral window provide 3 independent pieces of information about the vertical profile of N2O. The FTIR versus SOFRID comparisons display a better agreement in the mid-troposphere (MT, 700–350 hPa) than in the lower (LT, Surface–700 hPa) and upper (UT, 350–110 hPa) troposphere with correlation coefficients (R) in the 0.49–0.83 range and comparable variabilities (3–5 ppbv). The agreement for oceanic and coastal stations (R > 0.77) is better than for continental ones (R < 0.72). The SOFRID MT N2O mixing ratios are significantly biased high (up to 16.8 ppbv) relative to FTIR at continental stations while the biases remain below 4.2 ppbv and mostly unsignificant when oceanic data are considered. The average MT decadal trends derived from SOFRID at the 8 NDACC stations with continuous observations during the 2008–2018 period (1.05 ± 0.1 ppbv·yr−1) is in good agreement with the corresponding FTIR trends (1.08 ± 0.1 ppbv·yr−1) and the NOAA-ESRL trends from surface in-situ measurements (0.95 ± 0.02 ppbv·yr−1). In the Northern Hemisphere where they are clearly detected, the N2O MT seasonal variations from SOFRID and FTIR are phased (summer minima) and have similar amplitudes. SOFRID also detects the UT summer maxima indicating independent MT and UT information. The global MT N2O oceanic distributions from SOFRID display low geographical variability and are mainly characterized by enhanced tropical mixing ratios relative to mid and high latitudes.
Ultrasound-Assisted Extraction of Carotenoids from Orange Peel Using Olive Oil and Its Encapsulation in Ca-Alginate Beads
Authors: Savic Gajic Ivana M. , Savic Ivan M. , Gajic Dragoljub G. , Dosic Aleksandar
Published: February 2021

The paper was aimed at developing an ultrasound-assisted extraction of carotenoids from orange peel using olive oil as a solvent. A central composite design was used to define the optimal conditions for their extraction. Under the optimal conditions (extraction time of 35 min, extraction temperature of 42 ℃, and a liquid-to-solid ratio of 15 mL/g), the experimental and predicted values of carotenoid content were 1.85 and 1.83 mg/100 g dry weight, respectively. The agreement of these values indicated the adequacy of the proposed regression model. The extraction temperature only had a negative influence on carotenoid content. The impact of extraction parameters on the carotenoid content was decreased according to the following order: extraction time, liquid-to-solid ratio, and extraction temperature. Ca-alginate beads were prepared using the extrusion process to increase the stability and protect the antioxidant activity of olive oil enriched with carotenoids. The encapsulation efficiency and particle mean diameter were 89.5% and 0.78 mm, respectively. The presence of oil extract in Ca-alginate beads was confirmed by Fourier-transform infrared spectroscopy. The antioxidant activity of the oil enriched with carotenoids before and after encapsulation in the alginate beads was determined according to the DPPH assay.
PA28γ: New Insights on an Ancient Proteasome Activator
Authors: Cascio Paolo
Published: February 2021

PA28 (also known as 11S, REG or PSME) is a family of proteasome regulators whose members are widely present in many of the eukaryotic supergroups. In jawed vertebrates they are represented by three paralogs, PA28α, PA28β, and PA28γ, which assemble as heptameric hetero (PA28αβ) or homo (PA28γ) rings on one or both extremities of the 20S proteasome cylindrical structure. While they share high sequence and structural similarities, the three isoforms significantly differ in terms of their biochemical and biological properties. In fact, PA28α and PA28β seem to have appeared more recently and to have evolved very rapidly to perform new functions that are specifically aimed at optimizing the process of MHC class I antigen presentation. In line with this, PA28αβ favors release of peptide products by proteasomes and is particularly suited to support adaptive immune responses without, however, affecting hydrolysis rates of protein substrates. On the contrary, PA28γ seems to be a slow-evolving gene that is most similar to the common ancestor of the PA28 activators family, and very likely retains its original functions. Notably, PA28γ has a prevalent nuclear localization and is involved in the regulation of several essential cellular processes including cell growth and proliferation, apoptosis, chromatin structure and organization, and response to DNA damage. In striking contrast with the activity of PA28αβ, most of these diverse biological functions of PA28γ seem to depend on its ability to markedly enhance degradation rates of regulatory protein by 20S proteasome. The present review will focus on the molecular mechanisms and biochemical properties of PA28γ, which are likely to account for its various and complex biological functions and highlight the common features with the PA28αβ paralog.
TRPM4 in Cancer—A New Potential Drug Target
Authors: Borgström Anna , Peinelt Christine , Stokłosa Paulina
Published: February 2021

Transient receptor potential melastatin 4 (TRPM4) is widely expressed in various organs and associated with cardiovascular and immune diseases. Lately, the interest in studies on TRPM4 in cancer has increased. Thus far, TRPM4 has been investigated in diffuse large B-cell lymphoma, prostate, colorectal, liver, breast, urinary bladder, cervical, and endometrial cancer. In several types of cancer TRPM4 is overexpressed and contributes to cancer hallmark functions such as increased proliferation and migration and cell cycle shift. Hence, TRPM4 is a potential prognostic cancer marker and a promising anticancer drug target candidate. Currently, the underlying mechanism by which TRPM4 contributes to cancer hallmark functions is under investigation. TRPM4 is a Ca2+-activated monovalent cation channel, and its ion conductivity can decrease intracellular Ca2+ signaling. Furthermore, TRPM4 can interact with different partner proteins. However, the lack of potent and specific TRPM4 inhibitors has delayed the investigations of TRPM4. In this review, we summarize the potential mechanisms of action and discuss new small molecule TRPM4 inhibitors, as well as the TRPM4 antibody, M4P. Additionally, we provide an overview of TRPM4 in human cancer and discuss TRPM4 as a diagnostic marker and anticancer drug target.
Repeated Measurements of Cardiac Troponin T and N-Terminal Pro-B-Type Natriuretic Peptide to Assess Long-Term Mortality Risk in Subjects with Osteoarthritis
Authors: Rehm Martin , Büchele Gisela , Brenner Rolf Erwin , Günther Klaus-Peter , Brenner Hermann , Koenig Wolfgang , Rothenbacher Dietrich
Published: February 2021

Osteoarthritis (OA) is associated with higher cardiovascular mortality risk. High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are well-characterized prognostic cardiac markers. We aimed to describe the changes in biomarkers measured one year apart in a cohort of 347 subjects with OA who underwent hip or knee replacement surgery in 1995/1996 and to analyze the prognostic value of repeated measurements for long-term mortality. During a median follow-up of 19 years, 209 (60.2%) subjects died. Substantial changes in cardiac biomarkers, especially for NT-proBNP, and an independent prognostic value of NT-proBNP for long-term mortality were found for both baseline measurement concentration (hazard ratio (HR) 1.32, 95% confidence interval (CI) (1.13–1.55)) and follow-up measurement concentration (HR 1.39, 95% CI 1.18–1.64) (all HR per standard deviation increase after natural log-transformation). Baseline concentrations were correlated with follow-up concentrations of NT-proBNP and no longer showed prognostic value when included simultaneously in a single model (HR 1.08, 95% CI 0.86–1.37), whereas the estimate for the one-year measurement remained robust (HR 1.31, 95% CI 1.04–1.66). Therefore, no significant additional benefit of repeated NT-proBNP measurements was found in this cohort, facilitating the use of a single NT-proBNP measurement as a stable prognostic marker.
Temperature and Concentration Dependence of Human Whole Blood and Protein Drying Droplets
Authors: Pal Anusuya , Gope Amalesh , Iannacchione Germano
Published: February 2021

The drying of bio-colloidal droplets can be used in many medical and forensic applications. The whole human blood is the most complex bio-colloid system, whereas bovine serum albumin (BSA) is the simplest. This paper focuses on the drying characteristics and the final morphology of these two bio-colloids. The experiments were conducted by varying their initial concentrations, and the solutions were dried under various controlled substrate temperatures using optical and scanning electron microscopy. The droplet parameters (the contact angle, the fluid front, and the first-order image statistics) reveal the drying process’s unique features. Interestingly, both BSA and blood drying droplets’ contact angle measurements show evidence of a concentration-driven transition as the behavior changes from non-monotonic to monotonic decrease. This result indicates that this transition behavior is not limited to multi-component bio-colloid (blood) only, but may be a phenomenon of a bio-colloidal solution containing a large number of interacting components. The high dilution of blood behaves like the BSA solution. The ring-like deposition, the crack morphology, and the microstructures suggest that the components have enough time to segregate and deposit onto the substrate under ambient conditions. However, there is insufficient time for evaporative-driven segregation to occur at elevated temperatures, as expected.
Secondary Metabolites, Ferulic Acid and p-Hydroxybenzoic Acid Induced Toxic Effects on Photosynthetic Process in Rumex acetosa L.
Authors: Hussain M. Iftikhar , Reigosa Manuel J.
Published: February 2021

The elimination of broadleaf weeds from agricultural fields has become an urgent task in plant and environment protection. Allelopathic control is considered a potential approach because of its exclusive and ecological safety measures. Plant secondary metabolites also called allelochemicals are released from plant leaves, roots, stem, bark, flowers and play significant roles in soil rhizosphere signaling, chemical ecology, and plant defense. The present study was carried out to evaluate the impact of two allelochemicals; ferulic acid (FA) and p-hydroxybenzoic acid (pHBA) on photosynthetic characteristics; Fv/Fm: efficiency of photosystem II photochemistry in the dark-adapted state; ΦPSII: photosynthetic quantum yield; NPQ, non-photochemical quenching; qP, photochemical quenching, and photon energy dissipation (1−qP)/NPQ in Rumex acetosa following 6 days exposure. R. acetosa seedlings were grown in perlite culture, irrigated with Hoagland solution and treated with allelopathic compounds FA and pHBA and were evaluated against the photosynthetic attributes. Both compounds behaved as potent inhibitors of photosynthetic traits such as Fv/Fm, ΦPSII, qP, and NPQ in R. acetosa. Photon energy dissipation (1−qP)/NPQ increased significantly from days 3 to 6. Higher dissipation of absorbed energy indicates the inactivation state of reaction centers and their inability to effectively use the absorbed energy in photosynthesis. These results indicated the potential allelopathic application of FA and pHBA for control of broadleaf weed, Rumex acetosa.
Molecular Forces Governing the Biological Function of Per-Arnt-Sim-B (PAS-B) Domains: A Comparative Computational Study
Authors: de Souza João Victor , Zaborniak Piotr , Reznikov Sylvia , Kondal Matthew , Zhu Ruidi , Bronowska Agnieszka K.
Published: February 2021

Per-Arnt-Sim (PAS) domains are evolutionarily-conserved regions found in proteins in all living systems, involved in transcriptional regulation and the response to hypoxic and xenobiotic stress. Despite having low primary sequence similarity, they show an impressively high structural conservation. Nonetheless, understanding the underlying mechanisms that drive the biological function of the PAS domains remains elusive. In this work, we used molecular dynamics simulations and bioinformatics tools in order the investigate the molecular characteristics that govern the intrinsic dynamics of five PAS-B domains (human AhR receptor, NCOA1, HIF1α, and HIF2α transcription factors, and Drosophila Suzukii (D. Suzukii) juvenile hormone receptor JHR). First, we investigated the effects of different length of N and C terminal regions of the AhR PAS-B domain, showing that truncation of those segments directly affects structural stability and aggregation propensity of the domain. Secondly, using the recently annotated PAS-B located in the methoprene-tolerant protein/juvenile hormone receptor (JHR) from D. Suzukii, we have shown that the mutation of the highly conserved “gatekeeper” tyrosine to phenylalanine (Y322F) does not affect the stability of the domain. Finally, we investigated possible redox-regulation of the AhR PAS-B domain by focusing on the cysteinome residues within PAS-B domains. The cysteines in AhR PAS-B are directly regulating the dynamics of the small molecule ligand-gating loop (residues 305 to 326). In conclusion, we comprehensibly described several molecular features governing the behaviour of PAS-B domains in solution, which may lead to a better understanding of the forces driving their biological functions.
Predictors of Mental Health Status among Older United States Adults with Pain
Authors: Axon David R. , Chien Jonathan
Published: February 2021

Poor mental health is common among older adults with pain, resulting in high economic burden and impaired quality of life. This retrospective, cross-sectional database study aimed to identify characteristics associated with good mental health status among United States (US) adults aged ≥50 years with self-reported pain in the last four weeks using a weighted sample of 2017 Medical Expenditure Panel Survey data. Hierarchical multivariable logistic regression models were used to identify statistically significant predictors of good (versus poor) perceived mental health status. From a weighted population of 57,074,842 individuals, 85.5% (95% confidence interval (CI) = 84.4%, 86.7%) had good perceived mental health. Good mental health was associated most strongly with physical health status (adjusted odds ratio (AOR) = 9.216, 95% CI = 7.044, 12.058). Employed individuals were 1.7 times more likely to report good mental health versus unemployed (AOR = 1.715, 95% CI = 1.199, 2.452). Individuals who had completed less than high school education (AOR = 0.750, 95% CI = 0.569, 0.987) or who reported having a limitation (AOR = 0.513, 95% CI = 0.384, 0.684) were less likely to report good mental health. These key characteristics can be utilized to predict mental health status, which may be investigated to better manage concurrent pain and poor mental health.
Evaluation of Seismic Vulnerability of Hospitals in the Tehran Metropolitan Area
Authors: Ghaychi Afrouz Setareh , Farzampour Alireza , Hejazi Zahra , Mojarab Masoud
Published: February 2021

The Tehran metropolitan area is extremely vulnerable to earthquakes due to the location of its active faults and its dense population. Assessing the probable damage of a high magnitude earthquake on buildings and facilities relies on a precise structural survey, which has an empirical basis depending on historic ground motions. The probability of damage and failure in discrete limits based on different ground motions is estimated by fragility curves. Using the most matching fragility curves for buildings in Tehran, the vulnerability of the hospitals in the capital, as one of the most critical structures in crisis management of disasters, was investigated in this study. Subsequently, the existing fragility curves, developed for Tehran and the other seismic prone countries such as Japan and the United States, were compared considering the typology of Tehran’s hospitals. Finally, the possible damages for each hospital were calculated based on the most conservative fragility curve and the most pessimistic scenario, which were used to evaluate the seismic vulnerability of hospitals and health care systems for different damage states. After zoning the damage of therapeutic areas of Tehran, it was observed that at least 2% to 10% damage occurred in all hospitals of Tehran, and none of the healthcare centers would remain structurally undamaged after a strong earthquake with the moment magnitude of 7 or more. In addition, the healthcare buildings could be prone to significant structural damage, especially in southern parts, which necessitates proactive management plans for Tehran metropolitan area.
HER2 Expression Is Predictive of Survival in Cetuximab Treated Patients with RAS Wild Type Metastatic Colorectal Cancer
Authors: Khelwatty Said A. , Puvanenthiran Soozana , Essapen Sharadah , Bagwan Izhar , Seddon Alan M. , Modjtahedi Helmout
Published: February 2021

The overexpressed HER2 is an important target for treatment with monoclonal antibody (mAb) trastuzumab, only in patients with breast and gastric cancers, and is an emerging therapeutic biomarker in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) mAbs cetuximab and panitumumab. In this study, we investigated the relative expression and predictive value of all human epidermal growth factor receptor (HER) family members in 144 cetuximab-treated patients with wild type RAS mCRC. The relative expression of EGFR and HER2 have also been examined in 21-paired primary tumours and their metastatic sites by immunohistochemistry. Of the 144 cases examined, 25%, 97%, 79%, 48%, and 10% were positive for EGFR, HER2, HER3, and HER4 and all four HER family members, respectively. The expression of EGFR was an indicator of poorer overall survival and the membranous expression of HER2 and HER3 3+ intensity was associated with a shorter progression free survival (PFS). In contrast, the cytoplasmic expression of HER2 was associated with better PFS. In 48% and 71% of the cases, there were discordance in the expression of EGFR or one or more HER family members in paired primary and related metastatic tumours, respectively. Our results implicate the importance of a large prospective investigation of the expression level and predictive value of not only the therapeutic target (i.e., EGFR protein) but also HER2 and other HER family members as therapeutic targets, or for response to therapy with anti-EGFR mAbs and other forms of HER inhibitors, in both the primary tumours and metastatic sites in mCRC.
Fecal Immunochemical Tests Detect Screening Participants with Multiple Advanced Adenomas Better than T1 Colorectal Cancers
Authors: Gies Anton , Niedermaier Tobias , Gruner Laura Fiona , Heisser Thomas , Schrotz-King Petra , Brenner Hermann
Published: February 2021

Background: Fecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening. The detection of early-stage cancer and advanced adenoma (AA), the most important premalignant lesion, is highly relevant to reducing CRC-related deaths. We aimed to assess sensitivity for the detection of CRC and AA stratified by tumor stage; number; size; histology of AA; and by location, age, sex, and body mass index (BMI). Methods: Participants of screening colonoscopy (n = 2043) and newly diagnosed CRC patients (n = 184) provided a stool sample before bowel preparation or CRC surgery. Fecal hemoglobin concentration was determined in parallel by nine different quantitative FITs among 94 CRC patients, 200 AA cases, and 300 participants free of advanced neoplasm. Sensitivities were calculated at original cutoffs and at adjusted cutoffs, yielding 93% specificity among all FITs. Results: At adjusted cutoffs, UICC stage I cancers yielded consistently lower sensitivities (range: 62–68%) compared to stage II–IV cancers (range: 73–89%). An even stronger gradient was observed according to T status, with substantially lower sensitivities for T1 (range: 39–57%) than for T2–T4 cancers (range: 71–100%). Sensitivities for the detection of participants with multiple AAs ranged from 55% to 64% and were by up to 25% points higher than sensitivities for T1 cancers. Conclusions: FITs detect stage I cancers and especially T1 cancers at substantially lower sensitivities than more advanced cancer stages. Participants with multiple AAs were detected with slightly lower sensitivities than stage I cancers and with even higher sensitivities than T1 cancers. Further research should focus on improving the detection of early-stage cancers.
Mutational Landscape of Virus- and UV-Associated Merkel Cell Carcinoma Cell Lines Is Comparable to Tumor Tissue
Authors: Horny Kai , Gerhardt Patricia , Hebel-Cherouny Angela , Wülbeck Corinna , Utikal Jochen , Becker Jürgen C.
Published: February 2021

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy that is either associated with the integration of the Merkel cell polyomavirus or chronic UV exposure. These two types of carcinogenesis are reflected in characteristic mutational features present in MCC tumor lesions. However, the genomic characteristics of MCC cell lines used as preclinical models are not well established. Thus, we analyzed the exomes of three virus-negative and six virus-positive MCC cell lines, all showing a classical neuroendocrine growth pattern. Virus-negative cell lines are characterized by a high tumor mutational burden (TMB), UV-light-induced DNA damage, functionally relevant coding mutations, e.g., in RB1 and TP53, and large amounts of copy number variations (CNVs). In contrast, virus-positive cell lines have a low TMB with few coding mutations and lack prominent mutational signatures, but harbor characteristic CNVs. One of the virus-negative cell lines has a local MYC amplification associated with high MYC mRNA expression. In conclusion, virus-positive and -negative MCC cell lines with a neuroendocrine growth pattern resemble mutational features observed in MCC tissue samples, which strengthens their utility for functional studies.
Spatial Heterogeneity in Large Resected Diffuse Large B-Cell Lymphoma Bulks Analysed by Massively Parallel Sequencing of Multiple Synchronous Biopsies
Authors: Magnes Teresa , Wagner Sandro , Thorner Aaron R. , Neureiter Daniel , Klieser Eckhard , Rinnerthaler Gabriel , Weiss Lukas , Huemer Florian , Schlick Konstantin , Zaborsky Nadja , Steiner Markus , Greil Richard , Egle Alexander , Melchardt Thomas
Published: February 2021

Diffuse large B-cell lymphoma (DLBCL) usually needs to be treated immediately after diagnosis from a single lymph node biopsy. However, several reports in other malignancies have shown substantial spatial heterogeneity within large tumours. Therefore, we collected multiple synchronous biopsies of twelve patients that had diagnostic or therapeutic resections of large lymphoma masses and performed next-generation sequencing of 213 genes known to be important for lymphoma biology. Due to the high tumour cell content in the biopsies, we were able to detect several mutations which were present with a stable allelic frequency across all the biopsies of each patient. However, ten out of twelve patients had spatially discordant mutations and similar results were found by the analysis of copy number variants. The median Jaccard similarity coefficient, a measure of the similarity of a sample set was 0.77 (range 0.47–1), and some of the involved genes such as CARD11, CD79B, TP53, and PTEN have a known prognostic or therapeutic relevance in DLBCL. This shows that single biopsies underestimate the complexity of the disease and might overlook possible mechanisms of resistance and therapeutic targets. In the future, the broader application of liquid biopsies will have to overcome these obstacles.